View Details

Neither of the presenters have any conflicts of interest.

Transcript editing: Al-Baab Khan, Joanie Burns

Footnotes by: Joanie Burns

Access Blog with Footnotes here.

Other Places to listen: iTunes, Spotify

This episode covers topics related to addiction, which may include sensitive content or discussions of substance use. The views expressed are for informational purposes only and do not constitute medical or professional advice. If you or someone you know is struggling with addiction, please seek help from a qualified healthcare provider or reach out to trusted support organizations. Your experience matters—help is available.

https://www.aa.org/

https://na.org/

https://al-anon.org/

Puder:

Welcome back to the podcast. I am joined today with Eric Bender. He's a repeat guest and was previously on the Shrink Next Door and thenInside Out 2. He does a lot of YouTube breakdown videos of different movie themes. He's done some work with Facebook on their most recent Batman VR video game, and he's a psychiatrist in San Francisco. He is trained in child adolescent psychiatry and forensic psychiatry.

Bender:

Thanks, David. It's great to be here again.

Puder:

And a lot of what you do is psychotherapy in your practice.

Bender:

Yes. Psychotherapy based psychodynamic is really the method I use, but adding in elements of CBT and psychoanalytic things and just trying to do what helps my patients.

Puder:

Awesome. And today we are going to be talking about The Bear, which is a TV series. How do you want to begin?

Bender:

Sure. I think it's probably good for your audience if I give a summary in case anybody's not familiar with the show. It's a show on FX that tells the story of Carmen Berzatto,or ‘Carmy,’who has inherited his family's restaurant from his brother, who had died by suicide. And so the first season – and we're largely discussing the first season, and then an episode in the second season, some of the second season – and I know the third season happened, but we'll probably focus, from my understanding, more on the first two. The first season shows what it's like as Carmy comes in and tries to elevate this restaurant from an Italian beef joint that's a hole in the wall and dangerous to something that's much more elevated, and tells the story of that – but also the people that are involved, and how they react and their own psychological makeup.

Puder:

Yeah. And so we thought we would kind of break down some of the character types of things that are going on, the personality types. We talk about the representation of a lot of psychological themes in this show.

Bender:

Yeah. I think it's almost like a psychotherapist's dream. The whole show opens up with this scene of Carmy, the main character, hearing these growling noises and going up to a cage and seeing what's in this cage and wondering what's in there. So I think right off the bat, you have this fodder for interpretation of what is that? And throughout the season, and we'll be giving spoilers here, so if you haven't watched the show and wanna watch it, you should probably watch it on your own. But we are shown that there's a bear in there. And what does that bear represent in part? It's his last name, Berzatto, which in Italian, is Bear. But what else does that represent? So there's so much here to talk about just right off the bat.

The Bear in the Freezer: How Carmy Struggles with Work, Obsessions, and Emotional Loss (00:02:54)Puder:

Maybe let's talk about Carmy as a character and all the kind of things that we know about him that have led him to be who he is. Because he's an interesting character to me. He's deep. It's not like a simple, straightforward character.

Bender:

No, he’s not. And what I love about this show is that there are such rich backgrounds to each of the characters, and they are products of where they came from, just like people not in the TV world. So Carmy was very close to his brother, Mike, who died by suicide and was also addicted to painkillers. And he really didn't even know much about that part of his brother's life. So he's here carrying on this tradition of his family. It was his parents' restaurant. His brother then had it. So he sees his brother having been there. His brother never let him work there in the years that his brother was alive. And he always felt some distance. And I think in some ways this is Carmy connecting with his brother, but there's this huge pressure to make the restaurant succeed when it's already in jeopardy.

Puder:

It's in jeopardy in many ways, right?

Bender:

Yeah. This great line in the second episode where Uncle Jimmy, who had given Mike, when Mike was alive, a lot of money to help him survive. He says, “You know, Carmen, you gotta get outta here. You gotta get outta this place. You can't start it fucked.” And that's really what people say is that this restaurant is a mess. There's health violations, all kinds of things. But I love that line because all of our patients, I feel like, come in feeling like they are fucked when they're first starting therapy. At least a large number of patients that I see will come in feeling that way. And that is where we start, that's where we start asking for help when we feel that way.

Puder:

There was a kind of a nice thing that you mentioned that this is a good show because it's not about some billionaire, it's not about some unobtainable level of success that most people will never touch, but we can fantasize about it. But-

Bender:

Yeah, it's not the White Lotus. It's not your friends and neighbors. It's not Succession. It's not about these ultra billionaires. It's about people that are working. And I think that draws people to the show. They want to understand. Not that they just wanna understand, they wanna see themselves on the screen. That's when people gravitate towards shows when they can relate to it. And who cannot relate to working hard or seeing things that look insurmountable and being angry. The amount of f-bombs and anger in the show. We were talking about it, it kind of blows you away.

Puder:

It's jarring. I binged on this the last couple days, and it was exhausting. And the noises. There's always noises. There's always chaos. There's fire alarms going off. It's like there's scenes that are quiet and peaceful and you're like, oh, thank God. And then there's these moments where everyone's yelling, everyone's upset, you know, but it's kind of realistic at the same time. Like, this is what life is like. Right?

Bender:

It is. And I think people in the restaurant business have commented that there's something the show captures just about that noise, that craziness, that everything, and for this character, I think he's so used to living in chaos, which we learn about later. His upbringing, his family. I wonder sometimes if he's gravitated towards chaos, if he, if he needs that chaos almost.

Puder:

Yeah. So, before he comes back to try to take over this dying beef joint, he's at some of the top restaurants in the world. Under some of the top chefs who seem very sort of psychopathic almost.

Bender:

Yes. The boss that's portrayed, his boss, David Fields, the chef in the show tells him, “You're useless. Faster. You should be dead.” I mean, these kinds of comments are in his ear. Literally, the chef stands over him and says these things as he is plating, as he's trying to just serve in the restaurant. And it's jarring to hear, it's really upsetting to hear. But this is the kind of noise that's always in his head. And I think he's internalized it in the show, really feeling badly about himself.

Puder:

He's internalized it, and it repeats at the most dire moments. There's this one moment where there's a fire right in front of him. Right? The stove catches on fire and he freezes and he just dissociates and he goes blank. And everyone else is rushing to save this thing. Do you remember that?

Bender:

Yeah. I remember that scene. And it harkens back to another scene. He had told the chef, Marcus, the pastry chef in his restaurant, “Hey, you made a mistake today. I made a mistake once there was a grease fire I created. And I just watched it and thought maybe if it burns, everything will burn, including my anxiety. Everything will just go up.” And I think that scene where there's this fire in front of him, part of him was probably going back to that space. Like, maybe if this all goes up, my worries will go away too.

Puder:

Hmm. Yeah. It's almost like for me, when I saw that, I was like, oh, he's dissociating. Like, people cope in different ways and you really are rooting for these characters, right? You're really like, oh, I want him to succeed. But it's like they have these defenses, right?

Bender:

Yeah, they do. And I think you're right. I think it was a dissociative moment. Not that he's actively thinking maybe it'll all go up in smoke at that moment, but I'm sure he probably felt like, oh, there's some distance. There's something between me and what's going on right now.

Puder:

Right. Or, you know, sometimes people make sense of the dissociation afterwards. Like after trauma, they may have dissociated during the trauma, they may have gone limp, they may have not been able to move, and then afterwards they try to make sense of it. And they may put words to it. May be accurate, may not be accurate.

Bender:

Yeah. But I think in here we'd be remiss not to say that, given his upbringing with his mother, and we see a clear picture of the mother during the episode Fishes, in the second season [episode 6]. The Christmas dinner where she's cooked seven fish, the mother's played by Jamie Lee Curtis. We get a sense of this chaos that Carmy was involved in in his life, the way his mother acts. And we could talk about her in a bit, but there's some trauma from there. There's some trauma from the chef that's been in his ear, his boss. There's been so much trauma. I think he has a complex PTSD here as well, along with some obsessive and very rigid features to his personality, wanting things to be perfectionistic. Being a workaholic. There's lots here.

Puder:

Yeah. The obsessive compulsive personality style is definitely there with just his gravitation towards work. And it's interesting because I feel like in that world that is celebrated almost like this perfection, right?

Bender:

Yeah. Yeah. That's why Syd wants to work there, because Carmy is so good. She can learn from him. And people want this to be perfect. At least he does. And I think the thing that I recently saw summarizing Obsessive Compulsive Personality Disorder [OCPD] versus OCD, which I thought was interesting applying to this character, is with OCD you have those intrusive thoughts and you get anxious when those obsessions are there. With OCPD, when you try to do things your way and people don't do things your way, it's not anxiety you necessarily feel, it's anger. And I think there was a lot of anger that this character expressed too. And to go back to where he started, I think that bear he's unleashing is actually himself. Like what would happen if he were just himself? I think he would be so angry. So angry, like a bear, literally. And he has the anger towards how he grew up. He has the anger towards his brother's death. He has anger towards people he works with. He's got anger towards his boss. There's so much anger there.

Puder:

Yeah, with that sort of anger and the obsessiveness and the workaholism, that's kind of like keeping that under wraps. Sometimes with patients, I'll see where they can't work any longer or it's like the obsession or the ability to control stops, right? Maybe they get a medical illness, maybe something happens, they can't control it anymore, and then their life immediately unravels, right? And so, just like with someone with borderline personality disorder, when they have a chaotic interpersonal relationship that falls apart. Someone who's narcissistic the image of themself falls apart. Someone who's obsessive, if they can't work, if they can't control their environment, if that falls apart, they can go into these more dissociated rages, more like chaotic places.

Bender:

Yes. And you brought this up, the scene where Carmy ends up blocking himself in the freezer on the night of his restaurant opening, you mentioned about being dissociative or that he was a bit dissociative or dissociating in some way. And I think in that moment, like he says, “I don't need to amuse people. I don't need to entertain people.” It's almost like he's dissociating and separating himself from everything, literally. And also, I don't think he knows how to connect with people. I don't know that he does.

Puder:

This is one of the saddest moments in my mind because his girlfriend is hearing this and he doesn't know his girlfriend is hearing this. And so he's kind of like been in this cold environment, right? He's stuck. It's like in a freezer, it's metaphorical, you're in a cage, right? And it's cold. It's reducing his sensorium. I mean, when you're hours in a freezer, it's gonna do something to you psychologically. And so he's hearing the voices of his old mentor. They're tormenting him. And he's starting to blame himself, which is kind of a depressive personality feature maybe. And so part of that blaming himself is there's a little bit of a masochistic tone to it of, “I've been enjoying life, and because I've been enjoying life, I'm now suffering.”

And so, therefore, I shouldn't enjoy life. And so in the midst of this trauma slash dissociative moment where he is hearing punitive voices from his past, he's in this freezer and he's starting to talk out loud. His girlfriend at the time, Claire, hears him, who's a lovely person, right? Who's not like the chaotic mother who's kind of like the Winicott dream. This loving, empathic person, right? And she hears this and she says a couple words, and she just leaves and she thinks it's over, right?

Bender:

Yeah. The whole thing is very heartbreaking to watch. And I think what's also heartbreaking is that Carmy really believes that about himself. I think the experiences he had, he wasn't allowed to think about himself. If he didn't think about his mother, something was gonna go wrong. And we see that played out with his sister and his brother when there are flashbacks, when his brother is alive, how they look after their mother to make sure she doesn't collapse. So he wasn't able to ever really think about himself. And when he did, he would dream of having this restaurant called ‘The Bear’ with his brother, who ends up dying. And the brother also cuts him off from even working in a restaurant with him. So, I think he has felt he should not be thinking about himself. And when he does, he's gonna be punished. But at the same time, he doesn't realize how much he's thinking it needs to be done his way, and he's pushing people away.

Puder:

It's a mixture because his brother saved money for him. And his dying words were, “Make this spaghetti sauce.” And in the spaghetti sauce was the cash, right? To build your restaurant. And so I think his brother didn't want him to work in this place because he knew his talent would be obfuscated. It wouldn't be manifest. And so I think his brother kept him at a distance for a reason, and plus his brother was doing like selling cocaine in the back, you know? Like, I think his brother didn't want him to have any of that.

Bender:

I think you're right. I also think the message that somebody like Carmy would get from that though is, “I don't love you. I don't want you.”

Puder:

He was getting from it in the midst of going through it. I think it angered him. It drove him to be better, more obsessive. To master the craft even more.

Donna, the Family, and the Seven Fishes Reveal a Portrait of Borderline Chaos and Primitive Defenses (00:15:19)Bender:

Yeah. And I agree. I think this brings up an overarching theme of what I've watched in The Bear, or a message I've seen is this idea of so many people are yelling at each other and angry. But what I see in real life, I also see in the show, which is that kindness breeds confidence. And when these characters actually are confident, things start to change. So the character, Tina, she's so mean in the beginning to Carmy and to Syd. And when she actually learns how to cook potatoes, and Syd gives her a compliment, she starts to brighten up. She's kinder. So there's this idea of being confident and then learning. And then Carmy felt, I agree with you, so angry at his brother, he goes off. It's like, I'm gonna be the best in the world and do this better than anybody else. And as he gets that confidence, he can actually move forward with his life. But he's still stuck with a lot of this psychological trauma from his past.

Puder:

So, let's go back to the Fishes episode, season two. So it's this glimpse five years before, and they're at this family dinner and their mom is making the seven fishes meal, which is a big day-long ordeal for her. So she's cooking in there and she's drinking some alcohol. I saw that- I think Sugar, one of the daughters, is dumping vodka down the-

Bender:

Yeah, the daughter's actively trying to dump out vodka and dump out alcohol when she finds it.

Puder:

And she's kind of like the glue of the family, you know? But she gets beat up by her mother, psychologically blamed. Her and Carmy kind of get this treatment from the mom. And the mom is like one minute, she's very self-deprecating, very hostile towards herself. And then the next, she's just in this absolute rage. And she's like, back and forth, back and forth.

Bender:

I think she really embodies a lot of the borderline traits. There's this unstable sense of self. There's this fear of abandonment. Her telling Carmen, “I had to beg you to come home. Why didn't you wanna come home?” When she feels abandoned by anybody, she really feels terrible about herself. There are these suicidal gestures, including driving her car through the house. Now it's arguable whether she wanted to kill herself or just make a point that she was angry at anybody. But that rage that comes out of her too. I think a lot of these fit borderline traits and for the kids to grow up this way, it was really hard. Sugar even makes a comment, “I'm left to deal with this because you guys,” she's telling her brothers, “You guys are the way you are. I'm the one that has to make sure that everything's all right.” And that's really interesting because her brothers keep saying to her, do not ask, “Mom, are you okay?” Don't ask her if she is okay. But that was her job. And even her name, Sugar, comes from her adding a cup of sugar instead of a quarter cup to the sauce recipe. And that's why they call her Sugar because it was so overly sweet. But that's funny because that was her trying to do something good. And she's just known by that name, by that moniker.

Puder:

Interesting. Yeah. I recently had Kernberg on the episode and we talked about borderline level of functioning. And Donna definitely meets that, right? The borderline level of functioning. So there's the identity diffusion, you know, what is her identity? Is it mother? Is it nurture? Is it victim? Is it martyr? Is it the person that everyone hates? Is it the person that hates herself, right? And then there's the primitive defenses of splitting. So this is going to be the perfect dinner, I am the greatest host, right? And then I ruin everything.

Bender:

Yeah. I should just take a gun and go shoot myself right now, she says.

Puder:

Back and forth, back and forth, right? So there's splitting of herself. There's splitting of other people as well. Like her son. You know, “Oh, you have abandoned me. You won't come back once a year.” And part of that is not really seeing him and empathizing with his experience of this.

Bender:

Yeah. And that's what I find really interesting. It isn't seeing him, he wasn't allowed to be seen. He had to make sure the mom was okay. And then he is getting that message at work as he is training from his terrible boss, telling him you're nothing. You don't mean anything. And then there's the scene in that Fishes episode where the older brother, Michael, is being told by a family relative, someone who's not really family, but they call him uncle, “You're nothing. You're nothing. You're nothing.” He's getting that repeated. And then Sugar's essentially gotten that message too, that she's nothing. She's there to take care of the mom. So everybody has this idea that they don't matter. And that's what I was talking about in terms of kindness and confidence when you could start to feel like you matter. Maybe some of those things aren't as painful or you can move forward. But all those things you just mentioned are there that identity diffusion, all of that is there with this mother character. But she's impacted her kids too, in ways she can't see.

Puder:

Yeah. And it's not just like one incident between her and her son. It's like hundreds of incidents. Thousands of incidents. And the way he interacts with her is reminiscent of so many situations I've seen where it's like you have this image of the chaotic, impulsive, aggressive mother, and then he's calm and it doesn't look like he's lying, you know? I think he has been avoiding coming home to some degree. I think there is some truth in that. But he's like, “Mom, I'm here. I love you, mom. You did a great meal today.” You know, like, he's calming. “You don't love me.” And then one little thing said wrong, just sets her off. And it's almost like there's a misinterpretation in the midst of that as well.

Bender:

Yeah. I think the way the mother hears things in her state, which is fueled by alcohol as well at this point, it all comes in so negatively to her. And it's really painful for people around her to see, it's painful for them to have to take care of her, to have to make sure she's okay. It's a really, really awful scene. I've actually had some patients react to that episode, come and say, “That reminded me of a lot of things in my family, or that reminded me of the relationship I had with family members.” So it really did resonate with a lot of people because it's so ugly. And it's so hard to watch sometimes.

Puder:

Yeah. And it's interesting in this kind of family tension, you see spouses that didn't really have this, you know? And they're just like watching it, but it's like newer for them. But a couple of them are more like the passive acquiescing, like not wanting to worsen the situation, you know? Or like, maybe slightly making a mistake. Like this one guy brought an extra fish.

Bender:

Sugar’s husband, Pete, brings this tuna casserole and everybody starts getting furious. And it's funny because I think they're trying to make sure they don't- that the mom doesn't see it because she would get set off, but they end up getting set off very much like the mother. They all have those same kind of reactions to that fish.

Puder:

They know how painful it is for the mother to go from seven fishes to eight. And, and just even imagining that for them makes them like irate, right? And protecting, like, no throw it away. They throw it away. It's like, and he's just like, “Oh, I was just trying to do something nice”, you know? But it's this idea that they've been trained to try to not make her volatile.

Bender:

Yes. And if you think about it for our patients that go through that, or someone who's a child of a parent like that, it is really, really painful. And you have to be hypervigilant about life. You have to look over your shoulder all the time, make sure everything's okay. If that's the role you have, that breeds anxiety. It breeds an inability to think about what one wants in life because you're constantly thinking about something else. Everything is dangerous. Things can be flipped at any moment. It's really awful to watch that and to think about this as being maybe a series of hours in their life. But as you said, how many thousands of episodes or incidents happened before this episode?

Puder:

Since talking a lot about the personality styles on the podcast, people are like, well it seems like this is a trauma response or everything's a trauma response. I think we're talking about almost two different things there. Because even though there's a set of coping strategies that different people might have to specific types of traumas and specific types of situations, and different people can have different responses—like a depressive personality, they take all of the guilt on themself. Maybe the obsessive compulsive personality takes that anger and they drive it into productivity and they drive it into controlling their environment and being obsessive. And yet underneath it maybe some common threads, right? Like, how are they dealing with this awfulness?

Bender:

Yeah. And I think you're right to split it up that way by looking at the personality style in Kernberg's way, and then also looking at the reaction to that and what that that breeds in people. And I think it can be very traumatic. It really can be. I see that in real life, talking to people who played a role in their life very much the way Sugar did, or people who have distanced themselves from the family either willingly or not and what that's like. Also knowing that being away from your family might be healthier for you. I really liked, in that episode of Christmas, the Fishes episode, where the cousin Michelle stops Carmy and pulls him over to the side, saying, “I've been wanting to talk to you. I see what's going on here. You need to come to New York and stay with me for some time. I have some restaurants. It's better for you.” It was really heartening to say, “Wow, somebody sees this is a mess.” He needed a family ectomy at that point.

Puder:

And I thought, what a gift as well. Like, I'm gonna take you to some really good restaurants. I'm gonna help you get back in touch with this love of food because I see that in you. I see your giftedness and I wanna help you in that passion of yours. That was beautiful, and then she was like, “You're gonna come.” And she was like, she knew that he probably wouldn't come as well.

Bender:

She said, “I'm gonna hold you to this.” And there have been countless times where I'm with patients and they wished they had had somebody do that for them when they were younger. They told me, “If just somebody could have seen this or said something to me”, or they'll be in therapy and they'll feel like they're making progress and said, “Why couldn't I have had a space like this when I was younger?” And cousin Michelle offers him that space.

Puder:

I think when it comes to- I would say the patient- but the main character, it's like when he starts dating Claire, we're like, oh, he's getting that space. He has this person. At first I almost was like, is she too good to be true? And they were even joking around with him about it five years prior at this, like this seven fish meal. Like, she's too good for him. You know, and so there's this feeling of oh, he's found something really loving and really good. And he's waiting for the shoe to drop. I have patients who get into these loving attachment relationships, but they're so primed to chaos that it's almost hard to even just settle themselves into it, you know?

Bender:

Yeah. I think so. And what stuck out to me when you said that phrase prime for chaos, what I've found people react to sometimes is they'll say, “Oh, The Bear's too chaotic. It's too crazy. I don't wanna watch it.” But I think they've done a really good job of conveying the chaos these people live in, whether that's in their head or in their life, or both. And I think they do that really well with Carmy.

Puder:

Yeah. I think getting back to the mom, because I feel like there's a lot there that we could go through. Some of it is also in the sort of borderline level of functioning, the primitive defense of projective identification where she accuses others, like Carmy and Sugar, of rejecting her, right? But it's clear that this is her own self-hatred that's being projected outward and then, potentially, these people are gonna grab onto it and start to behave towards her, right?

Bender:

Exactly.

Puder:

And that would be the projective identification if they start to identify with the projection, which can often happen to people who are living in this kind of primitive defense. But instead, often they're calm, but they also do move away. They do kind of give her more and more space.

Bender:

They do. And what the brothers kept saying to Sugar not to say is, “Are you okay?” And at one point Sugar ends up asking, “Are you okay?” And she says, “Do I not look okay?” And Michelle says, “No, you don't.” And I think that's an example of what you're saying. That people are picking up on this, people are feeling something and they just can't reflect it back to her what they feel, otherwise she goes unhinged.

Puder:

Yeah. Another defense is idealization devaluation. So she (the mother) has this fantasy of this closeness with her kids. So she kind of has this ideal of, “I'm gonna be this great mother. I'm gonna cook this meal. I'm gonna have this closeness.” But then when they have any boundaries or they assert themselves, she'll rapidly devalue them right? Or she'll also, like, she shows up to the opening night of the restaurant, The Bear. And then she's like, “Oh, I'll destroy it.” So she devalues herself. So it's like this kind of back and forth, which it's painful to watch. Painful.

Bender:

Yeah. And I think sometimes we can see people do that too. See patients go devalue themselves and then back and forth, back and forth. And it's really hard to watch knowing that that's real. I think that's one reason why people might gravitate towards this show and also want to get away from it. There are real things that happen and people really do go through that.

Puder:

Yeah. I think there were times where I wanted to stop watching.

Bender:

Yeah. There are shows that I watch where people ask me, “Oh, can you take a look at this?” I'm like, “That's too much like work. I just don't want to do that.”

Puder:

That's happened a number of times between us. I'm like, let's watch, let's do this biography. And actually through this experience, I'm like, “I'm done. I want time off.”

Bender:

Yeah. You'd asked me about doing nonfiction. And my answer is the same to a lot of people as I feel like I've lived so much nonfiction with people. It's such a privilege to sit through their non-fictional lives. That at the end of the day I want something fictional, but when there is this crossover, it's an interesting thing to talk about. It's an interesting thing to understand my own reaction to.

Puder:

I can resonate with that though. I've been reading some Kafka and he wrote this letter to his father, and it's really sad though. It's really sad. And so sometimes I'm like, why is this so hard to get through? And it's because every line or every paragraph it's like I kind of know what this is like, you know, and this is a real story.

Bender:

Yeah.

Puder :

And so I could see why you would want some distance from like, okay, if it's fiction, if it's a story, it gives you some, it's like a little bit different for you.

Bender:

Yeah. And I really like the psychological depth that shows today seem to have, this being one of them. And then having a chance to add that depth to say characters doing some of the consulting I do. That's really rewarding because people want real characters and sometimes it just feels like it's too real. And some of the scenes here, it's like, “Oh, that reminds me of this or this”, or having seen this in a patient or in my own personal experience or whatever it is.

Puder:

Yeah. Absolutely. I think there's kind of a new wave of film and movies where people want that, like psychological depth in the depth that maybe we see in therapy. I had a patient today who was like, “You know, they say that real life is crazier than a story,” because she was telling me this story of her real life, and she's imagining me listening to this and that is kind of true, right? And so I feel like sometimes novelists or writers are only as good as their experience and their collective experience.

Bender:

And I felt like somebody in this show, somewhere in the writer's room—producers, directors, somebody—had a lot of experience with mental health or treatment or something. Because there are hidden lines where it's like, oh, is that aimed at a psychiatrist or a therapist? For instance, in one of the last episodes of season one, Fak is trying to fix the game, the ball breaker game, which is supposed to be this clone of Mortal Kombat. And he's looking at the game and he goes, “Do you ever get sad?” And the guy goes, “Of course I do, Neil, but I never let it out because I use all of that to beat the shit outta people.” So it's just, there's something there, like somebody understood that there are levels to emotions and what people do with them and how they respond to them. And you're right. It's coming out in shows. And I love that it even was mentioned here.

Puder:

I was like, “Oh, is this guy schizophrenic?” Because sometimes people with schizophrenia, they'll hear messages from their TV or, you know, they're hearing music references. They'll feel like the message is directed at them. And so I was like, oh, are they trying to portray kind of a pseudo of what that would be like? And I don't think it would look exactly like that, having had schizophrenic patients. But are they attempting to know?

Bender:

Yeah. I think it's just, again, part of this, okay, what are people doing with their emotions? Sometimes they're just holding them inside and it's causing all kinds of problems. It comes out in other ways. And that's what I often tell people is if you try to cut off your anger, it's gonna come off in ways that just don't serve you well. If you try not to feel sadness, it's gonna come out in another way. And, so that, I just had to laugh at that scene because it's kind of ridiculous. But it's also so true to hear that about people: I don't talk about my emotions. I just hold it inside and it comes out another way.

Puder:

Yeah. Okay. Going back to Donna because I feel like there's more to tease out.

Bender:

There’s a lot there, right? I know we're jumping around, but that's the way the show works too.

Puder:

Yeah. It's the way life works. The normal conversation jumps around. So I think it's really helpful to get into the different personality styles. So there's the obsessive, we talked about more of the depressive, and there's also a histrionic style. Which is kind of Donna—this volatile, emotional, excessive, dramatic, theatrical way of interacting where they need to be seen, admired, appreciated. They can sometimes be seductive or dependent. When it's healthy, there's this warmth or charm. And when it's pathological, there's this manipulative, shallow, prickly, especially when attention is withdrawn. So did you see that at all in Donna?

Bender:

I absolutely saw that. I think she said, “I make this beautiful meal and nobody gives a shit. Nobody cares about it at all.” And nobody's really asking for that meal. I'm sure people just want to come over and have pizza. That would be fine. But, yes, she has to be the center. There's this aspect of everybody needs to pay homage to her and attention: “Oh, this looks so beautiful, this looks great. This is amazing. You spent days on this.” But it's still not enough for her. But she absolutely needs to be the center of attention. And I don't know if you notice too, but she'll be in the kitchen and on the ground, and then she gets up and she'll take a few minutes and the next scene, like, her hair is perfect again. I don't think it's just a makeup thing. I think it was actually like she took time to make sure she looked nice again. It was very interesting when you think about the histrionic style.

Puder:

And going back to this freezer scene. Carmy’s in there, he just said the thing to Claire, Claire's walking away. His family member—

Bender:

A cousin, Richie. Yeah.

Puder:

Cousin Richie sees Claire walking away crying. He knows something's up. He knows the pattern of it, of what's going on. So he goes to the freezer and he's like, “What did you say?” And he calls Carmy what?

Bender:

He's like, “Okay, Donna”, calling Carmy his mother's name. Like, you've turned into your mom right now. You've totally sabotaged it. She can't let anything nice happen to you. You can't let anything good happen. And I caught it. I'm like, oh, wow. He knows. Richie, even though he is not a blood relative, he was the best friend of Mikey. He's been around the family long enough to know there's something wrong here with the way she goes about life and Carmy’s showing signs of it.

Puder:

Yeah. It's kind of a more masochistic self-defeating style of interacting with the world, right? To feel guilty from receiving help or being happy.

Bender:

Yeah. And what's really fascinating in that scene is there is exactly that response you described. And as Richie's yelling at him, “Can't you let anything good happen? Why do you have to sabotage this stuff?” Then he says, “I love you.” He can't even hear that. Carmy can't even hear that. He just continues to feel terrible about himself and also starts hurling insults at Richie too. So it's this really dysfunctional piece that just gets illustrated in this horrible moment.

Puder:

It's so painful to watch people being nasty to each other too. I'm like, “Oh guys. Oh, oh man.”

Bender:

Yeah. I feel thankful when there are scenes of, okay, this is how many forks we have and this is how much the napkin bin should be, or whatever it is. It just, it feels like, okay, that's a break from just chaos sometimes.

Puder:

And isn't that interesting? Is that there's that obsessive component. That's sort of spruced in the order. Like, I want that order in the kitchen. I don't want everyone to be yelling. I want everyone to be doing their specific job, right? I want more order. So I'm wanting the obsessiveness.

Childhood Role Reversal and Emotional Neglect Disrupt the Capacity for Genuine Adult Connection (00:38:26)Bender:

Yeah. And I found, sometimes, the people who have that kind of obsessiveness. I'm not sure about your experience, but as a therapist, something often was so chaotic and so out of control in individual's lives that something obsessive helps them feel like, “Okay, I can get through this.” Or if they really focus on this or they put their energies into this, or it's gotta be clean, it's gotta be perfect. It takes them away from chaos that they're experiencing and they funnel everything into this thing. They know how it should go. It's predictable.

Puder:

Yeah. And I think there are clinicians with high functioning forms of this style, right? So once again, I don't see these as disorders either. They're styles of how we interact. They're groupings of defenses. They're, at a higher level of functioning of that, in business, in practice, you can have very organized systems that allow you to accomplish great things for patients. And so you can have places like a kitchen that are just thriving, but the interpersonal life when that obsessiveness gets turned on romantic relationships that's when it becomes difficult.

Bender:

Yes. Yeah. It totally does. And you can't control somebody else. And you shouldn't try.

Puder:

Or because the vulnerability, which is like underneath the obsessiveness or the real emotion is hidden, right? So, underneath the working, underneath the obsession, is the real person, which is hidden. And so the partner gets this more intellectual version of you. They get more of the reaction formation. Like they get you human doing, not human being. It's harder to connect with. And then when they try to push through that, it can feel very destabilizing.

Bender:

Absolutely. Yeah. And are there any characters you're thinking of in particular where you see that or were you-

Puder:

I'm just thinking more from my clinical practice in regards to this, but I imagine this is kind of when Carmy had the obsessive structures of his kitchen disturbed, right? This is when he's psychologically unraveling. And so if I were Claire with all that I know as a psychiatrist in the midst of this, I would be like, “Hey, you know, your structure and your desire for control of the kitchen is phenomenal. And I fully embrace that. And at the same time, it's really hurtful to diminish what's going on between us. And I think that this is like one of the most peak stressful moments of your life. And so I think we need to kind of like, just have some grace for each other, get through this, realizing that this may be coming out of more than just our dynamic because you're stuck in a freezer. You're cold. You're tormented by the voices of your ex boss; of your mom. And so you're in this traumatic state. And it makes sense that you're in a place where you wanna push away.”

Bender:

Yeah. And that's what he's doing. He does push her away and she does want to go away. And I think that's very much something he saw with his mother. She wanted people close, but she pushes them away. And that's his reaction in this horrible moment to do the same thing. And it's probably not a conscious thing, but that's just what happens.

Puder:

And, and for him, like having an more avoidant attachment style was adaptive with his mother. Because he needed to show no emotion. He needed to dissociate in that dinner. Like he needed to go flat faced in order to try to help regulate her. And so having that more avoidant attachment style was actually adaptive.

Bender:

Yep. And I don't know about you, but I see that a lot more people will have either an avoidant attachment style where they'll have other things, behaviors, ways of thinking about things that serve them well when they were just trying to survive something pretty traumatic. And then later on it doesn't serve them well anymore. It's not helping, it's actually hurting. So that's where a lot of the work is. As you said, the way you described it, Claire would almost be like a therapist to say, “Hey, you're going through this right now and we should think about where else this is coming from.” But that's not her role. She's the girlfriend. But that is what a therapist would be able to do with him just to say, “Hey, look, this is pretty amazing, this control you have here. I wonder if that's serving you well in the rest of your life.”

Puder:

Right. If it was a good EFT therapist and he's frustrated that he feels out of control, eventually the EFT therapist is going to get him to voice some deeper emotions. Sadness. Loneliness. This feeling of powerlessness, maybe. And then when she hears that, the EFT therapist may then turn to her and say, “I heard that you heard the anger, but have you heard the sadness? Have you heard the loneliness? Is that new to you?”

“Yes, it's new.”

And then she probably would have an emotional reaction of like mutual sadness or mutual, like maybe some empathy for him and how his defenses have led to him needing to be like this. And then she would turn to him and maybe voice, “As I hear this, I feel distraught for you. You went through a lot as a kid. And of course it makes sense that you would want to push away.” So when, when we talk about avoidant or anxious attachment, it's like, do they move towards the other person in distress or do they move away. And he's the type that in the midst of the distress, he moves away. There are some people that move towards.

Bender:

Yeah. I also think, as I've mentioned earlier, he doesn't know how to attach largely because he had to be detached from his mother. We don't know much about his father. Maybe that will come up in season four when it starts at the end of this month. But we don't know why his father's not present. We don't know exactly all of this information, but we do know it's really hard for him to connect. And it was probably safer for him not to.

Puder:

There are moments where he's got this softer, gentler side towards different employees, or Sydney, and his connection with her, right? And then he goes into more anger. The outbursts. Interestingly, I posted this on X before, to get what people's takes were. And this one person thought he was narcissistic, which I tended to not think of because usually there's an emptiness in there. Whereas, more of the depressive personality has a lot of the negative voices in their head. Whereas, the more narcissistic, it's like there's a void. There's a nothingness in the core of that psychological sort of thing, you know? And then also with the more narcissistic, the vulnerable narcissist, you get more of the desire to protect your image. Which I don't really necessarily see that much.

Bender:

Yeah, well, I think he was concerned about his image, but only so much as it would impact his restaurants. And that's why in the third season he's eagerly anticipating this review of the restaurant. But I agree. I don't see as much narcissism. Maybe it seems like he is not empathic, but I think it's more obsessive. And I think he is more angry when things don't go his way. And there are moments, like you said, where he does tend to connect with an individual in the restaurant when he is encouraging Marcus, or in the first season, he's encouraging Syd. There's those moments but it doesn't seem to last. My suspicion is that he ends up feeling so terrible about himself and so bad and so awful that that disrupts any kind of connection he has. Like he doesn't deserve it, which is what he's saying in the freezer. I don't, I can't have this.

Puder:

Yeah. It's like that sort of masochistic depressive type of features of his personality that keeps him from seeing reality. Because with all of these things there's gaps in the reflective function. There's specific gaps within each personality style in how they're going to accurately see other people. And so it essentially brings the focus back into him a little bit and doesn't allow him to see other people and their unique experiences idiosyncratic and attune to them because he's kind of internally beating himself up too much.

Bender:

Yeah. I always- I shouldn't say always- I often will say to people, “It's hard to give to someone which you didn't get.” And I think with a lot of work and therapy, people can start to understand those things and then they can be a better friend, parent, spouse, partner, whatever it is. But it is really hard for him to do that, I think because it wasn't really modeled for him. He did feel like he had his brother there supporting him for a long time, but then it stopped. So, I think it's been really hard for him to do this consistently.

The Depth of Addiction, Guilt, and Powerlessness in Mikey’s Life (00:47:41)Puder:

And his brother's own issues created a lot of that disconnect. His brother's addiction to opiates. Maybe other drugs. We don't really know. His brother's a little bit more hotheaded, it seemed. He's a little bit more prone to anger. At the fishes meal he almost gets into a full fist match with this other guy.

Bender:

Yeah. He's throwing a fork at his, again, not a familial uncle, but a close family friend. He does that a few times. But that's worth talking about, too. There's the addiction. We don't know a ton, but this show depicts Carmy going to Al-Anon. Actually, Molly Ringwald is someone, an actress, who's portraying someone talking about what it's like to blame oneself for the addiction issues. And when she was with someone who had an addiction issue. So we see real life Al-Anon meetings, or what are supposed to be, are very accurate. And then Carmy shares what his experience was. So I really like that they do delve into that. It's really helpful, I think, for people because even though we're talking about fiction, people get ideas from fictional shows. So it's good that it's being done accurately.

Puder:

There's this moment in the Fishes episode where they're having an exchange, his brother. And externally he looks like he's doing pretty good, but there's this moment of kind of introspection where you see him and his face kind of goes downcast. And that's where I was like, oh, sometimes with patients they'll have this social veneer. They put off this, “I'm doing great.” But then they have these moments where you're like, oh, I feel their deep despondency or depression or I know what's coming ahead. I know I'm not going to want to live, you know, type of thing.

Bender:

Yeah. And I'm not sure if you're referring to this one scene where Carmy is at home for Christmas and talks to Mike, his brother. And this is a flashback before Mike has died and Carmy says, “Oh, I have something for you”; and he gives him a Christmas present. The present is a framed picture of what their restaurant, The Bear, could look like. And Carmen gets called away because he has to bring crackers to his mom. But you see Mike just cry, just crying. And maybe it's because he doesn't know how this is possibly gonna happen. He can't imagine it. Or he's actually feeling the love and admiration his brother has for him and feeling a connection that he probably hasn't had other than with his brother. So, there's a lot of powerful emotions in that scene. And in that episode.

Puder:

Maybe he's in the throes of his addiction and he knows he can't escape it fully, right? And it's consuming him in ways he didn't intend it to be consumed.

Bender:

Yeah. I think that's right. The uncle that he does get in a fight with later says, “Whatever haze you got going on right now. I don't know what you're on. If you could see through that.” So there were clearly signs that he was having problems and maybe he realizes, “I'm too far in to actually ever see this realized. This picture is the closest I'm gonna get to seeing this thing happen.”

Puder:

It's tragic. I feel like I have a bunch of patients who have relatives or people close to them that ended up dying from their own choices or from their own struggles. Maybe it's an overdose. Maybe it's a suicide. It's truly tragic.

Bender:

Yeah. It's one of the hardest things I see. And I have a colleague that specializes in addiction psychiatry, and I'll refer families to that person if that's an issue. But it is really tragic.

Puder:

It's kind of like the grief never ends completely, right? There's waves of grief that just kind of continue.

Bender:

And actively mourning somebody when they're alive, but are in the throes of addiction because that relationship you had doesn't feel like it's ever gonna come back.

Puder:

I get families that reach out and they want some solution. They want some help with their loved one. And it's really, really tough because just as they feel powerless, you can feel their powerlessness as a provider.

Are there other themes in the show that you wanted to hit on?

Spotlighting Dreams, Language, and a Relatable Struggle in The Bear (00:52:25)Bender:

You had mentioned dreams. There are just so many dreams that are depicted here. I thought of an interesting one. Again, we don't know a lot about this character, but Uncle Jimmy is telling Carmy about a dream that Uncle Jimmy himself had about Carmy’s dad. He says, “Back when we were talking,” suggesting maybe there's a falling out. And he does comment on that too. But the dream is that he and Carmy’s dad are driving with their friends. Carmy’s dad's in the front seat and they're driving through this area and all of a sudden a kid comes out onto the road and they stop a millimeter before hitting the kid, but the dad goes flying through the windshield. He wouldn't wear a seatbelt. And in the dream, the dad just keeps going and going and going and going. And Uncle Jimmy's talking about this. And to me it suggests, I don't know what the dad was involved in, but one interpretation is the dad was just gonna keep on doing what he was doing and no one could stop him. And maybe that's something like Michael has, maybe that's some kind of addiction. Maybe it’s references to gambling and bad business decisions. I don't know what, but to me it represents how when somebody is in the throes of addiction or maybe making decisions, as you said, that lead to their demise, you can't stop them. You can be there for them, but they have to want to change themselves. And then you can be there for them. But you can't literally hold them back from doing what they're gonna do.

Puder:

Yeah. We would like to imagine that we could have that power, right? We would like to have some omnipotent control. But we don't. And yeah. I love doing dream work. I often ask patients if they have had any new dreams because it's really telling—they’re glimpses into their inner world in a way that maybe they can't even express in words outside of the dream. The primitive emotions, sometimes it's just what's happening the day before. Sometimes it is that nightmare, right? Like, Carmy’s nightmare of his boss yelling at him.

Bender:

And then there's a nightmare that he had. I don’t know if you remember the scene, it opens up one of the episodes where he's on a TV show, a cooking TV show, and he turns around and someone's stolen his knives and then someone's stolen the meat. So he is left without the materials he needs to accomplish his goal. But there's clearly messages there, like, is he gonna be able to do this? Is he gonna be prepared? Is he gonna have everything he needs? What's gonna happen? Are people gonna sabotage him? So there's so many themes and dreams that come out here. And that was another fun part of The Sopranos, as a side note, you know, seeing all the dreams in that show too. So it's cool to see dream work back again in some of these TV shows.

Puder:

Yeah. It's, you know, that sort of performative anxiety. It's one thing working for someone else, especially if you're working for someone that reminds you of a family member. It's another thing to launch your own thing, and launching your own thing brings unique anxieties and fears. And I think that that gets manifested sometimes in dreams and kind of stepping out into the unknown, right?

Bender:

Yeah. The questions of your worthiness, your abilities, your, your confidence, all of those things come up and that's what's happening there is he's trying to revamp this joint.

Puder:

Yep. Any other themes we wanted to touch on before we kind of wrap up our time here?

Bender:

There was a great line in episode six in the first season where Sugar says to Carmy, “I'm really mad at you. You never ask me how I'm doing. You never ask me.” And Carmy's reaction is, “I guess all the time I feel like I'm kind of trapped because I can't describe how I'm feeling.” And he goes on to say, “So to ask somebody else how they're feeling just seems, I don't know, insane.” And I thought that, I remember that again, is really telling about this character. I don't know how I feel. I'm trapped by not knowing how I feel. And I think that is so true for so many patients that I see. I get lots of calls from people saying, I need you to see my partner. I need you to see my husband. I need you to see my wife.

Bender:

And it turns out, after starting to work with some of them, many of them don't even know the words for how they feel. They'll tell me, “Yeah, I'm not really good with feeling.” So I'll ask them, “Do you know what you feel some of the time?” And a lot of times they say, “Actually no, I don't think I do.” So there's a lot of work to be done there. And here's this character who feels this way. He's not in therapy, at least in the first season, he's going to Al-Anon, which is probably close. But his sister's saying, “You should think about how other people are doing, and I want to be close to you.” I think another way the message will come out of that conversation she has with him. And again, there's his limitations.

Puder:

Yeah. When he said that to her, I felt sad for her too, though. I felt sad. Because, you know, it's often the person that's maybe a little bit more healthy in the family that gets missed the most. Yeah. I felt for him, he's dissociated and needed to dissociate from any feelings. If you're in a family structure with a mom like his, and you get angry, like the hell that you have to pay for it is not worthy of the amount of anger that you're gonna express. So it's better to just dissociate and then to put on a nice face or to behave or to try to say soothing words. And so patients like that, they could have a difficulty in getting in touch with what they really feel. Sometimes I'll start to feel for them, or I'll see their facial expressions, kind of see what emotions might be there.

Sometimes it'll come out as a bodily sensation, like a tightness in their chest or heaviness. So it's like almost just describing the bodily sensations, but sometimes they're just very dissociative. And sometimes it's helpful to just decrease the shame of the dissociation itself. It's like, you know, it's at times it's okay to go numb and it's okay to not be in touch with what might be there, because maybe that was adaptive for you. And you know, I'm here for you in the midst of this sleepy stupor that you feel trying to get in touch with your emotions.

Bender:

I think so. The other way I felt bad for Sugar was because she didn't have an out. As I mentioned earlier, she said, “I'm the one who has to deal with this.” So she didn't get to disassociate. And I, in real life, see lots of people who took on the role that she had in their own families. When there were other siblings, say fighting with parents or having their own issues, they ended up becoming the designated caretaker in some ways. And possibly, the depressive style that I know Shedler just talked about on your show. You know, I think Sugar really had to be there for her mom. And I could see her being angry at both of her brothers for that as well.

Puder:

The depressive style is adaptive, especially in that context where your mother is completely impossible to predict– the highs and the lows. Because, if anything, you can take that frustration or anger you may feel and you turn it on yourself. And so it's another protective way of dealing with the anger and the frustration. And so I actually see Sugar reaching a point in her life, and I see that maybe she's done a little bit of work, and so she starts expressing her frustration to the family members, but not really getting back what she needs in the midst of it. But maybe at least it's being put out: “This is frustrating.” So you can kind of see them at different stages of development I think.

Bender:

That's right. And I don't think she fits completely that depressive personality style, but I do feel like she has had to put her own needs on the back burner. And interestingly, she marries the guy Pete, who her brothers and everybody Richie thinks is a milk toast guy. Nobody likes him, but he's just kind, he just wants to do what's right. And he even brought over that eighth fish because he’s like, “I couldn’t come empty-handed” and he's trying to make jokes with the aloof brothers.

Puder:

He's almost aloof. He's a little bit disconnected from what's going on socially. Like he's not picking up the cues, maybe.

Bender:

I think that's the way I would say more accurately. Because I think when I think ‘aloof,’ I think of people trying to convey, “I'm not gonna connect with anybody,” but he's overly trying in some ways and missing certain things.

Puder:

He's making it almost like he didn't socialize a lot growing up, and then he's subsequently in an environment with people who literally grew up on top of each other. So they've been overly socialized and they're kind of mean at the same time, so he's like trying to fit in.

Bender:

I think so. But I think for her, this is a guy that is normal, so to speak, and can take care of her.

Puder:

Oh yeah.

Bender:

And is just kind, is the opposite of what she saw in her life and in her family.

Puder:

And he's the one that interacts with Donna in the last episode of the second season. Donna comes to the restaurant—it's the opening day—and he's the one that kind of bears the burden, bears the weight of her outside.

Bender:

Yeah.

Puder:

And then he goes back inside and he doesn't tell his wife that he had seen the mom.

Bender:

Yeah. That scene really stuck with me. I mean, he's basically watching this woman not be able to be there to celebrate her children and their accomplishments and opening this restaurant. And it's potentially maybe part of the histrionic piece that she's not the center of attention. It wouldn't be about her, it would be about others. But that was really hard. And he did have to bear that. And he had to bear knowing that his mother-in-law would just break her kids' hearts, yet again.

Puder:

Yeah. You just can't show up quietly, eat your food and celebrate that? It's like, what is going on? And as someone watching this, maybe if you had a really healthy family, you're not a therapist, you're like, “This doesn't make sense to me. Why can't she just go in and enjoy the meal?” Whereas, it would almost be jarring to the reality for her to be able to go in and celebrate it would be too much, too much fuzzy, unrealisticness.

Bender:

It would be. I also wondered in that scene, and maybe you could tell me your thoughts on it, did she realize it would be too much for her kids? Like, did she have a glimpse of, “I'm too much”, or is it more as I was saying earlier, that she wouldn't be able to be the center of attention, therefore she wouldn't go?

Puder:

I think it's more that she was going “all bad” on herself. I think, someone like that, remember she could flip from idealizing herself—“I'm gonna be the star of the show”—to literally, 10 minutes later, devaluing herself. And so, she could have set out with this ideal like, I'm gonna come here as a queen and be greeted and cared for by my children and kind of fulfill this fantasy of being this life-giving force. And then when she gets there, something flips in her. And she's like, “I am gonna destroy this. I am the destroyer of the world.”

Bender:

It's interesting.

Puder:

It could be both, and.

Bender:

I think it's a good interpretation of it.

Puder:

Both. And maybe, you know. I don't know, is it insight as well though? “I'm really going to destroy this?”

Bender:

Well, I think to go ahead to the next season, there's a scene where Sugar needs to rely on the mother during a time when she's about to give birth. And there are a few moments where the mom recognizes her own problems that she brings. So I think you're right, that there can be a moment or two where she can see that. And I think that was wrapped into that too, which is kind of, “Oh, you're sparing your kids, but at the same time you're hurting your kids.” It's probably very much the way they felt about her. Like this love-hate thing.

Puder:

Yeah. Well, very good. I think this is a good kind of segue into us going to get some food together. Yes. Maybe some food. Not quite as good as The Bear .

Bender:

See, I wanna try that chocolate cake. I think there's a recipe on the internet somewhere for The Bear chocolate cake. I'll have to look that up. But, I do know that the next season's coming out, so we'll see more food. I'm sure.

Puder:

You know who's the character of respite for me? The guy that just is really bent on making the best pastries.

Bender:

Marcus.

Puder:

I love Marcus. Yeah. I love Marcus.

Bender:

Didn't talk much about him. There's so much to talk about here, but you know, he has his mom who's ill, he's trying to take care of her. There's just so much stuff with him.

Puder:

There's so much. It gives you a glimpse of how people's lives are complex. Like when you go to a coffee shop, treat the people, the baristas with kindness, not knowing what's behind their stories, you know?

And everyone's got a story. And if we can, if we can just be more patient and kind and considerate.

Bender:

Yeah. I agree. And, going back to where we started. I think the idea of a work environment, the idea of people struggling, many, many, many people, if not all, have struggled at some point. Not everybody can see themselves in Succession or in those shows about the ultra wealthy, but everybody has struggled and they can see something here, working for something. And I think it brings people in–Abbott Elementary, another show, set in an elementary school in Philadelphia, the idea of people at work. So I think people who work and go day to day, and really struggle. That does resonate with people.

Puder:

Yep. Yeah. And I think that everyone likes to portray a picture online that they have it all together. Right?

Bender:

Curated life.

Puder:

Curated life. And I'm going in about 11 years of personal therapy. Still trying to figure it out.

Bender:

Yeah. I'm on 25 years, so I'm the same way.

Puder:

I'm hoping to overcome Yalom's numbers, eventually. And in one of Irving Yalom’s books- I love his books- he's like, “And with this therapist I did three times a week for five years, and with this therapist…” And if you're not someone who gives therapy, you won't understand the need to be in chronic therapy, maybe.

Bender:

It's true. But it's ongoing work. Work in progress.

Puder:

We are all wounded healers. So. Good. Well, thank you so much for coming out here.

Bender:

Thanks for having me on again. I hope to be back and we'll see what happens in season four of The Bear.

Puder:

Nice. I'll have you come back if people want. And if you want us to cover a different show and you want me to agonize through the burdens of watching a show.

Bender:

Or people can reach out to me. Same here. If you want to email me a show you would like me look at, I'm at Doctor. Eric Bender all spelled out, and my website is: https://www.doctorericbender.com/. You can reach me there and I'll see if I can maybe pair up with you again. We can do another show.

ReferencesAmerican Psychological Association (APA). (2018, March). Primitive defense mechanism. In APA Dictionary of Psychology. https://dictionary.apa.org/primitive-defense-mechanism

American Psychological Association (APA). (2023a, Nov. 15). Identity diffusion. In APA Dictionary of Psychology. https://dictionary.apa.org/identity-diffusion

American Psychological Association (APA). (2023b, Nov. 15). Projective identification. In APA Dictionary of Psychology. https://dictionary.apa.org/projective-identification

Biography.com Editors. (2021, May 10). Franz Kafka biography. The Biography.com website. A&E Television Networks. https://www.biography.com/authors-writers/franz-kafka

DayHist. (n.d.). Feast of the Seven Fishes: Italian Americans. Retrieved June 11, 2025, from https://dayhist.com/holidays-and-occasions/feast-of-the-seven-fishes-italian-americans

Eakin, M. (2023, June 22). The Bear recap: The Christmas Guests (Season 2, Episode 6). Vulture. https://www.vulture.com/article/the-bear-season-2-episode-6-recap-fishes.html

Herman, J. L. (1992). Complex PTSD: A syndrome in survivors of prolonged and repeated trauma. Journal of Traumatic Stress, 5(3), 377–391. https://doi.org/10.1002/jts.2490050305

Kernberg, O. F. (1967). Borderline personality organization. Journal of the American Psychoanalytic Association, 15(3), 641–685. https://doi.org/10.1177/000306516701500309

Kernberg, O. F. (1975). Borderline conditions and pathological narcissism. New York: Jason Aronson. https://archive.org/details/borderlinecondit00kern

Kernberg, O. F. (2000). Borderline conditions and pathological narcissism. Jason Aronson. (The Master Work Series). https://www.scribd.com/document/425936113/the-Master-Work-Series-Otto-F-Kernberg-Borderline-Conditions-and-Pathological-Narcissism-Jason-Aronson-Inc-2000

Li, P. (2025, January 4). Avoidant attachment style: Causes, signs, effects, and treatment. Parenting Styles. Retrieved June 11, 2025, from https://www.parentingstyles.com/child-psychology/attachment-style/avoidant/

Mayo Clinic Staff. (2024, January 31). Borderline personality disorder – symptoms and causes. Mayo Clinic. Retrieved June 11, 2025, from https://www.mayoclinic.org/diseases-conditions/borderline-personality-disorder/symptoms-causes/syc-20370237

McWilliams, N. (2011). Psychoanalytic diagnosis: Understanding personality structure in the clinical process (2nd ed.). Guilford Press.​ https://nancymcwilliams.com/books-authored/

Penzel, F. (2000). Obsessive‑compulsive disorders: A complete guide to getting well and staying well (1st ed.). Oxford University Press. https://books.google.com/books?hl=en&lr=&id=GEGOIkEZP_AC&oi=fnd&pg=PP2&dq=obsessive+compulsive+disorder+Penzel,+2000&ots=VRUBC4SaBy&sig=YM_6exFyPq0gAAl7WJhAK5OPIVA#v=onepage&q&f=false

Psychology Lexicon.. (n.d.). Devaluation.. Retrieved June 11, 2025, from https://www.psychology-lexicon.com/cms/glossary/37-glossary-d/22816-devaluation.html

Puder, D. (Host). (2022, Dec. 2). Listening Psychodynamically (No. 164) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-164-listening-psychodynamically?rq=reaction%20formation

Puder, D. (Host). (2023, Jan. 23). Obsessive-compulsive Personality and the Personality Continuum with Dr. Shedler (No. 168) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-168-obsessive-compulsive-personality-and-the-personality-continuum-with-dr-shedler?rq=ocpd

Puder, D. (Host). (2023b, Oct. 11). Dr. Sue Johnson: Attunement, Attachment and the Development of Emotionally Focused Therapy (No. 194) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-194-dr-sue-johnson-attunement-attachment-and-the-development-of-emotionally-focused-therapy?rq=emotionally%20

Puder, D. (Host). (2024, March 29). PTSD and Cognitive Processing Therapy with Patricia Resick (No. 209) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-209-ptsd-and-cognitive-processing-therapy-with-patricia-resick

Puder, D. (Host). (2024b, May 17). Reflective Functioning: The Key to Attachment with Dr. Howard Steele (No. 213) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/reflective-functioning-the-key-to-attachment-with-dr-howard-steele

Puder, D. (Host). (2024c, Sept. 17). Paul Wachtel's Approach to Integrative Psychotherapy: Exploring Attachment, Anxiety, and the Disavowed Self (No. 222) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-222-disavowed-emotions-with-paul-wachtel?rq=anxious%20attachment

Puder, D. (Host). (2025a, April 25). Transference Focused Psychotherapy & Personality Disorders with Dr. Otto Kernberg (No. 239) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-239-transference-focused-psychotherapy-otto-kernberg-borderline-personality

Puder, D. (Host). (2025b, May 23). Depressive Personality Style with Jonathan Shedler (No. 241) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-241-depressive-personality-style-shedler

Yalom, I. D. (1989). Love's executioner and other tales of psychotherapy. Basic Books. https://www.yalom.com/loves-executioner

Yalom, I. D. (2002). The gift of therapy: An open letter to a new generation of therapists and their patients. HarperCollins. https://www.harpercollins.com/products/the-gift-of-therapy-irvin-yalom?variant=41231884386338

View Details

Transcription and footnotes edited by: Jonathan Shedler, PhD, David Puder, MD, Al-Baab Khan, Joanie Burns, Jonathan Nowlin

No conflict of interests to report for this episode.

By listening to this episode, you can earn 2 Psychiatry CME Credits.

Other Places to listen: iTunes, Spotify

Access Blog with Footnotes here.

An Introduction To Depressive Personality StylePuder:

Welcome back to the podcast. Today I'm joined by Dr. Jonathan Shedler to talk about depressive personality style. He has been on the podcast before to discuss narcissism, obsessive compulsive personality, beginning treatment, and psychodynamic psychotherapy.

We will be doing a lot of role play today to try and give a practical understanding of depressive personality dynamics, how it shows up in therapy, and how to help the person get in touch with their own needs, desires, and frustrations.

Individuals with a depressive personality style are often professionally and socially externally “successful” with a warm, engaging, empathic presence, and invested in making other people happy. Due to adaptive childhood dynamics, they developed an accommodating nature and can get stuck in relationships—even therapeutic ones—where their own needs, desires, and anger remain neglected, disavowed, and largely unconscious.

Depressive personalities are distinct from clinical depression; someone can have a depressive personality without necessarily experiencing clinical depressive episodes. Paradoxically, individuals with this personality style often appear outwardly successful and high-functioning despite inner feelings of inadequacy and chronic dissatisfaction. They typically struggle to experience genuine pleasure or joy.

Within psychodynamic circles, the concept of depressive personality remains influential, particularly through the work of Nancy McWilliams, Otto Kernberg and Jonathan Shedler. They emphasize underlying dynamics such as internalized self-criticism, unconscious guilt, and enduring interpersonal patterns.

There are common patterns that show up in how they relate to others including:

• Introjection: Internalizing negative experiences and anger
• Turning against the self: Engaging in self-directed criticism and punishment
• Gentle idealization of others coupled with profound self-devaluation

Transference may include gently idealizing the therapist while converting dissatisfaction into self-blame and guilt. Countertransference reactions involve protective impulses, feeling the patient’s disavowed frustration or feeling their helplessness.

This concept has a rich historical lineage. Emil Kraepelin first described depressive temperaments, highlighting their stable and chronic nature. Depressive personality disorder appeared as a proposed diagnosis in the appendices of both DSM-III-R and DSM-IV.

Depressive personality style is represented in the DSM-V as persistent depressive disorder and in ICD-11 as dysthymic disorder, but here we will discuss it as a personality style.

Can you talk about the historical context on how depressive disorder first came to be included in the DSM?

Shedler:

You brought up something that might be a useful little digression here about the impact of the DSM on how we understand personality. The concept of personality disorders actually didn't exist in the literature prior to DSM-III in 1980. The framers of DSM-III were very determined to produce a medical taxonomy of psychiatric difficulties. So they made a decision upfront: everything was going to be a disorder. This plays out in funny ways. For example, before DSM-III, people were anxious, but the concept of generalized anxiety disorder didn't exist. Anxiety was a state, not a disorder that you had. This shift really changed the landscape of how we think about mental health difficulties. They left personality out entirely—it wasn't even on their radar. They had basically completed the entire development of DSM-III without ever taking personality into account. Apparently, very late in the game, someone said, “What about personality?” So it was added as an afterthought, literally an afterthought. That’s why it was Axis-II in DSM-III through all the variants of DSM-IV. Since personality had to be made to fit into this taxonomy of disorders, they took the major personality styles that were familiar to psychoanalytic clinicians at the time, exaggerated their severity—sometimes to the point of cartoonish caricature—and called them “disorders.” All of a sudden, personality disorders became a thing on the map.

Puder:

I think it’s extremely important, in my mind, to have empathy for clients, to understand our reaction to clients, our countertransference, to deepen our reflectiveness into people’s experience, and to appreciate their individual personality styles. I like how you parse that out. Everyone has a personality style.

Shedler:

Yes, everybody has a personality. Every human being has a personality. But the unintended consequence is that now we have several generations of psychiatrists, psychologists, and mental health professionals who have no concept of personality—except when it’s a disorder. I do a lot of speaking, workshops, and podcasts, and this misunderstanding happens all the time. I'll say something about somebody’s personality dynamics or personality style, and the other person o will immediately start talking about personality “disorders,” as if that’s what I said.

The way I see it, there are certain recognizable patterns or constellations of personality functioning, that we see often enough that we can say: this is a recognized personality style. These styles all fall on a continuum of functioning from healthy, high functioning to really very seriously disturbed. Essentially, what DSM ended up doing was teaching generations of clinicians that if personality isn’t at the extreme of disturbance, it doesn’t count and we don’t need to consider it. So we can then talk about depression in isolation from the psychology of the person who has depression. We can talk about anxiety in isolation from the psychology or the person who has anxiety. But that’s not really a psychological understanding.

Depressive Personality Styles: Challenging Diagnosis And Therapy (00:08:55)Puder:

Today we are discussing someone with psychological defenses— these inner experiences lead to more of a chronic depression beginning in adolescence, and continuing until they engage in psychological work. How would you say it differently?

Shedler:

It’s important to consider what personality really is—a consistent pattern of functioning that originates fairly early in life and consolidates by adolescence. And it subsumes patterns of how we relate to other people, relate to ourselves, how we cope with difficulties, our defensive processes, our organizing psychological themes, our motivation—basically everything that we talk about when we refer to somebody’s psychological functioning is really in the domain of personality. So when we say a depressive personality style, it’s pretty important to understand that it's not the same as clinical depression. It often leads to depressive episodes that you could diagnose as depression, but not necessarily. So you could have people with depressive personality styles who are not in fact suffering from clinical depression. In principle, you could see someone with a depressive personality style who’s never had a clinical depressive episode. And lots of people have chronic, consistent, recurring depression who don’t have depressive personality styles. They’re different things.

Puder:

So how would you define depressive personality style?

Shedler:

It's a pattern of functioning in the world and a way of experiencing self and others. Characteristic features include being very prone to negative affect especially shame, guilt, feelings of failure, and inadequacy. The most defining hallmark of a depressive personality is that, if you were a psychologically sophisticated observer looking at this person from the outside, you might think they were their own worst enemy. They tend to be inhibited in seeking and experiencing pleasure, excitement, joy, satisfaction. It’s as if there is something inside them that’s squelching their ability to enjoy these feelings. In some cases, it appears as though they are unintentionally seeking out experiences that are going to cause hardship or suffering or unhappiness.

In that respect, we can say they seem like their own worst enemy. People with this personality style actually tend to be pretty high functioning. It’s generally not a disorder. It’s, if you think of a spectrum of levels of personality organization from healthy through neurotic through borderline to psychotic, they tend to be in the healthy and neurotic levels of organization. Interpersonally, they tend to be warm, engaging, empathic, and pleasant to deal with. They tend to be people pleasers. When they come into therapy, empirical data shows us that clinicians describe them as good patients. They feel really good about working with them.

And the trap is the fact that the clinician feels really good—because the patient is easy to deal with. They’re accommodating. They’re appreciative of what the clinician offers. So the clinician tends to come out of the session feeling like there’s a connection, feeling like they’re being helpful to the person. The danger is that the reason the clinician feels good is actually not a sign of progress, but rather a symptom. The symptom is that they end up recreating the patient’s relationship patterns in the therapy relationship. And the patient’s relationship patterns are that they’re very oriented toward other people's needs and feelings at the expense of their own. So when they enter into a relationship, they tend, in one way or another, to devote themselves to making the other person feel good about the relationship, but often at their own expense. So the other person’s needs get met, but their own needs don’t necessarily get met. They come in and they repeat this pattern with the therapist, that the therapist ends up feeling very good about the therapy. And even though they both appreciate one another, the patient doesn't change. That's the trap of treating depressive personality style.

Puder:

It’s like there can be some gentle idealization of the therapist and if they have frustration towards the therapist, they usually turn that towards themself.

Shedler:

Yeah. The typical manifestation in therapy is, they feel they’re not doing it right. They’re not being a good enough patient. They’re doing something wrong in therapy. So you often see it in therapy in a very direct form, like the therapist makes a mistake, which is inevitable. We all make mistakes every day. There's no such thing as a therapy session without a mistake, I don't think. And typically the patient either glosses over it, brushes past it, or patient actively takes responsibility for it (“Oh. It's not your mistake. I didn't explain it right. I gave you the wrong impression. I wasn't forthcoming enough. I didn't tell you all the information. It's on me as a patient, not on you.”). But it’s subtle because they’re usually higher functioning, at a healthier neurotic level of personality organization. It’s not idealization in the sort of icky way that you would see in narcissistic or borderline functioning. It’s generally in a very engaging and appealing sort of way.

Exploring The Inner World Of Depressive Personality (00:15:34)Puder:

So we have a role play.

Shedler:

I love it.

Puder:

I have a character. I've been working on this all week. Maybe I've been working on this for years. Maybe this is like early on in the therapy and so we could just start it off.

I'm gonna try to get into person here.

I like how you said you have to embody something that's real. When we were talking about this, at first I was thinking about doing Abraham Lincoln and having Shedler do some therapy for Abraham Lincoln, because I think he did have real depression episodes and I think he had a depressive personality. I really think he did.

Shedler:

Don’t know!

Puder:

I've been reading a biography on him. But I will not be Abraham Lincoln.

Shedler:

And the reason for this is that when we treat patients of our own, we draw on our own immediate personal experience. If we have a real patient in mind, we form identifications with the patient. We unconsciously identify with them, even if the patient never says the specific words that come out in the role play. There’s a way we can speak from within that person. It is not a conscious, planful process. If we’re a dedicated therapist, there’s a way we just take in our patients. And try to understand them, or not even understand—experience them—from the inside out, rather than just as an observer from the outside looking in.

Roleplay Begins: Puder:

You know, Dr. Shedler, I wanted to reach out to you, but I know you were on vacation. I felt bad wanting to reach out to you, wanting to disturb your vacation, so I didn't. But I feel, I had this email, I started to write it, but I felt kind of guilty for interrupting. Well, I don't know if you were on vacation, if you were lecturing. But anyways, my father passed away last week and it brought up a mixture of things for me.

Shedler:

Well, I mean, I'm hearing two things, I'm tempted to ask you to tell me about what it brought up for you. But I’m also hearing this happened while I was away, and it sounds like you were feeling bad about wanting to get in touch with me.

Puder:

Yeah and…I think as a therapist myself, when I'm on vacation, it’s like, I appreciate being on vacation. So I think I was just kind of leaning into that a little bit. And then I've had patients who reach out during vacation and sometimes you gotta talk to him and stuff. It's heavy. It’s mostly for my father, it’s weird. Everyone wants me to feel sadness. Everyone is like, “Oh, you must feel so sad.” We even had a funeral. It was pretty short. I would be like, “Oh, yeah, yeah, I feel sad,” and I would tell them that. But really what I felt was guilt that I didn't feel sad. And I felt more like I should feel sad, but I don't feel as sad. So…

Pause Role-Play:Shedler:

Just stepping out of the role play for a second. How long have we been in treatment? How well do I know this patient?

Puder:

Let's say this is like the third or fourth session.

Shedler:

Oh, it's very early on. So I don’t know. I don’t have a lot of history.

Puder:

Yeah. So you can ask the history.

Shedler:

Okay. So that’s all I needed to know. I’ll jump back in.

Resume Role-Play: Shedler:

I gather you must have had a complicated relationship with your father.

Puder:

Yeah. And I know the first couple sessions when we were meeting, it was mostly about patient issues. In my mind, I don’t know why I go there, but I almost don’t wanna burden you with the story of my father. Which I know you've like– consciously in my mind– you have been doing this a while.

Shedler:

But something in you feels like it would be a burden to me to hear about it, to listen to you.

Puder:

Yeah. So my father left our family at around sixth grade. He was in and out of our life afterwards. He probably had true bipolar. I didn't know that back then, but I know that now.

Shedler:

Undiagnosed bipolar then, I imagine.

Puder:

You know, I think for the first decade of my life, he probably drank himself out of any mania. But then he developed chronic pancreatitis and he couldn't drink, or he'd get acute pancreatitis and end up in the hospital. So eventually he became sober. And when he was sober, he was very miserable.

Shedler:

Miserable. Meaning how so?

Puder:

Well, he was always angry even when he was an alcoholic. But when he was sober, he would kind of go between up, out, having sexual flings with men and women. I would go to my grandma’s house every other weekend, and he would be there. And he would just really stay in his room.

Shedler:

When you say he was miserable, I'm understanding that to mean he was miserable to you. Maybe miserable to the whole family, but he was miserable to you. He treated you, I’m gathering, in ways that made you feel miserable.

Puder:

Yeah. He would call me “little bastard.” He met my mom during a fling. I don't think he really wanted me, mom didn't abort me. He would remind me of that.

Shedler:

Do you think he wished that? That she had aborted you?

Puder:

I think he felt trapped. And sometimes I feel responsible for his unhappiness. I know as a therapist now, I probably shouldn't feel that way, but it feels really true. He blamed me for that.

Shedler:

He blamed you for his difficulties, his instability?

Puder:

Well, his difficulty was my mom, which I can get to later. But yeah. So I mean, there were memories of him yelling.

Shedler:

At you?

Puder:

At me, spit flying. His face close to mine, you know? Hard to predict.

Shedler:

Was there physical abuse also?

Puder:

Yeah. There was, yeah. I mean punishment– just punishment that was random. It was chaotic. It was not, it was not like I did anything bad, per se. Or maybe I did, but…

Shedler:

Could you give me a for instance? Whatever comes to mind, just now. Just so I can get a better idea, when you say there was punishment, an idea of what you mean.

Puder:

He would come home, hadn’t been home for days, and he would be in a tirade. And he would just nonstop be ranting about how unclean the house was. And it’s not as if I didn't try to clean the house, I think this was around when I was like nine.

Shedler:

It was your responsibility when you were nine to clean the whole house?

Puder:

Well, my mother was at that point so heavy that she couldn’t get out of the couch very easily. I hate even talking about it in that way, but the reality was she was pretty physically weak compared to– so she couldn't really get up. And so…

Shedler:

I'm assuming if she was too heavy or too weak to take care of the household, she wasn’t really able to take very good care of you either.

Puder:

I hate to even get into this but we would live in squalor. It was outright poverty. We'd move every month. I think when I just turned 40 and I just realized I've lived in 39 houses. So I officially passed the number of houses that I've lived in.

Shedler:

It sounds awful.

Puder:

I have worked since I was 12. So, I would go to school, I'd work, do sports, go to work, come home at 11. Mom would talk to me from 11 to 1:00 AM.

Shedler:

Talk about what? Yeah, I'm sorry, go ahead.

Puder:

About her issues–things that have come up in the day, and…

Shedler:

About her issues. You mean her worries, her problems? Things that were bothering her?

Puder:

Her anxieties. The weight that she carries.

Shedler:

So I mean, you’re like nine or 10 years old, it sounds like. Well, you're a therapist too. I'm sure you know the concept. It sounds like you were—became responsible for taking care of your mother like you were the parent, rather than vice versa.

Puder:

She had a lot of reasons. She had a lot of anxieties and I think she needed someone to talk to.

Pause Role-Play:Shedler:

So let me make an aside for the listeners, because I haven't really done much by way of intervening yet. I’m still getting the lay of the land, the psychological lay of the land for this patient. But I'm about to– this is going to be my first actual intervention. So I'm just sort of flagging this. I'm about to do something that follows from an understanding of the personality dynamics that I see emerging. So jumping back in:

Resume Role-Play:Shedler:

I can’t help but notice I commented about your experience, the burden of being in the role of having to take care of your mother, and your response was about your mother.

Puder:

Yeah. And I think you gotta understand how hard, how difficult her life was. And she would tell me about how difficult it was, and she would tell me about– there would be men that would come and stay with us for a couple weeks at a time. And I would hear them– at first nice noises, giggling sometimes.

Shedler:

You mean men that she was involved with?

Puder:

Yeah. Yeah. Like…

Shedler:

Romantically or sexually.

Puder:

Oh. Oh, you could hear, you could hear them through the walls-

Shedler:

This was happening–

Puder:

Holes in the walls. Yeah.

Shedler:

So this was happening right under your nose in your house?

Puder:

Oh, yeah.

Shedler:

Your father’s out running around with other women, I guess was how I understood what you said. Your mother’s bringing other men into the home and there's something that doesn’t quite add up for me. Like, she’s overweight and too heavy or too depleted to take care of you. And yet it sounds like she has energy to bring in, not just one man, but it’s like a regular thing with different men.

Puder:

Yeah. And she would meet these men online. They would travel sometimes from cities away, lived with us for a couple weeks. I mean, these were not like my teachers, my coaches, who I looked up to. These were men that I hated or just disliked.

Shedler:

So who was taking care of you, because that doesn’t sound like your father was doing much of that. It doesn’t sound like your mother was doing much of that. Was there somebody in your life who was there for you and there to take care of you?

Puder:

I think I kind of figured out how to take care of things. I felt a lot of responsibility.

Shedler:

You mean, you were the person taking care of you, and it sounds like, in important ways, trying to take care of your mother and trying to take care of your father too.

Puder:

I mean, I think at around that time– like see, I feel like I'm really giving you too much here.

Shedler:

What do you mean, what do you mean “giving me too much?”

Puder:

Well, I mean, it feels like I'm burdening you too much. I feel like this is gonna be too heavy for you- like, it’s gonna be like a lot…

Pause Role-Play:Shedler:

Just as an aside, this is very fast. I mean, if this were real therapy, this would likely unfold over more sessions. But, I want to illustrate working with something here. If this were in real life, this would be pretty abrupt.

Resume Role-Play:Shedler:

But I wonder if something is going on here between us that is similar, or a continuation of what you're describing growing up with your parents. Because your mother was supposed to be taking care of your needs, physically, emotionally. But she would burden you with her problems, her anxiety. She’d keep you up until 11:00 p.m. and I get the sense that it felt like your role was to not burden them, right? To protect them from having to deal with your needs, your feelings, your distress. The little kid having to fend for yourself. You were protecting them from your needs. And I wonder if there’s something like that continuing here, with us, when you say you don’t wanna burden me, or it’s too much for me.

Puder:

Yeah. I may have misspoke earlier. I would get home from work at 11:00 p.m. in high school and junior high school. And then I would be listening till 1:00 am. I may have misspoke, so I apologize for that. But…

Shedler:

You assume that—well, there it is again, actually—so you assume that you misspoke, rather than that I misheard or I misunderstood.

Puder:

Well, if you think that you’re like my parents at all, like that's not the case. I mean, you remind me more of– I had a good basketball coach. I wasn’t the best basketball player.

Shedler:

Well, yeah. The ways that I might be like them, or not like them, that’s something else we can talk about. But just at the moment, what I was really getting at wasn't so much whether I am like them in reality or not. I was noticing your impulse to want to protect me, or your feeling that what you were telling me was too much, too much of a burden.

You know, it brings us back to where we started, which is that your father just passed away. I mean you must have very complicated feelings about it, to say the least. And you felt like reaching out to me. It was the same thing with that…. you shouldn't burden me. I was away, maybe I was on vacation, maybe I was teaching, whatever. But you felt you shouldn't ask for that from me. And I wonder, when you start to tell me about how difficult things were for you growing up, how alone and uncared for you were… your thoughts go to, it's too much for me, you shouldn't burden me with this.

Puder:

Mm-Hmm. Yeah. And like, I think–

Shedler:

Like therapists only want happy patients who are feeling good and don't have any actual difficulties to bring into therapy.

Puder:

Yeah. I think that I guess I'm getting confused. It's like I know logically I should not feel like I'm burdening you.

Shedler:

Well–

Puder:

And somehow, I feel almost critical of myself that I'm feeling that way. But then I can also see how deeply that resonates with so many things in my life. So–

Shedler:

What it brings up… it’s bringing up more for you.

Puder:

Yeah. Well I talked to you in the first couple sessions. Like whenever my patients are doing well, I don’t feel much gratification– I feel like that’s expected. They’re paying me, but when they don’t do well, I really, really ruminate.

Shedler:

When they’re doing well, it’s not to your credit. It’s hard for you to feel good about it, or feel like this is something you helped to accomplish. But when they’re not doing well, it’s your fault.

Puder:

Yeah. And so I've been thinking about that as kind of a theme of our first couple sessions. And I've been thinking about, hmm, maybe there’s some deeper reasons for that. So with my dad’s death, I feel maybe this is a good time to look at those deeper things. And I think it’s coming out. Yeah. I'm aware. Okay. So I may have some transference as well towards you. Now, I'm not as articulate as you are about these kinds of things, but I can see it happening right now consciously, like in my mind. I'm feeling guilty about multiple things in life.

Shedler:

You mean just here, just now between us? You’re feeling guilty? Or are you referring to other things also?

Puder:

Yeah, I'm feeling guilty in the here and now. And just sharing this, which is kind of how I felt growing up as well and how I feel with my patients. So there's like– I'm seeing that overlap.

Shedler:

Yeah. You were even feeling guilty about your reaction to hearing about your father’s death, guilty that you weren’t sad enough or weren’t reacting the way you think you should have.

Puder:

I think most of the people who are close to me don’t really know much about my childhood. I’ve kind of kept that in a separate container, because things are so different now. I think most people, most of my friends, they came from good backgrounds. They wouldn’t relate to the squalor, the decaying wood, the holes in the wall, the cockroaches on the ground, the duct tape. So I think most of them expected me to feel sad when he passed. And so most of them would get sad for me. But I think there was a part of me that kind of felt relieved.

Shedler:

Yeah. I could imagine. You got there first, but I was about to say, maybe you don’t feel sad.

Puder:

Yeah. He would come visit and he wouldn’t really interact that much. It was kind of hard to have a conversation with him.

Shedler:

And so I imagine there’s a lot of feelings in the mix, you’ve said there are complicated feelings. But among that mix of feelings, I imagine there’s a part of you that must be glad to be rid of him—therefore the relief.

Puder:

Ooh. I would feel– I’m glad to be rid of him– I don't know if I'm there yet. I mean, I do feel some relief.

Shedler:

Well, maybe I jumped the gun. Maybe—tell me more about the feeling of relief—I mean, I jumped the gun and put words in your mouth that don’t fit.

Puder:

Yeah. Well, thank you for that. Yeah. Letting me have the space to kind of get in touch with what I feel. So I haven’t told you this about him yet, but he would call me and I would get these calls. He would be gone for weeks. I would get these calls from him. He’s probably on a payphone– and then he would be telling me on the phone and now, I think back, was he on drugs back then? I didn't know. But back then, I’m young, and he would say things like, “I'm gonna kill myself.” And he would keep me on the phone and I wouldn’t say, “Oh, you're the best dad ever,” but I would say, “Dad, please don’t kill yourself. Dad, please don't kill yourself.” And so, yeah, there's a weightiness with, with those memories.

Shedler:

What I’m hearing is how you ended up being the emotional caretaker for two parents. Like you were trying to be a little kid, and trying to be a therapist to both of them at the same time.

Puder:

Yeah. Of course, back then, you never have the right words to say to make them feel better. And so–

Shedler:

It was your job to make them feel better.

Puder:

Well, what I’m saying is as much as I tried, I don’t feel like I ever really was able to do that.

Shedler:

Yeah. But I’m wanting to highlight something that I think was implicit in what you said. That you tried and you never could succeed, or never could succeed enough. But implicit in that is, it just seemed very natural and normal, that it was your job to make them feel better. And now you’re telling me how you failed at the job. You didn’t, you never could quite accomplish it, but it seems like in the background it's the default that of course it’s your job to make them feel better.

Puder:

Yeah. And now, I do that for my work. And yeah. I think the patients that I'm not good at doing it with gets to me. But–

Shedler:

So when the patients don’t get better, they’re like your mother or your father that you could just never do enough for. You could never succeed in making them feel better.

Puder:

Yeah. I guess I'd never seen– I should have seen it like that, but I've never seen it like that. But, yeah. It's kinda like that.

Aggression In Therapy (00:44:21)Pause Role-PlayShedler:

For purposes of the role play, suppose we skipped ahead about 10 sessions and your father’s death is still in

the air.

Puder:

How do you feel it’s going so far?

Shedler:

I think you’re doing an extraordinarily good job, maybe a little bit over the top in terms of the history, but an extraordinarily good job of inhabiting a certain kind of depressive person. What I'm thinking, and I didn't say during the role play, but it's going on– to let you and the listeners into what's going on in the back of my mind– so here's a personality dominated by guilt, dominated by a sense that they’re falling short, or something about them is bad, isn't good enough. Somebody who had that kind of depriving childhood would feel that. This is a combination of what we call anaclitic and introjective depression. There are two different things going on. I mean, one is the absence, the loss, of a real caretaker that every child needs.

And that loss stays with us. It gives rise to an emptiness within that is a hallmark of a particular kind of depressive personality. You sort of feel depleted and empty and try to fill that hole by bringing other people into your life and connecting with other people, except it doesn't quite fill it. And the connections are kind of a one-way street, not because the other person is necessarily requiring that it's a one-way street, but because the patient is making it a one-way street: It's about what they can do for the other person rather than what they can get and take in that meets their own needs. So that would be a kind of anaclitic– we call anaclitic depressive style, where the person is very sensitive to loss and relational disruptions.

But that's half of it, right? The other half that we didn't get to in this role play– which is why I was thinking of skipping ahead some sessions– is if somebody is mistreated like that, somebody berated, yelled at, the way your father– the way you were describing– it would be less than fully human to not feel angry, resentful, deprived, enraged about that. It is not just that you feel the people you needed to rely on didn’t do right by you, didn’t care for you well enough. It’s that they didn't do right by you, in this particular history that you're giving me.

Of course there'd be anger and resentment and I think we just heard just a whisper of that when your patient said, “Well, I felt relief when he died.” And of course, behind that word “relief” is a whole universe. If you're relieved about something, that means that there was something that you were experiencing as a burden, something you resented. You just hinted at that with the patient. And here's where you did such a good job of being this kind of patient. The patient is also very defended against their aggression. So they have a kind of introjective version of depression too. They have a kind of impossible internal dilemma. And the dilemma is that they are angry, but it's not okay to feel or express that anger. So when its extreme form, what this looks like in life is, that the person ends up becoming a kind of a doormat in other relationships. Not necessarily because they're surrounded by people who want to take advantage of them, but because they can't tap into constructive aggression to assert, express their needs, their wants. And so they go without.

Puder:

And this is where Otto Kernberg's thought, which was so interesting– when I asked him what was the main thing therapists need to learn, and he said, “I think the most important issue is first of all, comfort with one’s own aggression.” I had just prior asked him about depressive personality style, which Nancy McWilliams says is the most common personality style in therapists. So when he answers with the importance of getting in touch with aggression, I am now connecting that with what a person with a depressive personality style needs.

Shedler:

Yeah. So that raises another issue. Let's definitely make sure we get to talk about this. People gravitate toward roles in life that are consistent with their personality organization and their enduring psychological themes, conflicts, and defenses. Anyway, that said, depressive personality style is the most prevalent personality style among people in the mental health professions. And we'll talk about why, but let’s stay with your patient for just a moment, and then we can expand to how this plays out in the profession. So the person is in a really impossible dilemma, which is that they are angry, but it's really not okay to feel it, let alone express it. And well, what becomes of it? Where does it go? Because the one thing we understand psychologically is that "out of sight, out of mind" doesn't mean it’s gone. It's still there. It's still having its impact. And you actually did a beautiful job illustrating it. If you are angry with someone, if you really don't like someone and you're angry and you wanna punish them, what do you do? You treat them really badly, you blame them, you scold them, you shame them. You find fault with them constantly. You're depriving them—you don't want them to have a good time. If something bad is happening with them, you want to rub it in. Basically, if you're really angry with someone and you act on it, you treat the person like shit. Hopefully, most of us have the capacity, at least professionally, to feel angry, to be aware of the internal experience, and not have to act on it.

If you were really angry at someone and you acted on it, that’s how you might treat them. And what we see in this, what's called the introjective version of depression, is the person with depressive style is treating someone like shit—but it's themselves. And that's where you see the self-criticism, the self-deprivation, the self-punitiveness, which is empirically the hallmark of this personality style. So it comes up immediately in that role play, but in a very small way. And it's not present and palpable enough yet to work with in the session. So I let it go by. But the patient really wanted to call me. You wanted to call me when you heard your father died, and the reality was, for whatever reason, I wasn't there for you.

I took the time off. That wasn't your doing. I wasn't available to you. And I could easily imagine—it's not a capital offense, it’s a misdemeanor maybe—I could imagine that a patient in that position could feel upset with me. Why was I not available? And then your impulse, when you wanted to reach out to me, was that you were doing something wrong. "Oh no, you shouldn’t do that—you shouldn’t contact me when you’re upset." So, what happened immediately was that thought, "I'm doing something wrong," transformed into, "Oh, you can't contact me; you wouldn't be doing something wrong." And that's a very, very small instance of that kind of criticism or punitiveness directed at the self. So if we cast that in high relief, it’s not that the therapist is doing something bad. In your mind, it turns into you doing something bad. And there's the reversal.

Puder:

Yep.

Shedler:

And it takes a lot of doing in therapy. And I was thinking about this before the role plays, it's very hard to illustrate because it doesn't happen in a single compressed segment. But–

Puder:

I was thinking, man, we could, we could stretch this out for hours, right?

Shedler:

Yeah. There's a lot here. That's why I thought it might be good to jump forward some sessions. But the issue is that the therapist is going to fail in many ways, not necessarily intentionally, for reasons that are perfectly reasonable. I've had interactions like this– I can think of as a very specific patient. The most recent one being someone who's also a psychologist, a very good psychologist, by the way. And I'm not there when she needs me and expects me. And she feels bad about wanting something from me. And we had this discussion that was like– let me see if I can recapture it, it's kind of slipping away as I'm trying to put words to it.

Puder:

It could have been a little bit dissociated because it was so painful, right?

Shedler:

Yeah, oh, it's coming back. So, I got something wrong—I misunderstood something she said. That was the reality; it was actually my failing, a small one, a lowercase "f." Yet, she immediately took responsibility for it, similar to how you did in the role play: "Oh, I didn't explain it right."

Puder:

Yeah, and by the way, I did that on purpose. I've been thinking about this case a lot, and much of it is actually very true. It's not a patient, nor is it myself, but it's someone close to me whose story I know very well. So, when I speak about it, if you as a listener felt I was embodying it accurately, it’s because I genuinely care about this person who went through this experience.

Shedler:

That's why it's so important that there's a real person behind a role play, not a made-up case. I realize I'm thinking with my patient, I'm trying to also protect her confidentiality.

Puder:

Absolutely.

Shedler:

So let me just make up a kind of an equivalent example.

Puder:

And I'll say for the record, I got permission from my person.

Shedler:

So let's say I missed a session or I was late for a session. Or actually, let's use the example that you gave. I was away, I had something else scheduled and I canceled the appointment in advance—a good example. And I wasn't there for her when she wanted to reach out. And then she reacts very much like you did: “Well, I really wanted to reach out to you, but you were away and I didn't want to bother you.” And I said, “It must have felt pretty shitty that I wasn't there when you thought you could count on me.” She said, “Oh, well I know you have your own life and you were doing some important thing and you were teaching and I understand. And of course you didn't plan it that way, so of course I understand.” And I said to her, “everything you said is true. I did have a prior commitment, I did let you know well in advance. I was taking care of other business. It wasn't meant to harm you. All of that is true. I objectively had something else that I had to attend to.”

But—"What does that have to do with how it might feel on your end when I wasn't there? All of that is like your logical, rational mind telling me about external reality. Of course there's good reason I was away, I wouldn't just not show up for a session just for the hell of it. But who says your reactions to that are, like, only what's logical and rational and reasonable? Maybe there's some other parts of you in the mix that are harder to hear from, harder for both of us to hear from.” I didn't even bring up anger. She’s giving me a very reality-based, rational explanation for why of course it made sense that I would be away, so she shouldn't have a reaction to that. But that doesn't subsume the full range of our experience. We have lots of reactions that aren't so logical. And so what I'm doing is, in working with somebody like this, the anger and aggression is not going to come out naturally and we really have to very actively go out of our way to invite it in.

So an example I use in my chapter is that– I think you read it was– the therapist is late and the patient says, “Oh, I understand if you were running late, it happens. No worries.” Oh, I think it even came up in our last role play the last time I was on your podcast. And nine out of 10 times, the patient's lets the therapist off the hook and and just wants to move on to the real work. But that is the real work. The fact that the patient is so ready to let them off the hook and not bring in any other feelings except their positive feelings. That's where the acting is. That's where the work takes place.

Puder:

Maybe, we can go back into the role play and it could be a couple sessions later. It could be the same session. But maybe yeah, I'd be curious to kind of play that out some around the theme of the difficulty of reaching out. Let's go into another session and I'll bring up, kind of another kind of moment between us, and we'll see how you deal with it.

Shedler:

Yes. And just to make it crystal clear, this is the essence of depressive personality style and the essence of the problem. The challenge that we're trying to address in therapy is that the person is not getting their needs met in life—but the person who's obstructing getting their needs met is themselves. It's very, very difficult to get what you want, if you can't allow yourself to know what you want. This is the essence of the problem. The patient in therapy isn't getting their needs met, for whatever reason. We don't hear about their disappointment, their frustration, their resentment, their irritation, we don't hear about it. We have to actively pursue that.

The Betrayal Conflict And Struggling To Name the Harm (01:01:10)Resume Role-play:Puder:

Okay. You know, I had a dream between sessions that maybe I'll start out telling you that. Would that be okay? I don't remember a lot about it, but I remember I was in this church. It kind of felt like it was almost falling apart like an old church, like it was kind of like ruins of a church. And I go into a confessional and I start talking and then I realize that you're on the other side. And I feel like maybe watching some of your X stuff, your posts kind of triggered that from the night before. I remember reading a couple of them about the frame, about the importance of keeping the frame. And I was like– I went to bed and I had that dream.

Shedler:

Could you connect the dots for me? What about my post about the therapy frame, what about that do you think led to the dream?

Puder:

You know, and I think in session, I've never felt like you've been critical of me. But I think there's something about when I read some of the posts, I feel a sense of like, oh gosh.

Shedler:

Do you mean since you're a therapist too? Like you're not doing it well enough?

Puder:

Since I'm a therapist. Yeah.

Shedler:

You heard my post about as a criticism.

Puder:

Yeah. Like, I almost need to go into a confessional and just kind of–

Shedler:

Confess, repent your sins.

Puder:

Repent. Repent my sins. So, that's what I'm coming in with a little bit this week. And then I know we've been kind of talking about getting in touch with my frustration and anger. And I had one memory that came back to me, which actually felt like a tinge of frustration. I think I was about 14 or 15, and I was getting something from the back of the car– from my mom's car. And I got really close to stabbing myself with a needle. And I'm like, “Mom, why is there a needle in the back of the car?” And she said, “Oh, I needed the needle for something medical,” that she was going through.

Shedler:

You mean it was a syringe?

Puder:

It was a syringe, yeah.

Shedler:

I was picturing a sewing needle for a moment.

Puder:

Oh, a sewing needle. Yeah. No, so she had picked up HIV at this point. And so when I remembered this, I remembered at the time I had felt immediately like awful that she had HIV and that she had to deal with that. But in the– when it came to me the other day, I got tight in my chest because I was hanging out with my niece who's about the same age that I was. And I was like, I can't imagine putting them in potential harm's way to get HIV. And somehow that hit me for the first time.

Shedler:

That she was endangering you.

Puder:

Yeah. Yeah. I mean, I could have poked myself. I was so close to poking myself.

Shedler:

You said at the time that you felt, what did you say? That you felt guilty or…

Puder:

Oh, I just remember feeling at the time, like I just was really upset that she had to have HIV in the first place.

Shedler:

You were feeling bad for her.

Puder:

Bad for her, yeah.

Shedler:

That eclipsed, I guess, other feelings that were there, which was that she put you in harm's way.

Puder:

Yeah. And somehow, it didn't really occur to me. I mean, I think it occurred to me, she's putting me in harm's way at the time, but it didn't occur to me until I had my niece, who was my age at the time, hanging out with her.

Shedler:

You hadn't connected those dots until then?

Puder:

The memory came back and I was like, “Oh, like what? What was she like? Why did she, like, why was she so careless about my life to not clean up after herself when she knew she had HIV?”

Shedler:

She was putting your life in danger.

Puder:

And like, as I say that right now, I feel like in some way I'm betraying her, which is a weird feeling, like, but I feel also, like she was kind of betraying me. I mean, part of me doesn't want to believe that she would be so careless. But then the other part is like, she was so careless.

Shedler:

It gets a little confusing about who's betraying whom.

Puder:

Yeah.

Pause Role-play:Shedler:

An aside for the audience here. So, there's a kind of clinical dilemma that I'm working through in my mind, which is—it would be very, very easy to go into this experience about the syringe and the feelings and meanings connected to that. And it would likely be very rich and a constructive area to work. But the transference takes precedence. And this is on the heels of a dream that he recognizes is about me. This is followed by the syringe.

Puder:

Okay. I got it. So let's enter back in.

Shedler:

So I'll take responsibility for that. You're really embodying the role. And part of that role is that it's up to you to fix it. But actually, if I'm a therapist and we're doing this role play, it's up to me to fix it, right? That we got away from the dream and the feelings about me.

Puder:

Well, okay. Yeah. And patients do that, right? So that's like, of course!

Shedler:

So that incident is really filled with feeling, and there's two competing therapy principles here. One is that we really want to follow the affect and stay with what's emotionally meaningful, emotionally charged for the patient. That’s clearly the syringe memory. But the other principle is we want to track the transference, especially the negative transference. And especially with somebody with a depressive personality style where it's so hard to see and so hard to get a hold of in the treatment. So, I'm trying to balance those two considerations. You could make an argument for going either way, but I think the transference is important. So we'll pick up the role play, but I'll jump in, okay? So we just left off with– it's kind of confusing who's betraying who.

Resume Role-play:Shedler:

This experience with the syringe and HIV, it's really important. It's a big deal to have a mother with HIV, especially, I guess, because of her own recklessness. I do want to come back to that. But it's on the heels of remembering this dream that you think had to do with me. That feeling of being criticized by seeing one of my posts on social media. I wonder if you could help me connect the dots. They must have something to do with each other.

Puder:

You know, it's so interesting. I hadn't had this thought and you always say just share whatever comes to your mind. Like, if it comes all of a sudden, right?

Shedler:

Yeah.

Puder:

And so I had this thought that I think connects the two. There's a verse in the Bible, and it says if you hate your brother, you commit murder. And it has always been a part of my ethic to not hate anyone. And so I think after I had that thought about my mother that was the same day that the dream came after. And I thought, like, I'm gonna tell you about this because I had some frustration towards my mother. But then I think for some reason that sort of thought process comes through my mind that it's something bad to have any anger or like hatred, or– I'm not saying I hated her, of course. I'm just saying for some reason that that thought comes to my mind.

Shedler:

Comes to mind in connection with me?

Puder:

Yeah. Because in the confessional, I would be confessing that I murdered my mother with my hatred. That's the connection I'm drawing.

Shedler:

Maybe I misunderstood. I thought the confessional was your thoughts about hearing my social media post as a scold, that you're not doing it right. You're not maintaining the therapy frame properly. That that was your sin. That was your original sin before—

Puder:

That's what I thought. But in session right now, and I hadn't planned this. I hadn't thought about the connection. But the connection is that niece incident, that memory was the day before too. So I'm thinking that maybe the confessional– and I had thought at the time, I'm gonna talk to Shedler about this incident because of the new memory with my mom and the HIV syringe, and just thinking about being upset for my niece, like, oh my gosh. How could anyone have harmed my niece like that?

Shedler:

It's easier to be angry on your niece's behalf than on your own. Your niece wasn't the one being harmed and who could have jabbed herself with an HIV positive needle, right? I mean, it was you. It is easier to be upset on her behalf. And—just so we don't lose this, because I feel like it keeps slipping away and maybe we both have a role and it slipping away—that the starting point for this was you feeling scolded by something I posted on social media, or feeling you were being told you were bad. And it's in the context of, actually you are the one who's been wronged, who feels wronged. I think there may be more to this than meets the eye. That social media post really didn't sit very well with you.

Puder:

Yeah. I feel bad even for snooping on social media. In between sessions, I feel like I'm complicating the work here. I feel like I should be–

Shedler:

Another transgression on your part.

Puder:

Oh, I know, I know. And I feel bad that I'm recognizing that I'm double transgressing myself with this.

Shedler:

No, I'm not saying it's a transgression. I'm saying that you are talking about it as if it's a transgression. Like it your mind, it’s a transgression that you felt bad about my social media post. And it’s a transgression that you even saw it in.

Puder:

Okay, okay. I think there's part of me that sometimes—and I know I shouldn't feel this way—I feel like I'm gonna tell you something and you're gonna get really angry at me. Like, really angry. I feel like it's coming.

Shedler:

I guess we'll have to see…

Puder:

Oh, see, there's a part of me that thinks that there's gotta be something that I could tell you that, or I don't know. I just imagine maybe—I'm imagining incorrectly. I'm sorry. I'm confused about…

Shedler:

What just happened here? Just at the moment when you said it feels like I could get angry or blow up at you at any moment. I haven't yet. But you feel like the next one is gonna be the straw that breaks the camel's back, and I'm gonna erupt at you. And I said, "Well, we'll have to see." Something shifted right then. I'm not sure what came up for you, just in that moment.

Puder:

I feel like me sharing that would make you upset. I'm blaming you for something that you haven't done. Like, I'm accusing you–

Shedler:

You’re worried that I would get angry, that I would berate you or explode at you. Sharing that is–

Puder:

That feels dangerous to me.

Shedler:

Feels…?

Puder:

It feels dangerous.

Shedler:

You think I wouldn't want to hear your thoughts and feelings about me.

Puder:

It feels like maybe I'm blaming you for accusing you of something, or–

Shedler:

Well, that's a possibility. You might be worried or blaming me for something that’s coming from somewhere else— that isn't really about me. It's also possible that you're picking up on something about me in the background that we haven't talked about explicitly. Maybe there is something you're picking up on.

Puder:

Are you secretly angry at me between sessions?

Shedler:

I am leaving it open because we're really talking about your experience of me. And you seem to have the idea that it wouldn't be all right with me to tell me about things I do, or fail to do, that disappoint you or are upsetting, or make you feel bad about yourself, or make you feel like I'm secretly angry and I could explode at any moment. I think that if I answered your question, I think it kind of steers us into a dead end. And that it forecloses the opportunity to find out more about what's going on in your mind and in your experience.

Puder:

And I feel crazy even saying these things out loud because I know that you're professional and you're an expert. I'm sure you don't dislike your patients. And I have no evidence to support that. And I also realize I may be laying this on too thick and I may be laying on too much of my own worries.

Shedler:

I get the sense that you're working so very hard to be very reasonable and very fair with me. And what if you weren't so reasonable and fair with me?

Puder:

I think if I wasn't reasonable and fair, I think you would find some other patient to fill my slot or something.

Shedler:

You think I'd want to be rid of you.

Puder:

Yeah.

Shedler:

What an awful feeling that would be, to feel like the person, even the person that you come to for help, doesn't want to deal with you.

Puder:

I think it's just really weird to be in this role where I'm the one talking and all day long, I listen to my patients. I listen to my family.

Shedler:

Well, I think that's very comfortable. We both know, we've talked about this. It's a very comfortable and a familiar role. You were training for it, for that role since early childhood. What I'm starting to understand in a different way now is there's something about being here with me as a patient that's very fraught for you. You didn't say this in so many words, so if I'm not getting it right, I hope you'll correct me, but it seems to me like there's a way you're sort of walking on eggshells here. That at any moment, I might explode at you or punish you or throw you out of treatment entirely. And I know it hasn't been in the forefront of your mind. It's not like you're deliberately editing and censoring and curating your thoughts at every moment to be careful not to offend me, or not to say the wrong thing. But it seems like that's been with us in the background.

Puder:

Yeah. And I think that this is different because I think with my teachers and coaches, that I got good things from, of course I'd find that thing that they're interested in and read a couple books on it, be able to dialogue on the thing that they're into. And I think that–

Shedler:

Your role was to be a very good student, or very good athlete, and to be very appreciative.

Puder:

Yeah. And I don't want to come across as unappreciative.

Shedler:

I wouldn't like an unappreciative patient.

Puder:

See I know there's a little tongue in cheek in there. I'm really trying to get into this role, but I'm also realizing how hard it is to get into the role.

Shedler:

The role is one where you don't have to feel like you're walking on eggshells or taking care of me or protecting me from my feelings.

Puder:

I think there was something very hypervigilant about me when I was young. To be in that role with my dad, with my mom. It’s hard.

Shedler:

Well, I mean the word “hypervigilant”– it's technically the right word– but there's something that's, like, pathologizing about it. Your describe it as hypervigilant, whereas in fact you were doing what you had to do to function and survive in that environment. It's not like you had a lot of choice, you know? It's not like as a small child, you could have just picked a different family, or replaced your parents. You didn't have any choice. You had to function as best you could with the parents you had.

Puder:

Yeah. It's so interesting how my language pointed at me, at all times.

Shedler:

Yeah. Almost like it was your failing or your pathology, that you had to be vigilant in the ways you were. Versus that you were growing up with two angry, volatile, neglecting parents who could explode. Certainly your father could. And at any moment he could also just disappear and leave you to fend for yourself for weeks on end… as they both did. And it's like there's sort of two parts of you here. I mean, there's the adult rational mental health professional who thinks about things in a very rational and careful and accurate way. But then in the background, there’s a part of you that's expecting the same treatment from me, and feels like you have to be just as careful and just as cautious as you had to be growing up. A part that feels like you could say or do the wrong thing, and then I wouldn't be here for you either. At best, I wouldn't be here. At worst, I would actively attack you. Or I should say, I would actively attack you, too.

Puder:

Yeah. Something about you commenting that “hypervigilant” for me, it kind of puts it like something is bad with me. Whereas, I was responding the best I could in that environment and that was what was helpful at the time. And so I'm repeating that here.

Shedler:

I think that you were doing the best you could to survive that.

Puder:

I guess where I get confused is it brought me a lot of good things to be very good at reading people. Like my mentors, I had some good English teachers and stuff where I was like, for me, kind of getting onto their page. It gave me really good things to be able to read them and–

Shedler:

Yeah, I think you're 100% right. There's no question about it. It’s kind of your superpower, to be able to tune into other people that way. But like all superpowers, it also comes with a huge cost. Which is, you were focused on what you think the other person needs and wants, and your needs and wants go on the back burner. Or don't get on any burner at all.

Pause Role-play:Now, this was the place, if we had started with the first session and we had kind of gone through the process of why the patient is here, what is the purpose of our therapy, what are we trying to accomplish here together… we would have done all of this beforehand. This would be a place that I would refer back to. I'm just making this up now because we didn't have that conversation. But by objective external criteria, you're doing pretty well in your life: good practice, successful in your career, married, wife, family, but things feel empty and dark and sad and joyless on the inside. That's why you're here. If that was the reason the patient came—there could be many, many reasons—if that was the reason, I'd want to make a very explicit link between that and what we're talking about now. This is a sort of little micro instance of this superpower. He knows he is very, very good at accurately reading and responding to other people. I don't want to diminish that. I mean it’s true, right? He has that ability. And that's why a lot of people with depressive personality style are drawn to the therapy professions.

They have a kind of hypertrophied capacity for empathy, which can serve them very well as a psychiatrist or a therapist. But it can also come with a terrible price. So what we want to do at this point is link it specifically back to why he came to therapy. We can say, here's your superpower: You're very, very good at reading and responding to what other people need, but it comes at this terrible cost. The cost is that we—and I mean both of us, him and me both—–don't always get to hear what you need and want. What would make an interaction feel satisfying, or make life feel satisfying and meaningful, allow for pleasure and joy, for you. So I'd link these things because they're the flip side to the same coin. There's the superpower and there’s a real liability, not a liability that affects other people so much, but that gets in the way of you being able to live a life that you can enjoy. Whatever we had agreed is the purpose of therapy, why he came in the first place—I would take advantage of this opportunity to make the link to that. “This is why we're here.”

Resume Role-play:Puder:

Yeah. I think when I hear I should, it's interesting because I know that I need to get in touch with my own feelings and desires. And I think that was one of our initial goals that we identified. And also why am I extending myself too much at work. I think part of the conflict is I've always had the philosophy of serving others has intense value and to kind of put myself second or to diminish my own ego and the importance of it.

Shedler:

Yeah. You had the philosophy, a lot of people find meaning, deep meaning in living their lives, in choosing to live their lives that way. That's an option. What I'm concerned about, I think what we're both concerned about for you, is it's not clear, as of now, how much that's really a choice versus something that happens in an automatic, obligatory way. Like for instance, you saw a social media post of mine, you didn't like it, it felt critical. It makes you concerned about well, maybe you're not in the right hands after all. Maybe I could be–

Puder:

Oh, no, no, no. That's, that's not what I was thinking.

Shedler:

I know you didn’t say that. I'm saying it.

Puder:

Okay. Okay. But I like the post. It just was convicting that like, I came in talking about how I overextend and maybe I need to charge–

Shedler:

Well, what I was getting at is I'm not sure that if you were upset by the post, or if it made you worried that you’re not in good hands here, I'm not sure it would have felt okay just to say so. In fact, I'm pretty sure it felt not okay to say so. And to respond to what you said about your philosophy of how to live your life, it may be a valid choice, but for you just here and now, I'm not sure how much choice there's been. And I think that's why you came to therapy in the first place. It's entirely different to say here's something, here's the thing I want for myself. Here's something I desire. But there are other things that are more important to me that preclude that. And I'm going to make a choice, and I know this is something I want, but I'm going to choose something else that's more important to me. That’s different than not being able to want it in the first place.

Puder:

When I hear this, what I think about is that quote I've memorized from Dostoevsky: “I'm not worthy of happiness. My life is a series of errors, and perhaps this misery is what I must endure to atone for them.” I don't know why, but that resonated back in the day, like in college, and I memorized it. It's interesting because I feel like I reincarnated from some awful person to go through some of the suffering I went through.

Shedler:

It resonated because in a very important way, I think it speaks to the story of your life. This was the family you were born into, your role was to suffer and bear the suffering for all your parents' failings. And to feel like that was your lot, and what you deserved.

Puder:

Yeah. And so I think it's like something is shifting there. And maybe that's kind of– coming back to the dream– it feels like that kind of ruinous building that I was in, it feels like something is shifting. Maybe I can kind of look at things a little bit differently or maybe it makes me…

Shedler:

Well when you said the ruinous building that you were in in the dream, it seems like you just linked that to, it was right on the heels of just saying directly how ruinous your childhood was. It seems like you just connected those dots that you were literally living in ruins in childhood with holes in the walls and cockroaches and hypodermic syringes in the car seats, and your childhood and your family were the ruins. And in the dream, the dream depicts you as enduring this and confessing your sins.

Puder:

Oh, yeah. Somehow I still am blaming myself in the midst of that.

End Role-play:Shedler:

Okay, let's step back. So I'm being a bad therapist because I got kind of caught in the roles between talking to you as interviewer and to the listeners, versus the role of being therapist. And if it were therapy, it really got a little too intellectualized and away from the immediate experience. So not a very good model of doing therapy in this, you know that last–

Puder:

Which part? I think you're being hard on yourself here. I think it is really good.

From Obligation To Freedom: Therapy’s Role In Personal Choice (1:35:03) Shedler:

The part about the philosophy, because it's really about– I got a little didactic and explainy…”

Puder:

Oh, really?

Shedler:

A little, I thought so, yeah.

Puder:

Okay. Well, I think what I've realized is that as I reread this stuff over and over again, I'm like oh, people really adopt the philosophies based on their personality.

Shedler:

People adopt a philosophy that solves–

Puder:

That solves their personalities—

Shedler:

—psychological conflict. Oh yeah. Your choice of career, your choice of partner, your choice of lifestyle is a compromise.

Puder:

And that's not to negate a philosophy being true or not true because it still could be true.

Shedler:

Right, it still could be a perfectly reasonable and valid and meaningful life choice. But we have to understand that all life choices are overdetermined and reflect something of our own psychology.

Puder:

But what I think I appreciate– what you said there– is even with this guy, you wouldn't want it to be unconscious. You would want him to have a choice if he's going to choose to be sacrificial or if he's going to choose to be in touch with his aggression and have a boundary with his time.

Shedler:

This is ultimately the goal of psychodynamic or psychoanalytic therapy, and I would say of all good therapy that's aimed at self-understanding. The goal is to expand freedom and choice so that things that were previously automatic or experienced as obligatory become a matter of choice. That's the goal of the work—to expand freedom and life options. And the person might, in any given circumstance, make the decision to do whatever they would've done before therapy. But now it's a decision. It's a decision made freely.

I'm a little mindful of the time—I want to make sure we get this out because we haven't named it explicitly—but this is what you and I were working on in the role play. This is really the essence of this depressive personality style that we're speaking about: typically, a child growing up feels deprived or mistreated in some way—neglected, or in extreme cases, actively abused. But in the more common case—like if you were looking at the family from the outside, like a social worker doing an investigation—the parents could look adequate, maybe not neglecting in any externally obvious way, but emotionally neglecting. The child's experience is that they're not getting what they need because the parents aren't coming through. The parents are inadequate in meeting the child's needs—but that’s an incredibly, incredibly dangerous thought for a small child. It's extremely rare for a young child to consciously think, “I have bad parents. My life and my well-being are in the hands of people I can't count on.” A three- or four-year-old simply cannot tolerate this thought.

The child's solution to this horrible, impossible dilemma is, "Well, I'm getting mistreated, so it must be my fault. It must be because I am bad." So the child concludes that they're bad instead of the caretakers. In a very paradoxical way, there’s something hopeful in that for the child. It allows the child to sustain hope, because if the reason they aren't cared for is because they're bad, then it's potentially under their control. They could become good, and then they'd have parents who love and take care of them. So in the child’s thinking, if it's their fault—if it's because they are bad—at least there's a spark of hope that their parents could be good parents after all, if only the child weren’t bad.

If the child thinks their well-being and their survival is in the hands of people they can't rely on, that's just devastating. So that's the essence of this personality style. And then it comes out years later, in therapy as an adult. The therapist had to miss a week and isn't available—when your father died, for God’s sake. And your thought is, "Oh, I don't want to burden him." We could draw a line from that childhood experience—"I'm not getting what I need, and it's because I am bad"—to "I shouldn't call my therapist; that would be a burden."

Puder:

Yeah. So it's like the anger is turned into guilt. The transference is set up so that there's a gentle idealizing and anything bad from the therapist goes on to themself.

Shedler:

The criticism of the other is turned into self-criticism. What initially starts as, "This other person—my therapist—isn't here for me when I need them," becomes, "I'm too much of a burden. I'm asking too much. Something must be wrong with me."

Puder:

I think it's really helpful. I hope this episode has been helpful for listeners; it’s certainly been helpful for me to study and think through it carefully. I think the questions listeners might still have are about "the how," right? People always ask about "the how." In this conversation, they've been witnessing how to do it—how to help someone with these struggles. So any kind of–

Shedler:

Yeah. So we…

Puder:

Anything we haven't covered?

Shedler:

We have to recognize the core enactment, which is that the patient is going to treat the therapist in a way that makes the therapist feel good. It's easy to enter this kind of therapy pseudo-paradise where we both feel wonderful about each other: the patient is so appreciative of us, and we're happy with the patient because they work so hard in therapy, they always pay their bills promptly, they arrive on time without fail, and they're consistently appreciative. As therapists, we feel especially competent and helpful—like we're really effective therapists with this patient. But what quietly slips away unnoticed is that the patient isn't actually experiencing meaningful change in their life outside of therapy. That's the real issue.

To put it in biblical terms, if we've created an illusory paradise in therapy, we need to invite the snake into that paradise. It's not really a paradise; it's an illusion of paradise. We need to welcome the patient's anger and aggression into therapy, because it's already there—just not in a form that's being recognized or acknowledged. We need to make it increasingly possible for the person to bring in a wider range of their emotional experience, which of course must include the entire spectrum of human emotions: anger, resentment, rage, envy, punitiveness, vindictiveness. These are all human emotions, but the person with a depressive personality style doesn't experience it that way. They think, "Maybe they're human emotions for other people—but not for me. I would never feel that way." We want to help them experience and integrate a fuller range of their emotional life.

Puder:

Yeah. I think another way of saying this might be the most empathic thing to do, would be to invite that other side. It would be unempathetic for you not to invite it.

Shedler:

Exactly. And here's this enactment… this is where therapy goes south in treating patients with a depressive personality style, because the therapists are very likely to have a depressive personality style too. It's a perfect mesh and if you think about it, the therapy professions make an invitation you can't refuse for somebody with this personality style. What do you get if you go into the mental health profession, what does it give you the opportunity to do? Well, you get to focus intensely on other people's needs, not that that's bad on its own, that's the job. But you get to focus intensely on other people's needs at the expense of your own. You get to constantly fault yourself, however good you get at the work. Because perfection isn't attainable, as I said earlier. We're all making mistakes in every session all the time. You get to fault yourself perpetually for falling short of some unrealistic, unattainable, internal standard.

Puder:

A Jonathan Shedler, super ego!

Shedler:

Hah! Well, you put your own needs on the back burner. And here's where I see this—I'm so glad you brought this up because I see this all the time: the misuse of empathy as a defense for the therapist, against the therapist's own aggression. So what happens in therapy is the therapist is very, very, very empathic to the patient's hurt feelings, broken feelings, the sort of needy child-like feelings of needing to be taken care of. The therapist has empathy for that part of the patient—but no empathy whatsoever for their envy, their anger, their aggression, their resentment, their vindictiveness, their competitiveness, their rivalry. All of those things are there. How do I know those things are there? Because they're human. But the therapist has zero empathy for that. So it's empathy, I would say pseudo-empathy, as a defense both against the patient's aggression and maybe more importantly, as a defense against the therapist's aggression.

Puder:

And as someone who studied micro expression, a 10th-of-a-second flashes of emotion on people's faces. And every person has expressions of anger. Not everyone knows that they have the expressions of anger.

Shedler:

And it makes a world of difference because that's information, it's information in the interaction eith the patient, it's information in the countertransference. We don't want to shut down that channel. There are three major channels of communication going on in therapy. I don't think you talked about this, but this really comes from Otto Kernberg’s writings. One is the content of what the patient says. The other is the nonverbal things they express through facial expression, body language, tone of voice. That's the second channel. The third channel is the countertransference, what they evoke in us. If we shut down that channel, we shut out important information that otherwise should come through that channel. And we're really, really limiting our effectiveness as a therapist. We're having these reactions to patients for a reason. It's information.

Puder:

Can I show you the micro expression just for those who are watching the video here? So this, I actually filmed a lot of people watching YouTubes, and so this is what it looks like right here.

Shedler:

Very serious looking person here.

Puder:

But do you see the down and together of the eyebrows? Like, it's like one 10th of a second. Yes. Boom. That's the micro expression of anger.

Shedler:

That's a lovely example. And a therapist who wasn't defended against that might register it even if subliminally, maybe they didn't get the specific movement, the eyebrow. But they saw something.

Puder:

They saw something. Yeah.

Shedler:

And that's a good place to say—to just slow down there—and say, “something just happened here. Your expression changed. I wonder if we could just slow down here and notice what might come up.” So we notice what the patient evokes in us and then we use that– that becomes a signal to us to invite the patient to slow down and notice more.

Puder:

I could get onto other tangents here, but I think we gotta wrap it up. This was wonderful. I hope that people appreciate Jonathan Shedler and the expertise that you bring. Appreciate you coming back on. And we will be posting this on X. We'll be posting it on YouTube if you want to watch the video. I know a lot of people just watch the podcast, but if you wanna watch the video, you could jump on there. And yeah. Any closing words?

Shedler:

Yeah, just on a personal note, I have to say, I was very aware coming on the show… the last two podcasts of yours that I watched were Otto Kornberg and Frank Yeomans, and boy those are big shoes to follow.

Shedler:

Kernberg is a living legend for a reason. I mean, I could just– almost did actually in real life– but I could sit at his feet and just listen to him and take it in. And that actually happened, except it was at a dining table, but my experience was I could just sit here forever. And I think Frank Yeomans is one of the most gifted master clinicians who's publicly out there teaching. I mean, every time I hear him, it's a pleasure and I learn something every time. So I was very acutely aware, these are the people I'm following on your podcast.

Puder:

Oh, man. And I think I really appreciate– you sent me a message like that was a historic interview. And I think if anyone hasn't watched Kernberg or Yeoman's, both of them are amazing. Actually, when I was reading through the journal articles looking at transference focused therapy, if you read the methods section for a lot of these studies, Yeomans is the supervising therapist on these studies. Like he is the guy. And then Kernberg is just masterclass. I think you sent me a message, like “I understand everything he was saying and I love it.”

Shedler:

Yeah. It was kind of scary.

Puder:

Which I'm like as I get deeper into this material, most of it's understandable. And it makes so much sense. It makes so much sense.

Shedler:

Well, I'll just share with the audience what I wrote to you privately. So I remembered when I was a 20-something year old grad student trying to read Kernberg’s books. These are books written in the late seventies or early eighties. And for anyone who's tried to read Kerneberg’s writings of that time in the original, it's really, really, really hard to read. It is not an easy read. It's incredibly challenging and demanding. And I actually had the depressive thing, I was reading his book, and I'm like, “Oh my God, I feel stupid. I'm like, I'm not up to the work of this profession. If this is what it is, I’m inadequate.” So fast forward a few decades and now it's like, “no, I'm pretty much tracking with everything.”

Puder:

Yeah. I was not expecting an interview. That's the wild part. I was expecting a phone call where we would talk about an interview and then I would spend like a couple months reading and rereading. And so I jump into this and it's like, okay, here we go.

Shedler:

I think that interview and the fact that you made it happen, whatever it took, I think it's a historic event.

Puder:

Oh, and I'll say for those of you who have listened to it or listened to this, my new sort of approach to the write-ups is to do a really nice transcription where then I put in footnotes and I put in the footnotes for the beginner. It's not for the expert, it's for the beginner. So if you are confused, if you wanna go back, listen to this episode, something was confusing, you wanna go back, look at the transcript, eventually we'll have one up there with footnotes, Kernberg, we have one up there with footnotes on my website psychiatrypodcast.com. It's free for anyone. All my stuff is free.

Shedler:

I highly recommend it for whoever's listening.

Puder:

And we'll continue to produce good content. I think we were gonna go through every personality style eventually. So five years from now, we'll be done.

Shedler:

David, thank you so much. It was a pleasure to be here.

Puder:

Alright, we'll leave it there for today.

References:American Psychiatric Association. (n.d.). DSM: Previous editions. PsychiatryOnline. Retrieved May 21, 2025, from https://www.psychiatryonline.org/dsm/dsmPreviousEditions

American Psychiatric Association. (2022). Diagnostic and statistical manual of mental disorders (5th ed., text rev.). https://doi.org/10.1176/appi.books.9780890425787

Blatt, S. J. (2004). Experiences of depression: Theoretical, clinical, and research perspectives. American Psychological Association. https://www.apa.org/pubs/books/4317039

Grohol, J. M. (2013, May 29). DSM-5 changes: Personality disorders (Axis II). Psych Central. Retrieved May 21, 2025, from https://psychcentral.com/pro/dsm-5-changes-personality-disorders-axis-ii

Murphy, T. F. (2022, September 6). Axis II disorders: Exploring personality disorders in mental health. Psychology Fanatic. Retrieved May 21, 2025, from https://psychologyfanatic.com/axis-ii-disorders/

Puder, D. (Host). (2018, May 7). Microexpressions to Make Microconnections Part 1 (No. 015) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/microexpression-microconnection-empathy?rq=015

Puder, D. (Host). (2018, May 14). Microexpressions: Fear, Surprise, Disgust, Empathy, and Creating Connection Part 2 (No. 016) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/microexpressions-emotions-empathy?rq=016

Puder, D. (Host). (2018, May 23). Microexpressions in Psychotherapy Part 3 (No. 017) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/using-microexpressions-in-psychotherapy?rq=017

Puder, D. (Host). (2018, Sept. 19). What is psychodynamic theory? (No. 029) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/2018/9/19/what-is-psychodynamic-theory?rq=029

Puder, D. (Host). (2019, March 31). Therapeutic Alliance Part 4: What is Transference and Countertransference? (No. 041) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/strongepisode-041-strongtherapeutic-alliance-part-4-what-is-transference-and-countertransference?rq=041

Puder, D. (Host). (2019, Dec. 11). Therapeutic Alliance Part 6: Attachment Types and Application (No. 069) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/2019/12/11/therapeutic-alliance-how-to-build-an-attachment-with-your-patient?rq=069

Puder, D. (Host). (2021, June 14). Using Microexpressions To Improve Empathy, Therapeutic Alliance & Emotional Intelligence (Therapeutic Alliance Series Part 8) (No. 118) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-118-microexpressions-to-improve-empathy-emotional-intelligence-therapeutic-alliance?rq=118

Puder, D. (Host). (2022, Feb. 25). Borderline Personality Disorder: Common Factors In Effective Therapies With Dr. Robert Feinstein (No. 140) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-140-borderline-personality-disorder-common-factors-in-effective-therapies-with-dr-robert-feinstein?rq=140

Puder, D. (Host). (2022, Dec. 2). Listening Psychodynamically (No. 164) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-164-listening-psychodynamically?rq=164

Puder, D. (Host). (2023, Feb. 24). Using Transference To Improve Connection (No. 170) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-170-using-transference-to-improve-connection?rq=170

Puder, D. (Host). (2023, March 3). Nancy McWilliams on Mental Health, Transference, and Dissociation (No. 171) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-171-nancy-mcwilliams-on-mental-health-transference-and-dissociation?rq=171

Puder, D. (Host). (2023, June 30). Narcissism with Jonathan Shedler, PhD (No. 185) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/185-narcissism-with-jonathan-shedler?rq= 185

Puder, D. (Host). (2025, Feb. 22). Transference Focused Psychotherapy, Borderline Personality Disorder, Narcissism, with Frank Yeomans, MD (No. 234) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-234-transference-focused-psychotherapy-borderline-narcissism-frank-yeomans?rq=234

Puder, D. (Host). (2025, April 25). Transference Focused Psychotherapy & Personality Disorders with Dr. Otto Kernberg (No. 239) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-239-transference-focused-psychotherapy-otto-kernberg-borderline-personality?rq=239

Shedler, J. (2021). The personality syndromes. In R. Feinstein (Ed.), A primer on personality disorders: Multi-theoretical viewpoints (pp. 3–32). Oxford University Press. https://jonathanshedler.com/wp-content/uploads/2021/09/Shedler-2021-The-personality-syndromes.pdf

The Literature Network. (n.d.). Fyodor Dostoevsky. https://www.online-literature.com/dostoevsky/

World Health Organization. (n.d.). Classification of diseases. Retrieved May 21, 2025, from https://www.who.int/standards/classifications/classification-of-diseases

Yalom, I. D. (n.d.). Biography. Irvin D. Yalom, MD. Retrieved May 23, 2025, from https://www.yalom.com/biography

Yalom, I. D. (1989). Love's executioner and other tales of psychotherapy. Basic Books. https://www.yalom.com/loves-executioner

Yalom, I. D. (2002). The gift of therapy: An open letter to a new generation of therapists and their patients. HarperCollins.

https://www.harpercollins.com/products/the-gift-of-therapy-irvin-yalom?variant=41231884386338

Yeomans, F. E. (n.d.). Frank Yeomans, MD, PhD – Psychiatry & Psychotherapy. Retrieved May 21, 2025, fromhttps://www.frankyeomans.com/

View Details

Daniel Cuevas, Liam Browning, MD; Christopher Campbell, Danielle Liu, David Puder, MD

Corresponding Author: David Puder, MD

Reviewer: Erica Vega, Joanie Burns, PMHNP-BC

By listening to this episode, you can earn 1.25 Psychiatry CME Credits.

Other Places to listen: iTunes, Spotify

The authors declare no conflicts of interest and have no financial relationships with any pharmaceutical or cannabis companies.

We are at a time when cannabis use is increasing, becoming normalized as a healthier recreational option, and when higher-potency versions are increasingly accessible. The societal impact is still unfolding. Yet, as clinicians in the field, it is not uncommon to observe new cases of psychosis emerging in the wake of heavy, high-potency THC use, or existing patients with schizophrenia decompensating following new or increased consumption.

Real-world clinical scenarios underscore why this issue is so important. In one case, a young man with a long history of daily cannabis use began experimenting with “dabbing,” a method of inhaling extremely concentrated THC. Within weeks, he became intensely paranoid and hypervigilant—convinced that strangers in a black truck were following him—and grew too anxious to sleep at night. His downward spiral was halted only after he was hospitalized, treated with antipsychotic medication, and most importantly, stopped using cannabis. Once the high-THC dabs were out of his system, his paranoia and delusions quickly resolved.

In another case, a patient with an existing psychotic disorder remained trapped in persistent psychosis despite taking antipsychotic medication, simply because he continued to smoke marijuana daily. His family watched in frustration as each day of cannabis use sustained his hallucinations and erratic behavior. Only when they intervened—setting firm limits around car use (that enticed him to quit THC)—did his mind clear. In a matter of months, this individual experienced a remarkable turnaround to the point of successfully returning to college.

Cases like these have become increasingly familiar to psychiatrists and emergency physicians, reflecting a pattern seen in hospitals and clinics across the nation. They raise pressing clinical questions about the link between cannabis and psychosis. Can frequent use of high-potency THC actually trigger psychotic episodes or worsen an underlying mental illness? How does cannabis interact with the developing adolescent brain, and could early heavy use increase the risk of disorders like schizophrenia in vulnerable individuals? In the pages that follow, we will explore these questions in depth. We will examine the latest scientific research on cannabis’s impact on brain chemistry and neurodevelopment, review what is known about its role in psychotic illnesses, and discuss why today’s high-THC cannabis may pose unique challenges compared to the past.

Cannabis And Mental Health: Exploring The Connection Between Cannabis Use And PsychosisThe Growing Popularity of Cannabis and Its Mental Health ImpactsCannabis is an increasingly popular recreational drug, with 50% of Americans reporting having smoked marijuana at least once in their lifetime as of 2023, compared with just 4% in 1969 (McCarthy, 2023). Moreover, there has been a 15-fold increase in daily cannabis users from 1992 to 2022 (Caulkins, 2024).

As of 2021, according to the Substance Abuse and Mental Health Services Administration (SAMHSA, 2022b), up to 19% of Americans (approximately 52.5 million individuals) admitted to using marijuana at least once in the last year. Notably, in young adults (ages 18 to 25), use in 2021 was as high as 35.4%, followed by 17.2% of adults aged 26 and older, and 10.5% of adolescents aged 12 to 17 (SAMHSA, 2022b).

When examining daily cannabis use (defined as using cannabis at least 20 times in the last 30 days), 10.4% of young adults ages 19-30 engage in daily use, followed by 7.5% of adults ages 35 to 50, followed by 5.2% for adults ages 55-65 (Patrick et al., 2024). For comparison, the total population of daily marijuana users has now surpassed that of daily alcohol users (17.7 vs 14.7 million, respectively). Furthermore, the median alcohol consumer reports alcohol use 4 to 5 days per month, whereas the median cannabis user engages in cannabis use 15 to 16 days per month, highlighting the significant differences in typical use patterns between these commonly used recreational substances (Caulkins, 2024). Additionally, a 2014 longitudinal study by Hughes et al. found that on average daily users will use marijuana 3.2 times per day, leading to a consistent intoxication during waking hours. Consistent with prior prospective studies, this study also demonstrated that social factors and availability were the two most powerful predictive factors of marijuana use.

This increase in cannabis use coincides with a significant shift in cannabis policies and an increase in accessibility of cannabis over the last decade. As of April 2025, there are only 4 states where cannabis is completely illegal; the other 46 states have various forms of legality including legal for medicinal purposes, legal for recreational use, decriminalized, or some combination of these factors (DISA, 2025). However, despite recreational cannabis remaining illegal in more than half of U.S. states, it is nevertheless widely available due to loopholes in the 2018 Agriculture Improvement Act (commonly known as the Farm Bill), which allows for the legal sale of chemically similar compounds, produced through minor molecular modifications, that nonetheless have the same psychoactive effects of cannabis.

Unfortunately, despite the widespread public perception of cannabis as a relatively benign substance, cannabis use continues to be associated with a wide array of significant and deleterious mental and physical health effects. In this episode on cannabis, we aim to provide an evidence-based exploration of cannabis use, covering its use patterns, pharmacology, mental and physical health effects, and societal implications. By the end, we hope to equip listeners with a comprehensive and scientifically grounded perspective regarding this increasingly utilized substance.

“Marijuana Use in the Past Year: Among People Aged 18 or Older; by State, Percentages, 2021”

*Note.* Reprinted from “*2021 National Survey on Drug Use and Health: National maps of prevalence estimates, by state*.”, by Substance Abuse and Mental Health Services Administration (SAMHSA)., 2022a,U.S. Department of Health and Human Services.Figure 2e..

The Rising Potency of Cannabis and Its Mental Health ImplicationsNot only has cannabis use increased, but the potency of the cannabis itself has increased as well. Average THC levels in cannabis were around 4% in the 1990s, whereas modern strains can exceed 17-28% (Backman, 2023; Stuyt, 2018).

THC Concentrates and Their Increasing AvailabilityForms of cannabis with concentrations of THC exceeding 90%, also known as “THC concentrates,” are also becoming more commonplace, allowing for rapid consumption of high amounts of THC. Additionally, the availability and ease of use of THC vaporizers are points of concern, as people can use them without needing to prepare the substance for consumption, and they can be carried and used discreetly since they don’t require flower or produce the distinctive smell associated with flower. Moreover, high potency, bite-sized edibles make oral ingestion of high doses incredibly easy. Often, the delay in experiencing the effects of edibles, which can sometimes exceed two hours, can lead individuals to consume additional edibles at higher quantities than intended.

Understanding Cannabis And Its Effects On The BrainThe Endocannabinoid System: A Key Mechanism for THC’s Action in the BrainBefore describing how cannabis influences the brain and body, it is important to describe the body’s natural system it is acting on: the endocannabinoid system. The endocannabinoid system is a neuromodulatory network critical for maintaining homeostasis in many different domains through regulating appetite, sleep, memory, learning, emotional responses, movement, inflammation, and pain perception, to name a few (Lutz, 2020). Specifically, its primary mechanism in the central nervous system (CNS) is maintaining homeostasis of synapses via retrograde synaptic transmission. For example, if neuron A is exciting neuron B too much, neuron B can send endocannabinoids such as 2-arachidonoylglycerol (2-AG) back to neuron A. This will suppress neuron A’s activity and weaken the synapse between the two neurons.

The endocannabinoid system consists of cannabinoid receptors (i.e., CB1 and CB2), endogenous ligands (such as anandamide and 2-arachidonoylglycerol), and regulatory enzymes and transporters, which control synthesis and degradation of endocannabinoids (Hillard, 2015).

The Role of Cannabinoid Receptors in Mental HealthThe two primary cannabinoid receptors are CB1 and CB2, both of which are G protein-coupled receptors (Lutz, 2020):

CB1 receptors (CB1Rs) are expressed throughout the central nervous system, on neurons, astrocytes, and microglia, but most densely on presynaptic neurons in brain regions such as the prefrontal cortex, hippocampus, anterior cingulate cortex, and cerebellum. They are particularly prevalent on GABAergic interneurons, where they regulate inhibitory neurotransmission, and to a lesser extent on cortical glutamatergic projection neurons. When CB1Rs are activated, they inhibit presynaptic voltage-gated calcium channels and increase potassium channel activity, leading to suppressed release of neurotransmitters and to decreased synaptic transmission. This retrograde signaling mechanism is central to the endocannabinoid system’s ability to maintain homeostasis through fine-tuning neural activity for synaptic plasticity, implicating it in learning, memory, and neurodevelopment.

CB2 receptors (CB2Rs), by contrast, are expressed mostly on immune cells of the periphery (lymphocytes, macrophages, etc.). However, CB2Rs are upregulated on immune cells of the brain (microglia and macrophages) in response to insults such as stroke, pain, and neuroinflammation.

THC and the Endocannabinoid SystemEndocannabinoids, the system’s endogenous ligands, include anandamide (AEA) and 2-arachidonoylglycerol (2-AG), both derivatives of arachidonic acid. They are both synthesized on-demand and passively diffuse into the synapse, so they are not stored in vesicles.

Anandamide acts as a partial agonist at CB1Rs and TRPV1 (the capsaicin receptor, which responds to temperature) and is constantly released to provide steady modulation of synaptic activity, while 2-AG, a full agonist at both CB1 and CB2 receptors, is released retrogradely in response to heightened neural activity. Notably, endocannabinoids may also alter neurotransmission via other mechanisms, including interactions with neurosteroids (glucocorticoids, pregnenolone, etc.), mitochondria, and glial cells.

Endocannabinods play an important role in regulating mood and anxiety (Patel & Hillard, 2009), and are thought to increase with exercise and to play some role in producing the runner’s high (Siebers et al., 2021). Some early evidence suggests people with anxiety and PTSD may have lower levels of endocannabinoids (Bassir Nia et al., 2019), and phase 2 trials of CB1 antagonists were discontinued due to increased risk of suicide (Cohen et al., 2024), implicating them in psychiatric symptoms.

How THC and CBD Work in the Brain: Key Differences ExplainedTHC acts as a partial agonist at CB1Rs, thus mimicking anandamide. However, it does so with more persistent and indiscriminate binding across the brain, disrupting the balance of neuronal excitation/inhibition, and subsequently impacting cognition, mood, perception, and memory (Mayo et al., 2020). THC also induces euphoria by disinhibiting dopamine release in the reward system. Specifically, in the ventral tegmental area (VTA), THC inhibits GABAergic neurons that normally suppress dopamine activity, resulting in increased dopamine release in the nucleus accumbens and prefrontal cortex.

THC vs. CBD: Key Differences in How They Affect the BrainUnlike THC, cannabidiol (CBD) does not produce psychoactive effects and interacts with the endocannabinoid system more indirectly. It does not significantly bind to CB1 or CB2 receptors, but instead inhibits fatty acid amide hydrolase (FAAH, the enzyme responsible for degrading anandamide) to prolong the effects of anandamide. Additionally, CBD interacts with serotonin 5-HT1A and TRPV1 receptors, and may also act as an orthosteric modulator of CB1R through reducing the binding of THC.

It is worth noting that the practice of breeding cannabis plants to maximize THC concentration leads to a decrease in CBD. CBD may counteract some of the anxiogenic effects of high doses of THC (Englund et al., 2013; Karniol et al., 1974; Zuardi et al., 1982; Solowij et al., 2019), although that point is still the subject of debate (Hindocha et al., 2015; Karschner et al., 2011; Arkell et al., 2021; Englund et al., 2023; Lawn et al., 2023).

Cannabinoid Pharmacology: The Absorption, Distribution, And Action Of THC And CBDAbsorption(Lucas et al., 2018) Inhalation: When cannabis is smoked or vaporized, THC and CBD (as well as dozens of other phytocannabinoids, terpenoids, and flavonoids) are rapidly absorbed through the lungs, leading to quick onset of effects. This method bypasses first-pass metabolism. THC is highly lipophilic, meaning it can cross the blood-brain barrier quickly and exert psychoactive effects within minutes. Peak plasma concentrations of THC are typically achieved within 3–10 minutes (50-150 ng/mL via flower and up to 200-300 ng/mL with concentrate [vapes, resin, etc.]). * Oral Ingestion (Edibles)*: Oral consumption results in slower absorption due to gastrointestinal transit and first-pass metabolism in the liver. Peak plasma levels (<20 ng/mL) are usually reached around 120 minutes. First-pass metabolism in the liver converts THC into 11-hydroxy-THC, an active metabolite more potent than THC. It crosses the blood-brain barrier more easily and binds to CB1 receptors more efficiently (Kearn et al., 1999). Oral THC and CBD have poor bioavailability ranging from 6% to 20%.

Distribution(Lucas et al., 2018)* Cannabinoids distribute rapidly throughout the body. Due to its high lipophilicity, it crosses the blood-brain barrier and has high predilection for adipose tissue, where it can be stored for weeks in chronic users. THC and its inactive metabolite (THC-COOH) may become released from adipose tissue in response to weight loss or stress exposure (Gunasekaran et al., 2009). * THC is able to cross the placenta and is excreted in human breast milk because it is highly lipophilic. + The American Academy of Pediatrics (Ryan et al., 2018) advises against the use of THC in those who are pregnant or breastfeeding. In an analysis of two prior studies on pregnant mothers that monitored urine samples for the presence of nicotine or cannabis (Smid et al., 2022), it was found that children with intrauterine THC exposure had higher ratings on attention problem scales compared to unexposed peers, but without evidence for impairments in other cognitive domains or internalizing behaviors.

Metabolism and Elimination(Lucas et al., 2018) THC: Metabolized predominantly in the liver by CYP2C9 and CYP3A4 enzymes into psychoactive 11-hydroxy-THC (11-OH-THC) and inactive 11-carboxy-THC (11-COOH-THC). * CBD: Metabolized mainly by CYP2C19 and CYP3A4. The pharmacologic activity of CBD metabolites are not well studied. * Smoking cannabis or tobacco induces CYP1A2, potentially influencing plasma levels of olanzapine and clozapine (see also episode 236).* * Most metabolites are excreted fecally.

How Long Can THC Remain in the Body and Brain?Plasma (Blood):

THC and its metabolites are typically detectable in plasma only several hours after a single use (Kraemer et al., 2019). However, pharmacokinetic models suggest it might persist in the plasma with as little as weekly use and perhaps longer in heavier users (Mørland & Bramness, 2020).

Urine:

The limit of quantification in a urine test for cannabis is 4 ng/mL, and the amount of time it takes until it can no longer be detected in the urine depends on the degree of consumption, as is noted in Table 1.

*Note.* Reprinted from “Marijuana”, by Mayo Clinic Laboratories. (n.d.). *Mayo Foundation for Medical Education and Research,* Table 1. Retrieved February 15, 2025, from https://news.mayocliniclabs.com/therapeutics/drug-class-testing/marijuana/

Brain and Fat Tissues:

Unlike alcohol and many other drugs that clear from the body within a few days, THC can linger for much longer—potentially weeks (Lucas et al., 2018)—due to its high lipophilicity. This means people who consistently use cannabis at least twice per week likely have some THC in their brain at all times (Mørland & Bramness, 2020). However, whether these metabolites have any functional effect remains unknown.

Chronic THC Exposure: Impact on Brain FunctionPET studies of chronic, dependent cannabis users have shown lower CB1 receptor availability (by about 15-20%) throughout the brain, but this effect begins to reverse within just two days of abstinence and is normalized by four weeks (Glodosky et al., 2021; Hirvonen et al., 2011). This suggests that although THC and its metabolites may persist in the brain even after CB1 receptors normalize, their presence may not necessarily interfere with endocannabinoids or alter CB1 receptor function. This is also supported by studies of cannabis-induced cognitive impairment (deficits in attention, short term memory, verbal memory, processing speed), which improves and normalizes with increasing length of abstinence (for review, see Bourque & Potvin, 2021). However, it should be noted that the CB1 receptor is highly expressed during times of neurodevelopment, such as fetal development (Papariello et al., 2021) and again during adolescence (Meyer et al., 2018). Chronic exposure to THC during these times may downregulate these receptors and interfere with these critical periods of neurodevelopment (Lutz, 2020). One of the most contentious points in the field is whether heavy cannabis use during adolescence, or even later in life, can lead to schizophrenia by disrupting neurodevelopment during critical periods.

Cannabis, Psychosis, And Schizophrenia: A Psychiatric Risk OverviewDefinition and Presentation of Cannabis Induced Psychotic SymptomsThe link between cannabis usage and psychosis is one of supreme interest to healthcare professionals and members of the public alike. When engaging in such a hotly-debated topic, it’s important to clarify the vocabulary that will be used in the discussion of said topic. Cannabis can induce psychotic symptoms, including hallucinations, paranoia, and delusions, collectively termed cannabis-associated psychotic symptoms (CAPS), as well as a more severe cannabis-induced psychotic disorder, which mimics schizophrenia with positive symptoms (e.g., hallucinations, delusions), negative symptoms (e.g., blunted affect, emotional withdrawal), and cognitive impairments like disrupted word recall (D'Souza et al., 2004; Schoeler et al., 2024). These effects, observed in controlled studies, are dose-dependent, temporary, and linked to THC administration, often resembling schizophrenia’s psychophysiologic deficits (Sherif et al., 2016). Differential diagnosis is challenging due to overlaps with primary psychotic disorders and cannabis use disorder comorbidity, with limited treatment literature and no specific guidelines; acute management involves antipsychotics, dynamic assessment, and vigilant monitoring for safety (Pauselli, 2018; Baldaçara et al., 2023).

A case report by Rossi & Beck, (2020) described a patient who presented to the emergency department with acute paranoid behavior, insomnia, and hypervigilance, which had progressively worsened over the prior month. He reported paranoid delusions involving people following him in a black truck, and had a long history of cannabis use starting at age 13 to manage self-reported anxiety. Notably, his symptoms escalated after initiating “dabbing,” a method of consuming highly concentrated cannabis with THC levels up to 80%. The onset of psychotic symptoms coincided with this change in use, leading to a diagnosis of cannabis-induced psychosis and severe cannabis use disorder. He voluntarily admitted himself for inpatient psychiatric care, was treated with risperidone, and experienced a gradual resolution of symptoms. With continued outpatient care, he tapered off medication, returned to work and college, and remained relapse-free for over a year before discontinuing psychiatric treatment.

Risk Factors For Cannabis Induced Psychotic SymptomsIt’s important to characterize what puts people at risk for experiencing psychosis in connection to cannabis usage. To this end, a large international study analyzing data from 233,475 people who use cannabis (PWUC) examined the prevalence, risk factors, and treatment circumstances surrounding cannabis-associated psychotic symptoms (CAPS) requiring emergency medical attention (Schoeler et al., 2022).

• The study found that 0.47% of PWUC reported experiencing CAPS in their lifetime,

• and 0.19% had experienced CAPS in the past year requiring emergency treatment.

• Paranoia was the most common symptom, typically subsiding as the drug wore off.

• Risk factors for CAPS included being under 21 years old (RR = 2.66), living in Denmark—possibly due to the prevalence of high-potency resin (RR = 3.01), mixing cannabis with tobacco (RR = 2.15), and using high-potency resin compared to herbal cannabis (RR = 2.11).
• Individuals with existing psychiatric diagnoses, particularly psychotic disorders (RR = 14.01), bipolar disorder (RR = 4.30), anxiety (RR = 2.92), or depression (RR = 2.68), were significantly more likely to experience CAPS.
• CAPS events most commonly occurred after the use of high-potency cannabis (44%) or resin (24%), even when consumed in small quantities (≤1 g in 84% of cases).
• While most individuals recovered within a day, 21% reported symptoms lasting longer than four weeks.
• Of those seeking emergency care, 36% were hospitalized, with admission rates highest among individuals with a history of psychosis (76%) or prolonged CAPS (54%).
• CAPS in the study are comparable to rates of psychosis induced by other drugs such as alcohol-associated psychosis (around 0.4–0.7%).

Interestingly, frequency of cannabis use did not correlate with CAPS risk, possibly due to the development of tolerance. However, the study's reliance on self-reported, retrospective data and the influence of country-specific differences in cannabis use and treatment-seeking behavior limit the generalizability of its findings.

The 2023 meta-analysis by Robinson et al. addresses a major gap in the literature by quantifying psychosis risk across five levels of cannabis use frequency. Unlike previous studies that used broad categories, this analysis revealed a nuanced dose-response relationship that was most robust in a flexible non-linear model. It found no significant risk increase with yearly or monthly use, but a 35% increased risk with weekly use (RR = 1.35) and a 76% increase with daily or near-daily use (RR = 1.76), compared to non-users. The study highlights weekly use as a critical threshold for elevated psychosis risk, offering actionable insights for public health messaging to target heavy users. While the study did not assess cannabis potency or age of onset, the authors acknowledge these as important interacting risk factors.

Presentations of Other Forms of Substance-Induced PsychosisCannabis-induced psychosis differs in symptom presentation and severity from psychosis induced by substances like cathinone derivatives, cocaine, methamphetamine, MDMA, PCP, and ketamine.

• Cathinone and its derivatives can cause psychomotor agitation, paranoia, hallucinations, and, in rare cases, excited delirium, similar to cocaine and amphetamines.
• Cocaine-induced psychosis often involves paranoid delusions and auditory hallucinations.
• Methamphetamine psychosis includes persecutory delusions, auditory and visual hallucinations, hostility, and disorganized thinking, but lacks negative symptoms.
• MDMA psychosis features positive symptoms like delusions and hallucinations, alongside depressed mood and blunted affect.
• PCP and ketamine induce psychosis with positive symptoms (hallucinations, delusions, illogical thinking) and negative symptoms (apathy, reduced speech, catatonic posturing), with PCP eliciting a stronger response (Fiorentini et al., 2021).
• In contrast, cannabis-induced psychosis is characterized by heightened paranoia but less agitation and no visual hallucinations, distinguishing it from the more intense agitation and broader hallucinatory profiles of other substances.

Understanding the Limits of Current Cannabis and Psychosis ResearchChallenges and Tools for Assessing Causality in Cannabis ResearchMuch of the research on cannabis and mental health in humans are epidemiological studies. Although epidemiological studies can provide strong evidence for associations, they are not able to fully, or often sufficiently, account for the effects of confounding variables. The most famous study that demonstrates this (discussed in episode 64) is by Di Forti and colleagues (2019), which claimed up to 12-50% of first-episode psychosis could be attributed to high potency cannabis. It was a multicenter case-control study across ten European and one Brazilian site that found an increased association between odds of first-episode psychosis and daily use of high-potency cannabis. Major limitations with regards to investigating causality included the fact that data on cannabis usages was self-reported and could not be validated using biological measures, questions pertaining to cannabis usage were unable to assess potency, and recruitment of controls and patients were not random, as well as other factors. The population attributable fractions were calculated assuming causality, which has not been established in the study, much less the overall body of literature. Gillespie and colleagues (2019) argued in response to Di Forti et al. that their analysis did not adequately account for the genetic correlation between schizophrenia and cannabis use (previously identified at r = 0.25), nor sufficiently address the alternative hypothesis supported by their bidirectional Mendelian randomization study, which indicated that causality might predominantly flow from schizophrenia to cannabis use, rather than vice versa.

To help assess if a relationship in epidemiology is causal or not, the Bradford Hill Criteria can be of much use. They are a series of nine points that are commonly utilized to assess causality within epidemiology (Shimonovich et al., 2021). They are qualities intended to be kept in mind when assessing if a connection is due to something besides causality, as opposed to definitive rules that must all be checked off before a connection is deemed to be causal in nature. They can be quite helpful when evaluating the strength of studies as well as their claims of causal connections. These criteria are listed below, with commentary about their modern importance:

The nine criteria that constitute the Bradford Hill Criteria.

Examples of Prospective Studies Investigating Cannabis Use and PsychosisTo adequately address whether the effects of cannabis use in adolescence is causally related to schizophrenia, more prospective studies are needed. Studies, like the prospective historical cohort study by Zammit et al. (2002), which investigated the causal link between adolescent cannabis use and schizophrenia, utilizing data from a 1969-70 survey of 50,087 Swedish male conscripts (aged 18-20), representing over 97% of the country’s male population in that age group. The study employed a prospective longitudinal design, assessing cannabis use through structured interviews with psychologists and psychiatrists, diagnosing psychiatric conditions per ICD-8 criteria, and following subjects from 1970 to 1996.

• Potential confounders adjusted for included:
• psychiatric diagnosis at conscription
• IQ
• personality traits
• upbringing
• paternal age
• cigarette smoking
• childhood behavior
• alcohol misuse
• family psychiatric history
• financial situation

• father’s occupation

• The study found a dose-dependent association between cannabis use frequency and schizophrenia risk, with an adjusted odds ratio (OR) of 1.5 (95% CI 1.1-2.0) for lifetime use and3.1 (1.7-5.5) for heaviest use (>50 occasions).

• Among 1648 subjects using only cannabis, 1.1% developed schizophrenia, with a higher risk (adjusted OR 1.9, 1.1-3.1) compared to non-users.

• 5.7% of those cannabis users who developed schizophrenia (4/70) used >50 times.

• No association was found with other psychotic disorders, suggesting specificity to schizophrenia.

Although the study supports a possible causal connection due to its dose-dependent findings and rigorous adjustments, a key limitation is the low base rate of schizophrenia in the sample (0.71%), which may reflect the exclusion of individuals with psychiatric disorders at baseline.

A prospective population-based study by van Os et al. (2002) followed over 4,000 adults (ages 18–64) in the Netherlands who were free of psychosis at baseline and found that baseline cannabis use predicted later development of psychotic symptoms, including symptoms severe enough to require mental health care.

• The odds of developing pathology-level psychosis were over 24 times higher (OR = 24.17) in those who had used cannabis at baseline, compared to non-users even after controlling for age, sex, education, ethnicity, urbanicity, and discrimination.
• However, the OR of 24 here is also based on a sensitivity analysis, where those cases of psychosis at follow up are imputed because they lost so many people to follow up.
• In the other sensitivity analyses when they imputed missing participant cases differently, the authors only found an OR of 3.

• Also, while they controlled for baseline psychotic symptoms and age, it's likely that the people who were experiencing psychotic symptoms at the follow up clinical interview had a psychotic disorder at baseline.

• Importantly, the study claimed that there was a dose-response effect, in that greater cumulative use was associated with progressively higher risk. However, it is difficult to accurately assess dose response with only 10 cases and 4 categories of use severity.

• The authors also showed that cannabis use predicted psychosis independently of other substances like stimulants and psychedelics, and that cannabis use at baseline was a stronger predictor than more recent use, suggesting a temporal relationship.
• Furthermore, for those with an existing vulnerability to psychosis at baseline, cannabis use led to dramatically higher rates of poor outcomes, with 80% of psychosis cases in this group attributable to the synergistic effect of cannabis and baseline vulnerability.

These findings address some of the Bradford Hill criteria, including specificity, and biological gradient (dose-response) —and adds to the supporting evidence that cannabis may play a causal role in the development or exacerbation of psychosis.

Can Cannabis-Induced Psychosis Lead To Schizophrenia? What The Research SaysThe question of whether or not cannabis usage leads to long term psychosis or schizophrenia has been the subject of debate and research for decades. There have been recent studies looking at modern trends relating to cannabis usage potentially transitioning to long-term schizophrenia. A recent population-based cohort study from Ontario, Canada (Myran et al., 2025a) reported a significant increase in the population-attributable fraction (PARF) of schizophrenia linked to cannabis use disorder (CUD) following cannabis legalization. However, the study’s methodology defined CUD solely by emergency department visits or inpatient psychiatric admissions related to cannabis use, excluding outpatient cases. This flawed definition likely biased the results by capturing a subset of individuals already at higher risk for schizophrenia due to genetic or psychological predispositions. Furthermore, while cannabis use increased post-legalization, the incidence of schizophrenia actually declined by 27.2% between 2006 and 2022, contradicting the study’s projections. A related study using the same cohort (Myran et al., 2025b) found CUD associated with higher all-cause mortality (HR 2.79), but it relied on the same narrow and problematic definition of CUD. The subgroup defined as having CUD was more likely to be socioeconomically disadvantaged, have co-occurring mental health disorders, and use other substances, introducing substantial confounding variables. As a result, both studies’ conclusions are undermined by methodological limitations and confounding factors, making it difficult to isolate cannabis use as the primary driver of schizophrenia risk or increased mortality.

A 2023 retrospective cohort study of electronic medical records from the same cohort of nearly 10 million Ontario residents aged 14–65, excluding those with prior psychotic diagnoses, investigated the 3-year risk of transitioning to psychosis following emergency department (ED) visits for substance use or substance-induced psychosis, compared to the general population, while controlling for confounders like age, sex, neighborhood income, rurality, and prior mental health care (Myran et al., 2023).

• Of the 9,844,497 individuals, 407,737 (4.1%) had ED visits for substance use
• 13,784 (0.1% of the total population) presented with substance-induced psychosis

• Of whom 18.5% developed a chronic psychotic disorder within 3 years.

• The adjusted hazard ratio (aHR) for transitioning to schizophrenia spectrum disorder was significantly elevated for substance-induced psychosis (aHR 62.0; 95% CI, 58.8–65.4) and substance use without psychosis (aHR 4.8; 95% CI, 4.6–5.0), with cannabis-induced psychosis showing the highest risk (aHR 84.9; 95% CI, 78.7–91.6) when compared to other substances such as:

• amphetamines (22.3)
• cocaine (16.6)
• alcohol (16.3)

• or polysubstance use (48.8)

• Younger age and male sex further increased risk.

Despite adjustments, residual confounding likely persisted due to baseline differences, such as higher prior acute care for substance use among those with substance-induced psychosis (37% vs. 8.5% for non-psychosis substance use and 1.2% for the general population), and the occasional binary treatment of mental health care variables oversimplified complex histories.

This small subset (0.1% of the population) with substance-induced psychosis had more comorbidities, limiting generalizability to typical cannabis users, and the retrospective design could not address reverse causality or many other Bradford-Hill criteria, though it highlighted cannabis-induced psychosis as a stronger risk factor for psychotic disorders than psychosis induced by other substances.

**Table 3. Risk of Transition to Schizophrenia Spectrum Disorder Within 3 Years Based on Age, Sex, and Substance Use.**

Note. Reprinted from “Transition to schizophrenia spectrum disorder following emergency department visits due to substance use with and without psychosis”, by Myran et al., 2023, JAMA Psychiatry, 80(11), Table 3.

Explaining the Cannabis-Schizophrenia Connection: Three Leading HypothesesThere are three main lines of thinking in the literature to explain the association between cannabis and schizophrenia (Hamilton & Monaghan, 2019).

• The first hypothesis is that cannabis is causally associated with schizophrenia; this is based on multiple studies supporting the claim that frequent, high-dose cannabis use is associated with the development of psychosis, and the fact that cannabis can induce psychotic symptoms in those without a history of psychosis.
• The second hypothesis is that people with schizophrenia use cannabis at a higher rate to self-medicate negative symptoms.
• The last is that cannabis increases risk for psychosis in people who are already at risk due to genetic and environmental factors.

Hypothesis #1: Cannabis is Causally Associated with SchizophreniaThe Impact of Cannabis on the Developing Adolescent BrainThe endocannabinoid system plays a significant role in neurodevelopment by modulating synaptic strength and plasticity. Notably, CB1 receptor expression is highest during fetal and adolescent neurodevelopment. Heavy cannabis use during adolescence may downregulate these receptors during critical periods of synaptic pruning, potentially leading to lasting neurodevelopmental changes that increase susceptibility to psychosis. In rodent models, chronic THC exposure during adolescence has been shown to disrupt synaptic pruning, leading to premature dendritic atrophy or functional alterations in cortical glutamatergic pyramidal neurons—morphological changes that resemble those seen in schizophrenia and induced by chronic stress (Miller et al., 2019). This may stem from THC-induced impairments in specific subpopulations of GABAergic interneurons, particularly those containing parvalbumin and CCK (Renard et al., 2017). Schizophrenia is also associated with dysregulation of parvalbumin and somatostatin interneurons (Vid Prkačin et al., 2023).

How Cannabis Use During Adolescence Affects Brain StructureStructural MRI studies also tend to show some commonalities between chronic cannabis use and schizophrenia, mainly reduced right hippocampal volume. However, early studies typically do not control for the effects of early life adversity (Battistella et al., 2014), an independent factor affecting hippocampal volume, and the observed effects often disappear when controlling for alcohol use (Matochik et al., 2005; Weiland et al., 2015). However, in a study by Chye et al. (2019), people with cannabis use disorder exhibited reduced hippocampal volume even after adjusting for alcohol use. Further, a large-scale study of over 1000 participants (Owens et al., 2021) showed that people with recent cannabis use, as measured by positive THC urine tests, had bilateral reductions in hippocampal volume, whereas “effects may dissipate following prolonged abstinence” (Owens et al., 2021, Abstract ). A meta-analysis of 16 studies found no evidence that heavy cannabis use during adolescence or young adulthood leads to structural changes in cortical or subcortical gray matter or white matter integrity (Lorenzetti et al., 2023), but there was a trend for decreased PFC volume or thickness that warrant larger studies.

*Note.* Reprinted from “Brain Anatomical Alterations in Young Cannabis Users: Is it All Hype? A Meta-Analysis of Structural Neuroimaging Studies”, by Lorenzetti et al., 2023, *Cannabis and cannabinoid research*, 8(1), Figure 4, p. 191.

The authors concluded that “while prolonged and long-term exposure to heavy cannabis use may be required to detect gross volume alterations, more studies in young cannabis users are needed to map in detail cannabis-related neuroanatomical changes.” A separate review by Levine and colleagues (2017) noted that some studies did not assess brain changes over time, simply observing the brains of adolescents who used cannabis vs. those who did not. This led the authors to conclude, “It remains unclear whether the neuroanatomical and functional abnormalities are caused by, or exist prior to, the onset of cannabis exposure.”

However, the largest longitudinal study of adolescents to date, conducted by Albaugh and colleagues (2021) using the IMAGEN cohort, provides a more nuanced picture:

• 800 European participants received fMRI scans at ages 14 (prior to any substantial cannabis use) and 19 (after possible initiation).
• There was a dose-dependent association between cannabis consumption and accelerated cortical thinning by age 19—most pronounced in prefrontal regions densely populated with CB1 receptors.
• Importantly, no baseline differences in cortical thickness predicted future cannabis use, suggesting these neuroanatomical changes were likely driven by exposure rather than pre-existing traits.
• Further analysis from the same cohort at age ~23–24 showed that initiating cannabis use during adolescence produced distinctly greater changes in frontal cortical development compared to onset in the twenties (Albaugh et al., 2023).

Cannabis Use in Adolescence and its Influences on Brain ActivityfMRI studies examining resting-state activity and cognitive task performance have linked heavy cannabis use to altered activity and connectivity in brain regions involved in cognitive control and executive functioning (e.g., dlPFC, anterior cingulate, OFC). However, findings regarding the directionality of these changes (increased vs. decreased activity) remain inconsistent (Hammond et al., 2022; Harding et al., 2012). It is also unclear whether these alterations persist after abstinence or if they predate cannabis use, in which case they might serve as markers of vulnerability to both cannabis use and schizophrenia.

Additionally, while cannabis is often associated with dopamine dysregulation, a systematic review of nine fMRI studies using the monetary incentive delay task found no significant differences in reward-related brain responses among daily cannabis users. But this narrowly focused summary fails to acknowledge broader evidence from other paradigms and modalities like PET studies and neuromelanin-sensitive MRI (Beyer et al., 2024). However, people with cannabis use disorder (CUD) exhibit increased neuromelanin levels, as evidenced by elevated neuromelanin-sensitive MRI signals, particularly within specific ventral substantia nigra/ventral tegmental area (SN/VTA) voxels previously associated with heightened psychosis severity, suggesting elevated dopamine function related to cannabis use (Ahrens et al., 2025). Furthermore, some studies do suggest cannabis use in adolescence changes reward responsivity, increasing risk for anhedonia; however, other studies using different methodologies don’t support this finding.

Hypothesis #2: People With Schizophrenia Use Cannabis at a Higher Rate to Self-Medicate Negative SymptomsNearly half of people with schizophrenia develop a CUD in their lifetime (Ahmed et al., 2021). Some patients report that it helps with negative symptoms related to volition, affect, and poverty of thought. However, a systematic review and meta-analysis found no difference in negative symptoms between schizophrenic patients who used cannabis and those who did not (Sabe et al., 2020).

Hypothesis #3: Cannabis Increases Risk for Psychosis in People Who Are Already At Risk Due To Genetic and Environmental FactorsOverlapping Genetics Between Cannabis Use Disorder and Schizophrenia: What We KnowHeritability estimates for cannabis use disorder and schizophrenia are about 50% and 80% respectively (Chenoweth, 2024), suggesting both disorders are highly heritable. Considering the higher comorbidity between the two disorders, many have argued there is a genetic overlap. Some studies do suggest that people with schizophrenia and their healthy relatives experience greater rewarding effects or sensitivity to cannabis (Kuepper et al., 2013), which may suggest cannabis is more likely to be the drug of choice in people with schizophrenia (similar to nicotine). What’s unclear, however, is whether this effect is specific to cannabis, as people with schizophrenia are also more likely to use other illicit drugs.

Early research into the relationship between cannabis use disorder and schizophrenia often focused on candidate genes—specific genetic variants believed to interact with environmental factors (like adolescent cannabis use) to increase the risk of psychosis. Among these genes were COMT, which influences dopamine regulation (Caspi et al., 2005), AKT1, involved in glucose metabolism (Di Forti et al., 2012), and CNR1 (cannabinoid receptor gene, Benyamina et al., 2011). Some small-sample studies reported that adolescents carrying certain polymorphisms of these genes are at higher risk of developing schizophrenia if they begin using cannabis at a young age (Caspi et al., 2005; Di Forti et al., 2012). However, because candidate gene studies often use limited samples (thus limiting their power) and are prone to publication bias, replication has been inconsistent (Verweij et al., 2022). Therefore, the true effect size of any single gene in moderating the risk of developing schizophrenia due to cannabis use is minimal and the relationship between cannabis use and schizophrenia is influenced by multiple genes.

Because of this, Genome-Wide Association Studies (GWAS) are more commonly used now, as they screen the entire genome for common variants associated with schizophrenia or cannabis use in large samples (Verweij et al., 2017). These genes that are consistently associated with increased risk can be compiled to give polygenic risk scores for each of these outcomes. The polygenic risk scores that predict cannabis use can then be used to test whether they confer greater risk of schizophrenia. This type of study is called Mendelian randomization and allows for researchers to assess whether samples with high genetic risk for cannabis use are more likely to develop schizophrenia, even in the absence of actual cannabis use. One Mendelian randomization analysis found a causal effect of cannabis use on schizophrenia (Vaucher et al., 2018), while three others suggest reverse causation, in which genetic liability for schizophrenia predicts greater cannabis use or cannabis use disorder (Gage et al., 2017; Johnson et al., 2021; Pasman et al., 2018) and another study detected no clear evidence of a causal link between cannabis use and schizophrenia (Jang et al., 2022).

However, these studies require more robust and diverse sampling methods, a consistent and dose-related measurement of cannabis use, and clearer strategies to address the potential violations of Mendelian randomization assumptions—particularly pleiotropy (where one set of genetic variants can influence multiple traits associated with both schizophrenia and cannabis use). Because schizophrenia and CUD share overlapping genetic architectures, it is difficult to confirm whether specific variants are truly exerting causal effects or are influencing traits common to both disorders (i.e., horizontal pleiotropy), such as impulsivity, neuroticism (see also Episode 92), executive function, neurodevelopment, etc. (Johnson et al., 2024; Richter et al., 2019). Variants in genes related to the endocannabinoid system, glutamate signaling, dopamine, or stress sensitivity may act across these domains, complicating any causal inferences drawn from Mendelian randomization studies (Johnson et al., 2024; Richter et al., 2019 for specific genes discussed in the podcast).

Adverse Childhood Experiences (ACEs) Increase Risk for Both Cannabis Use Disorder and SchizophreniaAdverse Childhood Experiences (ACEs) are significant early-life stressors, including abuse, neglect, and household dysfunction, that increase the risk of both cannabis use and schizophrenia (see also episodes 203, 204, 217). Individuals with four or more ACEs face a substantially heightened risk for both substance use disorders–including CUD–in adolescence and later in life, and psychotic disorders.

ACEs are associated with lasting neurobiological changes, such as dysregulation of the HPA axis, increased systemic inflammation, reduced hippocampal volume, anhedonia, and increased amygdala reactivity to negative emotions. These alterations, combined with cannabis use—especially during critical developmental periods—may amplify the risk of psychosis.

It is important to recognize that most people who began using cannabis at an early age are more likely to have lived in unstable home environments with greater substance use and less parental oversight, which needs to be taken into account when interpreting studies of people who began using cannabis at a young age.

Cannabis Use and Risk of Psychotic Relapse in SchizophreniaRegardless of whether or not cannabis causes schizophrenia, it is evident from clinical experience and the literature that cannabis use can be incredibly destabilizing for patients who have a psychotic disorder. In the review of human laboratory studies mentioned earlier (Sherif et al., 2016), as well as a double-blind RCT (D'Souza et al., 2005) that compared the effects of intravenous THC vs. a placebo treatment in patients with schizophrenia spectrum disorder, it was shown that THC worsens symptoms of psychosis in a manner that is transient and dependent on the dosage.

However, the data on whether or not cannabis causes schizophrenia is mixed. A large 2023 individual participant data meta-analysis by Argote et al., using PANSS scores from over 3,000 individuals with schizophrenia spectrum disorders, offered more nuanced insight into how cannabis use affects symptom profiles​. After adjusting for key confounders (e.g., age, sex, illness duration, substance use), cannabis users exhibited significantly higher severity of positive symptoms (adjusted mean difference [aMD] = 0.38) and greater excitement symptoms (aMD = 0.16), but lower severity of negative symptoms (aMD = -0.50) compared to non-users. No association was found with disorganization or depressive symptoms. These results support the clinical observation that cannabis can exacerbate paranoid ideation and hyperactivation, while simultaneously appearing to attenuate negative symptoms like avolition or affective flattening. However, the authors caution that these findings do not imply causality and may reflect a self-selection effect, where individuals with fewer negative symptoms are more likely to use substances. Nevertheless, this study strengthens prior findings that continued cannabis use worsens positive symptom trajectories, and highlights the importance of differentiating symptom clusters when assessing cannabis impact​. In a different meta-analysis that aimed to determine the impact of cannabis use on the efficacy of antipsychotic dosage, the evolution of symptoms, therapeutic resistance, and the risk of relapse in patients with schizophrenia who are taking medication (Rault et al., 2022), cannabis use was not shown to be associated with poorer symptoms evolution but was shown to be associated with higher relapse rates.

This ties into one of the more important points with regards to cannabis use in patients with schizophrenia. Over the long term, symptoms may or may not be worse, but cannabis use will lead to more relapses, which is a serious problem given the nature of a relapse into psychosis. Possible explanations for this include the fact that patients who continue using cannabis and have more relapses might have worse schizophrenia symptoms at baseline, are more likely to be noncompliant on medications, or are experiencing more life stress. These possibilities were addressed by a prospective, longitudinal study by Scheffler et al. (2021) followed 98 patients with first-episode schizophrenia spectrum disorders over 24 months while on long-acting injectable antipsychotics, allowing for reliable assessment of medication compliance. Participants were divided into cannabis users (n=45) and non-users (n=53) and relapse was defined by specific increases in PANSS scores or CGI worsening. While both groups showed similar baseline psychotic symptoms (F=0.448, p=0.7), cannabis users exhibited poorer social and occupational functioning initially (p=0.008). Importantly, cannabis users experienced significantly more relapses (22.2% vs. 7.5%, p=0.039), despite similar rates of remission (76% for cannabis users vs. 83% for non-users). Furthermore, frequency of cannabis use, verified by urine toxicology, predicted relapse (ß=0.47, p=0.03). Despite similar symptom remission rates over time, the study suggests a dose-dependent relationship between cannabis use and relapse risk, potentially due to cannabis lowering the threshold for psychotic episodes or interacting with antipsychotic metabolism through the CYP450 system (Smith & Gruber, 2023). However, a literature review by Rault and colleagues (2022) found no evidence that cannabis use necessitates higher antipsychotic doses, suggesting it may not increase antipsychotic resistance. Notably, the Scheffler study effectively controlled for key confounds—baseline symptom severity and medication noncompliance—strengthening its conclusion that ongoing cannabis use elevates relapse risk independently of these factors.

Conclusion Regarding Cannabis And PsychosisWe’re living in an unprecedented era of cannabis use in North America. With legalization sweeping across most U.S. states—and only four now maintaining full prohibition—cannabis has become widely accessible, increasingly potent, and culturally normalized. Today’s products are far from the cannabis of the past: THC concentrations now regularly exceed 17–28%, with some concentrates reaching above 90% (Backman, 2023). Alongside this rise in potency is a shift in perception. Dispensaries promote cannabis as a natural remedy for anxiety, insomnia, and depression. Among young adults, cannabis is increasingly seen as a healthy alternative to alcohol—and for the first time in U.S. history, the number of daily cannabis users (17.7 million) has surpassed daily alcohol users (14.7 million) (Caulkins, 2024).

But those of us in clinical practice are seeing a different side of the story. Many of us have cared for patients experiencing cannabis-induced psychosis: young people arriving in the emergency department with paranoia, hallucinations, and delusions after consuming high-potency THC products. Others with schizophrenia relapse after prolonged stability—often following renewed cannabis use. These cases are becoming increasingly common, reinforcing what many psychiatrists now believe: cannabis is one of several environmental risk factors that can unmask or exacerbate psychotic disorders.

Frustratingly, the pace of research has failed to match the public’s growing use. Regulatory barriers restrict access to the very products people are using, while ethical limitations hinder the ability to conduct randomized controlled trials. As a result, most available data come from observational studies—which, while valuable, often struggle to account for confounding variables such as genetic risk, Adverse Childhood Experiences (ACEs), co-occurring substance use, and social adversity.

In this episode, we critically examined the existing literature through the lens of the Bradford Hill criteria. While numerous epidemiological studies demonstrate a consistent association between cannabis use and psychosis—with cannabis being associated with the highest risk of transition from substance-induced psychosis to schizophrenia compared to other substances—causality still remains difficult to “prove”. For example, a Swedish cohort of over 50,000 conscripts found that those who had used cannabis more than 50 times had more than triple the odds of later developing schizophrenia (Zammit et al., 2002), but even this rigorous design cannot fully isolate cannabis from other risk factors. However, regardless of whether cannabis is causally associated with the development of psychosis, it may still act as a catalyst for psychosis and other mental health problems in individuals with genetic or environmental vulnerabilities.

As the normalization of cannabis use accelerates and research struggles to keep pace, we find ourselves at a critical juncture. We as mental health professionals must remain informed and engaged to connect with our patients and the public. It is our responsibility to serve as trusted resources of critical discussion in an era where cannabis is marketed as a cure-all, often without regard for psychiatric risk. We must also advocate for more rigorous, unbiased research to ensure that public education and drug policy is grounded in science—not sentiment—and that we help shape the cultural narrative around cannabis in the critical years ahead.

We hope this episode has equipped you for future discussions about cannabis with patients, families, and colleagues and that you tune in for the next part of the series, where we will discuss cannabis and depression, anxiety, PTSD, cognition, and more.

References:Ahmed, S., Roth, R. M., Stanciu, C. N., & Brunette, M. F. (2021). The impact of THC and CBD in schizophrenia: A systematic review. Frontiers in Psychiatry, 12, 694394. https://doi.org/10.3389/fpsyt.2021.694394

Ahrens, J., Ford, S. D., Schaefer, B., Reese, D., Khan, A. R., Tibbo, P., Rabin, R., Cassidy, C. M., & Palaniyappan, L. (2025). Convergence of cannabis and psychosis on the dopamine system. JAMA Psychiatry. Advance online publication. https://doi.org/10.1001/jamapsychiatry.2025.0432

Albaugh, M. D., Ottino-Gonzalez, J., Sidwell, A., Lepage, C., Juliano, A., Owens, M. M., Chaarani, B., Spechler, P., Fontaine, N., Rioux, P., Lewis, L., Jeon, S., Evans, A., D’Souza, D., Radhakrishnan, R., Banaschewski, T., Bokde, A. L. W., Quinlan, E. B., Conrod, P., ... Garavan, H. (2021). Association of cannabis use during adolescence with neurodevelopment. JAMA Psychiatry. Advance online publication. https://doi.org/10.1001/jamapsychiatry.2021.1258

Albaugh, M. D., Owens, M. M., Juliano, A., Ottino-Gonzalez, J., Cupertino, R., Cao, Z., Mackey, S., Lepage, C., Rioux, P., Evans, A., Banaschewski, T., Bokde, A. L. W., Conrod, P., Desrivières, S., Flor, H., Grigis, A., Gowland, P., Heinz, A., Ittermann, B., … IMAGEN Consortium. (2023). Differential associations of adolescent versus young adult cannabis initiation with longitudinal brain change and behavior. Molecular Psychiatry, 28(11), 5173–5182. https://doi.org/10.1038/s41380-023-02148-2

Argote, M., Sescousse, G., Brunelin, J., Baudin, G., Schaub, M. P., Rabin, R., Schnell, T., Ringen, P. A., Andreassen, O. A., Addington, J. M., Brambilla, P., Delvecchio, G., Bechdolf, A., Wobrock, T., Schneider-Axmann, T., Herzig, D. A., Mohr, C., Vila-Badia, R., Usall, J., … Rolland, B. (2023). Association between cannabis use and symptom dimensions in schizophrenia spectrum disorders: An individual participant data meta-analysis on 3053 individuals. eClinicalMedicine, 64, 102199. https://doi.org/10.1016/j.eclinm.2023.102199

Arkell, T. R., Kevin, R. C., Vinckenbosch, F., Lintzeris, N., Theunissen, E., Ramaekers, J. G., & McGregor, I. S. (2022). Sex differences in acute cannabis effects revisited: Results from two randomized, controlled trials. Addiction biology, 27(2), e13125. https://doi.org/10.1111/adb.13125

Backman, I. (2023, August 30). Not your grandmother’s marijuana: Rising THC concentrations in cannabis can pose devastating health risks. Yale School of Medicine. https://medicine.yale.edu/news-article/not-your-grandmothers-marijuana-rising-thc-concentrations-in-cannabis-can-pose-devastating-health-risks/

Baldaçara, L., Ramos, A., & Castaldelli-Maia, J. M. (2023). Managing drug-induced psychosis. International Review of Psychiatry, 35(5–6), 496–502. https://doi.org/10.1080/09540261.2023.2261544

Bassir Nia, A., Bender, R., & Harpaz-Rotem, I. (2019). Endocannabinoid system alterations in posttraumatic stress disorder: A review of developmental and accumulative effects of trauma. Chronic Stress, 3, 1–10. https://doi.org/10.1177/2470547019864096

Battistella, G., Fornari, E., Annoni, J. M., Chtioui, H., Dao, K., Fabritius, M., Favrat, B., Mall, J. F., Maeder, P., & Giroud, C. (2014). Long-term effects of cannabis on brain structure. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 39(9), 2041–2048. https://doi.org/10.1038/npp.2014.67

Benyamina, A., Kebir, O., Blecha, L., Reynaud, M., & Krebs, M.-O. (2011). CNR1 gene polymorphisms in addictive disorders: A systematic review and a meta-analysis. Addiction Biology, 16(1), 1–6. https://doi.org/10.1111/j.1369-1600.2009.00198.x

Beyer, E., Poudel, G., Antonopoulos, S., Thomson, H., & Lorenzetti, V. (2024). Brain reward function in people who use cannabis: A systematic review. Frontiers in Behavioral Neuroscience, 17, 1323609. https://doi.org/10.3389/fnbeh.2023.1323609

Bourque, J., & Potvin, S. (2021). Cannabis and cognitive functioning: From acute to residual effects, from randomized controlled trials to prospective designs. Frontiers in Psychiatry, 12, 596601. https://doi.org/10.3389/fpsyt.2021.596601

Caspi, A., Moffitt, T. E., Cannon, M., McClay, J., Murray, R., Harrington, H., Taylor, A., Arseneault, L., Williams, B., Braithwaite, A., Poulton, R., & Craig, I. W. (2005). Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: Longitudinal evidence of a gene × environment interaction. Biological Psychiatry, 57(10), 1117–1127. https://doi.org/10.1016/j.biopsych.2005.01.026

Caulkins, J. P. (2024). Changes in self-reported cannabis use in the United States from 1979 to 2022. Addiction, 119(9), 1648–1652. https://doi.org/10.1111/add.16519

Chenoweth, M. J. (2024). Cracking the chicken and egg problem of schizophrenia and substance use: Genetic interplay between schizophrenia, cannabis use disorder, and tobacco smoking. Neuropsychopharmacology, 49, 1653–1654. https://doi.org/10.1038/s41386-024-01898-z

Chye, Y., Lorenzetti, V., Suo, C., Batalla, A., Cousijn, J., Goudriaan, A. E., Jenkinson, M., Martin-Santos, R., Whittle, S., Yücel, M., & Solowij, N. (2019). Alteration to hippocampal volume and shape confined to cannabis dependence: A multi-site study. Addiction Biology, 24(5), 822–834. https://doi.org/10.1111/adb.12652

Cohen, Y., Kolodziej, A., & Morningstar, M. (2024). Seventeen years since rimonabant's downfall: Reassessing its suicidality risk profile. Obesity (Silver Spring), 32(7), 1235–1244. https://doi.org/10.1002/oby.24019

Di Forti, M., Iyegbe, C., Sallis, H., Kolliakou, A., Falcone, M. A., Paparelli, A., Sirianni, M., La Cascia, C., Stilo, S. A., Marques, T. R., Handley, R., Mondelli, V., Dazzan, P., Pariante, C., David, A. S., Morgan, C., Powell, J., & Murray, R. M. (2012). Confirmation that the AKT1 (rs2494732) genotype influences the risk of psychosis in cannabis users. Biological Psychiatry, 72(10), 811–816. https://doi.org/10.1016/j.biopsych.2012.06.020

Di Forti, M., Quattrone, D., Freeman, T. P., Tripoli, G., Gayer-Anderson, C., Quigley, H., Rodriguez, V., Jongsma, H. E., Ferraro, L., La Cascia, C., La Barbera, D., Tarricone, I., Berardi, D., Szöke, A., Arango, C., Tortelli, A., Velthorst, E., Bernardo, M., Marta Del-Ben, C., ... Murray, R. M. (2019). The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): A multicentre case-control study. The Lancet Psychiatry, 6(5), 427–436. https://doi.org/10.1016/S2215-0366(19)30048-3

DISA Global Solutions. (2025, April 28). Marijuana legality by state. https://disa.com/marijuana-legality-by-state

D'Souza, D. C., Perry, E., MacDougall, L., Ammerman, Y., Cooper, T., Wu, Y. T., Braley, G., Gueorguieva, R., & Krystal, J. H. (2004). The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: Implications for psychosis. Neuropsychopharmacology, 29(8), 1558–1572. https://doi.org/10.1038/sj.npp.1300496

D’Souza, D. C., Abi-Saab, W. M., Madonick, S., Forselius-Bielen, K., Doersch, A., Braley, G., Gueorguieva, R., Cooper, T. B., & Krystal, J. H. (2005). Delta-9-tetrahydrocannabinol effects in schizophrenia: Implications for cognition, psychosis, and addiction. Biological Psychiatry, 57(6), 594–608. https://doi.org/10.1016/j.biopsych.2004.12.006​

Englund, A., Morrison, P. D., Nottage, J., Hague, D., Kane, F., Bonaccorso, S., Stone, J. M., Reichenberg, A., Brenneisen, R., Holt, D., Feilding, A., Walker, L., Murray, R. M., & Kapur, S. (2013). Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. Journal of psychopharmacology (Oxford, England), 27(1), 19–27. https://doi.org/10.1177/0269881112460109

Englund, A., Oliver, D., Chesney, E., Chester, L., Wilson, J., Sovi, S., De Micheli, A., Hodsoll, J., Fusar-Poli, P., Strang, J., Murray, R. M., Freeman, T. P., & McGuire, P. (2023). Does cannabidiol make cannabis safer? A randomised, double-blind, cross-over trial of cannabis with four different CBD:THC ratios. Neuropsychopharmacology, 48, 869–876. https://doi.org/10.1038/s41386-022-01478-z

Fiorentini, A., Cantù, F., Crisanti, C., Cereda, G., Oldani, L., & Brambilla, P. (2021). Substance-induced psychoses: An updated literature review. Frontiers in Psychiatry, 12, 694863. https://doi.org/10.3389/fpsyt.2021.694863

Gage, S. H., Jones, H. J., Burgess, S., Bowden, J., Davey Smith, G., Zammit, S., & Munafò, M. R. (2017). Assessing causality in associations between cannabis use and schizophrenia risk: a two-sample Mendelian randomization study. Psychological Medicine, 47(5), 971–980. doi:10.1017/S0033291716003172

Gillespie, N. A., Pasman, J. A., Treur, J. L., Derks, E. M., Verweij, K. J. H., & Vink, J. M. (2019). High-potency cannabis and incident psychosis: Correcting the causal assumption. The Lancet Psychiatry, 6(6), 464. https://doi.org/10.1016/S2215-0366(19)30174-9

Glodosky, N. C., Cuttler, C., & McLaughlin, R. J. (2021). A review of the effects of acute and chronic cannabinoid exposure on the stress response. Frontiers in neuroendocrinology, 63, 100945. https://doi.org/10.1016/j.yfrne.2021.100945

Gunasekaran, N., Long, L. E., Dawson, B. L., Hansen, G. H., Richardson, D. P., Li, K. M., Arnold, J. C., & McGregor, I. S. (2009). Reintoxication: the release of fat-stored delta(9)-tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure. British journal of pharmacology, 158(5), 1330–1337. https://doi.org/10.1111/j.1476-5381.2009.00399.x

Hamilton, I., & Monaghan, M. (2019). Cannabis and psychosis: Are we any closer to understanding the relationship? Current Psychiatry Reports, 21(48). https://doi.org/10.1007/s11920-019-1044-x

Hammond, C. J., Allick, A., Park, G., Rizwan, B., Kim, K., Lebo, R., Nanavati, J., Parvaz, M. A., & Ivanov, I. (2022). A Meta-Analysis of fMRI Studies of Youth Cannabis Use: Alterations in Executive Control, Social Cognition/Emotion Processing, and Reward Processing in Cannabis Using Youth. Brain Sciences, 12(10), 1281. https://doi.org/10.3390/brainsci12101281

Harding, I. H., Solowij, N., Harrison, B. J., Takagi, M., Lorenzetti, V., Lubman, D. I., Seal, M. L., Pantelis, C., & Yücel, M. (2012). Functional connectivity in brain networks underlying cognitive control in chronic cannabis users. Neuropsychopharmacology, 37(7), 1923–1933. https://doi.org/10.1038/npp.2012.39

Hillard, C. J. (2015). The Endocannabinoid Signaling System in the CNS: A Primer. International review of neurobiology, 125, 1–47. https://doi.org/10.1016/bs.irn.2015.10.001

Hindocha, C., Freeman, T. P., Schafer, G., Gardener, C., Das, R. K., Morgan, C. J., & Curran, H. V. (2015). Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: a randomised, double-blind, placebo-controlled study in cannabis users. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 25(3), 325–334. https://doi.org/10.1016/j.euroneuro.2014.11.014

Hirvonen, J., Goodwin, R. S., Li, C.-T., Terry, G. E., Zoghbi, S. S., Morse, C., Pike, V. W., Volkow, N. D., Huestis, M. A., & Innis, R. B. (2012). Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers. Molecular Psychiatry, 17, 642–649. https://doi.org/10.1038/mp.2011.82

Hughes, J. R., Fingar, J. R., Budney, A. J., Naud, S., Helzer, J. E., & Callas, P. W. (2014). Marijuana use and intoxication among daily users: an intensive longitudinal study. Addictive behaviors, 39(10), 1464–1470. https://doi.org/10.1016/j.addbeh.2014.05.024

Hutter, C. M. (n.d.). Genome-wide association studies (GWAS). National Human Genome Research Institute. Genome.gov. Retrieved April 30, 2025, from https://www.genome.gov/genetics-glossary/Genome-Wide-Association-Studies-GWAS

Jang, S.-K., Saunders, G., Liu, M., Jiang, Y., Liu, D. J., & Vrieze, S. (2022). Genetic correlation, pleiotropy, and causal associations between substance use and psychiatric disorder. Psychological Medicine, 52(5), 968–978. https://doi.org/10.1017/S003329172000272X

Johnson E. C., Hatoum A. S., Deak J. D., Polimanti R., Murray R. M., Edenberg H. J., Gelernter J., Di Forti M., and Agrawal A. (2021) The relationship between cannabis and schizophrenia: a genetically informed perspective. Addiction, 116: 3227–3234. https://doi.org/10.1111/add.15534

Johnson, E. C., Austin-Zimmerman, I., Thorpe, H. H. A., Levey, D. F., Baranger, D. A. A., Colbert, S. M. C., Demontis, D., Khokhar, J. Y., Davis, L. K., Edenberg, H. J., Di Forti, M., Sanchez-Roige, S., Gelernter, J., & Agrawal, A. (2024). Cross-ancestry genetic investigation of schizophrenia, cannabis use disorder, and tobacco smoking. Neuropsychopharmacology, 49, 1655–1665. https://doi.org/10.1038/s41386-024-01886-3

Karniol, I. G., Shirakawa, I., Kasinski, N., Pfeferman, A., & Carlini, E. A. (1974). Cannabidiol interferes with the effects of delta 9 - tetrahydrocannabinol in man. European journal of pharmacology, 28(1), 172–177. https://doi.org/10.1016/0014-2999(74)90129-0

Karschner, E. L., Darwin, W. D., McMahon, R. P., Liu, F., Wright, S., Goodwin, R. S., & Huestis, M. A. (2011). Subjective and physiological effects after controlled Sativex and oral THC administration. Clinical pharmacology and therapeutics, 89(3), 400–407. https://doi.org/10.1038/clpt.2010.318

Kearn, C. S., Greenberg, M. J., DiCamelli, R., Kurzawa, K., & Hillard, C. J. (1999). Relationships between ligand affinities for the cerebellar cannabinoid receptor CB1 and the induction of GDP/GTP exchange. Journal of neurochemistry, 72(6), 2379–2387. https://doi.org/10.1046/j.1471-4159.1999.0722379.x

Kraemer, M., Madea, B., & Hess, C. (2019). Detectability of various cannabinoids in plasma samples of cannabis users: Indicators of recent cannabis use? Drug Testing and Analysis, 11(10), 1498–1506. https://doi.org/10.1002/dta.2682

Kuepper, R., Ceccarini, J., Lataster, J., van Os, J., van Kroonenburgh, M., van Gerven, J. M. A., Marcelis, M., Van Laere, K., & Henquet, C. (2013). Delta-9-tetrahydrocannabinol-induced dopamine release as a function of psychosis risk: 18F-fallypride positron emission tomography study. PLOS ONE, 8(7), e70378. https://doi.org/10.1371/journal.pone.0070378

Lawn, W., Trinci, K., Mokrysz, C., Borissova, A., Ofori, S., Petrilli, K., Bloomfield, M., Haniff, Z. R., Hall, D., Fernandez-Vinson, N., Wang, S., Englund, A., Chesney, E., Wall, M. B., Freeman, T. P., & Curran, H. V. (2023). The acute effects of cannabis with and without cannabidiol in adults and adolescents: A randomised, double-blind, placebo-controlled, crossover experiment. Addiction, 118(7), 1282–1294. https://doi.org/10.1111/add.16154

Levine, A., Clemenza, K., Rynn, M., & Lieberman, J. (2017). Evidence for the risks and consequences of adolescent cannabis exposure. Journal of the American Academy of Child & Adolescent Psychiatry, 56(3), 214–225. https://doi.org/10.1016/j.jaac.2016.12.014

Lorenzetti, V., Kowalczyk, M., Duehlmeyer, L., Greenwood, L. M., Chye, Y., Yücel, M., Whittle, S., & Roberts, C. A. (2023). Brain Anatomical Alterations in Young Cannabis Users: Is it All Hype? A Meta-Analysis of Structural Neuroimaging Studies. Cannabis and cannabinoid research, 8(1), 184–196. https://doi.org/10.1089/can.2021.0099

Lucas, C. J., Galettis, P., & Schneider, J. (2018). The pharmacokinetics and the pharmacodynamics of cannabinoids. British Journal of Clinical Pharmacology, 84(11), 2477–2482. https://doi.org/10.1111/bcp.13710

Lutz, B. (2020). Neurobiology of cannabinoid receptor signaling
. Dialogues in clinical neuroscience, 22(3), 207–222. https://doi.org/10.31887/DCNS.2020.22.3/blutz

Matochik, J. A., Eldreth, D. A., Cadet, J.-L., & Bolla, K. I. (2005). Altered brain tissue composition in heavy marijuana users. Drug and Alcohol Dependence, 77(1), 23-30. https://doi.org/10.1016/j.drugalcdep.2004.06.011

Mayo Clinic Laboratories. (n.d.). Marijuana. Retrieved February 15, 2025, from https://news.mayocliniclabs.com/therapeutics/drug-class-testing/marijuana/

Mayo, L. M., Asratian, A., Lindé, J., Holm, L., Nätt, D., Augier, G., Stensson, N., Vecchiarelli, H. A., Balsevich, G., Aukema, R. J., Ghafouri, B., Spagnolo, P. A., Lee, F. S., Hill, M. N., & Heilig, M. (2020). Protective effects of elevated anandamide on stress and fear-related behaviors: Translational evidence from humans and mice. Molecular Psychiatry, 25, 993–1005. https://doi.org/10.1038/s41380-018-0215-1

McCarthy, J. (2023, August 10). Fully half of Americans have tried marijuana. Gallup. https://news.gallup.com/poll/509399/fully-half-americans-tried-marijuana.aspx

Meyer, H., Lee, F., & Gee, D. (2018). The role of the endocannabinoid system and genetic variation in adolescent brain development. Neuropsychopharmacology, 43, 21–33. https://doi.org/10.1038/npp.2017.143

Miller, M. L., Chadwick, B., Dickstein, D. L., Purushothaman, I., Egervari, G., Rahman, T., Tessereau, C., Hof, P. R., Roussos, P., Shen, L., Baxter, M. G., & Hurd, Y. L. (2019). Adolescent exposure to Δ⁹-tetrahydrocannabinol alters the transcriptional trajectory and dendritic architecture of prefrontal pyramidal neurons. Molecular Psychiatry, 24(4), 588–600. https://doi.org/10.1038/s41380-018-0243-x

Mørland, J., & Bramness, J. G. (2020). Δ9-tetrahydrocannabinol (THC) is present in the body between smoking sessions in occasional non-daily cannabis users. Forensic Science International, 309, 110188. https://doi.org/10.1016/j.forsciint.2020.110188

Myran, D. T., Harrison, L. D., Pugliese, M., Solmi, M., Anderson, K. K., Fiedorowicz, J. G., Perlman, C. M., Webber, C., Finkelstein, Y., & Tanuseputro, P. (2023). Transition to schizophrenia spectrum disorder following emergency department visits due to substance use with and without psychosis. JAMA Psychiatry, 80(11), 1169–1174. https://doi.org/10.1001/jamapsychiatry.2023.3582

Myran, D. T., Pugliese, M., Harrison, L. D., Solmi, M., Anderson, K. K., Fiedorowicz, J. G., Finkelstein, Y., Manuel, D., Taljaard, M., Webber, C., & Tanuseputro, P. (2025a). Changes in incident schizophrenia diagnoses associated with cannabis use disorder after cannabis legalization. JAMA Network Open, 8(2), e2457868. https://doi.org/10.1001/jamanetworkopen.2024.57868

Myran, D. T., Pugliese, M., McDonald, A. J., Xiao, J., Fischer, B., Finkelstein, Y., Tanuseputro, P., Firth, J., Pakpour, A., Hsu, C.-W., Chang, W.-C., & Solmi, M. (2025b). Cannabis use disorder emergency department visits and hospitalizations and 5-year mortality. JAMA Network Open, 8(2), e2457852. https://doi.org/10.1001/jamanetworkopen.2024.57852

Owens, M. M., Sweet, L. H., & MacKillop, J. (2021). Recent cannabis use is associated with smaller hippocampus volume: High-resolution segmentation of structural subfields in a large non-clinical sample. Addiction Biology, 26(1), e12874. https://doi.org/10.1111/adb.12874

Papariello, A., Taylor, D., Soderstrom, K., & Litwa, K. (2021). CB1 antagonism increases excitatory synaptogenesis in a cortical spheroid model of fetal brain development. Scientific Reports, 11, 9356. https://doi.org/10.1038/s41598-021-88750-2

Pasman, J. A., Verweij, K. J. H., Gerring, Z., Stringer, S., Sanchez-Roige, S., Treur, J. L., Abdellaoui, A., Nivard, M. G., Baselmans, B. M. L., Ong, J.-S., Ip, H. F., van der Zee, M. D., Bartels, M., Day, F. R., Fontanillas, P., Elson, S. L., 23andMe Research Team, de Wit, H., Davis, L. K., MacKillop, J., ... Vink, J. M. (2018). GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability. Nature Neuroscience, 21(8), 1161–1170. https://doi.org/10.1038/s41593-018-0206-1

Patel, S., & Hillard, C. J. (2009). Role of endocannabinoid signaling in anxiety and depression. In D. Kendall & S. Alexander (Eds.), Behavioral neurobiology of the endocannabinoid system (Vol. 1, pp. 347–371). Springer. https://doi.org/10.1007/978-3-540-88955-7_14

Patrick, M. E., Miech, R. A., Johnston, L. D., & O’Malley, P. M. (2024). Monitoring the Future Panel Study annual report: National data on substance use among adults ages 19 to 65, 1976–2023. Institute for Social Research, University of Michigan. https://monitoringthefuture.org/wp-content/uploads/2024/07/mtfpanel2024.pdf

Pauselli, L. (2018). Chapter 8 - Cannabis-induced psychotic disorders. In M. T. Compton & M. W. Manseau (Eds.), The complex connection between cannabis and schizophrenia (pp. 183–197). Academic Press. https://doi.org/10.1016/B978-0-12-804791-0.00008-2

Puder, D. (Host). (2019, May 1). Marijuana and Mental Health (No. 44) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/2019/5/1/marijuana-and-mental-health?rq=marijuana

Puder, D. (Host). (2019, Oct. 23). Does Cannabis Use Increase Schizophrenia and Psychosis? (No. 64) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/2019/10/17/does-cannabis-increase-schizophrenia-and-psychosis-thc?rq=marijuana

Puder, D. (Host). (2020, Sept. 17).The Big Five: Neuroticism Part 1 (No. 92) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/strongepisode-092-strongthe-big-five-neuroticism-part-1

Puder, D. (Host). (2024, January 19). Adverse Childhood Experiences and Their Lasting Impact on Health: A Comprehensive Guide (No. 203) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-203-adverse-childhood-experiences-and-their-lasting-impact-on-health-a-comprehensive-guide?rq=203

Puder, D. (Host). (2024, February 2). Adverse Childhood Experiences Part 2: Measurement, Impact on Future Mental Health, Dissociation, and Timing of Trauma (No. 204) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-204-adverse-childhood-experiences-part-2-measurement-impact-on-future-mental-health-dissociation-and-timing-of-trauma?rq=204

Puder, D. (Host). (2024, July 19). Adverse Childhood Experiences - HPA axis & Brain changes: cortisol, amygdala, hippocampus, cytokines, & epigenetics (Part 3 of ACE series) (No. 217) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-217-adverse-childhood-experiences-part-3-aces?rq=217

Puder, D. (Host). (2025, March 28). Clozapine & Schizophrenia with Michael Cummings, MD (No. 236) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-236-clozapine-schizophrenia-treatment-michael-cummings

Rault, O., Romeo, B., Butlen-Ducuing, F., Rari, E., Benyamina, A., & Martelli, C. (2022). Impact of cannabis use and its cessation on the dosage and the efficacy of antipsychotic drugs in in- and outpatients with schizophrenia taking medication: A systematic review and meta-analysis. Journal of Psychiatric Research, 156, 713–721. https://doi.org/10.1016/j.jpsychires.2022.11.012

Renard, J., Szkudlarek, H. J., Kramar, C. P., Jobson, C. E. L., Moura, K., Rushlow, W. J., & Laviolette, S. R. (2017). Adolescent THC Exposure Causes Enduring Prefrontal Cortical Disruption of GABAergic Inhibition and Dysregulation of Sub-Cortical Dopamine Function. Scientific reports, 7(1), 11420. https://doi.org/10.1038/s41598-017-11645-8

Richter, M., Murtaza, N., Scharrenberg, R., White, S. H., Johanns, O., Walker, S., Yuen, R. K. C., Schwanke, B., Bedürftig, B., Henis, M., Scharf, S., Kraus, V., Dörk, R., Hellmann, J., Lindenmaier, Z., Ellegood, J., Hartung, H., Kwan, V., Sedlacik, J., … Calderon de Anda, F. (2019). Altered TAOK2 activity causes autism-related neurodevelopmental and cognitive abnormalities through RhoA signaling. Molecular Psychiatry, 24(9), 1329–1350. https://doi.org/10.1038/s41380-018-0025-0

Robinson, T., Ali, M. U., Easterbrook, B., Hall, W., Jutras-Aswad, D., & Fischer, B. (2023). Risk-thresholds for the association between frequency of cannabis use and the development of psychosis: a systematic review and meta-analysis. Psychological medicine, 53(9), 3858–3868. https://doi.org/10.1017/S0033291722000502

Rossi, G., & Beck, M. (2020). A little dab will do: a case of cannabis-induced psychosis. Cureus, 12(9). https://pmc.ncbi.nlm.nih.gov/articles/PMC7544610/

Ryan, S. A., Ammerman, S. D., O’Connor, M. E., Gonzalez, L., Patrick, S. W., Quigley, J., Walker, L. R., Meek, J. Y., Johnston, M., Stellwagen, L., Thomas, J., Ware, J., & the Committee on Substance Use and Prevention, & Section on Breastfeeding. (2018). Marijuana use during pregnancy and breastfeeding: Implications for neonatal and childhood outcomes. Pediatrics, 142(3), e20181889. https://doi.org/10.1542/peds.2018-1889

Sabe, M., Zhao, N., & Kaiser, S. (2020). Cannabis, nicotine and the negative symptoms of schizophrenia: Systematic review and meta-analysis of observational studies. Neuroscience and biobehavioral reviews, 116, 415–425. https://doi.org/10.1016/j.neubiorev.2020.07.007

Scheffler, F., Phahladira, L., Luckhoff, H., du Plessis, S., Asmal, L., Kilian, S., Di Forti, M., Murray, R., & Emsley, R. (2021). Cannabis use and clinical outcome in people with first-episode schizophrenia spectrum disorders over 24 months of treatment. Psychiatry Research, 302, 114022. https://doi.org/10.1016/j.psychres.2021.114022

Schoeler, T., Ferris, J., & Winstock, A. R. (2022). Rates and correlates of cannabis-associated psychotic symptoms in over 230,000 people who use cannabis. Translational Psychiatry, 12, 369. https://doi.org/10.1038/s41398-022-02112-8

Schoeler, T., Baldwin, J. R., Martin, E., Barkhuizen, W., & Pingault, J.-B. (2024). Assessing rates and predictors of cannabis-associated psychotic symptoms across observational, experimental, and medical research. Nature Mental Health, 2, 865–876. https://doi.org/10.1038/s44220-024-00261-x

Sherif, M., Radhakrishnan, R., D’Souza, D. C., & Ranganathan, M. (2016). Human laboratory studies on cannabinoids and psychosis. Biological Psychiatry, 79(7), 526–538. https://doi.org/10.1016/j.biopsych.2016.01.011

Shimonovich, M., Pearce, A., Thomson, H., Keyes, K., & Katikireddi, S. V. (2021). Assessing causality in epidemiology: Revisiting Bradford Hill to incorporate developments in causal thinking. European Journal of Epidemiology, 36, 873–887. https://doi.org/10.1007/s10654-020-00703-7

Siebers, M., Biedermann, S. V., Bindila, L., Lutz, B., & Fuss, J. (2021). Exercise-induced euphoria and anxiolysis do not depend on endogenous opioids in humans. Psychoneuroendocrinology, 126, 105173. https://doi.org/10.1016/j.psyneuen.2021.105173

Smid, M. C., Metz, T. D., McMillin, G. A., Mele, L., Casey, B. M., Reddy, U. M., Wapner, R. J., Thorp, J. M., Saade, G. R., Tita, A. T. N., Miller, E. S., Rouse, D. J., Sibai, B., Costantine, M. M., Mercer, B. M., Caritis, S. N., & the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. (2022). Prenatal nicotine or cannabis exposure and offspring neurobehavioral outcomes. Obstetrics & Gynecology, 139(1), 21–30. https://doi.org/10.1097/AOG.0000000000004632

Smith, R. T., & Gruber, S. A. (2023). Contemplating cannabis? The complex relationship between cannabinoids and hepatic metabolism resulting in the potential for drug-drug interactions. Frontiers in Psychiatry, 13, 1055481. https://doi.org/10.3389/fpsyt.2022.1055481

Solowij, N., Broyd, S., Greenwood, L. M., van Hell, H., Martelozzo, D., Rueb, K., Todd, J., Liu, Z., Galettis, P., Martin, J., Murray, R., Jones, A., Michie, P. T., & Croft, R. (2019). A randomised controlled trial of vaporised Δ9-tetrahydrocannabinol and cannabidiol alone and in combination in frequent and infrequent cannabis users: acute intoxication effects. European archives of psychiatry and clinical neuroscience, 269(1), 17–35. https://doi.org/10.1007/s00406-019-00978-2

Stuyt, E. (2018). The problem with the current high potency THC marijuana from the perspective of an addiction psychiatrist. Missouri Medicine, 115(6), 482–486. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312155/

Substance Abuse and Mental Health Services Administration (SAMHSA). (2022a). 2021 National Survey on Drug Use and Health: National maps of prevalence estimates, by state. U.S. Department of Health and Human Services. https://www.samhsa.gov/data/sites/default/files/reports/rpt39463/2021NSDUHsaeMaps110122/2021NSDUHsaeMap110122.htm#fig2e

Substance Abuse and Mental Health Services Administration (SAMHSA). (2022b). Key substance use and mental health indicators in the United States: Results from the 2021 National Survey on Drug Use and Health (HHS Publication No. PEP22-07-01-005, NSDUH Series H-57). Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. https://www.samhsa.gov/data/report/2021-nsduh-annual-national-report

van Os, J., Bak, M., Hanssen, M., Bijl, R. V., de Graaf, R., & Verdoux, H. (2002). Cannabis use and psychosis: A longitudinal population-based study. American Journal of Epidemiology, 156(4), 319–327. https://doi.org/10.1093/aje/kwf043

Vaucher, J., Keating, B. J., Lasserre, A. M., Gan, W., Lyall, D. M., Ward, J., Smith, D. J., Pell, J. P., Sattar, N., Paré, G., & Holmes, M. V. (2018). Cannabis use and risk of schizophrenia: A Mendelian randomization study. Molecular Psychiatry, 23(6), 1287–1292. https://doi.org/10.1038/mp.2016.252

Verweij, K. J. H., Abdellaoui, A., Nivard, M. G., Sainz Cort, A., Ligthart, L., Draisma, H. H. M., Minică, C. C., Gillespie, N. A., Willemsen, G., Hottenga, J.-J., Boomsma, D. I., & Vink, J. M. (2017). Erratum to “Short communication: Genetic association between schizophrenia and cannabis use” [Drug Alcohol Depend. 171 (2017) 117–121]. Drug and Alcohol Dependence, 173, e1–e2. https://doi.org/10.1016/j.drugalcdep.2017.02.001

Verweij, K. J. H., Vink, J. M., Abdellaoui, A., Gillespie, N. A., Derks, E. M., & Treur, J. L. (2022). The genetic aetiology of cannabis use: From twin models to genome-wide association studies and beyond. Translational Psychiatry, 12(1), 489. https://doi.org/10.1038/s41398-022-02215-2

Vid Prkačin, M., Banovac, I., Petanjek, Z., & Hladnik, A. (2023). Cortical interneurons in schizophrenia - cause or effect?. Croatian medical journal, 64(2), 110–122. https://doi.org/10.3325/cmj.2023.64.110

Weiland, B. J., Thayer, R. E., Depue, B. E., Sabbineni, A., Bryan, A. D., & Hutchison, K. E. (2015). Daily marijuana use is not associated with brain morphometric measures in adolescents or adults. The Journal of neuroscience : the official journal of the Society for Neuroscience, 35(4), 1505–1512. https://doi.org/10.1523/JNEUROSCI.2946-14.2015

Zammit, S., Allebeck, P., Andreasson, S., Lundberg, I., & Lewis, G. (2002). Self-reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: Historical cohort study. BMJ, 325(7374), 1199. https://doi.org/10.1136/bmj.325.7374.1199

Zuardi, A. W., Teixeira, N. A., & Karniol, I. C. (1984). Pharmacological interaction of the effects of delta 9-trans-tetrahydrocannabinol and cannabidiol on serum corticosterone levels in rats. Archives internationales de pharmacodynamie et de therapie, 269(1), 12–19. https://pubmed.ncbi.nlm.nih.gov/6087750/

View Details

Podcast Host: David Puder, MD

Transcription Editing: Al-Baab Khan

Footnotes and editing: Andrea Witham, FNP-C, PMHNP-BC , Joanie Burns, PMHNP-BC, David Puder, MD

Reviewer: Joanie Burns, PMHNP-BC

By listening to this episode, you can earn 1.5 Psychiatry CME Credits.

Other Places to listen: iTunes, Spotify, X

Link To Blog With Footnotes Here.00:47 Fleeing Nazi Austria

05:49 Early Influences

22:55 Borderline Level of Functioning and Primitive Defenses

30:24 Sexual Life in Borderline and Narcissistic Personality

45:08 Transference-Focused Psychotherapy and Reflective Function

1:03:52 Histrionic Personality

1:09:35 Paranoid Personality

1:11:19 Schizoid Personality

1:18:37 Why Therapists Want to Help

Fleeing Nazi Austria (00:47)Puder:

I'm here with Dr. Otto Kernberg. He is a psychiatrist, born in Vienna, Austria. Immigrated to Chile. Subsequently came to America and is the founder of transference focused Psychotherapy and was instrumental in our understanding of things like borderline level of organization [he clearly defined its core components—including identity diffusion, primitive defense mechanisms, and intact reality testing]. We're gonna have a discussion today about his life, about the things that he wrote and ideas that he came up with and the evolution of it. So, welcome to the podcast. Can we start by, I know, you were born in Austria, Vienna in 1928. And you fled Nazi occupied Austria with your family to Chile. Tell me a little bit about that.

Kernberg:

Well, I was nine years and a half. Hitler invaded March, 1938, and I left with my parents on July 16th, 1939. My father didn't want to leave. He happened to be an Austrian monarchist and he believed all of this was going- just passing by. Hitler was a transitory phenomenon. He had a strong belief in Austrian survival. My mother had paranoid features. She was frightened to death with the invasion. And then after Kristallnacht, which in Vienna occurred on December 10th, 1938, she convinced my father that we had to leave. And so we got the Visa to Chile. And of course, I didn't know anything-I'm an only child, I was nine years and a half about.

Kernberg:

And on July 16th, 1939, she told me to pack everything- all toys that you have into this suitcase. We are leaving this afternoon, [sadness] and you are not supposed to tell a word to anybody. And by then, I was already acutely aware of the danger. And so that's how we left. I spent one year and a half under the Nazis, and it was a bad [anger], a bad experience. Violent [anger] antisemitism naturally. And all Jewish kids were expelled from schools, put into Jewish schools. Forbidden [anger] to go to movies, parks- everywhere Jews [sadness] and dogs are forbidden.

So although I was a child, I got the feeling for it. One day I was working with my mother on the street and this army man, who was in Hitler’s lower military guards, the SA [Sturmabteilung also known as the “Brownshirts”] in contrast to the SS, forced my mother to wash the street, the pavement. And my mother was washing the pavement and the crowd gathered, making fun of us. And I was standing there, I mean, this kind of bad experiences. And that was before the war started. It was started I think in October 1st, 1939. So we just managed to escape in time because after that, the border was closed and the rest of my family all ended up in the concentration camps. And they had except one cousin who managed to escape to England with the children's transport and then to the United States. That's- and we spent then six months in Italy before finally the visa came and we immigrated to Chile where I lived for more than 20 years before coming to the United States.

Puder:

I imagine in part, witnessing violent antisemitism- seeing signs reading “Jews and dogs are forbidden” or watching your mother forced to wash the pavement, even at that age, was both awful and degrading, a horrible feeling.

Your mom’s heightened sensitivity and adaptive paranoia, as you described, was a gift in this situation, yet I imagine to leave so quickly and without telling anyone, brought its own sense of loss.

With these early experiences in mind, could you tell me about the formative influences you encountered during your early years in Chile?

Dr. Otto Kernberg’s Early Influences with Psychoanalysis and Development of Transference Focused Psychotherapy (00:05:49)Kernberg:

Well I studied medicine in Chile and was fascinated by the psychiatry professor, Ignacio Matte Blanco, who was trained in England. He was originally a neurologist trained in psychoanalysis by the client school in London, and he started the Psycholytic Society and Training Institute in Chile. He was a very outstanding man and became a personal idea.

I was interested, actually, in psychoanalysis since adolescence. I had read Freud and in immigration to Chile I came under the influence of a Jungian analyst. And by the time I entered medical school, I was already interested in psychoanalysis and within psychiatry, then that culminated. And I decided to study psychoanalysis in Chile under the leadership of Ignacio Matte Blanco, and graduated there. And before I came to the United States with the Rockefeller Foundation Fellowship to study research in psychotherapy, I was interested in psychotherapy: was it effective or not?

And did my first research efforts in Chile and then came to the United States, spent a year at Johns Hopkins with Sir Jerome Frank and his research group on psychotherapy. And then at the Menninger Foundation in Topeka, Kansas. Well, I mean, in between I went to Chile, did all the teaching that I had committed myself to the Rockefeller Foundation, who gave me the fellowship. So I fulfilled my obligation with the Rockefeller Foundation and then returned to the United States to participate in the psychotherapy research of the Menninger Foundation.

A huge project that I participated in several ways until I became the director of it after Robert Wallerstein, who was the leader, left this professor of psychiatry in San Francisco. So during my work at the Menninger Foundation, I was there about 12 years, I became interested and learned all I could about the diagnosis and treatment of severe personality disorders and within the Menninger project, then I developed my own interest in studying outcome, comparing patients who were treated in supportive psychotherapy, in expressive or analytic psychotherapy and psychoanalysis.

And came to the conclusion that patients with severe personality disorder, the so-called borderline patients who fell in between neurosis and psychosis, really responded best to a treatment that was a well-structured psychotherapy, not standard psychoanalysis, nor the usual supportive psychotherapy that was the fashion at that point.

And so I developed a project about an ideal treatment for severe personality disorders, and at the same time had to differentiate severe personality disorders from non-severe and had to deal with the entire diagnostic differentiation within psychiatry in which Ignacio Matte Blanco helped me enormously. When he learned in Chile, that I spoke German, he said I had to read German, classical German psychiatry Bumke. I went to the library to get Bumke and I found out it was 12 volumes. I didn't dare to ask him which volume he wanted me to read. And I studied all 12 volumes of Bumke. It gave me knowledge in classical German psychiatry that helped me enormously. Then of course, in the United States, I got the American approach to diagnosis, but I became, I made myself an expert in differential diagnosis and concluded that the common features of severe personality disorders was a lack of integration of their concept of self and the lack of integration of their concept of significant others.

Kernberg:

What Erik Erickson had described is identity diffusion. I picked up Erickson's concept of identity diffusion, applied it to the differential diagnosis of severe personality disorders, and developed simultaneously a view of psychological development, depending not on the internalization of representation of significant others, is kind of mental representation of others from reality. But under the influence of a lecture I heard from Talcott Parsons, a leading sociologist in the United States, I learned that what is internalized are not representation of others, but representation of the relationship between self and others.

So we interact with others, we internalize our representation of the other and the self interacting. This explains, for example, why children who have been physically abused, severely abused over years become abusers in turn. We say that they identify with the abuser, yes. But in a deep sense, they have internalized the whole experience and simultaneously internalizing in their mind the representation of abuser and abused. And are able then to, in order to avoid- so they, their world becomes a relationship of abusers and abuse, all relationships are between abusers and abused. And it's better to be the abuser rather than the abused. So they learn role reversals and take on the role of the abuser, while the role of the abused is projected onto somebody else. So the internalized relationship with others becomes the guiding principle that organizes habitual behavior, what we call character.

So the character, what we now call personality- actually personality is a broader concept that includes cognitive functions and everything else. Character, habitual behavior patterns they are essential part of personality and so I defined borderline personality organization as those alteration, habitual alterations of the personality that had in common identity diffusion.

And developed a clinical instrument, a clinical interview, the so-called structural interview to diagnose identity diffusion and differentiate severe personality disorders from non-severe personality disorders. And of course, the entire field of personality disorder from ordinary forms of psychosis, madness in the usual sense and organic brain syndrome, such as mental retardation and dementias.

So I linked the specific instruments for diagnosing personality disorders with the general psychiatric diagnostic approach, and placed personality disorder within the general area of psychiatric diagnosis. And regarding the treatment, as I mentioned to you, proposed the combination of a psychotherapy under strictly controlled circumstances inspired by psychoanalysis, but different from psychoanalysis by modification of psychoanalytic instruments or methods, and different from supportive forms of psychotherapy.

More generally speaking, I would say that transference focused psychotherapy is a psychoanalytic psychotherapy, not psychoanalysis proper. Psychoanalysis is reserved by patients with less severe neurotic illness. But the severe personality disorders that we now call borderline personality organization can be treated with transference focused psychotherapy [TFP]. And that's preferable to treat them than to treat them with a supportive approach, which may be carried out within a psychoanalytic perspective or a cognitive behavioral approach. In general, you can divide treatments into cognitive behavioral ones that are very effective for some patients in some circumstances. In psychoanalytic psychotherapies that are effective with other patients in other circumstances. So I defined this specific psychotherapy for borderline patients. And this is how- what my career changed. In the middle of this, I became the head of the psychotherapy research project of the Menninger Foundation, but then was appointed director of the Menninger Hospital.

So I, some years, I was simultaneously medical director of the hospital and director of the research project. And then I felt I had nothing more to learn but I felt I needed a learning atmosphere to find different approaches, different ways of dealing with psychiatry and psychotherapy. Menninger Foundation seemed to me a more limited place. And I accepted an invitation to become a professor at the Columbia University of New York. Went to Columbia where I really began to start out the treatment that I devised. I was in charge of their inpatient service for severe personality disorder. And I gathered a group of people, who after a few years, we accepted moving to Cornell. And I became director of Westchester Division Hospital of the Department of Psychiatry at Cornell. And together with the group, we formed the Personality Disorders Institute.

And 20 years later after I completed my directorship of the hospital, I dedicated myself exclusively to being the director of the Personality Disorders Institute at Cornell with the help of some distinguished scientist, John Clarkin, and the director of our empirical research, Frank Yeomans, whom you have interviewed, who is the director of overall training. He's a fantastic psychotherapist. And there were two or three more people, a group of six or seven, who we first developed the diagnosis more clearly, more sharply, and described different types of personalities functioning at that borderline level. The narcissistic personality, the most important one which we have been studying in great depths, but we also studied the paranoid personality, the schizoid personality, the infantile or histrionic personality. So we did a journal study of personality disorders, their description and differentiation into those with normal identity or neurotic personality organization with identity diffusion or borderline personality organization.

And those atypical psychotic cases that presented as if they were personality disorders, but with a more severe illness, a psychosis is a potential that might blow up or not in different cases. So we did- we spent the time first on differential diagnostic studies and publications, and then set up an empirical study comparing transference focused psychotherapy with supportive psychotherapy and with cognitive behavioral therapy. And confirmed the effectiveness of transference focused psychotherapy [TFP], both in research carried out in the United States, in New York, and then replicated in Europe under the direction of Stefan Doering, professor of psychoanalysis in psychiatry at the University of Vienna, who gathered internally group that carried out parallel empirical research in the in the German speaking countries. And of course, now we have groups in many different countries and are continuing both research training and treating patients. That's in a nutshell.

Borderline Personality Disorder and Primitive Defenses (00:22:55)Puder:

Nice. Can you, can you…

Kernberg:

I hope I didn't put this into the technical terms.

Puder:

No, no, it's, it's good. Can you specifically talk about how in the borderline level of functioning, you have identity diffusion and primitive defenses. And can you talk about the primitive defenses that you see? How do you identify them?

Kernberg:

Yes. Freud had defined the ego defenses against awareness of unconscious conflicts, particularly repression and related defenses of suppression, rationalization, intellectualization, reaction formation. Those were unconscious defenses to be discovered in the course of the treatment of psychoanalytic treatment- searching for the unconscious conflicts of these patients. Melanie Klein, who influenced me very importantly in my psychoanalytic development, discovered a group of primitive defenses centering around splitting or primitive dissociation, in which the way to deal with conflicts between love and aggression, by sharp splitting of the emotional experience. So it is not, erotic patient may act lovingly and repress his aggression. Or he may act aggressively and repress his loving potential. Borderline patients express simultaneously love and aggression, but under different emotional conditions. And they have memory of when they felt opposite to the way they feel now, but they can't help it and have to feel now, the way they feel now.

So when they feel enraged, they are all rage- then there's no love. And when they feel love, all love and no rage, and they may shift from one to the other rather easily. So that's the mechanism of splitting, and it creates chaos in their relationship because they are violent and brusk changes of mood and attitude that creates difficulty with other people who in turn respond to that chaotic behavior with their own difficulties. And so, personality disorders tend to create abnormal interactions with other people and distort all relationships.

Another primitive mechanism is projective identification. Projective identification is a tendency to attribute to the other person what one cannot tolerate at the moment in oneself. So that while you are in a state of idealization, you project your own aggression onto somebody else, attribute somebody else as having aggressive motivation, aggressive behavior, and you induce it in him without being aware of it, and then try to control it.

So project identification is perception combined with induction- effort and control. And it is the primitive form of what advanced mechanisms show in projection, which is attributing something internal to somebody else, but without any internal contact anymore, with what you are projecting. In projection, you just declare the other one is what you are not, and you don't feel like that. In projective identification, you attribute it to the other one, but you know how it feels to feel like the other one, and you produce it in the other one, and you have to control it. So projective identification is primitive form of projection. Another mechanism is that of a very primitive idealization that doesn't tolerate in opposite of modifying it with the realization of your own aggression toward the ideal object. The idealization, or the higher level idealization, recognizes one's own limitations. The primitive one- there's somebody ideal, and you identified with that implicitly become ideal as well.

And the wish to omnipotent control the other person. The effort to deny that you've had a feeling or an action that you've had, but it no longer exists because of splitting operation. This is the primitive mechanism. So splitting, projective identification, omnipotent control, denial. These are typical primitive defensive operations. And they show the behavior of people, the advanced mechanism only showing the treatment. Primitive defenses show in the behavior, in the habitual behavior of people who use projective identification and splitting and omnipotent control, and deny aspects of themselves that have been evidence at other times.

And so we can diagnose through these behaviors the personality disorder. How do we diagnose a personality disorder? We try to find out how the person is functioning in work and profession, love and sex, social life, family relation, self-affirmation, and free time interests- hobbies. And what we, in the structural interview, what we ask people mostly, how are you doing in your work? Are you happy or not? Are you effective or not? Are you- do you get along with other people or not?

Sexual life in Borderline and Narcissistic Personalities (00:30:24)And we ask the same about their sexual life. Are you happy? Do you have a relationship?

When sex becomes complicated, not only because it's a fundamental aspect of life that is in conventional reality, is usually suppressed and highly privileged, but because it involves implicitly the integration of the erotic dimension, sexual excitement, orgasm and sexual behavior with the emotional feelings of love and tenderness.

And when we study sexuality, we study the extent to which the erotic and the emotional have been integrated, which is what happens maturely normally. In contrast to conflictual lack of integration by which the erotic and the emotional remains separate and create serious problems in intimate relations. So we try to find out about that. And regarding social life, we find out to what extent the person, his friend, his social environment that enriches life or feels isolated for whatever reason, incapable of establishing such a social life. And to what extent is he able to establish relationship in depth, in friendship, not only in sexual love or to what extent is this not possible? And with patients having borderline personality organization, usually there are serious problems in work and profession, in love and sex, and in their social life, family life such as between parents and children. And so the present, the careful study of functioning in present life leads to the diagnosis of the personality disorder.

Puder:

Can you say a little bit more about when someone has this borderline level of organization and their sexual intimacy is separated from more of the erotic side. Like how does that show up? What would a patient be saying to let you know that they've separated those two things?

Kernberg:

First of all, I need to modify what I said- that in that they are patients on a higher level of functioning, or the neurotic level of functioning, who also have such separation between love and sex, namely people with a masochistic personality, which is a non-borderline personality disorder. But the borderline personality organization, patients have the greatest difficulties. The most typical is presented by the narcissistic personality. The most typical cases, they have great difficulty for intimate relations. They can't maintain an intimate relation. The men have relation with women for a few months- it's all they tolerate before the relationship goes up in smoke. So they replace the lack of intimacy of love with freedom in sex. So you find men, and the same thing holds for women, and men get involved with many women, have great sexual relations and infatuation that lasts for weeks or a few months. Then they get bored, fed up, end of relationship, on with the next.

So that sex determines the capacity to maintain brief, repetitive relationships without a capacity for relation in depth. On the other hand, they may maintain a very dependent relationship with one woman who has a kind of a motherly function with whom they have no sexual interest, but are very dependent and exploitive. So they may be married men who act like children who are exploitative to women who tolerate it while they have sexual pleasure with a number of women. That would be one way. Another possibility is there is a full sexual relation, but in which there is an alternation between intense aggression and rejection. And then re-encounter sex permits them to re-encounter the relationship in which there is depth and dependency. In contrast to narcissistic personality, the ordinary, non-narcissistic borderline patient is capable of maintaining long-term relationships, but within each of them, chaos in which love and aggression shift rapidly and create chronic couple conflicts.

There are patients who- of course there are some patients with a total inhibition of their sexual impulses in which there has been too much aggression in very early development to permit eroticism to develop, or this strictly rigid, excessively rigid education has kind of severely inhibited their sexual behavior or forced it into remaining at the level of infantile sexuality. Sexual life begins with birth- what we now know is that children, if you leave, if you leave babies alone, in the sense you don't forbid sexual behavior, they start masturbating in the second half of the first year of life. And during the second year of life, boys and girls masturbate. Girls in general tend to end this first masturbation phase around age three, around age three, but reestablish it later at age five or six. Boys tend to, if not forbidden, tend to masterbate all through until adulthood.

Masturbation is a normal sexual activity when there is no other sexual outlet. And we have learned that it's a normal aspect of infantile psychology. It has taken us, Sigmund Freud, and a hundred years later to have this slowly sinking in. Even in the modern forms of the various Western religions, masturbation is no longer a major sin. And so science has been able to modify our attitude towards sexuality. But in general, in borderline personality organization, either sexuality is combined so much with aggression that chronic chaotic conflict prevents a good sexual relationship, a stable one with stable love, stable sexual erotic gratification- excitement is an alternative to not being able- a woman may be sexually excited and or orgastic with one man, totally non responsive to another one. So there may be a sharp way of splitting or division within erotic life. I don't know whether I've answered your question.

Puder:

Do you see with the narcissism, specifically, more of the sadism in the sexuality? Or is it specific to a certain personality type? How do you see that play out in the work that you've done?

Kernberg:

We all have a potential for love and for aggression. That's universal. Usually love wins over aggression. From babyhood on, we have more experience of good relations than bad ones. But of course, there are traumatized children whose life has mostly bad experiences. They are- everything goes wrong. Under ordinary circumstances, we use aggression constructively by self-affirmation, by endurance, by defending ourselves realistically. And aggression also enters— sexuality — in the sense that from the beginning of life, there is a pleasure in penetrating and being penetrated that already has an erotic quality. There is an erotic quality in biting, in being bitten, in fusing lovingly with the other by touching skin— as well as the feeling as one penetrates the body of the other, or as being penetrated. So the erotic impulses show from the beginning of life in the capacity to experience sexual excitement and to the erotic pleasure in watching once partner, the baby watching mother and mother watching the baby, which is the origin of voyeurism or sexual pleasure with seeing the sexually prohibited part of others.

And exhibitionism, which is the opposite, the erotic pleasure in showing one's forbidden parts to others, to excite them. In masochism, the slight pleasure in mild pain, that is part of sexual excitement. And sadistic pleasure in inducing pain in the other, which is part of sexual excitement when it is within a dominant loving atmosphere and signals the erotic pleasure of mutual fusing. When there's an excessive degree of aggression, then these tendencies become dominant and create problems.

And the most important problem is that excessive aggression makes ordinary sexual intercourse dangerous— dangerous to penetrate, dangerous to be penetrated. And so one remains with a childlike equivalence of masturbation, voyeurism, exhibitionism, fetishism. We call them perversions, or paraphilias, when they become indispensable preludes to sexual intercourse when the individual only acquires the security of sexual excitement and orgasm after having fulfilled these pregenital, early erotic desires. So, perversions are really sexual inhibitions of ordinary sexual behavior— retreat from it into the infantile equivalence.

Normal sexual relations, however, include all those infantile components. So a couple that has a good, mature sexual relationship may have games, plays, and fantasies, and activities of a masochistic, sadistic, exhibitionistic, voyeuristic, heterosexual and homosexual quality, and apropos homosexuality and heterosexuality unconsciousness— we have both tendencies, although usually one clearly predominates in most cases. But there are persons who, of course, who maintain both homosexual and heterosexual impulses of various degrees. So sexuality becomes complicated. This has been accentuated in recent fashions and political movements.

Transference Focused Psychotherapy and Reflective Function (00:45:08)Puder:

One thing that I really loved about the- when I read the transference focused psychotherapy articles is when they looked at reflective function before and after transference focused psychotherapy therapy. And I think transference focused psychotherapy is one of the only therapies that has shown an improvement in reflective function. Reflective function being measured by the adult attachment interview. Fonagy was the main originator of that manual. Do you have any thoughts on why transference focused psychotherapy increases reflective function where things like dialectical behavioral therapy (DBT) did not show any change in reflective function?

Kernberg:

Because transference focused psychotherapy (TFP) permits the full expression of a conflict in its positive and negative aspects. Patients who develop a negative transference, we don't try to reduce it. To the contrary, we try for the patient to experience fully the negative transference in terms of identifying with the hostility of the object and the self as victim, and then with the hostility of the self and the object as victim. In other words, we try to familiarize the patient to make him accept the extreme of his reaction, to then confront him with the opposite extreme that we also tolerate of the intensity of loving and erotic impulses to the therapist, both is dual and recipient of love. So that by permitting the full expression of the extremes of love integration, we facilitate the interpretive integration of them and permit the patient to tolerate the simultaneous contradictory impulses that are part of normal human ambivalence.

And the patient then is able to see that yes, he has an ideal view of himself as a very nice person, but in part of him is also a nasty person. And introspection, insight consists in the capacity of an integrated view of all potential that one has. In contrast to remain splitting into a false idealized version completely separate from all aggression. So self reflection signifies a realistic way of assessing one in one's strength and weaknesses. Good and bad aspects are a mature distance from oneself acting in any concrete interaction.

Puder:

Okay. Okay. So a lot of people do not like the idea that we all have aggression. Right? And what I'm hearing from you is that you really allow the patient to feel the full weight of their aggressiveness. And that's very different than like trying to give them coping strategies or trying to tell them, no, you're not really aggressive, or you're not really angry. So like, give me some examples or help me understand how you might help someone tolerate their own aggression.

Kernberg:

Take a marital conflict. A woman hates her man because he has been treating her badly during breakfast, has not been coming home, has forgotten something important, gets enraged at him. He in turn gets enraged defending himself. They're in the middle of a big fight, but at the same time, they both have a consciousness that they love each other. And that fight is going to end in a good way into a good relationship. They have no doubts about that. They tolerate bad momentary interaction with a deep conviction of the consistency of a dominant love. In contrast to another couple who, when they are enraged, they feel this is the end. I'm walking out of this. I don't want to see that man ever again, or that woman, never again.

So the tolerance of one's fighting mood when one is angry with the consciousness of the permanent, of the deep relationship, that transcends the momentary one. That is what characterizes self reflectiveness: the capacity to see one's overall relationship rather than being victim of a certain mood and then having the sense that there is no other possibility is that particular mood. A man gets enraged at the way his wife is treating the children and gets so enraged to say, “You do this once again, I walk out.” And he's ready to walk out, and drop the relationship. So there is an intolerance of the bad, unavoidable, bad aspects of any relationship of daily life. Tolerance of ambivalence is really what marks self-reflectiveness. What Kleinian psychoanalysis calls the depressive position, which is the sense of the potential for sadness for treating badly people one really loves.

All of us have moments in which we don't treat those we love well. It takes a baby a year or two to realize that the mother that he hates, when he hates her, is the same mother that he loves when he loves her. And eventually is the capacity of feeling depressed when he's angry at the mother that he loves, and he sad over losing the mother that he loves because he's so angry. That is an indication of mature reflection. The capacity for reaction with sadness about one's own reaction and the awareness that one has different- general relationship with somebody with one is in a momentary mood, very different from the usual habitual one.

Kernberg:

A person who tends to be kind of rough and is acting superior with subordinates has a kind of inappropriate grandiosity, may recognize that he has that tendency and accept that he has a problem in the way he treats others that he has to correct. And that becomes part of his personality watching out what he knows of problems in his own tendencies. That indicates self-reflection. The general intention, how we should behave with others controls the immediate behavior, even if it's very different from what his general attitude is. This is what we mean by an integrated view of self and an integrated view of others. I mean, a man comes home with his serious mind and his wife thinks, oh, he doesn't love me anymore.

Then he comes home with a little friendly face, ah, he loves me. She doesn't have the capacity to know that he loves her, whether it's in a good mood or a bad mood. The integration of his present mood into his general relation with her indicates maturity, integration of the object representation. So integration of self-representation and integration of object representation. Mark normality, normal identity and capacity for reflectiveness. And we develop that throughout the treatment that tends to resolve primitive defensive operations, normalize identity, and therefore normalize the capacity of dealing with a major task of work and profession, love and sex, social life, and one's own creativity.

Envy, Promiscuity, and the Link with Personality Disorders (00:55:43) Puder:

Tell me about your thoughts on envy and how someone with maybe more narcissistic borderline level functioning, how envy shows up for them versus maybe normal people.

Kernberg:

A very good question. Envy is a normal aggressive affect with very specific characteristics. It is anger at somebody who has something that we want and we don't have. So we want something that we don't have and are angry at whoever has it when we don't. It is a normal way in which a baby sees another baby has a toy that it- he wants to have that toy and gets angry if he doesn't get that toy or something exactly like it. So it is a human emotion. That is one of the negative aspects of our potential that normally we have. We tolerate it. It doesn't control our lives. With narcissistic personality, the problem is they present very intense aggression that takes the form of envy. Usually the cause of that is a lack of loving, sufficiently loving relationships in very, very early life in the first two or three years of life.

When one feels loved, one internalizes a good representation of others, and feels fulfilled by the people who have been good to one. If one doesn't have any of this, there's a sense of emptiness and one gets the painful observer that other people feel so good about their relation with others while we feel so bad. So envy becomes a very strong motivation because basically we don't feel the internalization of love that others have. And envy then grows to the extent that whatever we like and don't have enrages us. It destroys our relationship because whomever we could love, and be friendly with. Turns out to have things that we don't have to begin with, the very capacity to love. So the way that envy gives one a painful sense of lacking, of emptiness. And the way to fight it off is to devalue what one end is.

Normally, when we get a good response to our behavior from others, we feel very happy that others love us, and we see it as a gift. In other words, normally we have a feeling of gratitude for the love that we get. Envious people lack the capacity of gratitude, because what they get gives them a sense of what they didn't have. It reminds them of what they didn't have, which colors what they get. They're happy that they get it, but they don't have that feeling of happiness. With the happiness that the other feels in giving them something. So envy tends to spoil what one end is, which means that narcissistic personality fall in love with the woman, unconsciously hate what they admire in her from her physical appearance to her capacity, to her potential. And so unconsciously, they tend to devalue it and that makes this woman indifferent and boring, and they have to drop her.

So unconscious envy, the defense against it by devaluation is what motivates the sexual promiscuity of narcissistic personalities. The counterpart of envy is an unconscious destruction of the values that others have and that one doesn't. Students with a narcissistic personality can learn only what they feel they learn because they take over what others know. They incorporate the knowledge from others. That's kind of, it's like stealing from others makes them feel good. But when they have to acknowledge that they depend on the other, it spoils it. Because then envy is unavoidable. Narcissistic personalities can learn from what they learn, by what they feel they are learning by themselves without anybody giving them anything. They take it from others, but they can't read a book. They can't learn from a book because they have to- they have is independent knowledge from them, and they resent it. So you find very intelligent people who can't read a book or spoil their own capacity of interest in a certain field. So envy tends to ruin the capacity to absorb good things, establish good relationship. In the worst case, any area, one cannot enjoy anything except being admired, which is recognizing of one's greatness by the others. And if one of the predisposition to the narcissistic personality are parents who really don't love the children, but they are happy with admirable things that children have, that others admire the child. The parent, the narcissistic parent, uses the child as something great, “Look what beautiful children I have.” So they admire their child, but they don't love it.

So when the- when love is replaced by admiration is the only source of what loved one receives, it fosters narcissistic personality. One has no hope for love. Only when others admire one, one can feel good about oneself. So the psychopathology of envy is very damaging. And any major issue in the treatment that one solves by analyzing all its causes and consequences.

Histrionic vs. Hysterical Personality: Otto Kernberg Clarifies Neurotic and Borderline Levels of Functioning and Sexual Dynamics (01:03:52)Puder:

I'm also curious about- you mentioned histrionic personality before. Do you see this on the borderline level of functioning or more the neurotic or both?

Kernberg:

Yeah. There is a confusion in the literature about this. There exists a high level personality disorder, the hysterical personality disorder. Which has normal identity and the main problem is sexual inhibition and efforts to overcome the sexual inhibition by various means. Sexuality is a great problem. They act quite maturely except when it comes to sex, when they become quite childish. Now, because politically hysterical personality usually went together with an attack of women because the impression was that only women had hysterical personality, which is false. Men also present hysterical personalities. The official classification of personality disorders called it histrionic personality disorder, so to take it away from its political implication. And the histrionic personality disorder, in the official classification, covers both the hysterical and the histrionic in a strict sense equivalent to the infantile personality, which are patients who have sexual difficulties, but part of a general severe personality disorder with identity diffusion. So that the histrionic personality, how it is used generally refers to a broad spectrum. Most of them are really their borderline personality organization, when in fact, a subgroup is part of a higher level neurotic organization.

How do we make that differentiation? The histrionic personality disorder is childlike or infantile in all aspects of life, work, professional, school, love, sex, social life. And is part of this childlike regression. Feelings are expressed through behavior more than verbally. And the exaggeration of behavior is what from the outside looks at theatricality, an exaggeration. Theatrical exaggerated behavior, which has an infantile quality to it, and is important aspects of those personality disorders. Histrionic means behavioral exaggeration of real feelings one has and conveys a sense of artificiality in contrast to the expression of real feelings in a profound sense. So these are patients who give the feeling that they exaggerate, that they do theater with what they feel to impress others, as if it were profound. It’s lack of sincerity, lack of honesty, when it is really part of a general childlike regression to childlike communication of affect.

So the histrionic personality of personalities with childlike behavior in all their interactions may include sexual inhibition, but very often surprisingly doesn't. So often, the histrionic personality on a borderline level are freer sexually than the hysterical personality on a neurotic level, because the hysterical personality, using the mechanism of repression, inhibits totally the sexual response. While the borderline personality, by the splitting mechanism, is able to have great sex with one partner and zero with others. So in a strange way, borderline patients may be freer of sexually than higher level neurotic patients. The main problem is in the relationship with others, and of course, borderline patients who, on top of all their problems, have an extremely severe sexual inhibition with zero capacity for any sexual excitement or enjoyment constitute the most serious part of sexual inhibition that requires long term treatment.

Paranoid Personality (01:09:35) Puder:

Hmm. Do you want to talk about borderline level of functioning with the paranoid personality type? Like what is kind of like the thing that is most common with that group?

Kernberg:

Paranoid personalities are using the mechanism of projective identification as a dominant mechanism. They are part of borderline personality organization with intense aggression that they attribute to others because of that mechanism, meaning that they are hypersensitive to anything that can be interpreted as a negative attitude toward them. They're suspicious that others' behavior indicates hostility toward the person- hostility or the effort to disguise or hide hostility. At the same time, they tend to be very aggressive because they have excessive aggression, and they tend to use omnipotent control efforts to control the other person whom they see is dominated by aggression toward them. So the combination of aggressive behavior, hyper-suspiciousness, and efforts of sadistic control of others are the main characteristics of the paranoid personality.

Schizoid Personality (1:11:19)Puder:

And, and you touched on schizoid a little bit. Schizoid with borderline level of functioning.

Kernberg:

Yeah. The schizoid personality uses predominantly the mechanism of splitting in efforts to avoid conflicts by such generalized splitting of the expression of all affects, that it is as if they had no affects. There is a kind of a fragmentation of affect as if extreme forms of splitting. So they fragment both their aggressive affects and withdraw from contacts in order not to be tempted to become aggressive. And they fragment the view of themselves as aggressive to avoid it. And sometimes they show a very sharp perception of others because they're so suspicious and so observant. Nothing escapes them. They are very good in spite of the identity diffusion, to know exactly what to expect from others. But about self, they have a complete confusion because of the fragmentation of all affective experience. So the identity diffusion shows in sharp description of others while they look and integrated view of them. It's- they see the wood, they see the trees, but they don't see the wood. And they withdraw protectively from avoiding aggressive induction with others. They are in-they look as if they didn't need affective relation and love. That's a mistake. They do need love, but they are afraid that their own aggression will destroy the affective potential of a good relation with significant others.

So the withdrawal protects them from direct search for love. And to the contrary, they have to do a tremendous effort to be able to express any close relationship with others. So their relationships are distant. The affect is dispersed, so it's hard for them to know what they really want, and they are ignorant of their own deep needs for love, that they have to reject out of fear of being rejected. And so there is hyper-alertness to what's going on, but without the aggression of the paranoid personality.

Social withdrawal rather than omnipotent control. And the sense of uncomfort and loneliness and distance in group situations. So a sense of loneliness, confusion about the self, not clear awareness of their need of significant others, and they are capturing the great details of the personality of others without really putting it together in an integrated view. These are the main characteristics of the schizoid personality, and the so-called schizotypal is just the more severe form of that, except that in the schizotypal there is genetic stronger genetic, hereditary disposition than in the schizoid personality.

Puder:

What role does fantasy play for schizotypal and schizoid? What role did you understand my question?

Kernberg:

Where, where does that play…

Puder:

Fantasy?

Kernberg:

In withdrawing from immediate social reality for the reasons that I mentioned, they replace their interaction with others by an intense fantasy life. They find in their intense fantasy life, an expression of their needs relating to others. So they are particularly prone to create their own internal world, gratifying their needs, because they don't dare to express it in external reality, out of the fear of their own aggression.

Puder:

Hmm. How about someone who's classically borderline personality disorder? Do you- how do you make sense of their intense fear of disconnection, of the withdrawal of the other?

Kernberg:

Well because the splitting operation and the activation of intense aggression toward people whom they love they project the aggression and any real frustration creates an exaggerated reaction. They are afraid of being left, of being dropped, of being abandoned because they see others with the intense aggression that they can't tolerate in themselves.

So they take one way to solve the dilemma between love and aggression is to look for an ideal relation with the other as a protection against the field. Aggressive rejection by the other, they become very dependent and intolerable of being separate, that intolerance of separation has to do with the fact that any separation is immediately translated into a sense of an aggressive rejection of the patient.

Why Therapists Want to Help (01:18:37) Puder:

Good. Good. I, what do you think of most therapists who come into practice? Do you find them more of the depressive personality type? Or what kind of range have you seen?

Kernberg:

Well, I've had a long professional life and I've seen, I think, a very broad spectrum of patients. Yes. I believe I've seen probably most patients described in the literature.

Puder:

Is there a commonality of the helper of the person that wants to help? Maybe of the person where there was a role reversal early on in their childhood where they were the ones who were like the family therapist, even at a very young age. Like, what is-like how- where do those people fit in your sort of…

Kernberg:

I think that therapists may have many reasons for becoming a therapist. Very often, persons who have had strong personal problems that they have overcome, they then want to become therapists out of an experience of gratitude and identification with the people who help them. Some people are looking for solutions to their own problems in helping others. For some people it is a source of great gratification to have a profession that helps others. And there go all the motivations for medical professions, nursing, psychology, including that of psychotherapist interested in the psychological functioning of self and others, and how to modify it. There are some people who become psychotherapists secondary to their interests in neurobiology with the functioning of the brain. Sometimes psychotherapists have the unconscious motivation of helping others out of the situation in which the therapist had been in the past broadening the effect of his treatment. And one thing that was important for me was that sense of being able to change one's way of behavior. I had ways of behaving I was not happy with, and I had difficulty changing, and I wanted to know how much change can one or turn in self and in others. That drew me to get into a personal psychoanalysis first, and then became interested in psychotherapy in general.

Puder:

And how much did you change?

Kernberg:

Well, I changed significantly. I changed significantly. I had two personal analysis, so I had people helping me, and I had the luck of great teachers, really an unusual luck that- and met a number of the leaders of the field and with some of them became real friends, and that was very important. I owe a great deal to people such as Jacob Arlow and Andre Green and Betty Joseph and many others.

Puder:

But it sounds like you were also a great student because when he gives- when he tells you to read the book, you read the 12 volumes. Sounds like you, which-

Kernberg:

Yeah.

Puder:

It's an unusual student to come back and said, “I read the 12 volumes!”

Kernberg:

I read the- I admired him greatly and it was worth it. I learned the descriptive psychiatry more than most psychiatrists of my generation. It helped me to become very observant about small issues of behavior. It really wasn't- I got a specialized training..

Puder:

What would you say is something that you feel a lot of therapists don't understand that you wish they would understand at this point?

Kernberg:

It's very difficult to- generalize. My experience is mainly with the psychodynamic psychotherapists. I have limited experience of working with the cognitive behavioral therapist. Although I do have some, and very impressed by what some cognitive behavior therapy can achieve. But for psychoanalytic psychotherapists, I think the most important issue is first of all, comfort with one’s own aggression.

Therapists have to be comfortable with their own aggression, not having to act it out nor being afraid of it. That's one important issue. One, of course, a crucial issue is having a real interest in people and getting to know about people. Being curious about how other people are functioning. There are many therapists who don't pay sufficient attention to that. Then I think psychotherapists need to have a great, a great common sense. Psychotherapy starts where common sense ends. And in order to deal with the subtlety of conflicts, one has to have first a good hold of solid reality. I think that therapists can come from many directions. They can come from a very intuitive emotional direction or very intellectual ones, and they have to learn to compliment what comes natural with what they have to learn. The very intellectual ones have to learn about expression of emotions, and the most emotionally intuitive ones have to learn how to formulate things cognitively. And it really is a strong wish to help other people. I think these are the most important ingredients.

Puder:

Yeah. Yeah. That's good. Well, as we kind of- I don't want to take too much of your time today, and I'm- I feel like almost a part two is necessary to hash out some more of these ideas, or part 10 or part 11. But I'm curious, as we've talked today, if any lingering ideas are going through your mind that you haven't had adequate time to express.

Kernberg:

I think the great goals of treatment are to help people to become more effectively self affirmative, and at the same time more capable to develop relationships in depth with others. These are two basic issues of normal functioning, to take care of one's relations with others and to take care of oneself in a reasonable way. Acquire full responsibility for one's behavior in one's life.

Puder:

Do you, okay, so one more- one more question.. What was- do you feel like there's any room to explore the thing that you were doing before you did the psychoanalysis two times that you wanted to change? And did you actually feel it changed?

Kernberg:

Are you asking me what I was considering some other profession?

Puder:

No, no, no, no. You said earlier there was something about yourself that you wanted to change through psychoanalysis. Is there anything else you would be willing to share about that publicly?

Kernberg:

Yeah. Well, I don't want to share too many personal issues, but I used to be quite obsessive, excessively intellectual, and I have become much freer with my emotions.

Puder:

Well, I thank you for that and thank you for coming on. I've really enjoyed my time talking to you, Dr. Kernberg. It's a pleasure. And I'm very grateful for your many articles and books. And there was just a recent biography that was written about you [Otto Kernberg: A Contemporary Introduction]. I think Yeomans wrote it in part that I've appreciated and I know the people that I've been listening to my podcast for a while have been grateful for his expertise, and I'm sure they'll be grateful for you coming on today. So thank you so much.

Kernberg:

You're most welcome. It has been a pleasure. I'm glad it worked out.

Puder:

Fantastic. Thank you so much. I will stop the recording now.

Kernberg:

Okay.

🌐 Interested in learning more about personality disorders and Transference-Focused Psychotherapy? Visit https://istfp.org/ to explore insightful resources and information.

🛠️ Are you a mental health professional seeking specialized training in Transference-Focused Psychotherapy? Discover upcoming training programs here: https://istfp.org/training/tfp-trainings/

Additional Resources

Episode 029: What is psychodynamic theory?

Episode 087: Disorganized Attachment: Fear without Solution

Episode 115: Borderline Personality Disorder: History, Symptoms, Environment, Genetics & Brain Science

Episode 130: Borderline Personality Disorder: Psychotherapy Schema Therapy

Episode 171: Nancy McWilliams on Mental Health, Transference, and Dissociation

Episode 206: Mentalization Based Therapy (MBT), with Dr. Anthony W. Bateman, MA, FRCPSYCH and Dr. Peter Fonagy, PhD, FBA

Episode 213: Reflective Functioning: The Key to Attachment with Dr. Howard Steele

Episode 215: Understanding Complex PTSD and Borderline Personality Disorder

Episode 224: Understanding Borderline Personality Disorder (BPD) Medications & Treatment

Episode 231: Borderline Personality Disorder: Splitting & Identity Diffusion with Mark Ruffalo

ReferencesAmerican Psychological Association. (n.d.). Identity diffusion. In APA Dictionary of Psychology. Retrieved April 23, 2025, from https://dictionary.apa.org/identity-diffusion

Amos, A. (2015). Melanie Klein. Institute of Psychoanalysis. Retrieved April 23, 2025, from https://psychoanalysis.org.uk/our-authors-and-theorists/melanie-klein

Anderson, R. (n.d.). Betty Joseph. Institute of Psychoanalysis. https://psychoanalysis.org.uk/our-authors-and-theorists/betty-joseph

Assink, M., Spruit, A., Schuts, M., Lindauer, R., van der Put, C. E., & Stams, G.-J. J. M. (2018). The intergenerational transmission of child maltreatment: A three-level meta-analysis. Child Abuse & Neglect, 84, 131–145. https://doi.org/10.1016/j.chiabu.2018.07.037

Bailey, R., & Pico, J. (2023, May 22). Defense mechanisms. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK559106/

Brenner, C. (2006). Jacob A. Arlow (1912–2004). American Journal of Psychiatry, 163(9), 1518. https://doi.org/10.1176/ajp.2006.163.9.1518

Bumke, O. (Ed.). (1928–1939). Handbuch der Geisteskrankheiten [Handbook of mental disorders] (Vols. 1–12). Julius Springer. https://link.springer.com/book/10.1007/978-3-642-47333-3

Clarkin, J. F., Caligor, E., Stern, B., & Kernberg, O. F. (2004). Structured Interview of Personality Organization (STIPO). Personality Disorders Institute, Weill Medical College of Cornell University. Retrieved from https://www.borderlinedisorders.com/structured-interview-of-personality-organization.ph

Doering, S. (n.d.). Curriculum vitae. European Society for the Study of Personality Disorders. Retrieved April 23, 2025, from https://www.esspd.eu/wp-content/uploads/2020/07/CV_Doering.pdf

Erikson, E. H. (1968). Identity: Youth and crisis. W. W. Norton. https://archive.org/details/identityyouthcri00erik

Florenzano R. (2009). Docencia universitaria y psicoanálisis: Los aportes de Ignacio Matte Blanco [Ignacio Matte Blanco, MD, and the development of psychiatry teaching to medical students]. Revista medica de Chile, 137(9), 1248–1252. https://pubmed.ncbi.nlm.nih.gov/20011967/

Fonagy, P., Target, M., Steele, H., & Steele, M. (1998). Reflective Functioning Scale (RF) [Database record]. APA PsycTests. https://doi.org/10.1037/t03490-000

George, C., Main, M., & Kaplan, N. (1985). Adult Attachment Interview (AAI) [Database record]. APA PsycTests.

https://doi.org/10.1037/t02879-000

Johns Hopkins Gazette. (2005, April 18). Obituary: Jerome Frank, 95, noted psychotherapy researcher. Johns Hopkins Gazette, 34(30). Retrieved April 23, 2025, from https://pages.jh.edu/gazette/2005/18apr05/18frank.html

Jordan-Moore, J. (1995). Obituary: Ignacio Matte Blanco 1908–1995. International Journal of Psychoanalysis, 76, 1035–1041. https://pep-web.org/browse/document/ijp.076.1035a

Kansas Historical Society. (2017, July). Menninger Clinic. Kansapedia. Retrieved https://www.kansashistory.gov/kansapedia/menninger-clinic/12147

Kernberg, O. F. (1967). Borderline personality organization. Journal of the American Psychoanalytic Association, 15(3), 641–685. https://doi.org/10.1177/000306516701500309

Kernberg, O. F. (1975). Borderline conditions and pathological narcissism (pp. 24–25). New York: Jason Aronson. https://archive.org/details/borderlinecondit00kern

Kernberg, O. F. (1984). Severe personality disorders: Psychotherapeutic strategies. Yale University Press. https://archive.org/details/severepersonalit00kern

Kernberg, O. F. (2000). Borderline conditions and pathological narcissism. Jason Aronson. (The Master Work Series). https://www.scribd.com/document/425936113/the-Master-Work-Series-Otto-F-Kernberg-Borderline-Conditions-and-Pathological-Narcissism-Jason-Aronson-Inc-2000

Kernberg, O. F., Yeomans, F. E., Clarkin, J. F., & Levy, K. N. (2008). Transference focused psychotherapy: overview and update. The International journal of psycho-analysis, 89(3), 601–620. https://doi.org/10.1111/j.1745-8315.2008.00046.x

Kernberg, O. F. (2016). Psychoanalytic education at the crossroads: Reformation, change and the future of psychoanalytic training. Routledge/Taylor & Francis Group. https://psycnet.apa.org/record/2016-16118-000

Klein M. (1996). Notes on some schizoid mechanisms. The Journal of psychotherapy practice and research, 5(2), 160–179. https://pmc.ncbi.nlm.nih.gov/articles/PMC3330415/

Levy, K. N., Meehan, K. B., Kelly, K. M., Reynoso, J. S., Weber, M., Clarkin, J. F., & Kernberg, O. F. (2006). Change in attachment patterns and reflective function in a randomized control trial of transference-focused psychotherapy for borderline personality disorder. Journal of Consulting and Clinical Psychology, 74(6), 1027–1040. https://doi.org/10.1037/0022-006X.74.6.1027

McWilliams, N. (2011). Psychoanalytic diagnosis: Understanding personality structure in the clinical process (2nd ed.). Guilford Press.​ https://nancymcwilliams.com/books-authored/

Orenstein, G. A., & Lewis, L. (2022, November 7). Erikson's stages of psychosocial development. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK556096/

Perelberg, R. ( 2015). André Green. Institute of Psychoanalysis. https://psychoanalysis.org.uk/authors-and-theorists/andr%C3%A9-green

Sam, N. (2018, November 28). Descriptive psychiatry. In PsychologyDictionary.org. https://psychologydictionary.org/descriptive-psychiatry/

Santander, P. (n.d.). Chilean Psychoanalytic Association. International Psychoanalytical Association. Retrieved April 23, 2025, from https://www.ipa.world/IPA/en/Societies/societies_focus/chilesoc.aspx​

Weill Cornell Medicine Psychiatry. (n.d.). John F. Clarkin, Ph.D., appointed director of the Personality Disorders Institute (PDI). Retrieved April 23, 2025, from https://psychiatry.weill.cornell.edu/news/john-f-clarkin-phd-appointed-director-personality-disorders-institute-pdi

Yeomans, F. E., Diamond, D., & Caligor, E. (2024). Otto Kernberg: A contemporary introduction (1st ed.). Routledge. https://doi.org/10.4324/9781003053415

View Details

Joshua Mangunsong, Liam Browning, Brandon Luu, MD; Nicholas Fabiano, MD; David Puder, MD

Corresponding author: David Puder, MD

Reviewer: Erica Vega, Joanie Burns, PMHNP-BC

None of the authors/presenters have any conflicts of interest.

By listening to this episode, you can earn 1.5 Psychiatry CME Credits.

Other Places to listen: iTunes, Spotify

**Abstract:**Creatine, widely known for enhancing athletic performance, is gaining attention for its potential as a novel adjunct psychiatric treatment. Beyond muscle function, creatine supports brain energy metabolism, which has increasing evidence for a role in mood disorders like depression and bipolar disorder.

Recent studies suggest creatine supplementation can enhance treatment outcomes in psychiatric conditions. Sherpa et al. (2025) found that adding creatine to cognitive behavioral therapy (CBT) significantly improved depressive symptoms. Similarly, Lyoo et al. (2012) reported creatine enhanced response to SSRIs in women with major depressive disorder.

Neuroimaging studies indicate creatine boosts phosphocreatine levels in brain regions linked to mood regulation, and doses above the normal 5 grams per day have added increases in brain creatine levels. Observational data also suggest an inverse relationship between dietary creatine intake and depression prevalence.

This article and accompanying podcast episode provides a scoping review of the evidence on creatine’s psychiatric applications, exploring its mechanisms, clinical relevance, and future research directions.

IntroductionCreatine is a naturally occurring compound essential for cellular energy metabolism, primarily through its role in adenosine triphosphate (ATP) regeneration via the phosphocreatine system (Miller, 2022). It is widely recognized for its benefits in sports performance, muscle growth, and recovery, as well as its potential neuroprotective properties. Beyond its established role in muscle physiology, emerging evidence suggests creatine may have significant effects on brain bioenergetics, cognition, and mental health (Prokopidis et al., 2023). There are several mechanisms that may explain these effects.

Animal models offer additional support for creatine’s neurotherapeutic potential. In a study examining the impact of dietary creatine on experimental traumatic brain injury in rats, supplementation with a diet containing 1% creatine for four weeks significantly reduced cortical damage by 50% (p < 0.01). Given typical daily food consumption in rats, this 1% dietary supplementation approximates a daily intake of around 0.5–1 g/kg, translating to approximately 35–70 grams of creatine per day—for a 70 kg human. The observed neuroprotective effects are thought to arise from enhanced mitochondrial bioenergetics, characterized by increased mitochondrial membrane potential, reduced calcium accumulation, lower reactive oxygen species production, sustained ATP levels, and inhibited opening of mitochondrial permeability transition pores (MPTP) (Sullivan et al., 2000). Another study found that high-dose creatine supplementation (approximately equivalent to 280 g/day in a 70 kg human, significantly higher than typical human dosages) attenuated striatal dopamine depletion in a mouse model of Parkinson’s disease, reducing dopamine loss from 56% in untreated mice to 33% in creatine-treated mice (p < 0.05) (Yang et al., 2009). In a mouse model of chronic mild stress-induced depression, creatine supplementation significantly reduced depressive behaviors measured by the forced swim test, decreasing immobility time from 106.7 seconds in stressed controls to 39.0 seconds with creatine alone, and further down to 34.1 seconds with combined creatine plus exercise treatment. Serotonin (5-HT)-positive neurons in the dorsal raphe nucleus increased substantially from 55.0 cells in stressed controls to 126.8 cells with creatine alone, and even more markedly to 206.1 cells with the combination of creatine and exercise. The creatine dose used (~4% dietary inclusion) translates to approximately 140 grams per day for a 70 kg human, far exceeding the standard human supplementation dose of 5 grams per day, indicating results achieved at a high pharmacological dose​ (Ahn et al., 2016).

In humans, a study found that creatine supplementation as an add-on to cognitive-behavioral therapy (CBT) demonstrated potential in treating depression, as evidenced by a greater reduction in Patient Health Questionnaire-9 (PHQ-9) scores compared to CBT with placebo (Sherpa et al., 2025).

Emerging neurobiological research has highlighted creatine’s role in brain bioenergetics, with supplementation shown to increase brain phosphocreatine levels and enhance cognitive processes such as memory, attention, and information processing speed (Avgerinos et al., 2018; Xu et al., 2024). Meta-analyses have found more pronounced effects in older adults and under conditions of metabolic stress, such as sleep deprivation, although evidence for broader executive function remains inconclusive (Avgerinos et al., 2018, Prokopidis et al., 2023). These findings suggest creatine’s utility may extend beyond its known ergogenic effects into domains of cognitive and mental health.

Mental health disorders are a leading cause of disability worldwide. In 2019, approximately 1 in every 8 people, or 970 million individuals globally, were living with a mental disorder, with anxiety and depressive disorders being the most common (World Health Organization, 2022). Conventional treatments, including pharmacotherapy and psychotherapy, are effective for many but often have limitations such as delayed onset, incomplete response, and adverse side effects (Hoskins et al., 2015; Howes et al., 2022; Leichsenring et al., 2022). The growing field of nutritional psychiatry emphasizes the role of diet and supplementation in mental health, leading to increasing interest in creatine due to its safety profile, accessibility, and emerging evidence supporting its use in psychiatric treatment.

Concerns about creatine’s long-term renal safety have been common, largely due to elevated serum creatinine levels, which can be misinterpreted as signs of kidney dysfunction. However, a frequently cited study done in 1999 followed nine healthy athletes who had used creatine for 10 months to 5 years at doses ranging from 1 to 20 g/day (Poortmans & Francaux, 1999). Compared to 85 non-supplementing controls, no significant differences were found in serum creatinine, BUN, creatinine clearance, or urinary creatinine excretion. These findings support the renal safety of prolonged creatine use in healthy individuals, and remain one of the most cited pieces of real-world safety data.

While several systematic reviews have investigated creatine’s effects on cognition and neurological function, few have comprehensively addressed its psychiatric applications. Existing reviews often focus on general populations or specific cognitive outcomes, leaving gaps in understanding its role across diverse psychiatric disorders (Avgerinos et al., 2018; Xu et al., 2024). Despite promising preliminary findings, research on creatine’s psychiatric applications remains in its early stages. Many studies focus on specific diagnoses, often with small sample sizes and inconsistent methodologies, leading to mixed findings (Juneja et al., 2024). Additionally, while the potential mechanisms of creatine’s effects on mood and cognition are being explored, they remain incompletely understood. Notably, no comprehensive synthesis has systematically examined creatine’s role across multiple psychiatric disorders, leaving a critical gap in the literature.

This scoping review aims to systematically map the existing literature on creatine supplementation across various psychiatric disorders. By synthesizing findings from diverse studies, this review seeks to provide a clearer picture of creatine’s potential clinical applications, effectiveness, and underlying mechanisms. Identifying knowledge gaps will also help guide future research directions and inform potential clinical recommendations.

The primary objective of this review is to explore and summarize current knowledge on creatine supplementation in relation to different psychiatric conditions. By assessing the breadth of existing evidence, this review will help determine the extent of creatine’s potential benefits for mental health and highlight areas where further investigation is needed. Before we begin the review, we will first introduce creatine’s potential mechanism for mood disorders and also prior studies on sleep as they add to the overall understanding of prior research.

Creatine’s Potential Mechanism For Mood DisordersWith regard to its mechanism, creatine is most well-known for its role in the creatine/phosphocreatine (Cr/CrP) buffer system. Phosphocreatine can transfer a phosphate group to ADP in order to regenerate ATP during periods of high energy demand (Adhihetty & Beal, 2008). While glycolysis and oxidative phosphorylation can take between 30 seconds and a few minutes to replenish ATP, the Cr/CrP system can regenerate ATP in as little as 5–10 seconds. In exercising muscle, this ATP supplied by phosphocreatine is often what allows someone to perform an extra rep or two during sets.

Muscle cells typically rely first on aerobic respiration, fueled by pyruvate entering the TCA cycle and by fat oxidation. When energy demands escalate and less oxygen is available, anaerobic respiration increases, burning glucose for short-term fuel but yielding less ATP and producing lactic acid (leading to the “burn” felt in muscles). Because anaerobic pathways take up to 30 seconds to 2 minutes to recover, the Cr/CrP system steps in to supply rapid energy for approximately 5–10 seconds until muscle exhaustion (Mahoney et al., 2002).

Additionally, the Cr/CrP system buffers intracellular ATP levels, improving mitochondrial function. One study by Walsh et al. (2001) showed creatine increased mitochondrial ATP production by 60% in muscle tissue during intense exercise. The authors suggest that excess ATP (and thus limited ADP availability) within the cell inhibits key metabolic enzymes, signaling that no further glucose or fat breakdown is needed. This can lead to an accumulation of substrates and metabolic intermediates, some of which may be toxic at high concentrations and reduce mitochondrial efficiency. A buildup of ATP can also slow the electron transport chain, potentially increasing the leakage of electrons and the formation of reactive oxygen species (ROS), known to damage cells. Several studies in mouse models of neurodegenerative diseases (e.g., ALS, Huntington’s disease, Parkinson’s disease) suggest creatine’s ROS-reducing properties and mitochondrial membrane stabilization capabilities may improve neuronal survival, motor function, and overall survival (Dedeoglu et al., 2003). However, these benefits have not consistently translated to humans (Forbes et al., 2022).

To recognize creatine’s potential role in neurons, it is important to understand how neurons generate and use ATP. Neurons constantly consume energy, with the brain using around 20% of the body’s calories despite being only ~2% of its mass (Attwell & Laughlin, 2001). However, unlike muscle cells, neurons do not uptake a significant amount of glucose or fat, meaning their glycolytic and fat oxidation capacities are limited. Instead, neurons mainly rely on aerobic respiration with lactate serving as the primary fuel source via the astrocyte-neuron lactate shuttle. Astrocytes take in glucose from the blood, perform glycolysis to generate lactate, and shuttle this lactate to neurons; the neurons then convert lactate into pyruvate for use in the TCA cycle (Mason, 2017). Nevertheless, because some neuronal processes require energy on the order of milliseconds, the Cr/CrP system in the brain helps meet these immediate energy demands. Examples of some of the most time-sensitive, energetically demanding processes at the cellular level include the Na⁺/K⁺-ATPase pump (regulates resting membrane potential), synaptic vesicle release and recycling, and calcium regulation through Ca²⁺-ATP pumps. Burst-firing neurons—such as CA3 neurons in the hippocampus, thalamic relay neurons, cortical pyramidal cells, Purkinje neurons in the cerebellum, and dopaminergic neurons in the substantia nigra and ventral tegmental area—have high energy demands and are particularly susceptible to energy deficits (Joo et al., 2021; Krahe & Gabbiani, 2004). Other energetically demanding states also include sleep deprivation, hypoxia, aging, and depression.

It should be noted that the brain is one of the few organs (alongside the liver, kidneys, pancreas) that endogenously produces creatine, likely owing to the time-sensitive and energetically demanding tasks mentioned above. However, because of this endogenous production, brain cells store significantly less creatine than muscle tissue and have limited ability to transport creatine across the blood-brain barrier, which is cause for debate about creatine supplementation’s ability to increase brain creatine levels (Forbes et al., 2022). Nevertheless, studies in which participants are placed under energetically demanding states or have lower brain creatine at baseline consistently show increased brain creatine uptake and improvements in cognitive function (Forbes et al., 2022).

Based on the neuroenergetics hypothesis, one proposed antidepressant mechanism is that exogenous creatine, by bolstering ATP availability, may facilitate optimal neuronal firing for complex cognitive processes, especially in patients with limited brain creatine stores or who are engaging in intensive cognitive tasks, such as therapy. Higher cognitive processes, including complex meta-conscious activities (awareness of the contents of one’s consciousness) and insight formation, place significantly greater energetic demands on the brain than do simple sensory processing or brainstem functions (Chen & Zhang, 2021). These higher-order brain activities require more extensive spatiotemporal coordination among neurons in disparate brain regions, often manifesting through synchronized gamma oscillations (40–100 Hz), which are energetically costly and rely on robust ATP availability (Joo et al., 2021). Consequently, maintaining or enhancing functional connectivity of these higher-order networks is crucial for meta-cognition (awareness of one’s thought process), as a limitation in ATP in one set of neurons can disrupt the synchronized neural firing within these disparate circuits and thus limit the individual’s ability to maintain focus and to generate new insights (Chen & Zhang, 2021). In this context, creatine supplementation may help buffer neuronal energy demands, thus supporting neural synchronization that underlies the advanced cognition necessary for deeper self-awareness and therapeutic insight. However, more studies are needed to adequately assess this hypothesis, as most studies in cognition assess cognitive battery tasks that do not test novel insight generation.

In addition to supporting neuroenergetics, creatine supplementation may exhibit antidepressant effects through several other mechanisms, including reducing glutamate-induced excitotoxicity and ROS species production, as well as potentiating synaptogenesis and synaptic plasticity.

Creatine Supplementation Enhances Cognitive Performance and Brain Function During Sleep Deprivation and Hypoxia Emerging research demonstrates creatine supplementation significantly improves cognitive performance, executive functioning, and brain excitability under conditions of sleep deprivation and oxygen deprivation (hypoxia). This highlights creatine's potential as a neuroprotective supplement during periods of neural energy stress.

In a double-blind, randomized, placebo-controlled trial (McMorris et al., 2006), 19 healthy young adults received creatine supplementation (20 g/day, administered as four daily doses of 5 g) or placebo for 7 days, followed by 24 hours of sleep deprivation combined with mild intermittent exercise. Cognitive and psychomotor performance were assessed at baseline (0 h) and after 6, 12, and 24 hours of sleep deprivation using tests including random movement generation, verbal and spatial recall, choice reaction time, static balance, and mood state. At 24 hours, the creatine group showed significantly less impairment compared to placebo in performance on tasks reliant on executive function and psychomotor skills, including better random movement generation (Adjacency score significantly improved, p < 0.05), faster choice reaction times (~0 ms change vs. ~21 ms deterioration in placebo, p < 0.05), and improved static balance (fewer corrections needed, p < 0.01). Mood state was also better preserved with significantly lower reported fatigue (p < 0.005) and higher vigor (p < 0.02) in the creatine group. However, simpler short-term memory tasks (verbal and spatial recall) were unaffected by creatine supplementation. Plasma concentrations of norepinephrine and dopamine increased significantly after 24 hours of sleep deprivation, while cortisol levels significantly decreased, but these effects did not differ between the creatine and placebo groups. The study suggested creatine supplementation selectively benefits tasks that tax the prefrontal cortex under conditions of prolonged wakefulness and mild stress, likely due to enhanced energetic support in these brain regions.

In a subsequent double-blind, randomized, placebo-controlled trial, (McMorris et al. (2007) 19 healthy young adults were assigned to either creatine supplementation (20 g/day, provided as four daily doses of 5 g) or placebo for 7 days, followed by a 36-hour period of continuous wakefulness accompanied by intermittent moderate-intensity exercise. Creatine supplementation selectively improved performance only on the central executive random number generation task at the 36-hour time point, where the creatine group's performance significantly surpassed the placebo group’s (p < 0.05), with random number generation index (RNG) scores progressively improving from baseline to 36 hours in the creatine group (p < 0.01). In contrast, creatine supplementation did not significantly affect simpler cognitive tasks such as verbal recall or choice reaction time, nor did it affect dynamic balance, mood states, cognitive effort, or cortisol concentrations. These findings indicate creatine's cognitive benefits appear selective, occurring primarily under prolonged sleep deprivation conditions and specifically on complex executive tasks that heavily engage the prefrontal cortex.

In a randomized, double-blind, placebo-controlled crossover trial (Turner et al., 2015), 15 healthy adults supplemented with creatine (~20 g/day for 7 days) or placebo. Instead of sleep loss, subjects experienced acute hypoxia by breathing a gas mixture containing 10% oxygen for 90 minutes. Main outcomes included cognitive performance, specifically complex attentional capacity, corticomotor excitability assessed by transcranial magnetic stimulation (TMS), and subjective alertness or fatigue. Creatine supplementation significantly preserved cognitive performance during hypoxia, particularly complex attention tasks, and markedly enhanced corticomotor excitability by approximately 70% compared to placebo. Supplementation also effectively increased brain creatine concentrations by an average of 9.2%.

In a randomized, double-blind, placebo-controlled crossover trial (Gordji-Nejad et al., 2024), healthy adults received a single oral high-dose of creatine monohydrate (0.35 g/kg, ~25 g for a 70 kg individual) or placebo during 21 hours of sleep deprivation. Cognitive performance and cerebral energy metabolism were assessed at baseline and at 3.5, 5.5, and 7.5 hours post-supplementation using ^31P-MRS and ^1H-MRS imaging. Creatine supplementation significantly improved cognitive performance, enhancing processing speed by approximately 16–29% and memory by about 10%, while also reducing subjective fatigue by roughly 8%. At a metabolic level, creatine increased cerebral phosphocreatine (PCr) by ~4–6% and total creatine (tCr) by approximately 5%, reduced inorganic phosphate (Pi) by 8–10%, lowered ATP levels by up to 18%, and prevented the sleep deprivation-induced reduction in cerebral pH. These findings suggest a single high-dose creatine supplement effectively counteracts the cognitive and energetic impairments associated with acute sleep deprivation.

Creatine also improved cognitive performance and processing speed.

Note. Reprinted from “Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation”, by Gordji-Nejad et al., 2024, Scientific Reports, 14, p. 4937.

  *Note.* Reprinted from “Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation”, by Gordji-Nejad et al., 2024, *Scientific Reports, 14*, p. 4937.

Taken together, these findings strongly support creatine's selective benefit for cognitive tasks demanding high executive functioning and attentional capacity under conditions of prolonged wakefulness and acute hypoxia. Creatine supplementation appears most beneficial when neural energy supply is compromised, suggesting potential clinical and practical applications for maintaining cognitive performance under stress.

MethodsObjectiveThis scoping review aims to map the existing literature on creatine supplementation in mental health across various psychiatric diagnostic categories, identifying key themes, research gaps, and implications for clinical practice and future research.

FrameworkThis review follows Arksey and O’Malley's methodological framework for scoping reviews, enhanced by the recommendations of the Joanna Briggs Institute (JBI) (Peters et al., 2015). It is reported in accordance with the PRISMA extension for Scoping Reviews (PRISMA-ScR) checklist (Tricco et al., 2018).

Identifying the Research QuestionOur primary research question was: “What is known from the existing literature about the effects and implications of creatine supplementation across different psychiatric diagnostic categories?” In this study, we defined a scoping review as a research method designed to systematically explore the existing literature on a specific topic or field, with the goal of identifying key themes, research gaps, and various types of evidence that can guide practice, policy development, and future research (Munn et al., 2022).

Search StrategyA comprehensive search was conducted in the following databases: PubMed, EMBASE, and Cochrane Library. Search terms included various combinations and synonyms of the following keywords:

• Creatine or creatine supplementation AND mental health, psychiatric disorders, depression, anxiety, schizophrenia, bipolar disorder, cognitive disorders, neurodevelopmental disorders, PTSD, substance use disorders

The search was restricted to peer-reviewed articles published in English, with no limitations on date to ensure comprehensive literature coverage.

Study SelectionStudies were eligible if they met the following inclusion criteria:

• Empirical studies (qualitative, quantitative, mixed methods)
• Human studies across any age group
• Studies specifically assessing creatine supplementation effects on mental health outcomes in any defined psychiatric diagnostic category.

Exclusion criteria included:

• Animal studies
• Non-original research (reviews, editorials, opinion pieces)
• Studies with non-oral creatine administration routes
• Non-English articles

Data ExtractionData were systematically extracted using a standardized extraction template capturing:

• Authors, publication year, and country
• Study design and methodology
• Diagnostic categories studied
• Participant demographics (age, gender, clinical diagnosis, number)
• Details of creatine supplementation (dosage, frequency, duration)
• Outcome measures used
• Summary of primary and secondary mental health outcomes
• Reported adverse effects or safety concerns

Data SynthesisResults were synthesized narratively to identify overarching themes, diagnostic-specific findings, methodological approaches, and gaps in the literature. The data were categorized and summarized according to psychiatric diagnostic groups to facilitate a clear understanding of the current evidence landscape.

ResultsReportingThis scoping review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist (Tricco et al., 2018), ensuring methodological transparency and completeness.

Study Selection ProcessA total of 21,858 records were identified through database searches. After title and abstract screening of each record, 5.682 full-text articles were assessed for eligibility. Ultimately, 15 studies met inclusion criteria and were included in this review.

The study selection process is illustrated in Figure 1 (PRISMA-ScR flow diagram).

**Figure 1.** PRISMA-ScR flow diagram of study selection process.

Characteristics of Included StudiesThe included studies spanned from 2006 to 2025, covering diverse psychiatric populations including depression, bipolar disorder, PTSD, schizophrenia, and substance use disorders. Most studies (n = 15) were randomized controlled trials, with additional open-label studies, pilot trials, and case reports.

Table 1 presents detailed characteristics of each study, including study design, sample size, diagnosis, creatine dosage, duration, and mental health outcomes assessed.

Table 1. Summary of Included Studies Evaluating Creatine Supplementation Across Psychiatric Disorders (n = 15)

      **Narrative Synthesis by Diagnostic Categories**Mood Disorders (Depression, Bipolar Disorder)The majority of studies focused on depressive disorders, with creatine supplementation often evaluated as an adjunct to SSRIs, CBT, or other psychotherapies. Doses ranged from 3–10g/day, with durations of 4 to 8 weeks. Several studies reported statistically significant improvements in depression severity, though some findings were limited by small sample sizes and short durations (Sherpa et al., 2025; Lyoo et al., 2012).

Adjunctive Creatine Boosts CBT Effectiveness in Depression Treatment (Sherpa et al., 2025)In this double-blind, randomized, placebo-controlled feasibility trial, researchers investigated the effects of oral creatine monohydrate supplementation as an adjunct to cognitive behavioral therapy (CBT). 100 adults with major depressive disorder (MDD) received biweekly CBT with either 5g/day of creatine or placebo for 8 weeks. The creatine group saw a greater reduction in PHQ-9 scores, with an adjusted mean difference of −5.12 (95% CI: −7.20 to −3.52; p < 0.05). Practically, this means that, by adding creatine to CBT, several symptoms like “little interest or pleasure in doing things” would go from “more than half the days” to “several days” in a two week period. Of note, the creatine group was also found to have lower treatment discontinuation rates and no significant increase in adverse events when compared to placebo. However, diarrhea (15 vs. 6 reports) and abdominal pain (9 vs. 1 reports) were more frequently reported in the creatine group, while vomiting (2 vs. 9 reports) and pruritus (4 vs. 11 reports) were more common in the placebo group. These findings support creatine’s safety and tolerability. This study was done on a mixed-gender population (50% female; mean age ~30 years old), and is one of the few on creatine supplementation in a lower-resourced clinical setting. Below are some of the data from this study as mentioned above.

*Note.* Reprinted from “Efficacy and safety profile of oral creatine monohydrate in add-on to cognitive-behavioural therapy in depression: An 8-week pilot, double-blind, randomised, placebo-controlled feasibility and exploratory trial in an under-resourced area”, by Sherpa et al., 2025, *European Neuropsychopharmacology*, *90*, p. 32.

Creatine Augmentation Enhances Antidepressant Efficacy in Women with Depression (Lyoo et al., 2012)This 8-week double-blind, placebo-controlled RCT recruited 52 women with MDD. Participants received escitalopram in addition to either creatine or placebo. The dosage of creatine started at 3g/day for week 1, going up to 5g/day from weeks 2-8. Four weeks into the study, mean Hamilton Depression Rating Scale (HAM-D) scores dropped 21.8% more in the creatine group versus the placebo group. By week 8, mean HAM-D scores had decreased from 26.9 to 5.4 in the creatine group, versus 26.7 to 9.8 in the placebo group (p < 0.001) Researchers reported an effect size of Cohen’s d = 1.13 for the difference in HAM-D score reduction from baseline to the end of the study (8 weeks). By week 8, significantly more participants in the creatine group achieved remission compared to placebo (52.0% vs. 25.9%; p = 0.008).

*Note.* Reprinted from “A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder”, by Lyoo et al., 2012, *The American journal of psychiatry*, *169*(9), p. 941.

Creatine Shows Higher Remission Rates for Bipolar Depression Despite Mixed Results on Symptom Reduction (Toniolo et al., 2018)In this randomized, double-blind, placebo-controlled trial, Toniolo et al. (2018) investigated the efficacy of creatine monohydrate (6g/day) as an adjunctive treatment for patients with bipolar disorder type I or II experiencing a depressive episode. Over the course of 6 weeks, patients either received 6g/day of creatine or placebo. Efficacy was primarily measured using the Montgomery–Åsberg Depression Rating Scale (MADRS) scores. While a statistically significant difference in score reduction was not found between the groups (p = 0.560; Cohen’s d = 0.231), the creatine group did see a significantly greater rate of remission (defined as MADRS score ≤ 12). On ITT analysis, the creatine group saw a remission rate of 52.9% versus the placebo group’s rate of 11.1% (p = 0.012, OR = 9.0). Of note, one patient from the creatine group experienced a hypomanic switch, and another had a manic switch.

*Note.* Reprinted from “A randomized, double-blind, placebo-controlled, proof-of-concept trial of creatine monohydrate as adjunctive treatment for bipolar depression”, by Toniolo et al., 2018, *Journal of Neural Transmission, 125,* p. 253.

Creatine Improves Depression Symptoms and Boosts Brain Energy Metabolism in SSRI-Resistant Adolescents (Kondo et al., 2011)In this open-label pilot study by Kondo et al. (2011), five female adolescents (ages 14-18) with SSRI-resistant major depressive disorder (MDD) received adjunctive treatment of creatine monohydrate at 4g/day for 8 weeks. All participants continued their stable fluoxetine treatment throughout the study. Depression severity was measured using the Children’s Depression Rating Scale–Revised (CDRS-R), which saw mean scores drop from 69.0 at baseline to 30.6 by the end of the study (56% decline). The study also utilized 31-phosphorus magnetic resonance spectroscopy (31P-MRS) to measure brain phosphocreatine levels, which showed a significant increase of 6.4% in the frontal lobe of participants when compared to scans of healthy female adolescents (p = 0.02). This study was among the first to report measurable increases in brain PCr associated with creatine supplementation in a psychiatric population. However, its small sample size and lack of a placebo control limit broader generalizability.

Creatine Supplementation Shows Rapid Antidepressant Effects but Potential Risk of Manic Switch in Bipolar Disorder (Roitman et al., 2007)This was a 4-week open-label trial of oral creatine monohydrate (titrated from 3g to 5g/day) supplementation in 8 patients with unipolar depression and 2 with bipolar depression. Of the ten participants, one significantly improved after the first week and withdrew, and the two patients with bipolar disorder experienced manic/hypomanic switches, also withdrawing early; therefore, statistical analyses included only the seven remaining unipolar participants who completed at least three weeks. Participants showed significant improvement across multiple scales, with mean HAM-D dropping from 23.14 to 12.57 (p = 0.002), mean Clinical Global Impression (CGI) scores dropping from 4.43 to 3.00 (p = 0.02), and mean Hamilton Anxiety Scale (HAS) scores dropping from 18.71 to 12.00 (p = 0.016).

Creatine Reduces Depression and Methamphetamine Use While Increasing Brain Energy in Females with Dual Diagnosis (Hellem et al., 2015)In this open-label pilot study, 14 women with Major Depressive Disorder and active methamphetamine use were given 5g/day creatine monohydrate over the course of 8 weeks. Eleven participants (78.6%) completed the trial, experiencing significant reductions in mean HAM-D scores from 16.86 at baseline to 7.36 by week 8 (56.4% decrease). Participants also underwent 31-Phosphorus-magnetic resonance spectroscopy, which showed an increase in mean frontal lobe PCr from 0.223 to 0.233 (p < 0.01, Cohen’s d = 0.92). Additionally, significant reductions in anxiety (Beck Anxiety Inventory scores) were seen as early as week 2 and sustained through study completion. Methamphetamine use also decreased by over 50% by week 6, as measured by urine drug screens. This was the first study to show the potential effectiveness of creatine in a dual-diagnosis population.

Creatine Monohydrate Increases Brain Phosphocreatine and Correlates with Improved Depression Symptoms in SSRI-Resistant Adolescent Females (Kondo et al., 2016)This randomized, placebo-controlled, dose-ranging study recruited 34 adolescent females aged 13-20 years with SSRI-resistant depression, assigning each to 2g, 4g, or 10g/day of either creatine or placebo for 8 weeks. In contrast to the studies discussed above, depression scores (CDRS-R scores, in this study) were the secondary outcome in this study. The primary outcome was frontal lobe phosphocreatine as measured on 31P-MRS. The mean frontal lobe PCr increased by 4.6%, 4.1%, and 9.1% in the 2g, 4g, and 10g groups respectively, while the placebo group showed a decrease of 0.7%. However, these differences did not reach statistical significance between groups (p = 0.69), and the study may have been underpowered to detect statistically significant differences. While researchers did not find a statistically significant between-group difference in CDRS-R score reduction, regression analysis did reveal an inverse correlation between frontal lobe PCr and depression scores (p = 0.02). Creatine supplementation was generally well-tolerated, with no significant differences in adverse effects, weight gain, or renal function between groups.

*Note.* Reprinted from “Creatine target engagement with brain bioenergetics: a dose-ranging phosphorus-31 magnetic resonance spectroscopy study of adolescent females with SSRI-resistant depression”, by Kondo et al., 2016, *Amino Acids, 48*, p. 1948.

Creatine Augmentation Shows No Significant Benefit for SSRI-Resistant Depression but May Induce Rapid Improvement in Select Female Patients (Nemets & Levine, 2013)This 4-week, randomized, double-blind, placebo-controlled, dose-finding trial investigated oral creatine as an add-on to ongoing antidepressant treatment in 18 adults with MDD refractory to SSRIs, SNRIs, or NASA antidepressants (e.g. citalopram, venlafaxine, mirtazapine). Participants were divided into 4 groups, receiving either creatine or placebo of up to 5g/day or 10g/day. Mean HAM-D scores were measured, which saw a decrease in all who received creatine from 27.6 to 13.4 (versus 28.2 to 15.3 in the placebo group); however, these findings were not statistically significant (p = 0.4). Researchers also find no dose effect.

*Note.* Reprinted from “A pilot dose-finding clinical trial of creatine monohydrate augmentation to SSRIs/SNRIs/NASA antidepressant treatment in major depression”, by Nemets & Levine, 2013, *International clinical psychopharmacology, 28*(3), pp. 127-133.

Creatine Supplementation Enhances Brain Metabolism, Rich-Club Networks, and Depression Outcomes in Women with MDD (Yoon et al., 2016)This study was an extension of the Lyoo et al. (2012) RCT discussed above. Researchers studied the effects of 5g/day of oral creatine in women with MDD who were undergoing treatment with escitalopram. Of the 52 participants, 34 agreed to additionally undergo pre- and post-treatment neuroimaging via ¹H-MRS and diffusion tensor imaging (DTI). Metabolic and network outcomes were measured for changes in prefrontal N-acetylaspartate, a marker of neuronal viability and mitochondrial function. Participants in the creatine group saw significant increase in NAA versus the placebo group (p = 0.01, Cohen’s d = 0.73) and versus healthy controls (p = 0.03, Cohen’s d = 0.66). “Rich-club” networks (sets of highly connected brain regions associated with efficient global communication, reported to expend large amounts of metabolic energy, thus rendering them vulnerable to altered bioenergetics) were also measured, showing a significant increase in the creatine group versus placebo group and healthy controls (p = 0.01, Cohen’s d = 0.79; p = 0.03, Cohen’s d = 0.64). All of these findings on neuroimaging correlated with greater improvements in depressive symptoms.

*Note.* Reprinted from “ Effects of creatine monohydrate augmentation on brain metabolic and network outcome measures in women with major depressive disorder.”, by Yoon et al., 2016, *Biological Psychiatry, 80*(6), pp. 439–447.

  *Note.* Reprinted from “ Effects of creatine monohydrate augmentation on brain metabolic and network outcome measures in women with major depressive disorder.”, by Yoon et al., 2016, *Biological Psychiatry, 80*(6), pp. 439–447.

Creatine and 5-HTP Combination Significantly Improves Depression in SSRI/SNRI-Resistant MDD (Kious et al., 2017)This was an open-label, 8-week pilot study investigating the effects of creatine monohydrate in conjunction with 5-hydroxytryptophan as adjunctive treatment in 15 women with SSRI/SNRI-resistant MDD. Participants received 5/g day of oral creatine monohydrate and 100 mg twice daily of 5-HTP. Depression severity was measured using HAM-D, showing significant improvement with mean scores dropping from 18.9 at baseline to 7.5 by the conclusion of the study (p < 0.00001).

*Note.* Reprinted from “An open-label pilot study of combined augmentation with creatine monohydrate and 5-hydroxytryptophan for selective serotonin reuptake inhibitor–or serotonin-norepinephrine reuptake inhibitor–resistant depression in adult women”, by Kious et al., 2017, *Journal of clinical psychopharmacology, 37*(5), pp.578-583.

Creatine Improves Verbal Fluency but Not Mood Symptoms in Bipolar Depression (Toniolo et al., 2017)This 6-week, randomized, double-blind, placebo-controlled trial investigated the effects of 6g/day of creatine monohydrate on mood symptoms and cognitive performance in 18 participants (ages 18-59) with bipolar depression. Patients received either creatine or placebo across the 6 weeks, in addition to their prior established mood-stabilizing regimens. MADRS and HAM-D scores were measured at baseline and at the end of the study, with no statistically significant differences between treatment groups (p = 0.496). However, there was a significant improvement in the FAS verbal fluency test for the creatine group (p = 0.017, Cohen’s d = 1.252). Other neuropsychological tests were also administered, including the Wisconsin Card Sorting Test (assesses cognitive flexibility and problem-solving) and the Stroop test (measures attention and inhibitory control), both of which did not show statistically significant differences between groups.

Creatine Improves Mood, Pain, and Quality of Life in Treatment-Resistant Depression (Amital et al., 2006b)This case report studied the effects of oral creatine monohydrate supplementation in a 52-year-old woman with treatment-resistant depression, PTSD, and fibromyalgia. The patient received 3g/day of creatine in week 1, increasing to 5g/day for weeks 2 through 4. Additionally, she continued to receive her ongoing pharmacotherapy with citalopram. Throughout the study, her HAM-D score dropped from 24 to 16 (33% decrease). Her pain severity was also measured using the Visual Analog Scale (VAS), which saw a decline from 80 to 40. The Short Form 36 Health Status Questionnaire (SF-36) was used to measure her quality of life, and her score increased by 30% throughout the study. Of note, the patient noted improved sleep and cognitive functioning, and requested to continue creatine supplementation after the conclusion of the study.

Creatine Supplementation Shows Modest Benefits for Anxiety Symptoms as Secondary OutcomeFew studies directly assessed anxiety outcomes. Where measured, anxiety symptoms tended to improve in parallel with depression, but no studies focused on anxiety as a primary endpoint. For example, in studies primarily focused on depression or PTSD, anxiety symptoms were assessed as secondary outcomes using instruments like the Hamilton Anxiety Rating Scale (HAM-A) or Beck Anxiety Inventory (BAI), with modest improvements reported (Amital et al., 2006a; Kious et al., 2017).

Creatine Supplementation Yields Inconsistent Results for Schizophrenia TreatmentTwo studies evaluated creatine supplementation in individuals with schizophrenia. One RCT (Kaptsan et al., 2007) found no significant benefits, while an open-label study (Levental et al., 2015) showed potential improvement in schizophrenia symptoms with high-dose creatine. After 6 months of daily creatine supplementation, PANSS (Positive and Negative Syndrome Scale) scores and PANSS general subscale scores showed significant reduction from 92.6 to 87.4 (-5.2) and 46.9 to 43.9 (-3.0), respectively (p = 0.004 and p = 0.021, respectively).

Creatine Supplementation Does Not Improve Schizophrenia Symptoms in Double-Blind, Placebo-Controlled Trial (Kaptsan et al., 2007)This was a randomized, double-blind, placebo-controlled, crossover study on the effects of oral creatine monohydrate on 12 patients diagnosed with schizophrenia. Patients received either creatine (3g/day for the first month, 5g/day for the following two months) or placebo for 3 months at a time, after which they would switch to the alternative treatment for another 3 months. There were several outcomes measured, including the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions (CGI) scale, and Abnormal Involuntary Movement Scale (AIMS). There were no statistically significant differences found between creatine and placebo for any of these scales. Creatine supplementation was well tolerated, with the main side effect noted being nausea in two of the patients.

High-Dose Creatine Improves Negative Symptoms and Ward Behavior in Treatment-Resistant Schizophrenia (Levental et al., 2015)This was a 6-month, open-label, pilot study investigating high-dose creatine monohydrate augmentation in 7 male patients (age 35-55) with schizophrenia and treatment-resistant negative symptoms. Creatine dosing was titrated starting at 3g/day (weeks 1–2), 5g/day (weeks 3–4), 7g/day (weeks 5–6), and finally 10g/day (week 7 onward). Several outcomes were measured across the study, including the Positive and Negative Symptoms Scale (PANSS), Clinical Global Impressions (CGI), Nurse Observation Scale for Inpatient Evaluation (NOSIE; a sensitive rating scale for ward behavior), Extrapyramidal Symptom Rating Scale (ESRS, designed to rate the severity of four types of drug-induced movement disorders), and the Mindstreams computerized cognitive battery (a validated computerized neuropsychological test battery assessing memory, attention, executive function, and processing speed). Researchers found a significant change in mean total PANSS scores with creatine augmentation (p = 0.004); however, it was noted that this may have limited clinical value due to there only being mild improvement in the mean general psychopathology PANSS subscale scores (46.9 at baseline to 43.9 by the end of month 6, p = 0.021). Mean total NOSIE scores also saw a significant improvement (108.6 to 134.3, p = 0.043), particularly in personal neatness (p = 0.038), psychomotor retardation (p = 0.043), and social competence (p = 0.023).

*Note.* Reprinted from “ A pilot open study of long term high dose creatine augmentation in patients with treatment resistant negative symptoms schizophrenia”, by Levental et al., 2015, *Israel Journal of Psychiatry, 52*(1). p. 9.

Creatine Improves PTSD Symptoms and Quality of Life in Small Clinical StudiesTwo studies examined PTSD: an open-label trial and a case study (Amital et al., 2006a & 2006b), both of which reported symptom improvement when creatine was added to ongoing treatment. In the open-label trial (Amital et al., 2006a), total CAPS (Clinician Administered PTSD Scale) scores saw an average 5.8 point reduction (p = 0.003). The case study was focused on a patient with comorbid PTSD, depression, and fibromyalgia (Amital et al., 2006b). While there was no formal PTSD symptom scale used in the study, there was a 30% improvement in overall quality of life as measured by the SF-36 Health Status Questionnaire, particularly in domains related to vitality, social functioning, and mental health.

Creatine Supplementation Reduces PTSD and Depressive Symptoms in Open-Label Trial (Amital et al., 2006a)This was a 4 week, open-label pilot study investigating the effects of oral creatine monohydrate in 10 patients (8 men, 2 women; ages 43-61) diagnosed with PTSD. Creatine dosing was 3g/day for week 1 and 5g/day for weeks 2 through 4 (in addition to ongoing psychiatric treatment). The Clinician Administered PTSD Scale (CAPS) was used to assess PTSD severity, and total scores dropped from 75.6 at baseline to 69.8 at the end of week 4 (p = 0.003). Depressive symptoms were also measured using the HAM-D scale, with scores also dropping from 24.1 to 20.4 (p = 0.006).

Creatine Supplementation Reduces Depression and Increases Brain Energy but Not Methamphetamine Use in Substance Use Disorder One pilot study discussed above (Hellem et al., 2015) evaluated creatine as an adjunctive treatment in females with methamphetamine dependence and comorbid depression. While methamphetamine use was monitored via urine drug screen and self-reports, there were no significant reductions in use throughout the study. Researchers did find a significant reduction in depressive symptoms, with mean HAM-D scores dropping from 16.9 to 7.36. Brain phosphocreatine levels were also measured during the study via phosphorus magnetic resonance spectroscopy, with levels significantly increasing from 0.223 to 0.233 (p < 0.01). This suggests increased brain energy metabolism associated with creatine supplementation.

Cognitive and Neurodevelopmental Disorders (e.g., Autism, ADHD)No RCTs were found in ADHD or learning disorders.

Summary Of Outcomes And ThemesAmong all psychiatric diagnoses reviewed, creatine supplementation demonstrated the greatest benefit in reducing depressive symptoms, particularly when used as an adjunctive treatment alongside established antidepressant medications or psychotherapies. Cognitive outcomes were less consistently measured but showed significant improvements in specific cognitive domains, notably verbal fluency, processing speed, and attentional capacity in selected studies. Across the reviewed literature, study designs, sample sizes, and creatine dosages varied considerably (ranging from 3g/day to 10g/day). Given previous studies reviewed on sleep deprivation, hypoxia, and animal models, it appears that many studies included in this review may have utilized suboptimal dosing strategies. Higher creatine doses—approximately 20 grams/day used in human studies involving sleep and oxygen deprivation, and doses proportionally higher in animal models—suggest potential underdosing in several psychiatric studies, which could partly explain mixed findings and modest effect sizes.

Common methodological limitations throughout included small sample sizes, short trial durations, open-label designs, absence of placebo controls in some studies, and limited diversity in patient populations. Adverse effects were generally minimal and infrequent; however, two studies involving bipolar patients (Roitman et al., 2007; Toniolo et al., 2018) reported cases of manic or hypomanic switches, highlighting the need for cautious monitoring in bipolar populations.

The bulk of available evidence focuses on depressive disorders, resulting in substantial research gaps in other psychiatric conditions, including anxiety disorders, PTSD, schizophrenia, substance use disorders, and neurodevelopmental disorders such as ADHD and autism. Future studies should aim to address these gaps through rigorous randomized controlled trials with adequately powered sample sizes, appropriate placebo controls, diverse patient populations, longer treatment durations, and consideration of higher-dose creatine supplementation strategies supported by prior literature.

DiscussionOverview of Included StudiesThis scoping review analyzed 15 different studies across 5 diagnostic categories, with mood disorders seeing the greatest representation (10 articles primarily studying MDD, 2 articles focused on bipolar disorder). Several of the studies investigated patient populations with multiple diagnoses (e.g. MDD and SUD). Of note, there were no studies found focusing on creatine supplementation in anxiety disorders. The majority of the studies utilized creatine as an adjunct therapy alongside ongoing psychiatric treatments (e.g. CBT, SSRIs, etc.). Creatine dosage ranged from 3-10g/day, with most studies titrating up from a lower initial dose. Across the mood disorder studies, creatine consistently improved depressive symptoms, with multiple studies reporting statistically significant reductions in mean PHQ-9, HAM-D, and MADRS scores. Neuroimaging outcomes were also measured in 3 studies (via 31P-MRS or 1H-MRS), which saw increased PCr and NAA levels when measuring after creatine supplementation.

Interpretation and Clinical ImplicationsCreatine’s potential role in psychiatry is supported by biological rationale grounded in its function as a cellular energy buffer. It facilitates rapid regeneration of ATP via the PCr system. Regions of the brain that have high metabolic activity, such as the prefrontal cortex and hippocampus, rely on this mechanism in order to regulate emotion and cognition. Studies have shown creatine also having the ability to enhance gamma-band oscillations, support astrocyte-neuron energy transfer, and stabilize mitochondrial function—all of which contribute to maintaining neural efficiency and resilience under stress (Chen & Zhang, 2021). This aligns with the bioenergetic framework proposed by Fabiano and Stubbs (2025), who argue that depression involves mitochondrial dysfunction and ATP instability under chronic stress, and that creatine may restore energetic balance and promote neuroplasticity.

Clinically, creatine has shown promise as an adjunctive treatment across various psychiatric populations, particularly in unipolar and bipolar depression, where it has been associated with reductions in symptom severity and improvements in cognitive domains such as verbal fluency. Given prior evidence from human studies involving sleep and oxygen deprivation (using doses around 20 g/day), as well as animal studies employing significantly higher doses, many of the reviewed psychiatric studies may have used suboptimal creatine dosing, potentially underestimating its therapeutic efficacy. Its strong safety profile—supported by consistent tolerability across studies with doses ranging from 3g to 10g/day—makes it an appealing low-risk intervention, especially in low-resource or integrative care settings. While no serious adverse events were reported in the studies reviewed, isolated cases of manic switching in bipolar participants underscore the need for monitoring and further investigation in this population. Overall, the convergence of clinical, cognitive, and neurobiological data suggests that creatine holds meaningful therapeutic potential and warrants further study as a complementary psychiatric intervention.

Strengths and Limitations of This Scoping ReviewThis scoping review adhered to pre-specified protocol as specified by the Arksey and O’Malley framework and PRISMA-ScR checklist. Our search strategy applied comprehensive coverage by searching for studies from five different databases (PubMED, EMBASE, Cochrane Library, PsycINFO, and Web of Science), with manual reference list screening, citation tracking and keyword refinement across multiple diagnostic categories. Our inclusion criteria were clearly defined, with relevance screening occurring subsequently. Data extraction methods were standardized, focusing on detailed information on study design, dosing, outcomes, and effect sizes. Additional synthesis was done by diagnostic group and outcome domain (e.g. neuroimaging, cognition). This review is among the first to systematically explore studies investigating creatine as a supplement to psychiatric disorders. To our knowledge, this is one of the first reviews to systematically examine the use of creatine supplementation across psychiatric disorders, and the most comprehensive.

Despite our broad inclusion criteria, our review focused only on oral creatine monohydrate supplementation in human studies. Excluding animal research/studies, or IV/topical creatine administration may have caused us to miss out on potentially informative outcomes. The variety of the studies reviewed (sample size, outcome measures, duration, etc.) limited our ability to synthesize findings quantitatively or conduct formal comparisons between studies. Most of the studies had small sample sizes and were open-label designs, both of which increase risk of bias and decrease generalizability. Limiting our search to English-language studies may have prevented us from incorporating relevant research published in other languages or in gray literature. While screening and data were conducted systematically, interpretation of findings was partially subject to reviewer judgment.

RecommendationsFuture research on creatine supplementation in psychiatric populations should implement larger, multicenter randomized controlled trials to robustly confirm efficacy across diverse diagnostic groups. Future studies should explicitly investigate anxiety disorders and psychotic disorders, given the notable scarcity of research in these areas. Optimal creatine dosing (including higher doses such as 10g to 20g/day) and longer treatment durations (e.g., 10–12 weeks or longer) should be systematically explored to identify the most effective supplementation protocols. Objective biomarkers (e.g., 31P-MRS, cognitive batteries) should continue to be incorporated to elucidate the biological mechanisms underlying treatment response. Long-term safety data would be invaluable, especially for patient subgroups at higher risk of adverse outcomes (e.g., manic switching in bipolar disorder).

While creatine’s mood-related effects have been more widely studied, its potential to enhance cognitive performance under stress remains an important area for future investigation. Preliminary studies suggest that creatine may selectively improve executive function in energy-demanding conditions such as sleep deprivation and oxygen deprivation (McMorris et al., 2007; Turner et al., 2015). These effects appear to be task-dependent, with benefits most pronounced for prefrontal-mediated functions like attention and working memory, rather than simpler recall tasks (McMorris et al., 2007). This specificity points to the value of studying creatine in psychiatric and neurologic populations that experience cognitive slowing, attentional deficits, or neuroenergetic dysfunction. Future trials should incorporate standardized cognitive testing and, where feasible, neuroimaging modalities such as ³¹P-MRS to evaluate whether cognitive benefits correspond with changes in brain energy metabolism (Gordji-Nejad et al., 2024).

ConclusionThis comprehensive scoping review highlights creatine monohydrate as a promising adjunctive therapeutic intervention for various psychiatric conditions, particularly demonstrating robust efficacy in mood disorders such as unipolar and bipolar depression. Creatine supplementation consistently improved depressive symptoms, enhanced cognitive function, and supported critical neuroenergetic processes, including elevated brain phosphocreatine and neuronal viability. Notably, studies employing rigorous methodologies, such as randomized controlled trials with neuroimaging biomarkers, reinforce the validity of these findings.

Despite its demonstrated potential, current studies often employ lower dosages (3–10g/day) than those proven effective in neurophysiologically demanding conditions such as sleep deprivation and hypoxia, or in animal models where higher dosages yielded greater therapeutic benefits. Human neuroimaging studies have shown that creatine doses between 2–5g/day typically produce modest brain phosphocreatine increases of approximately 4–6%, while higher doses of around 10g/day for 8 weeks or 20g/day for 7 days have resulted in more substantial elevations (approximately 9–10%) in brain creatine concentrations, correlating with enhanced cognitive function and reduced fatigue. Therefore, future research should rigorously investigate higher-dose regimens and extended supplementation durations to optimize therapeutic outcomes. Additionally, expanding the scope to address under-examined psychiatric disorders—particularly anxiety disorders and psychosis—could uncover broader clinical applications for creatine.

Creatine’s strong safety and tolerability profile, combined with its accessibility and low cost, position it uniquely as an attractive adjunctive treatment, especially relevant in resource-limited settings. Nevertheless, vigilance regarding potential adverse effects, such as manic switching in vulnerable bipolar populations, remains crucial.

Importantly, creatine supplementation represents just one piece of a broader strategy aimed at improving metabolic function. Future research should prioritize exploring combinations of interventions, such as integrating creatine with structured exercise programs, sauna, dietary interventions including ketogenic diets, and other metabolic-enhancing therapies. Given the substantial evidence supporting exercise's role in enhancing cognitive health, promoting neurogenesis, and reducing inflammation, (Episode 165) future studies should particularly emphasize combining creatine supplementation with structured exercise programs to optimize cognitive and psychiatric outcomes. Such integrative approaches could potentially yield more comprehensive improvements in psychiatric and cognitive outcomes.

In summary, the existing evidence compellingly supports creatine monohydrate’s role as a viable adjunctive treatment capable of significantly enhancing mood, cognitive performance, and neurobiological resilience across psychiatric populations. To fully capitalize on creatine's therapeutic potential, forthcoming research must prioritize robust, adequately powered clinical trials exploring optimized dosing strategies, long-term outcomes, integrative metabolic therapies, and broader psychiatric applications. Consequently, clinicians and researchers alike should consider creatine supplementation not merely as an experimental option, but as a scientifically substantiated intervention poised to substantially augment existing psychiatric treatment paradigms.

References:Adhihetty, P. J., & Beal, M. F. (2008). Creatine and its potential therapeutic value for targeting cellular energy impairment in neurodegenerative diseases. Neuromolecular medicine, 10(4), 275–290. https://doi.org/10.1007/s12017-008-8053-y

Ahn, N., Leem, Y. H., Kato, M., & Chang, H. (2016). Effects of creatine monohydrate supplementation and exercise on depression-like behaviors and raphe 5-HT neurons in mice. Journal of Exercise Nutrition & Biochemistry, 20(3), 24–31. https://doi.org/10.20463/jenb.2016.09.20.3.4

Amital, D., Vishne, T., Roitman, S., Kotler, M., & Levine, J. (2006a). Open Study of Creatine Monohydrate in Treatment-Resistant Posttraumatic Stress Disorder. The Journal of Clinical Psychiatry, 67(5), 836–837. https://doi.org/10.4088/jcp.v67n0521c

Amital, D., Vishne, T., Rubinow, A., & Levine, J. (2006b). Observed effects of creatine monohydrate in a patient with depression and fibromyalgia. American Journal of Psychiatry, 163(10), 1840-1841. https://doi.org/10.1176/ajp.2006.163.10.1840b​

Arksey, H., & O'Malley, L. (2005). Scoping Studies: Towards a Methodological Framework. International Journal of Social Research Methodology: Theory & Practice, 8(1), 19–32. https://doi.org/10.1080/1364557032000119616

Attwell, D., & Laughlin, S. B. (2001). An energy budget for signaling in the grey matter of the brain. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 21(10), 1133–1145. https://doi.org/10.1097/00004647-200110000-00001

Avgerinos, K. I., Spyrou, N., Bougioukas, K. I., & Kapogiannis, D. (2018). Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. Experimental gerontology, 108, 166-173. https://doi.org/10.1016/j.exger.2018.04.013

Chen, Y., & Zhang, J. (2021). How energy supports our brain to yield consciousness: Insights from neuroimaging based on the neuroenergetics hypothesis. Frontiers in Systems Neuroscience, 15, 648860. https://doi.org/10.3389/fnsys.2021.648860

Dedeoglu, A., Kubilus, J. K., Yang, L., Ferrante, K. L., Hersch, S. M., Beal, M. F., & Ferrante, A. R. J. (2003). Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice. Journal of Neurochemistry, 85(6), 1359–1367. https://doi.org/10.1046/j.1471-4159.2003.01706.x

Fabiano, N., & Stubbs, B. (2025). Creatine as a treatment for depression: A brain bioenergetics perspective. European Neuropsychopharmacology, 96, 3-4. https://doi.org/10.1016/j.euroneuro.2025.03.014

Faulkner, P., Paioni, S. L., Kozhuharova, P., Orlov, N., Lythgoe, D. J., Daniju, Y., Morgenroth, E., Barker, H., & Allen, P. (2021). Relationship between depression, prefrontal creatine and grey matter volume. Journal of Psychopharmacology, 35(12), 1464–1472. https://doi.org/10.1177/02698811211050550

Forbes, S. C., Cordingley, D. M., Cornish, S. M., Gualano, B., Roschel, H., Ostojic, S. M., Rawson, E. S., Roy, B. D., Prokopidis, K., Giannos, P., & Candow, D. G. (2022). Effects of Creatine Supplementation on Brain Function and Health. Nutrients, 14(5), 921. https://doi.org/10.3390/nu14050921

Gordji-Nejad, A., Matusch, A., Kleedörfer, S., Patel, H. J., Drzezga, A., Elmenhorst, D., Binkofski, F., & Bauer, A. (2024). Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. Scientific Reports, 14, 4937. https://doi.org/10.1038/s41598-024-54249-9

Hellem, T. L., Sung, Y.-H., Shi, X.-F., Pett, M. A., Latendresse, G., Morgan, J., Huber, R. S., Kuykendall, D., Lundberg, K. J., & Renshaw, P. F. (2015). A pilot study of creatine as a novel treatment for depression in methamphetamine using females. Journal of Dual Diagnosis, 11(3–4), 189–195. https://doi.org/10.1080/15504263.2015.1100471

Hoskins, M., Pearce, J., Bethell, A., Dankova, L., Barbui, C., Tol, W. A., van Ommeren, M., de Jong, J., Seedat, S., Chen, H., & Bisson, J. I. (2015). Pharmacotherapy for post-traumatic stress disorder: systematic review and meta-analysis. The British journal of psychiatry : the journal of mental science, 206(2), 93–100. https://doi.org/10.1192/bjp.bp.114.148551

Howes, O. D., Thase, M. E., & Pillinger, T. (2022). Treatment resistance in psychiatry: state of the art and new directions. Molecular Psychiatry, 27(1), 58-72. https://doi.org/10.1038/s41380-021-01200-3

Joo, P., Lee, H., Wang, S., Kim, S., & Hudetz, A. G. (2021). Network Model With Reduced Metabolic Rate Predicts Spatial Synchrony of Neuronal Activity. Frontiers in computational neuroscience, 15, 738362. https://doi.org/10.3389/fncom.2021.738362

Juneja, K., Bhuchakra, H. P., Sadhukhan, S., Mehta, I., Niharika, A., Thareja, S., Nimmakayala, T., & Sahu, S. (2024). Creatine Supplementation in Depression: A Review of Mechanisms, Efficacy, Clinical Outcomes, and Future Directions. Cureus, 16(10), e71638. https://doi.org/10.7759/cureus.71638

Kaptsan, A., Odessky, A., Osher, Y., & Levine, J. (2007). Lack of efficacy of 5 grams daily of creatine in schizophrenia: a randomized, double-blind, placebo-controlled trial. Journal of Clinical Psychiatry, 68(6), 881-884. https://doi.org/10.4088/jcp.v68n0609

Kious, B. M., Sabic, H., Sung, Y. H., Kondo, D. G., & Renshaw, P. (2017). An open-label pilot study of combined augmentation with creatine monohydrate and 5-hydroxytryptophan for selective serotonin reuptake inhibitor–or serotonin-norepinephrine reuptake inhibitor–resistant depression in adult women. Journal of clinical psychopharmacology, 37(5), 578-583. https://doi.org/10.1097/JCP.0000000000000754

Kondo, D. G., Sung, Y. H., Hellem, T. L., Fiedler, K. K., Shi, X., Jeong, E. K., & Renshaw, P. F. (2011). Open-label adjunctive creatine for female adolescents with SSRI-resistant major depressive disorder: a 31-phosphorus magnetic resonance spectroscopy study. Journal of affective disorders, 135(1-3), 354-361. https://doi.org/10.1016/j.jad.2011.07.010

Kondo, D. G., Forrest, L. N., Shi, X., Sung, Y. H., Hellem, T. L., Huber, R. S., & Renshaw, P. F. (2016). Creatine target engagement with brain bioenergetics: a dose-ranging phosphorus-31 magnetic resonance spectroscopy study of adolescent females with SSRI-resistant depression. Amino Acids, 48, 1941-1954. https://doi.org/10.1007/s00726-016-2194-3

Krahe, R., & Gabbiani, F. (2004). Burst firing in sensory systems. Nature Reviews Neuroscience, 5(1), 13–23. https://doi.org/10.1038/nrn1296

Leichsenring, F., Steinert, C., Rabung, S., & Ioannidis, J. P. A. (2022). The efficacy of psychotherapies and pharmacotherapies for mental disorders in adults: an umbrella review and meta-analytic evaluation of recent meta-analyses. World psychiatry : official journal of the World Psychiatric Association (WPA), 21(1), 133–145. https://doi.org/10.1002/wps.20941

Levental, U., Bersudsky, Y., Dwalatzky, T., Lerner, V., Medina, S., & Levine, J. (2015). A pilot open study of long term high dose creatine augmentation in patients with treatment resistant negative symptoms schizophrenia. Israel Journal of Psychiatry, 52(1), 6. https://pubmed.ncbi.nlm.nih.gov/25841104/

Lyoo, I. K., Yoon, S., Kim, T. S., Hwang, J., Kim, J. E., Won, W., Bae, S., & Renshaw, P. F. (2012). A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder. The American journal of psychiatry, 169(9), 937–945. https://doi.org/10.1176/appi.ajp.2012.12010009

Mason, S. (2017). Lactate shuttles in neuroenergetics—Homeostasis, allostasis and beyond. Frontiers in Neuroscience, 11, 43. https://doi.org/10.3389/fnins.2017.00043

McMorris, T., Harris, R. C., Swain, J., Corbett, J., Collard, K., Dyson, R. J., Dye, L., Hodgson, C., & Draper, N. (2006). Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. Psychopharmacology, 185(1), 93–103. https://doi.org/10.1007/s00213-005-0269-z

McMorris, T., Harris, R. C., Howard, A. N., Langridge, G., Hall, B., Corbett, J., Dicks, M., & Hodgson, C. (2007). Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior. Physiology & Behavior, 90(1), 21–28. https://doi.org/10.1016/j.physbeh.2006.08.024

Miller, E. (2022, October 15). Metabolic pathways explained. Cleveland Clinic. https://health.clevelandclinic.org/metabolic-pathways-metabolic-conditioning

Munn, Z., Pollock, D., Khalil, H., Alexander, L., Mclnerney, P., Godfrey, C. M., Peters, M., & Tricco, A. C. (2022). What are scoping reviews? Providing a formal definition of scoping reviews as a type of evidence synthesis. JBI evidence synthesis, 20(4), 950–952. https://doi.org/10.11124/JBIES-21-00483

Nemets, B., & Levine, J. (2013). A pilot dose-finding clinical trial of creatine monohydrate augmentation to SSRIs/SNRIs/NASA antidepressant treatment in major depression. International clinical psychopharmacology, 28(3), 127-133. https://doi.org/10.1097/YIC.0b013e32835ff20f

Pan, J. W., & Takahashi, K. (2007). Cerebral energetic effects of creatine supplementation in humans. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 292(4), R1745-R1750. https://doi.org/10.1152/ajpregu.00717.2006

Peters, M. D., Godfrey, C. M., Khalil, H., McInerney, P., Parker, D., & Soares, C. B. (2015). Guidance for conducting systematic scoping reviews. International journal of evidence-based healthcare, 13(3), 141–146. https://doi.org/10.1097/XEB.0000000000000050

Poortmans, J. R., & Francaux, M. (1999). Long-term oral creatine supplementation does not impair renal function in healthy athletes. Medicine and science in sports and exercise, 31(8), 1108-1110. https://doi.org/10.1097/00005768-199908000-00005

Prokopidis, K., Giannos, P., Triantafyllidis, K. K., Kechagias, K. S., Forbes, S. C., & Candow, D. G. (2023). Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials. Nutrition reviews, 81(4), 416–427. https://doi.org/10.1093/nutrit/nuac064

Roitman, S., Green, T., Osher, Y., Karni, N., & Levine, J. (2007). Creatine monohydrate in resistant depression: a preliminary study. Bipolar Disorders, 9(7), 754-758. https://doi.org/10.1111/j.1399-5618.2007.00532.x

Sherpa, N. N., De Giorgi, R., Ostinelli, E. G., Choudhury, A., Dolma, T., & Dorjee, S. (2025). Efficacy and safety profile of oral creatine monohydrate in add-on to cognitive-behavioural therapy in depression: An 8-week pilot, double-blind, randomised, placebo-controlled feasibility and exploratory trial in an under-resourced area. European Neuropsychopharmacology, 90, 28-35.https://doi.org/10.1016/j.euroneuro.2024.10.004

Smith, A. N., Morris, J. K., Carbuhn, A. F., Keller, J. E., Sullivan, D. K., & Taylor, M. K. (2023). Creatine as a therapeutic target in Alzheimer's disease. Current Developments in Nutrition, 7(11), 102011. https://doi.org/10.1016/j.cdnut.2023.102011

Sullivan, P. G., Geiger, J. D., Mattson, M. P., & Scheff, S. W. (2000). Dietary supplement creatine protects against traumatic brain injury. Annals of neurology, 48(5), 723–729. https://pubmed.ncbi.nlm.nih.gov/11079535/

Toniolo, R. A., Fernandes, F. B. F., Silva, M., Dias, R. D. S., & Lafer, B. (2017). Cognitive effects of creatine monohydrate adjunctive therapy in patients with bipolar depression: Results from a randomized, double-blind, placebo-controlled trial. Journal of affective disorders, 224, 69–75. https://doi.org/10.1016/j.jad.2016.11.029

Toniolo, R. A., Silva, M., Fernandes, F. D. B. F., Amaral, J. A. D. M. S., Dias, R. D. S., & Lafer, B. (2018). A randomized, double-blind, placebo-controlled, proof-of-concept trial of creatine monohydrate as adjunctive treatment for bipolar depression. Journal of Neural Transmission, 125, 247-257. https://doi.org/10.1007/s00702-017-1817-5

Tricco, A. C., Lillie, E., Zarin, W., O'Brien, K. K., Colquhoun, H., Levac, D., Moher, D., Peters, M. D. J., Horsley, T., Weeks, L., Hempel, S., Akl, E. A., Chang, C., McGowan, J., Stewart, L., Hartling, L., Aldcroft, A., Wilson, M. G., Garritty, C., Lewin, S., … Straus, S. E. (2018). PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Annals of internal medicine, 169(7), 467–473. https://doi.org/10.7326/M`18-0850

Turner, C. E., Byblow, W. D., & Gant, N. (2015). Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation. The Journal of Neuroscience, 35(4), 1773–1780. https://doi.org/10.1523/JNEUROSCI.3113-14.2015

Vittengl, J. R., Clark, L. A., Smits, J. A., Thase, M. E., & Jarrett, R. B. (2019). Do comorbid social and other anxiety disorders predict outcomes during and after cognitive therapy for depression? Journal of Affective Disorders, 242, 150–158. https://doi.org/10.1016/j.jad.2018.08.036

Walsh, B., Tonkonogi, M., Söderlund, K., Hultman, E., Saks, V., & Sahlin, K. (2001). The role of phosphorylcreatine and creatine in the regulation of mitochondrial respiration in human skeletal muscle. The Journal of physiology, 537(3), 971-978.https://doi.org/10.1111/j.1469-7793.2001.00971.x

World Health Organization (WHO). (2022). Mental disorders Fact Sheet. Retrieved March 3, 2025 from https://www.who.int/news-room/fact-sheets/detail/mental-disorders

Xu, C., Bi, S., Zhang, W., & Luo, L. (2024). The effects of creatine supplementation on cognitive function in adults: A systematic review and meta-analysis. Frontiers in Nutrition, 11. https://doi.org/10.3389/fnut.2024.1424972

Yang, L., Calingasan, N. Y., Wille, E. J., Cormier, K., Smith, K., Ferrante, R. J., & Flint Beal, M. (2009). Combination therapy with coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson’s and Huntington’s diseases. Journal of neurochemistry, 109(5), 1427-1439. https://doi.org/10.1111/j.1471-4159.2009.06074.x​

Yoon, S., Kim, J. E., Hwang, J., Kim, T. S., Kang, H. J., Namgung, E., Ban, S., Oh, S., Yang, J., Renshaw, P. F., & Lyoo, I. K. (2016). Effects of creatine monohydrate augmentation on brain metabolic and network outcome measures in women with major depressive disorder. Biological Psychiatry, 80(6), 439–447. https://doi.org/10.1016/j.biopsych.2015.11.027

View Details

Matt Bernstein, MD; David Puder, MD

Joining today’s episode is Dr. Matt Bernstein, the Chief Executive Officer of Accord and a leading voice in metabolic psychiatry, a field exploring how metabolism, nutrition, circadian rhythms, and exercise influence brain function and mental health. A summa cum laude graduate of Columbia University and a trained psychiatrist from the MGH McLean Psychiatry Residency Program, he has held leadership roles at McLean Hospital and Ellenhorn, organized the first public conference on metabolic psychiatry in 2023, and serves on the clinical advisory board of Metabolic Mind.

By listening to this episode, you can earn 1.75 Psychiatry CME Credits.

Other Places to listen: iTunes, Spotify

Editor: Joanie Burns, PMHNP

Reviewer: Erika Vega, MD, Liam Browning

Metabolic Interventions for Psychiatric Conditions: Reassessing Treatment Strategies Through a Metabolic LensIntroductionA surge in public interest, evidenced by popular YouTube channels (e.g., Lauren Kennedy West with 300K+ subscribers; Metabolic Mind with 60K subscribers) and high‐view interviews as well as successful books by experts like Dr. Georgia Ede and Chris Palmer, reflects a growing belief that targeting metabolic dysfunction may offer a more sustainable path to mental health. This interest is particularly compelling given the shortcomings of current pharmacotherapies, which, while effective in acute symptom management, often yield suboptimal functional outcomes and carry significant metabolic and neurological side effects.

I. Foundations in Neurology: Evidence from EpilepsyA. The Ketogenic Diet in Pediatric and Adult Epilepsy

The ketogenic diet (KD) has been a cornerstone of treatment for refractory epilepsy for over a century. Originally introduced in 1921 by Wilder at the Mayo clinic (Höhn et al., 2019) to mimic the metabolic effects of fasting, the KD rapidly gained acceptance for its ability to reduce seizure frequency and severity—especially in children with treatment-resistant epilepsy.

Key Findings in Pediatric Epilepsy:Multiple randomized controlled trials (RCTs) and meta-analyses have demonstrated the efficacy of the KD in pediatric populations. For example, Neal et al. (2008) conducted a landmark RCT (145 children ages 2-16) showing that children with drug-resistant epilepsy on the classic KD experienced a 75% reduction in seizure frequency, with nearly 38% of patients achieving greater than a 50% reduction in seizures compared to 6% of controls (28/73 vs 4/72 patients, p<0.0001). In many cases, prolonged adherence to the KD has resulted in complete seizure freedom in up to 30% of patients (Freeman et al., 2007; Neal et al., 2008). Additionally, two Cochrane reviews by Martin‐McGill et al. (2018 and 2020) confirmed that the KD is effective in reducing seizure frequency in children with drug-resistant epilepsy, noting improvements not only in seizure control but also in quality of life and cognitive outcomes over long-term follow-up.

Sustained Seizure Control After Diet Discontinuation:Notably, several studies have reported that the beneficial effects of the KD may extend beyond the period of strict dietary adherence. For instance, Martinez et al. (2007) observed that a majority of children who achieved seizure control on the KD maintained their improved outcomes even after tapering the diet. Another study (Patel et al., 2010) found that excellent seizure control actually improved from 52% to 79% after an average of 6 years post-discontinuation of the diet. These findings suggest that early seizure control in pediatric epilepsy may be predictive of long-term remission even after dietary discontinuation.

Diverse Dietary Approaches:Over time, variations of the KD have been developed, such as the modified Atkins diet (MAD) and the low glycemic index treatment (LGIT), which offer greater flexibility while preserving the core metabolic benefits. These alternative protocols have expanded the applicability of metabolic therapy in both pediatric and adult epilepsy, providing clinicians with additional tools to tailor treatment to individual patient needs.

Findings in Adult Epilepsy:Although the majority of research has focused on pediatric populations, the KD has also been applied in adult patients with epilepsy. A meta-analysis by Ye et al. (2015) indicates that adults with intractable epilepsy can benefit from the KD, with more than 50% efficacy rate with the classic KD and slightly lower response rates, but higher compliance with a modified Atkins diet (MAD).

B. Clinical Implications for Psychiatry

The well-validated efficacy of KD in epilepsy supports the rationale for exploring its “off label” use in psychiatry. In both fields, treatments that modulate neuronal excitability and energy metabolism offer the potential to improve clinical outcomes with fewer long-term side effects. Psychiatrists frequently employ treatments that originated in clinical neurology. Valproic acid and lamotrigine originated as FDA approved treatments for epilepsy and were later studied and approved by the FDA as treatments for bipolar disorder. Vagus nerve stimulation was originally approved for epilepsy but later won approval by the FDA as treatments for major depression and obesity.

II. The Bidirectional Relationship Between Metabolic and Brain DisordersA robust body of evidence indicates that metabolic disorders, including diabetes, insulin resistance, and cardiovascular disease, are closely intertwined with mental health disorders such as depression, bipolar disorder, and schizophrenia. This bidirectional relationship implies that metabolic dysregulation can predispose individuals to psychiatric conditions and vice versa.

Longitudinal Evidence Linking Metabolic Dysfunction to Psychiatric Outcomes

Perry et al. (2021) provided compelling longitudinal data in a large cohort of children. Their study found that those with the highest levels of insulin and other metabolic abnormalities in childhood had a significantly increased risk of developing mental health disorders in young adulthood, such as schizophrenia and major depressive disorder. This research underscores the importance of early metabolic health in predicting later psychiatric outcomes.

In a complementary study, Pan et al. (2010) examined a cohort of women over time and found a bidirectional association between depression and type 2 diabetes. Women with a history of depression were more likely to develop diabetes and, conversely, those with diabetes had an elevated risk of subsequent depression. These findings emphasize that mood disorders and metabolic disturbances share common physiological pathways, such as chronic inflammation, dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, and impaired insulin signaling.

Meta-analytic research by Luppino et al. (2010) further corroborates this bidirectional link. Their systematic review and meta-analysis showed that obesity not only increases the risk of developing depression but that depression can lead to subsequent weight gain and metabolic syndrome. This reciprocal relationship suggests that metabolic dysregulation and mental illness are interconnected via overlapping biological mechanisms.

The convergence of evidence from these diverse studies highlights that poor metabolic health in early life is a predictor of later psychiatric morbidity and that the presence of mental health disorders further exacerbates metabolic risk.

*These studies collectively suggest that early metabolic dysregulation is not only a marker, but may be a modifiable risk factor for later mental health disorders.*

Implications of the Bidirectional Relationship

The evidence supports a model in which metabolic and psychiatric disorders are interconnected through shared pathophysiological processes. Chronic inflammation, oxidative stress, poor mitochondrial function and impaired insulin signaling are common threads that link these conditions. Recognizing the bidirectional relationship has several important clinical implications:

• Early Intervention: Screening for metabolic abnormalities in childhood and early adulthood may allow for the early identification of individuals at risk for developing psychiatric disorders.
• Integrated Treatment Approaches: Interventions that address metabolic dysfunction such as the ketogenic diet, exercise, mindfulness and circadian rhythm alignment could potentially mitigate the development or severity of mental health disorders. In fact, there are multiple case reports and case series demonstrating dramatic clinical benefits of ketogenic diets, as discussed in Section V below, and the evidence for the power of exercise as a metabolic and mental health intervention has been well documented elsewhere (see also Episodes 10, 96, 142, 165, 179, and 230). Mindfulness interventions and circadian rhythm alignment also have been demonstrated to improve both mental and metabolic health, but a presentation of the evidence for these interventions is outside the scope of this review.
• Holistic Patient Care: Understanding the interplay between metabolic and psychiatric health underscores the need for integrated care models that simultaneously address both physical and mental health (see also Episode 207).

In summary, the convergence of data from multiple longitudinal studies not only reinforces the association between metabolic dysregulation and mental illness, but also provides a compelling rationale for employing metabolic interventions as part of a comprehensive treatment strategy in psychiatry.

III. Metabolic Health and Functional Outcomes in Serious Mental IllnessPatients with serious mental illnesses (SMIs) such as schizophrenia, bipolar disorder, and major depressive disorder (MDD) are at significantly increased risk for metabolic disturbances. These patients exhibit higher rates of obesity, insulin resistance, type 2 diabetes, dyslipidemia, and cardiovascular disease compared to the general population. These metabolic abnormalities contribute substantially to the reported 15–20 year reduction in life expectancy observed among these individuals.

A. Metabolic Dysregulation in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

Recent studies have consistently shown that the prevalence of metabolic syndrome is alarmingly high in patients with SMIs. For instance, Mazereel, et al. (2020) reviewed how psychotropic medications exacerbate obesity and metabolic syndrome in these populations, while Barton et al. (2020) reported significantly higher rates of metabolic syndrome and diabetes in psychiatric inpatients compared with the general population. In schizophrenia, systematic reviews (e.g., Rognoni et al., 2021) confirm that second-generation antipsychotic drugs are associated with significant metabolic and cardiovascular side effects. Similar challenges are observed in bipolar disorder, where studies such as Vancampfort et al. (2013) have confirmed the high metabolic risk in that population that is exacerbated by second-generation antipsychotics.

B. Adverse Metabolic Effects of Psychotropic Medications

Psychotropic medications are often necessary for managing acute psychiatric symptoms, but they frequently exacerbate underlying metabolic dysfunction. Key observations include:

• Antipsychotics: Second-generation antipsychotics such as clozapine, olanzapine, quetiapine and risperidone are well documented to induce weight gain, hyperglycemia, and dyslipidemia (Bernardo et al., 2021; Rognoni et al., 2021). These side effects contribute to a significantly elevated risk of metabolic syndrome and cardiovascular disease in patients with schizophrenia and bipolar disorder, as well as those with other conditions such as major depressive disorder and anxiety disorders (OCD, PTSD), where these medications are also used at increased frequencies.
• Mood Stabilizers:

• Valproic acid and lithium are both associated with significant weight gain. One review of a few studies reported the effect is greater with lithium (Dols et al., 2013) while a small prospective cohort trial found that valproic acid had significantly greater weight gain than lithium over a 6 month period (Banihashem et al., 2022).

• Antidepressants: Several recent studies have shown that antidepressant treatment, particularly with certain SSRIs, is associated with weight gain, reduced muscle mass, and heightened cardiometabolic risk (Andersson et al., 2024). Such metabolic side effects can further impact overall health and functional recovery in patients with major depressive disorder.

These findings underscore the importance of regularly monitoring metabolic parameters in patients receiving psychotropic medications and employing integrated treatment approaches that address both psychiatric and metabolic health.

C. Improved Long-Term Functional Outcomes Through Progressive Antipsychotic Dose Reduction

Research suggests that long-term functional outcomes may be significantly improved by systematically reducing antipsychotic dosages in stable patients. Wunderink et al. (2013) demonstrated that first-episode psychosis patients who underwent structured antipsychotic dose reduction in the first two years achieved better social and vocational recovery five years later compared to those maintained on higher doses in the first two years. Key mechanisms may include:

• Reduced Dopamine Blockade: Given the importance of dopamine signaling to reward and motivation, lowering doses of medications that block dopamine receptors may alleviate cognitive and negative symptoms.
• Mitigation of Metabolic Side Effects: Decreasing antipsychotic dosage can stabilize weight and may improve insulin sensitivity.

IV. Patient Selection for Metabolic InterventionsIdentifying patients who may benefit most from metabolic interventions is critical. Categories to consider include:

• Patients stable on psychiatric medications with inadequate symptom relief and/or with poor metabolic health: These individuals often experience incomplete functional recovery which may be due to insufficient symptom reduction, medication side effects, and metabolic dysfunction. Metabolic interventions may allow for improved symptom control, safer medication reductions, and improved functional outcomes.
• Patients preferring holistic approaches: Some individuals opt for non-medical treatments for many reasons. Some are concerned about the side effects of medications and other treatments such as ECT or TMS. Some are drawn to treatments that are considered more natural such as those rooted in diet and exercise.
• Patients intolerant to psychiatric medications: Many individuals have tried medications and could not tolerate the side effects or did not like the way they subjectively felt on these medications. For these patients, metabolic therapies may provide an alternative route to symptom relief and functional recovery.
• Additional categories: This may include individuals with comorbid metabolic diseases (e.g., diabetes, obesity, PCOS, etc.) who might derive dual benefits from a program of metabolic interventions.

V. Evidence for Metabolic Interventions in PsychiatryOver the last few years, accumulating research has highlighted the therapeutic potential of metabolic interventions—particularly the ketogenic diet (KD)—in managing psychiatric conditions such as bipolar disorder, schizophrenia, and major depressive disorder (MDD). Below is a summary of key studies and their clinical significance. There are additional studies documenting the benefits of ketogenic diets in anorexia nervosa (Calabrese et al., 2022), autism spectrum disorders (Schrickel et al., 2025), alcohol withdrawal symptoms (Wiers et al., 2021 and 2024), and dementia (Anderson et al., 2025). Of note, most of these studies did not have a control group and therefore could be subject to multiple types of bias.

A. Summary of Key Studies

1. Calkin et al. (2022):
2. Design & Population: The TRIO-BD study was a randomized, quadruple-masked, placebo-controlled clinical trial that evaluated the effects of treating insulin resistance with metformin in patients with treatment-resistant bipolar depression.
3. Findings: The study demonstrated that reversing insulin resistance through metformin treatment led to a significant improvement in depressive symptoms, with a higher proportion of patients achieving remission compared to the placebo group. Importantly, the clinical improvement was strongly correlated with improvements in metabolic parameters, including HOMA-IRscores (fasting insulin, fasting glucose), suggesting that the antidepressant effect of metformin may be mediated through enhanced insulin sensitivity.
4. Clinical Significance: This study highlights the critical role of metabolic health in the management of treatment-resistant depression and suggests that targeting insulin resistance may be a viable therapeutic strategy. The findings support the broader hypothesis that metabolic interventions, including dietary approaches like the ketogenic diet, could provide significant psychiatric benefits by addressing underlying metabolic dysfunction.
5. Sethi et al. (2024):
6. Design & Population: A 4-month pilot trial involving patients with bipolar disorder and schizophrenia.
7. Adherence: High adherence (80–100% ketosis) correlated with more pronounced improvements in both psychiatric and metabolic parameters.
8. Bipolar disorder: 76% (16 out of 21 participants)
9. Schizophrenia spectrum disorders (including schizophrenia and schizoaffective disorder): 24% (5 out of 21 participants)
10. Participants maintained their usual psychotropic medications throughout the trial without restrictions on dose adjustments with their doctor.
11. Participants were not asked to track calories; instead, they were instructed to limit their carbohydrate intake to approximately 20 grams daily (excluding fiber), consume one cup of vegetables and two cups of salad per day, and were encouraged to drink eight glasses of water daily.

12. Adherence was defined by blood ketone levels: adherent participants had ketone levels between 0.5 – 5 mM for 80–100% of measurements.

13. Findings: Participants adhering to a KD experienced a 32% reduction in psychotic symptoms (in schizophrenia), a significant improvement in mood symptoms in those with bipolar (with greater adherence to the diet associated with more improvements), improvements in life satisfaction, global functioning and marked metabolic improvements (e.g., reduced weight, visceral adipose tissue and insulin resistance).

14. Fourteen participants were fully adherent to the diet (ketone levels >0.5 in at least 80% of measurements), six were partially adherent (ketone levels >0.5 between 60–80% of the time), and one participant was non-adherent.
15. Metabolic Outcomes:
16. 10% average weight reduction
17. 11% reduction in waist circumference
18. Reduction of Fat Mass Index by 17%
19. 36% reduction in visceral adipose tissue for adherent participants
20. 27% reduction in HOMA-IR (insulin resistance measure) among adherent participants.
21. High-sensitivity C-reactive protein (hs-CRP), a marker of inflammation, decreased by 23% overall
22. Triglycerides reduced by 25% in adherent participants
23. LDL cholesterol increased by 21%; however, this was primarily large buoyant LDL rather than small dense LDL, suggesting lower cardiovascular risk
24. Complete resolution of metabolic syndrome criteria in all participants initially diagnosed

25. HbA1c reduced by 3.6% overall and 4.9% in adherent participants

26. 17% improvement in insulin sensitivity

27. Psychiatric Outcomes:

28. Schizophrenia participants experienced a 32% reduction in psychotic symptoms (Brief Psychiatric Rating Scale).
29. Participants with bipolar disorder specifically saw an increase in the proportion classified as “recovered or recovering,” going from 38% to 81%, with 100% of adherent bipolar participants reaching a “recovered or recovering” state.
30. Clinical Global Impression (CGI) scores improved by an average of 31%.
31. Among those with baseline symptoms, 79% showed clinically meaningful improvement.
32. Overall improvements in depression (PHQ-9 score reduced by 33%), anxiety (GAD-7 reduced by 8.9%), sleep quality (PSQI improved by 19%), and global functioning (GAF improved by 17%).

33. Qualitative patient feedback highlighted significant personal improvements such as reduction in anxiety attacks, mood stabilization better than previous medications (e.g., lamotrigine), increased sexual activity after years of inactivity, and subjective feelings of significant recovery.

34. Clinical Significance: Demonstrates the potential for KD to address both psychiatric and metabolic dimensions of illness in severely ill outpatients, paving the way for randomized controlled studies in similar populations.

35. Common ketogenic diet-related side effects (e.g., fatigue, constipation, headache) were mostly transient, resolving within 3 weeks.
36. Danan et al. (2022):
37. Design & Population: A retrospective analysis of 31 inpatients with refractory mental illness in a psychiatric hospital who received a ketogenic diet with regular psychiatric care.
38. Bipolar disorder type II: 13 patients (42%)
39. Schizoaffective disorder: 12 patients (39%)
40. Major depressive disorder: 7 patients (23%)

41. Among the 28 patients who adhered to the diet for over two weeks, urine ketone testing was conducted once during the intervention and showed positive results in 18 patients (64%). Dietary adherence was rated as excellent for 11 patients (39%), good for 12 patients (43%), and fair for 5 patients (18%).

42. Findings: KD intervention led to substantial reductions in Hamilton Depression Rating Scale, Montgomery-Åsberg Depression Rating Scale scores, Positive and Negative Symptom Scale and Clinical Global Impression, with effect sizes far surpassing those typically reported for medication trials. Metabolic parameters improved and a majority of patients had their medication doses decreased during the study.

43. Depression: Substantial reductions in depression severity scores:
44. HAM-D: Reduced from 25.4 to 7.7 (69% improvement).

45. MADRS: Reduced from 29.6 to 10.1 (67% improvement).

46. Psychosis: For patients with schizoaffective disorder, PANSS scores improved from 91.4 to 49.3 (45% improvement).

47. Clinical Global Impression (CGI-S): Improved from 4.9 to 2.0, with 43% achieving clinical remission.

48. 64% of patients had their psychotropic medication doses reduced during the intervention.

49. Clinical Significance: Suggests that metabolic therapies can yield robust psychiatric symptom improvements in treatment refractory inpatients, opening opportunities for randomized controlled studies in similar populations.

50. Limitations:
51. Retrospective design, small sample size, lack of randomization or control group, and potential biases (e.g., expectancy, selection bias).
52. Short and variable duration of KD adherence (ranging from 15–248 days).

In conclusion, the Danan et al. (2022) study provides compelling preliminary evidence supporting the ketogenic diet’s therapeutic potential for severe, treatment-refractory mental illness, aligning well with calls for more rigorous future studies.

1. Calabrese et al. (2024):
2. Design & Population: A retrospective case series examining personalized ketogenic metabolic therapy in outpatients with depression and anxiety in 3 adults age 32 to 36.
3. Adherence defined by achieving and maintaining capillary BHB ≥0.8 mmol/L and GKI <6.

4. Integrated support system: bi-weekly consultations, virtual groups, daily food journaling, nature activities, community engagement, and ongoing psychiatric follow-up.

5. Findings: Complete remission of mood and anxiety symptoms within 7–12 weeks, accompanied by significant metabolic enhancements.

6. Notable improvements in associated psychiatric conditions, including cessation of binge eating behaviors and obsessive-compulsive symptoms.

7. Anxiety symptoms generally remitted earlier than depression (within 2–6 weeks).

8. Clinical Significance: Illustrates how KD can rapidly improve mood disorders, potentially decreasing the need for polypharmacy.

9. Campbell et al. (2025)
10. Design & Population: A pilot study for 6-8 weeks of a KD in euthymic bipolar disorder, assessing clinical, metabolic, and magnetic resonance spectroscopy (MRS) findings.
11. Findings: There were significant correlations between ketone levels and mood, energy, anxiety and impulsivity. Significant reductions were seen in weight and systolic blood pressure. MRS showed significant reductions in glutamine, glutamate and myo-inositol in relevant brain regions.
12. Decreased glutamate + glutamine (Glx):
13. 11.6% decrease in anterior cingulate cortex (ACC, p=0.025)
14. 13.6% decrease in posterior cingulate cortex (PCC, p<0.001)
15. Glutamate (Glu) and glutamine (Gln), collectively called Glx, are key excitatory neurotransmitters and neuromodulators. Elevated glutamate is frequently observed in mood disorders like bipolar disorder and depression, suggesting excessive neuronal activity, excitotoxicity, or dysregulated energy metabolism.

16. A significant reduction of Glutamine in the anterior cingulate cortex (ACC, a region involved in emotional regulation and cognitive control) and posterior cingulate cortex (PCC, important for self-reflection, rumination, and emotional processing) indicates that a ketogenic diet (KD) might reduce excitatory neurotransmission or normalize glutamate-related disturbances. Clinically, this might help stabilize mood, reduce anxiety, and mitigate symptoms of emotional dysregulation common in bipolar disorder.

17. Decreased total choline in ACC (p=0.004) and PCC (p<0.001)

18. Total choline (tCho) measured via spectroscopy is associated with cell membrane metabolism, myelination, and membrane turnover. Elevated choline often suggests increased cellular turnover, inflammation, or metabolic stress.

19. The observed reduction in choline in the ACC and PCC suggests a decrease in cellular turnover or reduced inflammation and neuronal stress. This may reflect an improvement in neuronal integrity or reduced inflammatory processes—potentially beneficial changes in bipolar disorder.

20. Reduced myo-inositol in PCC (p=0.025)

21. Myo-inositol (mI) is involved in cell signaling, particularly in phosphoinositide signaling pathways associated with mood regulation and insulin sensitivity. Elevated myo-inositol often reflects disturbed signal transduction and metabolic dysfunction and is associated with bipolar disorder, depression, and anxiety disorders.

22. A reduction in myo-inositol, especially in the PCC, may reflect improved insulin signaling, reduced inflammation, or improved neurochemical regulation associated with mood stabilization.

23. No significant metabolite changes in the right dorsolateral prefrontal cortex (RDLPFC).

Clinical Significance: MRS revealed changes in brain energy metabolism suggestive of improved neuronal bioenergetics. Clinically, this underscores the possibility of achieving better functional outcomes through targeted metabolic therapies.

*Note.* Reprinted from “A pilot study of a ketogenic diet in bipolar disorder: Clinical, metabolic and magnetic resonance spectroscopy findings”, by Campbell et al., 2025, *BJPsych Open, 11*, e34, 1–8.

Note the step up in improvement, better modeled by a non-linear step up.

B. Relevance to Clinical Practice and Functional Outcomes

1. Dual Benefits on Metabolic and Psychiatric Health:Each of these studies underscores the capacity of metabolic interventions to address both core psychiatric symptoms and the metabolic side effects commonly associated with psychotropic medications. This dual action is particularly valuable for patients with severe mental illness (SMI), who often experience significant metabolic comorbidities.
2. Potential for Medication Optimization and Reduced Side Effects:The large effect sizes observed (e.g., Calabrese et al., 2024 and Danan et al., 2022) suggest that KD and other metabolic therapies can provide robust symptom relief, thereby creating opportunities to lower psychotropic dosages. Such dose reductions may mitigate long-term adverse effects (including metabolic dysregulation) and promote better functional recovery.
3. Enhanced Quality of Life and Functional Recovery:Improvements in mood and psychotic symptoms, coupled with metabolic stabilization, can lead to gains in social, vocational, and cognitive functioning. Studies like Wunderink et al. (2013) have shown that judicious medication reduction supports better long-term outcomes. Metabolic interventions, by further alleviating medication-induced metabolic strain, may amplify these benefits.

C. Conclusion: Pathway to Optimal Outcomes

Collectively, these studies reinforce the growing awareness that metabolic interventions—particularly the ketogenic diet—hold promise as potent adjunctive or alternative treatments in severe mental illness. By targeting both psychiatric symptoms and metabolic dysfunction, clinicians can aim for improved functional outcomes that extend beyond mere symptom management. As future research continues to elucidate the underlying mechanisms and refine patient selection criteria, metabolic therapies may become a cornerstone of comprehensive care for individuals with schizophrenia, bipolar disorder, and major depressive disorder.

VI. Mechanistic Insights: How Ketogenic Diets Improve Brain HealthKetogenic metabolic therapies confer benefits through several interrelated biological pathways. Due to the success of ketogenic diets in improving clinical benefits in epilepsy, there has been tremendous interest in trying to understand the mechanisms underlying this phenomenon. There is now an extensive literature that has accumulated in this area, giving clinicians confidence that these interventions have a strong basis in relevant neuroscience.

1. Alternative Energy Substrate Provision

• Ketone Bodies as Fuel: In states of glucose hypometabolism, often associated with insulin resistance, ketone bodies (e.g., beta-hydroxybutyrate) provide a stable energy source for neurons, generate fewer reactive oxygen species, and help stabilize neuronal excitability (Newman & Verdin, 2017; Veech, 2004).

2. Anti-inflammatory and Antioxidant Effects

• Inflammasome Inhibition: BHB inhibits the NLRP3 inflammasome, reducing pro-inflammatory cytokines (Youm et al., 2015).
• Oxidative Stress Reduction: Ketone metabolism increases the NAD⁺/NADH ratio, boosting endogenous antioxidant defenses (Newman & Verdin, 2017).

3. Enhanced Mitochondrial Function and Biogenesis

• Mitochondrial Efficiency: Activation of PGC-1α promotes mitochondrial biogenesis and improves ATP production, crucial for synaptic plasticity (Anderson et al., 2025; Rho, 2017). In addition to their well‐known role in ATP production, mitochondria are also crucial regulators of brain function through their involvement in neurotransmitter release, intracellular calcium homeostasis, and retrograde signaling that influences nuclear gene transcription and synaptic plasticity, processes that are essential for neuroprotection and have been implicated in the pathophysiology of various mental health disorders (Picard & McEwen, 2018).

4. Neurotransmitter Modulation

• Balancing Excitation and Inhibition: KD increases GABA synthesis while reducing glutamate excitotoxicity, thus stabilizing neural networks (Anderson et al., 2025).

5. Epigenetic Regulation and Neurotrophic Support

• Histone Deacetylase (HDAC) Inhibition: BHB’s inhibition of HDACs leads to increased histone acetylation and upregulation of neuroplasticity-related genes (e.g., brain-derived neurotrophic factor (BDNF)) (Newman & Verdin, 2017).

6. Modulation of the Gut-Brain Axis

• Microbiome Changes: KD alters gut microbiota composition, reducing systemic inflammation and producing neuroactive metabolites (Olson et al., 2018).

7. Improved Insulin Sensitivity

• Restoration of Insulin Signaling: Agents like metformin enhance both peripheral and central insulin sensitivity, which is linked to better cognitive function and can improve treatment resistant bipolar depression (Calkin, et al., 2022). Ketogenic diets have been shown to be a potent way to restore insulin sensitivity (Hallberg et al., 2018).

VII. Ideal Metabolic Treatment Plan: A Multimodal ApproachWhile there is emerging evidence that the ketogenic diet on its own can markedly improve outcomes in serious mental illness and a large body of evidence that exercise can be an excellent treatment for mild to moderate depression, it is intriguing to consider that an approach that combines multiple interventions could have an even greater impact.

Mindfulness practices have been shown to have a wide range of benefits, including decreasing distressing emotions, depressive symptoms, and perceived stress, as well as increasing positive psychological and physical well-being markers. These benefits are at least partially mediated through safety signaling, during which energetic resources are directed toward cellular optimization and away from energy-demanding stress states (Crosswell et al., 2024)

Circadian rhythm alignment plays a crucial role in regulating hormonal cycles and metabolic processes. When internal clocks are properly synchronized, the timed release of hormones, such as cortisol, insulin, and melatonin, is optimized, which promotes efficient glucose metabolism and improves insulin sensitivity. Moreover, this alignment enhances sleep quality and stabilizes neural circuits involved in mood regulation, thereby reducing the risk of depression and anxiety. For instance, Scheer et al. (2009) demonstrated that circadian misalignment impairs glucose tolerance and insulin sensitivity, suggesting that restoring circadian regularity may counteract these metabolic disruptions and support better mental health.

A proposed quartet of lifestyle interventions to create the ideal conditions for metabolic and mental health improvement:

• An Individualized Well-Formulated Ketogenic Diet: Including a predominance of whole foods, adequate high quality protein, healthy fats, plentiful fiber and phytonutrients from a variety of vegetables. It also may involve eliminating foods to which the individual is sensitive (can commonly mean gluten, dairy and other foods to which many individuals are sensitive).
• Individualized Exercise Plan: Including resistance training, high-intensity interval training (HIIT), and aerobic training, all of which have independent benefits on metabolic health, mental health, and neuroplasticity. This should be geared to the fitness level and preferences of the individual, and ideally both time efficient, enjoyable and progressive in intensity over time.
• Mindfulness Practices: This can include a variety of options such as meditation, prayer, visualization, chanting, yoga, Tai Chi and Qigong. Technology such as biofeedback devices (Heartmath, the Muse) can be useful tools to facilitate the ability to achieve deep rest states in some individuals.
• Circadian Rhythm Alignment: Through strategies such as morning sunlight exposure and more time outside, regular sleep and meal times, and minimizing all blue-light before bedtime and overnight.

Each modality independently improves both metabolic and mental health and, when combined, they may yield synergistic benefits that further enhance overall clinical outcomes.

VIII. Special Populations and ContraindicationsA. Special Populations

Ketogenic diets and other metabolic interventions have demonstrated benefits in populations with comorbid conditions:

• Diabetes and Obesity: Improved glycemic control and weight loss (Hallberg et al., 2018).
• Polycystic Ovarian Syndrome (PCOS): Beneficial hormonal and metabolic effects (Mavropoulos et al., 2005).
• Migraine Headaches: Reduction in migraine frequency and intensity (Tereshko et al., 2023).
• Autism Spectrum Disorder: Improvements in behavior and cognitive function in some cases (Schrickel et al., 2025).
• Mild Cognitive Impairment and Neurodegenerative Conditions: Enhanced brain energy metabolism and improvements in cognition and functioning (Anderson et al., 2025).
• Substance Abuse Disorders: Reduced withdrawal symptoms and cravings (Wiers et al., 2021 and 2024).
• Pregnancy: Data regarding the safety of ketogenic diet (KD) use during pregnancy are limited and predominantly originate from contexts involving epilepsy and metabolic disorders. Current evidence consists mostly of small case reports, observational data, and animal studies, making definitive risk assessments challenging and individualized. Animal studies, such as Sussman et al. (2013), have shown significant alterations in fetal organ growth (e.g., enlarged hearts, reduced brain size), changes in brain structure, impaired neuronal density, and delayed neurological development linked to maternal KD, raising concerns about potential developmental impacts. In humans, observational studies like epidemiological research by Desrosiers et al. (2018) noted increased neural tube defect risks associated with very low carbohydrate intake, potentially due to decreased folate consumption. Kramer and Smith (2021) provided a contrasting perspective, reporting a successful KD pregnancy outcome in a case of metabolic disorder (Glut1 deficiency syndrome), highlighting the importance of individualized and supervised clinical management. Recent reviews by Miłosz et al. (2025) reinforce these concerns, noting risks of nutritional deficiencies, metabolic disturbances, increased genome methylation variability, ketoacidosis, and developmental abnormalities, balanced by therapeutic benefits in specific contexts such as epilepsy, PCOS, and Glut1 deficiency. While most direct human evidence from epilepsy and metabolic disorder contexts reports generally favorable short-term outcomes, isolated minor anomalies and nutritional deficiencies (particularly folate and essential vitamins) have been noted. Experts thus emphasize careful monitoring and nutritional supplementation. KD therapy may offer therapeutic benefits in carefully selected and medically supervised scenarios; however, broader and long-term studies are essential to clarify its safety profile during pregnancy (Van der Louw et al., 2017; Miłosz et al., 2025).

B. Contraindications

While KD can be highly effective, it is not appropriate for everyone. Contraindications include:

• Certain Metabolic Disorders: Inborn errors of metabolism that impair fat oxidation. These are rare and typically discovered in early childhood.
• Medications Requiring Glycemic Stability: Some drugs (e.g., SGLT2 inhibitors) may need to be adjusted to avoid adverse effects like euglycemic ketoacidosis.
• Severe Liver or Pancreatic Disease: May impair fat metabolism.

IX. Practical Tips and Clinical Pearls (Clinical Opinion Section) Patient Selection: Ideal candidates include those with insufficient functional recovery, poor metabolic health, and/or medication intolerances. An assessment of someone’s motivation to engage in these types of lifestyle interventions is a crucial first step in the process. * Multidisciplinary Support: Effective implementation often requires collaboration among psychiatrists, dietitians, primary care providers, mental health professionals, personal trainers, family, and other community supports. * Monitoring and Assessment: Regular metabolic assessments including weight, vital signs, blood glucose, lipids, thyroid panel, insulin resistance score, specific micronutrients, daily ketones. * Medication monitoring and adjustment: Careful attention needs to be paid to certain medications such as: + Lithium, valproic acid and carbamazepine (and other medications with narrow therapeutic indices) may need to be adjusted in the early KD adaptation period, when diuresis and fluid shifts are common. + Anti-hypertensives may need to be lowered as blood pressure typically improves with the ketogenic diet, sometimes rapidly. + Diabetes medications* may need to be lowered as early as the first few days, as some carry a risk of hypoglycemia when carbohydrate intake is severely restricted. Collaboration with an endocrinologist and the use of a continuous glucose monitor are strongly recommended.

• Patient Education/Close Collaboration: Use clear, accessible language to explain how metabolic therapies work and their potential benefits. There may need to be close collaboration with patients and members of the care team, especially in the early stages, to avoid adjustment effects (“keto flu”) and to ensure that the plan is being followed appropriately
• Individualized Pace of Implementation: Some individuals may benefit from a step-wise or gradual implementation process. This is especially true when attempts at implementing the whole plan at once seem overwhelming and may enhance long-term adherence. One may start with small dietary changes and a modest exercise program. It is important to notice and celebrate the early metabolic and mental health improvements and build on the progress that has been made by adding more interventions. On the other hand, there may be advantages in many individuals to engaging in an immersive and comprehensive approach from the beginning, as it allows for rapid and noticeable benefits, which can greatly enhance motivation.
• Adjusting Psychotropic Medications: Careful consideration should be given to reducing doses of psychotropic medications if the expected improvement is occurring in metabolic and mental health, always in a controlled and monitored manner.
• Medication Potentiation: As things are improving on a metabolic plan, clinicians and patients sometimes see an increase in physical symptoms, which are best understood as the effects of medication potentiation. While there is little research in this area, clinicians theorize that there may be enhanced bioavailability or altered pharmacokinetics (possibly due to changes in cytochrome P450 enzyme activity from a high-fat diet) which may lead to increased drug effects. With antipsychotics, one may see increased sedation, orthostatic hypotension, or even new extrapyramidal symptoms (EPS). Similarly, for mood stabilizers and antidepressants, potentiation might lead to heightened side effects such as increased sedation or other side effects typical of that particular medication.
• Individualized Plans: Emphasize the importance of personalized treatment plans that factor in patient preferences and comorbidities.

X. Future Directions and Clinical IntegrationThe rapid pace of research in metabolic psychiatry promises further clarity on optimal protocols and long-term outcomes. Ongoing randomized controlled trials with advanced imaging and biomarker analyses will help delineate which patient subgroups benefit most and which protocols are most effective. Ultimately, integrating metabolic interventions into standard psychiatric practice may lead to a paradigm shift toward personalized, biologically-based treatments. See the following table for some of the studies that are in progress at this time:

Note. Ongoing studies in metabolic psychiatry. Adapted from "Metabolic Mind," by the Baszucki group, 2025 (https://www.metabolicmind.org/research). Copyright 2024 by Metabolic Mind.

Supplements for Ketogenic DietSodium: Amount: 3,000–5,000 mg per day: Approximately 1.5–2 teaspoons of added salt daily, especially during the first 4 weeks. * Reason:* Keto reduces insulin, causing the kidneys to excrete more sodium and water. Glycogen depletion also leads to less water and more diuresis. Increased sodium intake prevents fatigue, muscle cramps, headaches (“keto flu”), and dizziness.

Potassium: Amount: 3,000–4,700 mg per day * Reason: When insulin levels drop due to carbohydrate restriction, the kidneys not only excrete more sodium but also potassium. This renal potassium excretion is often secondary to sodium loss, causing an increased need for potassium replacement. Helps maintain electrolyte balance, prevents muscle cramps, heart palpitations, and weakness. * Sources:* + Ideally, potassium should come from dietary sources rather than supplements. However, it’s important to consult your doctor, as excessive potassium intake can lead to health complications. + Avocado (~700 mg per avocado) + Spinach (~500–800 mg per cooked cup) + Salmon (~500 mg per 6 oz serving) + Potassium chloride supplement (e.g., “lite salt”) if needed (¼ teaspoon ~700 mg potassium)

Magnesium: Amount: Aim for 300–400 mg/day ideally, mostly through foods. * Reason: It is estimated thatmore than 50% of Americans may be deficient in magnesium which is a cofactor for more than 300 enzymes that regulate diverse reactions in the body. Magnesium is required for energy production, contributes to the structural development of bone and is required for the synthesis of DNA, RNA, and the antioxidant glutathione. Magnesium also plays a role in the active transport of calcium and potassium ions across cell membranes, a process that is important to nerve impulse conduction, muscle contraction, and normal heart rhythm. * Sources* + Pumpkin seeds: ~150 mg per 1 oz (28 g) + Spinach: ~150–160 mg per cooked cup + Swiss chard: ~150 mg per cooked cup + Almonds: ~75–80 mg per 1 oz (23 almonds) + Dark chocolate (70–85%+ cacao): ~65 mg per 1 oz square + Avocado: ~60 mg per medium avocado + Hemp seeds: ~70 mg per 2 tablespoons + Chia seeds: ~95 mg per 2 tablespoons + Mackerel: ~80 mg per 3 oz serving + Brazil nuts: ~105 mg per 1 oz (6–7 nuts)

Optimize Hydration During Keto Adaptation

In the first weeks of adapting to a ketogenic diet, increasing water intake is often beneficial and, along with the above electrolytes, should prevent the side effects of this adaptation phase, also known as the “keto flu”. This can include effects such as headaches, muscle aches or cramps, low energy, nausea and brain fog. While there is some debate over whether one should “drink to thirst” or to attempt to meet a certain volume of water, a reasonable quantity of water in the first two weeks of adaptation is 0.5 oz. per pound of body weight along with electrolyte supplementation through diet or other means. So, that would be 100 oz. for a 200 pound person or 60 oz for a 120 pound person.

Labs to Do When Starting the Ketogenic DietStrongly Recommended Baseline Labs (need periodic rechecking):1. Comprehensive Metabolic Panel (CMP)

Why: Evaluates kidney and liver function, electrolyte status, and baseline glucose, essential because keto affects fluid and electrolyte balance and can impact liver metabolism.

1. Complete Blood Count (CBC)
   Why: Screens for anemia, infection, inflammation, or blood disorders. Helpful due to dietary shifts affecting nutrient status and absorption.
2. Fasting Lipid Panel
   Why: Provides baseline cholesterol levels (HDL, LDL, triglycerides) and monitors changes in cardiovascular risk markers due to the high-fat content of keto diets.
3. Vitamin D (25-OH Vitamin D)

Why: Many people are deficient and it is vital to maintain immune, bone, and metabolic health. Helps identify deficiency and potential need for supplementation.

1. Vitamin B12
   Why: Essential for nerve health, cognitive function, and red blood cell production. Helps identify baseline status and potential need for supplementation.
2. Carnitine Levels
   Why: Critical for transporting fatty acids into mitochondria for fat metabolism. Low levels impair the effectiveness of the ketogenic diet and are also associated with depression, causing fatigue or muscle weakness.
3. Thyroid Stimulating Hormone (TSH)
   Why: Thyroid hormones regulate metabolism; keto diets can slightly affect thyroid function. Monitoring helps prevent thyroid-related metabolic slowdown.
4. Hemoglobin A1c (HbA1c)
   Why: Establishes baseline glucose control and identifies insulin resistance or prediabetes; tracks keto’s effect on long-term glucose metabolism.
5. Magnesium (RBC Magnesium preferred)

Why: Keto diets can induce magnesium deficiency due to increased renal excretion and dietary restriction, causing muscle cramps, fatigue, and anxiety. Use caution when interpreting magnesium blood tests and clinical assessment may be more accurate.

Optional Labs Helpful for Deeper Nutritional and Metabolic Assessment (available at standard laboratories):1. Iron Panel (Total Iron, Iron Binding Capacity, Ferritin)
Why: Identifies iron deficiency or overload. Iron deficiency is common in the general population (especially in menstruating women), and impairs mitochondrial function. Iron overload is common in those who are supplementing with iron. 1. Homocysteine
Why: Elevated levels indicate increased cardiovascular risk and potential deficiencies in B vitamins (folate, B12), which is common in the general population. 2. Uric Acid
Why: Keto may initially elevate uric acid levels, increasing gout risk. Helpful to monitor, particularly in susceptible individuals. 3. Celiac Disease Screening Panel (Tissue Transglutaminase AB IgA and Immunoglobulin A)
Why: Screens for underlying gluten sensitivity or celiac disease, which can impact nutrient absorption and gut health, especially important if the ketogenic diet doesn’t resolve digestive issues. 4. Copper and Ceruloplasmin
Why: Assess copper status; imbalance can affect energy metabolism, neurological health, and iron utilization. Useful in restrictive or highly selective diets. Excess free copper is also common in the general population and is associated with anxiety and other psychiatric symptoms, as it is an essential cofactor for the enzyme that converts dopamine to norepinephrine. 5. hs-CRP (High-sensitivity C-Reactive Protein)
Why: Evaluates systemic inflammation; helpful for assessing cardiovascular risk and inflammation status, potentially improved by the ketogenic diet. 6. HOMA-IR (or Fasting Insulin)
Why: Directly measures insulin sensitivity and metabolic health. The ketogenic diet commonly improves insulin resistance; baseline is valuable for tracking metabolic progress. 7. Additional Thyroid Studies (Free T3, Free T4, Reverse T3, Thyroid Antibodies)
Why: Provides comprehensive thyroid function assessment, especially useful if symptoms of low metabolism, fatigue, or weight stagnation occur despite dietary compliance.

ConclusionThe extensive evidence from the well-established efficacy of the ketogenic diet in epilepsy to emerging data in psychiatric populations supports the promise of metabolic interventions in mental health. With the potential for effect sizes exceeding those of conventional medications (as demonstrated by Danan et al., 2022), and a robust mechanistic rationale spanning energy metabolism, inflammation, mitochondrial function, and neurotransmitter balance, metabolic therapies offer a transformative potential. When implemented in a multimodal, patient-centered approach, these interventions may not only reduce psychiatric symptoms and side effects, but also improve overall functional recovery and quality of life.

References:Anderson, J., Ozan, E., Chouinard, V.-A., Grant, G., MacDonald, A., Thakkar, L., & Palmer, C. (2025). The ketogenic diet as a transdiagnostic treatment for neuropsychiatric disorders: Mechanisms and clinical outcomes. Current Treatment Options in Psychiatry, 12(1). https://doi.org/10.1007/s40501-024-00339-4

Andersson, P., Linge, J., Gurholt, T. P., Sønderby, I. E., Hindley, G., Andreassen, O. A., & Dahlqvist Leinhard, O. (2024). Poor muscle health and cardiometabolic risks associated with antidepressant treatment. Obesity, 32(10), 1857–1869. https://doi.org/10.1002/oby.24085

Banihashem, S. S., Ashrafzadeh, S., Esfahani, M. P., Morsalivachin, Z., Shamsi, A., Motazedian, S., & Mousavipour, M. (2022). Body composition changes in psychiatric patients treated with lithium and valproate. Journal of Mental Health & Clinical Psychology, 6(3), 23–28. https://doi.org/10.29245/2578-2959/2022/3.1255

Barton, B. B., Zagler, A., Engl, K., Rihs, L., & Musil, R. (2020). Prevalence of obesity, metabolic syndrome, diabetes and risk of cardiovascular disease in a psychiatric inpatient sample: Results of the Metabolism in Psychiatry (MiP) Study. European Archives of Psychiatry and Clinical Neuroscience, 270(5), 597–609. https://doi.org/10.1007/s00406-019-01043-8

Bernardo, M., Rico-Villademoros, F., García-Rizo, C., Rojo, R., & Gómez-Huelgas, R. (2021). Real-world data on the adverse metabolic effects of second-generation antipsychotics and their potential determinants in adult patients: A systematic review of population-based studies. Advances in Therapy, 38(5), 2491–2512. https://doi.org/10.1007/s12325-021-01689-8

Calabrese, L., Frase, R., & Ghaloo, M. (2024). Complete remission of depression and anxiety using a ketogenic diet: A case series. Frontiers in Nutrition, 11, 1396685. https://doi.org/10.3389/fnut.2024.1396685

Calabrese, L., Scolnick, B., Zupec-Kania, B., Beckwith, C., Costello, K., & Frank, G. K. W. (2022). Ketogenic diet and ketamine infusion treatment to target chronic persistent eating disorder psychopathology in anorexia nervosa: A pilot study. Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity. https://doi.org/10.1007/s40519-022-01455-x

Calkin, C. V., Chengappa, K. N. R., Cairns, K., Cookey, J., Gannon, J., Alda, M., Reardon, C., Sanches, M., & Růzicková, M. (2022). Treating insulin resistance with metformin as a strategy to improve clinical outcomes in treatment-resistant bipolar depression (the TRIO-BD study): A randomized, quadruple-masked, placebo-controlled clinical trial. Journal of Clinical Psychiatry, 83(2), 21m14022. https://doi.org/10.4088/JCP.21m14022

Campbell, I. H., Needham, N., Grossi, H., Kamenska, I., Luz, S., Sheehan, S., Thompson, G., Thrippleton, M. J., Gibbs, M. C., Leitao, J., Moses, T., Burgess, K., Rigby, B. P., Simpson, S. A., McIntosh, E., Brown, R., Meadowcroft, B., & Creasy, F. (2025). A pilot study of a ketogenic diet in bipolar disorder: Clinical, metabolic and magnetic resonance spectroscopy findings. BJPsych Open, 11, e34, 1–8. https://doi.org/10.1192/bjo.2024.841

Crosswell, A. D., Mayer, S. E., Whitehurst, L. N., Picard, M., Zebarjadian, S., & Epel, E. S. (2024). Deep rest: An integrative model of how contemplative practices combat stress and enhance the body’s restorative capacity. Psychological Review, 131(1), 247–270. https://doi.org/10.1037/rev0000453

Danan, A., Westman, E. C., Saslow, L. R., & Ede, G. (2022). The ketogenic diet for refractory mental illness: A retrospective analysis of 31 inpatients. Frontiers in Psychiatry, 13, 951376. https://doi.org/10.3389/fpsyt.2022.951376

Desrosiers, T. A., Siega-Riz, A. M., Mosley, B. S., Meyer, R. E., & National Birth Defects Prevention Study (2018). Low carbohydrate diets may increase risk of neural tube defects. Birth defects research, 110(11), 901–909. https://doi.org/10.1002/bdr2.1198

Dols, A., Sienaert, P., van Gerven, H., Schouws, S., Stevens, A., Kupka, R., & Stek, M. L. (2013). The prevalence and management of side effects of lithium and anticonvulsants as mood stabilizers in bipolar disorder from a clinical perspective: A review. International Clinical Psychopharmacology, 28(6), 287–296. https://doi.org/10.1097/YIC.0b013e32836435e2

Freeman, J. M., Kossoff, E. H., & Hartman, A. L. (2007). The ketogenic diet: One decade later. Pediatrics, 119(3), 535–543. https://doi.org/10.1542/peds.2006-2447

Hallberg, S. J., McKenzie, A. L., Williams, P. T., Bhanpuri, N. H., Peters, A. L., Campbell, W. W., Hazbun, T. L., Volk, B. M., McCarter, J. P., & Volek, J. S. (2018). Effectiveness and safety of a novel care model for the management of type 2 diabetes at one year: An open-label, non-randomized, controlled study. Diabetes Therapy, 9(2), 583–612. https://doi.org/10.1007/s13300-018-0373-9

Höhn, S., Dozières-Puyravel, B., & Auvin, S. (2019). History of dietary treatment from Wilder's hypothesis to the first open studies in the 1920s. Epilepsy & Behavior, 101(Part A), 106588. https://doi.org/10.1016/j.yebeh.2019.106588

Kramer, J., & Smith, L. (2021). Ketogenic diet in Glut 1 deficiency through the life cycle: Pregnancy to neonate to preschooler. Child Neurology Open, 8. https://doi.org/10.1177/2329048X211034655

Luppino, F. S., de Wit, L. M., Bouvy, P. F., Stijnen, T., Cuijpers, P., Penninx, B. W. J. H., & Zitman, F. G. (2010). Overweight, obesity, and depression: A systematic review and meta-analysis of longitudinal studies. Archives of General Psychiatry, 67(3), 220–229. https://doi.org/10.1001/archgenpsychiatry.2010.2

Martin-McGill, K. J., Jackson, C. F., Bresnahan, R., Levy, R. G., & Cooper, P. N. (2018). Ketogenic diets for drug-resistant epilepsy. Cochrane Database of Systematic Reviews, 11, CD001903. https://doi.org/10.1002/14651858.CD001903.pub4

Martin-McGill, K. J., Jackson, C. F., Bresnahan, R., Levy, R. G., & Cooper, P. N. (2020). Ketogenic diets for drug-resistant epilepsy. Cochrane Database of Systematic Reviews, 6, CD001903. https://doi.org/10.1002/14651858.CD001903.pub5

Martinez, C., Pyzik, P.L., & Kossoff, E.H. (2007). Discontinuing the Ketogenic Diet in Seizure-Free Children: Recurrence and Risk Factors. Epilepsia, 48(1):187–190. https://doi.org/10.1111/j.1528-1167.2006.00911.x

Mavropoulos, J. C., Yancy, W. S., Hepburn, J., & Westman, E. C. (2005). The effects of a low-carbohydrate, ketogenic diet on the polycystic ovary syndrome: A pilot study. Nutrition & Metabolism, 2(1), 35. https://doi.org/10.1186/1743-7075-2-35

Mazereel, V., Detraux, J., Vancampfort, D., van Winkel, R., & De Hert, M. (2020). Impact of Psychotropic Medication Effects on Obesity and the Metabolic Syndrome in People With Serious Mental Illness. Frontiers in endocrinology, 11, 573479. https://doi.org/10.3389/fendo.2020.573479

Miłosz, A., Michalczyk, J., Morawik, I., Długoborska, K., & Gesek, M. (2025). Possible impact of use of a ketogenic diet in pregnancy on the fetus: Review of animal and human studies. NFS Journal, 38, 100212. https://doi.org/10.1016/j.nfs.2025.100212

Neal, E. G., Chaffe, H., Schwartz, R. H., Lawson, M. S., Edwards, N., Fitzsimmons, G., Whitney, A., & Cross, J. H. (2008). The ketogenic diet for the treatment of childhood epilepsy: A randomised controlled trial. The Lancet Neurology, 7(6), 500–506. https://doi.org/10.1016/S1474-4422(08)70092-9

Newman, J. C., & Verdin, E. (2017). β-Hydroxybutyrate: A signaling metabolite. Annual Review of Nutrition, 37, 51–76. https://doi.org/10.1146/annurev-nutr-071816-064916

Olson, C. A., Vuong, H. E., Yano, J. M., Liang, Q. Y., Nusbaum, D. J., & Hsiao, E. Y. (2018). The gut microbiota mediates the anti-seizure effects of the ketogenic diet. Cell, 173(7), 1728-1741.e13. https://doi.org/10.1016/j.cell.2018.04.027

Pan, A., Lucas, M., Sun, Q., van Dam, R. M., Franco, O. H., Willett, W. C., Manson, J. E., & Hu, F. B. (2010). Bidirectional association between depression and type 2 diabetes mellitus in women. Archives of Internal Medicine, 170(21), 1884–1891. https://doi.org/10.1001/archinternmed.2010.356

Patel, A., Pyzik, P. L., Turner, Z., Rubenstein, J. E., & Kossoff, E. H. (2010). Long-term outcomes of children treated with the ketogenic diet in the past. Epilepsia, 51(7), 1277–1282. https://doi.org/10.1111/j.1528-1167.2009.02488.x

Perry, B. I., Stochl, J., Upthegrove, R., Zammit, S., Wareham, N., Langenberg, C., Winpenny, E., Dunger, D., Jones, P. B., & Khandaker, G. M. (2021). Longitudinal trends in childhood insulin levels and body mass index and associations with risks of psychosis and depression in young adults. JAMA Psychiatry, 78(4), 416–425. https://doi.org/10.1001/jamapsychiatry.2020.4180

Picard, M., & McEwen, B. S. (2018). Psychological stress and mitochondria: A systematic review. Psychosomatic Medicine, 80(2), 141–153. https://doi.org/10.1097/PSY.0000000000000545

Puder, D. (Host). (2018, March 22). Sensorium Part 3: Exercise as a Prescription for Depression, Anxiety, Chronic Stress (like Diabetes) and Sensorium (No. 010) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-10-sensorium-part-3-exercise-as-a-prescription-for-depression-anxiety-chronic-stress?rq=010

Puder, D. (Host). (2020, Sept. 30). The Best Exercise Program For Depression (No. 096) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/the-best-exercise-program-for-depression?rq=096

Puder, D. (Host). (2022, March 15). Exercise as a Drug for Mental Health and Longevity (No. 142) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-142-exercise-as-a-drug-for-mental-health-and-longevity?rq=exercise

Puder, D. (Host). (2022, Dec. 9). Exercise for the Brain (No. 165) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-165-exercise-for-the-brain?rq=exercise

Puder, D. (Host). (2023, May 12). Exercise & Mental Health 2023 Update (No. 179) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-179-exercise-amp-mental-health-2023-update?rq=exercise

Puder, D. (Host). (2024, March 8). 5 Factors and Domains of Psychiatric Care (No. 207) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-207-5-factors-and-domains-of-psychiatric-care?rq=207

Puder, D. (Host). (2024, Dec. 20). Exercise Compared to Medications or Therapy for Depression (No. 230) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-230-exercise-vs-medications-therapy-depression-treatment?rq=exercise

Rho, J. M. (2017). How does the ketogenic diet induce anti-seizure effects? Neuroscience Letters, 637, 4–10. https://doi.org/10.1016/j.neulet.2015.07.034

Rognoni, C., Bertolani, A. & Jommi C. (2021). Second-generation antipsychotic drugs for patients with schizophrenia: Systematic literature review and meta-analysis of metabolic and cardiovascular side effects. Clinical Drug Investigation, 41(9), 763–775. https://doi.org/10.1007/s40261-021-01000-1

Schrickel, A., Groeneweg, J., & Dekeyster, E. (2025). Exploring the potential of the ketogenic diet in autism spectrum disorder: Metabolic, genetic, and therapeutic insights. Metabolic Brain Disease, 40, 94. https://doi.org/10.1007/s11011-024-01518-1

Sethi, S., Wakeham, D., Ketter, T., Hooshmand, F., Bjornstad, J., Richards, B., Westman, E. C., Krauss, R. M., & Saslow, L. (2024). Ketogenic diet intervention on metabolic and psychiatric health in bipolar and schizophrenia: A pilot trial. Psychiatry Research, 335, 115866. https://doi.org/10.1016/j.psychres.2024.115866

Scheer, F. A., Hilton, M. F., Mantzoros, C. S., & Shea, S. A. (2009). Adverse metabolic and cardiovascular consequences of circadian misalignment. Proceedings of the National Academy of Sciences, 106(11), 4453-4458. https://doi.org/10.1073/pnas.0808180106

Sussman, D., van Eede, M., Wong, M. D., Adamson, S. L., & Henkelman, M. (2013). Effects of a ketogenic diet during pregnancy on embryonic growth in the mouse. BMC pregnancy and childbirth, 13, 109. https://doi.org/10.1186/1471-2393-13-109

Tereshko, Y., Dal Bello, S., Di Lorenzo, C., Pez, S., Pittino, A., Sartor, R., Filippi, F., Lettieri, C., Belgrado, E., Garbo, R., Merlino, G., Gigli, G. L., & Valente, M. (2023). 2:1 ketogenic diet and low-glycemic-index diet for the treatment of chronic and episodic migraine: A single-center real-life retrospective study. The Journal of Headache and Pain, 24, Article 95. https://doi.org/10.1186/s10194-023-01635-9

Vancampfort, D., Vansteelandt, K., Correll, C. U., Mitchell, A. J., De Herdt, A., Sienaert, P., Probst, M., & De Hert, M. (2013). Metabolic syndrome and metabolic abnormalities in bipolar disorder: A meta-analysis of prevalence rates and moderators. American Journal of Psychiatry, 170(3), 265–274. https://doi.org/10.1176/appi.ajp.2012.12050620

Van der Louw, E. J. T. M., Williams, T. J., Henry-Barron, B. J., Olieman, J. F., Duvekot, J. J., Vermeulen, M. J., Bannink, N., Williams, M., Neuteboom, R. F., Kossoff, E. H., Catsman-Berrevoets, C. E., & Cervenka, M. C. (2017). Ketogenic diet therapy for epilepsy during pregnancy: A case series. Seizure, 45, 198–201. https://doi.org/10.1016/j.seizure.2016.12.019

Veech, R. L. (2004). The therapeutic implications of ketone bodies: The effects of ketone bodies in pathological conditions: Ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 70(3), 309-319. https://doi.org/10.1016/j.plefa.2003.09.007

Wiers, C. E., Manza, P., Wang, G.-J., & Volkow, N. D. (2024). Ketogenic diet reduces a neurobiological craving signature in inpatients with alcohol use disorder. Frontiers in Nutrition, 11, 1254341. https://doi.org/10.3389/fnut.2024.1254341

Wiers, C. E., Vendruscolo, L. F., van der Veen, J. W., Manza, P., Shokri-Kojori, E., Kroll, D. S., Feldman, D. E., McPherson, K. L., Biesecker, C. L., Zhang, R., Herman, K., Elvig, S. K., Vendruscolo, J. C. M., Turner, S. A., Yang, S., Schwandt, M., Tomasi, D., Cervenka, M. C., Fink-Jensen, A., ... Volkow, N. D. (2021). Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents. Science Advances, 7, eabf6780. https://doi.org/10.1126/sciadv.abf6780

Wunderink, L., Nieboer, R. M., Wiersma, D., Sytema, S., & Nienhuis, F. J. (2013). Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: Long-term follow-up of a 2-year randomized clinical trial. JAMA Psychiatry, 70(9), 913–920. https://doi.org/10.1001/jamapsychiatry.2013.19

Ye, F., Li, X. J., Jiang, W. L., Sun, H. B., & Liu, J. (2015). Efficacy of and patient compliance with a ketogenic diet in adults with intractable epilepsy: A meta-analysis. Journal of Clinical Neurology, 11(1), 26–31. https://doi.org/10.3988/jcn.2015.11.1.26

Youm, Y.-H., Nguyen, K. Y., Grant, R. W., Goldberg, E. L., Bodogai, M., Kim, D., D'Agostino, D., Planavsky, N., Lupfer, C., Kanneganti, T. D., Kang, S., Horvath, T. L., Fahmy, T. M., Crawford, P. A., Biragyn, A., Alnemri, E., & Dixit, V. D. (2015). The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease. Nature Medicine, 21(3), 263–269. https://doi.org/10.1038/nm.3804

View Details

Date Published: 3/28/25
Liam Browning, Joanie Burns, DNP, APRN, PMHNP-BC, Al-Baab Khan, David Puder, MD

Corresponding author: David Puder, MD

Peer reviewed: Erika Vega, MD

By listening to this episode, you can earn 1.75 Psychiatry CME Credits.

Other Places to listen: iTunes, Spotify

Clozapine remains the gold-standard antipsychotic for treatment-resistant schizophrenia (TRS). Discovered in the 1950s and reintroduced in 1989 after initial concerns about agranulocytosis (Khokhar et al., 2018), clozapine has a unique efficacy in patients who fail to respond to other antipsychotics. It is also the only FDA-approved agent to reduce suicidal behavior in schizophrenia and schizoaffective disorder, and this advantage translates into lower overall mortality. Despite its unparalleled benefits, clozapine is underutilized due to its complex side effect profile and monitoring requirements (Dell’Osso et al., 2024). This article provides an up-to-date clinical guide on clozapine for practicing psychiatrists, synthesizing current research, and insights from an interview with Dr. Michael Cummings. We will review clozapine’s pharmacology, best practices for initiation and side effect management, and emerging uses.

The FDA is Ending Clozapine REMSOn February 25th, 2025, the FDA rescinded the Risk Evaluation and Mitigation Strategy (REMS) for clozapine. Clozapine had been pulled from the market in the 1970s after fatal cases of severe neutropenia in Finland, but the pivotal Kane and colleagues trial in 1988 showed clozapine to be highly effective for treatment-resistant schizophrenia. In order to bring the drug back to the market, the REMS imposed stringent requirements on clinicians and patients.

Under REMS, prescribers were required to monitor absolute neutrophil counts (ANC) weekly for the first six months, then every two weeks for another six months, and monthly thereafter (Dell’Osso et al., 2024). The cumulative 12-month risk of any neutropenia (ANC < 1500/μ) is about 3-4%, while severe, life-threatening neutropenia (ANC < 500/μ) is about 0.8-0.9% (Li et al., 2020; Myles et al, 2018). However, data show that the absolute risk of severe neutropenia peaks during the first three months, then drops to roughly 1 in 6,000–10,000 after the one-year mark—a rate comparable to other non-chemotherapy drugs that can affect the bone marrow (e.g., anticonvulsants, antibiotics, antithyroid medications, fluoxetine, etc.).

*Note.* Reprinted from “Clozapine-induced agranulocytosis. Incidence and risk factors in the United States”, by Alvir et al., 1993, *New England Journal of Medicine,* 329, 162–167.

To ensure proper oversight following these risk patterns, many European guidelines have required only weekly monitoring for 18 weeks, then monthly until one year, and discontinued routine checks thereafter. Morbidity and mortality rates in Europe are on par with those seen under the stricter U.S. REMS, indicating that the REMS schedule for monitoring does not significantly improve safety—but presents a barrier to using the medication.

With the REMS program abolished, the FDA no longer imposes a centralized or mandatory monitoring schedule for clozapine, shifting the responsibility to clinicians. They advise clinicians to follow best practices as outlined in the prescribing information and use clinical judgment, especially in the high-risk window of the first 6 months:

• Weekly ANC checks for the first 6 months.
• Every 2 weeks for the next 6 months.
• Option to discontinue mandatory routine checks after 12 months, provided the patient has had no episodes of significant neutropenia, remains clinically stable, and is properly educated on early signs of infection.

The advent of rapid, point-of-care fingerstick ANC testing also offers an additional practical advantage, as it simplifies lab checks and further reduces barriers. With these changes, more patients will have access to this life-changing medication.

Indications and Unique Efficacy in SchizophreniaClozapine’s primary indication is treatment-resistant schizophrenia, defined by failure to respond to at least two antipsychotic trials that were of adequate duration (6 or more weeks) and dose (therapeutic plasma levels or an LAI). Approximately one-third of people with schizophrenia meet this criterion. Once these criteria are met, the odds of a patient achieving remission with a non-clozapine antipsychotic are less than 7% (Howes et al., 2017), compared to about 40% with clozapine. In one study response rate was 53.2% in the optimal range of 223–558 ng/mL (Northwood et al., 2023). However, if treatment-resistant schizophrenia is not addressed early on, Clozapine’s effectiveness begins to decline (40%-60% to around 30%). Therefore, it is beneficial to switch patients sooner to offer the best chance for improvement.

In addition to symptom reduction, clozapine is the only FDA-approved drug to reduce recurrent suicidal behavior in schizophrenia or schizoaffective disorder (Dell’Osso et al., 2024). This stems from the InterSePT trial findings that patients treated with clozapine (n = 490) showed less suicidal behavior compared to patients treated with olanzapine (n = 490; 20.8% vs. 28.8%, 26% relative risk reduction) (Meltzer et al., 2003).

Clozapine is also effective for comorbid aggression and violence. Research and clinical consensus indicate that clozapine can reduce hostile and aggressive behaviors in schizophreniamore than other antipsychotics and that this may be independent of its effects on psychotic symptoms or sedation, but can be attributed to its effects on cognition and executive functioning (Faden & Citrome, 2024).

Emerging and Off-Label Uses: Beyond schizophrenia, clozapine’s off-label uses are expanding. Low-dose clozapine is highly effective for Parkinson’s disease psychosis, treating hallucinations without exacerbating motor symptoms (Friedman, 2022). It was the first antipsychotic shown to improve Parkinson’s psychosis while improving tremor in some cases (Taylor et al., 2022). However, because Parkinson’s patients are prone to aspiration and clozapine can increase saliva production, it is important to weigh these risks and benefits appropriately (see below section on managing side effects). Clozapine has also been used in treatment-refractory bipolar disorder (especially with psychotic features or rapid cycling), though evidence is primarily from case series. Additionally, emerging research supports clozapine’s efficacy incatatonia, particularly when associated with schizophrenia or treatment-resistant psychotic disorders (Saini et al., 2024). “An important caveat with catatonia is catatonia is always a secondary syndrome…so you ultimately have to treat the underlying condition if you hope to control catatonia,” Dr. Cummings states. Clozapine may not only treat underlying psychosis but also modulate GABAergic and glutamatergic pathways implicated in catatonia. It has shown promise in benzodiazepine-refractory cases and, in some instances, may reduce reliance on electroconvulsive therapy (ECT) for chronic catatonic states.

Pharmacology: Mechanism of Action and Receptor ProfileClozapine’s efficacy and side effect profile are best understood through its distinctive pharmacology. It is classified as a “multi-receptor” atypical antipsychotic, with a mechanism markedly different from first-generation antipsychotics (FGAs):

• Dopamine Receptor Binding: Clozapine is a relatively weak dopamine D₂ receptor antagonist, with fast dissociation kinetics and less than 20-68% D₂ receptor occupancy at therapeutic doses (Nordström et al., 1995). This contrasts with FGAs and the -dones subclass of antipsychotics (e.g. risperidone), which require ~70–80% D₂ blockade for antipsychotic effect and often exceed the threshold for extrapyramidal symptoms (EPS) (de Greef et al., 2011). Clozapine’s lower striatal D₂ occupancy, especially in the nigrostriatal pathway, explains its minimal EPS liability (de Greef et al., 2011). Its inverse agonist activity on 5-HT2A has also been proposed to increase nigrostriatal dopamine release while decreasing mesolimbic dopamine, thereby treating psychosis without causing significant parkinsonism (Dell’Osso et al., 2024). Interestingly, clozapine does bind D₄ receptors with high affinity, though the clinical significance of D₄ blockade is unclear.
• Serotonin Antagonism: Clozapine potently acts as an antagonist at 5-HT2A receptors (more specifically, it is an inverse agonist at 5-HT2A, as it decreases 5-HT2A activity when bound, unlike true antagonists that simply prevent agonist binding without changing receptor activity) (Li et al., 2014). By blocking 5-HT2A in the cortex and striatum, clozapine disinhibits dopamine release in the striatum, counteracting D₂ blockade effects on movement (Dell’Osso et al., 2024). This mechanism, in addition to its limited dopamine antagonism at therapeutic doses, explains why clozapine has lower risks of EPS compared to other antipsychotics. 5-HT2A antagonism may also contribute to improvements in negative symptoms and mood.
• Adrenergic, Muscarinic, and Histaminergic Effects: Clozapine’s broad receptor profile includes antagonism at α₂-adrenergic receptors, multiple muscarinic acetylcholine receptors, and H₁ and H₂ histamine receptors (Dell’Osso et al., 2024):
• α₂-Adrenergic antagonism may enhance norepinephrine and dopamine release in the prefrontal cortex, which some hypothesize helps with negative symptoms and cognitive deficits (Dell’Osso et al., 2024).
• α₁-adrenergic antagonism contributes to orthostatic hypotension.
• Muscarinic receptor antagonist (M1–M5), particularly at M1, M3, and M5. Dr. Cummings notes that 50-100 mg of clozapine is as anticholinergic as 1 mg of benztropine (de Leon, 2005). This underlies many side effects (e.g. constipation, tachycardia, urinary retention, blurred vision). When high doses of clozapine are stopped abruptly, this can lead to a rebound cholinergic delirium due to the greater number of M receptors available to bind to acetylcholine (Stanilla et al.,1997). This rebound can also be associated with other classic symptoms of excessive cholinergic activity, such as sweating, nausea, diarrhea, urinary urgency, insomnia, and vivid dreams. If stopping clozapine abruptly due to serious complications such as severe neutropenia or myocarditis, start benztropine (or another strong anticholinergic [e.g. trihexyphenidyl, diphenhydramine]) at the equivalent dose (1 mg benztropine per 50-100 mg clozapine). Otherwise, taper clozapine gradually to reduce the likelihood of cholinergic rebound and EPS if initiating an antipsychotic with strong D2 antagonism.
• Norclozapine, the active metabolite of clozapine, is also thought to act as a muscarinic partial agonist on M4 receptors of salivary glands, contributing to drooling.
• Histamine H₁ blockade explains the prominent sedation and weight gain, while H2 interactions have been speculated to aid clozapine’s efficacy in TRS (Dell’Osso et al., 2024).

Key point: Do not stop clozapine abruptly! Sudden withdrawal could cause delirium…

Pharmacokinetics: Smoking and Drug-Drug Interactions with ClozapineAfter oral administration, clozapine’s plasma half-life typically ranges from about 8 to 16 hours (though it can be longer in chronic use or at higher doses), and the parent drug is extensively transformed by CYP1A2 and, to a lesser extent, by CYP3A4 and CYP2D6 into the active metabolite N-desmethylclozapine (norclozapine) and clozapine N-oxide, an inactive metabolite.

Smoking candramatically affect clozapine levels. The aryl hydrocarbons produced by cigarette smoking (not the nicotine) induces CYP1A2, leading to a significant decrease in plasma levels. As little as 7-12 cigarettes per day can induce CYP1A2 activity, and full induction of the enzyme increases its activity by about 1.7 fold (Haslemo et al., 2006; Zhou et al., 2009). Therefore, smokers often require 50% higher doses, and if a patient stops smoking, clozapine levels can rise sharply, risking toxicity. Routine inquiry about tobacco use (including cannabis smoking) is essential, as is coordinating any smoking cessation with proactive dose adjustment (Blacker, 2020; Montville et al., 2021). Other drugs, such as phenytoin, rifampin, and carbamazepine can induce CYP3A4.

Nicotine vaping (e.g., e-cigs, vapes), however, do not affect clozapine levels like cigarettes do. Therefore if a patient switches from cigarette smoking to vaping, plasma concentrations of clozapine can increase drastically, so similar precautions must take place.

Key point: consistent smoking or caffeine habits should be maintained once a clozapine dose is established, or doses must be adjusted with changes.

Drugs with the greatest inhibitory effect on CYP1A2 include fluvoxamine, ciprofloxacin, and enoxacin can increase clozapine levels by 2- to 5-fold. Similarly, high amounts of caffeine (in excess of 400mg) can mildly raise clozapine levels (about 5-10%) by competing for CYP1A2 (Hägg et al., 2000).

Here are tables summarizing how various CYP450 enzyme inducers, inhibitors, and other factors impact clozapine levels and metabolism (see alsoEpisode 141):

   **Initiation and Dosing Strategies for Clozapine** Initiating clozapine requires a gradual titration to balance efficacy, tolerability, and safety. The standard approach is to “start low and go slow.”

A typical schedule begins at 12.5-25 mg once at bedtime on day 1. Giving the initial doses at bedtime is recommended because clozapine’s sedative and orthostatic effects (via α₁ and H1 receptors) are most prominent when initiating the drug. If this dose it tolerated, then increase to 12.5-25 mg twice daily, then up to 100mg per day by the end of the first week and 200mg per day by the end of the second week.

Slower titration of 50 mg increments (or less) once or twice per week is recommended to allow the body to acclimate to clozapine’s sedative and cardiovascular effects and reduces the risk of seizures. It usually takes about 2–3 weeks to reach a therapeutic dose (e.g. 300+ mg/day), though titration can be faster in a hospital setting with close monitoring. Dr. Cummings notes that after a dose increase it takes only about two weeks to reach 80% of that dose’s expected plasma concentration, so titrating slower than two week increments is unnecessary in most cases.

Therapeutic Dosing and Monitoring Plasma ConcentrationsThe effective dose range for clozapine in schizophrenia is broad (usually 200–600 mg/day). Many patients respond around 300–450 mg/day, but some require higher doses (600–900 mg/day) for full remission. Importantly, response is correlated with plasma clozapine levels.

Therapeutic drug monitoring is recommended to ensure plasma levels are above approximately 350 ng/mL, which is often cited as the minimum level for response, according to a recent meta-analysis (Northwood et al., 2023). Plasma concentrations can be expected to scale nearly 1:1 with oral dosing in men (350 mg dose = 350 ng/mL plasma level), while plasma concentrations in women scale at about 1:1.3 (350mg dose = about 500 ng/mL plasma level). Dr. Cummings mentions that with dosing, pushing higher concentrations can lead the patient to develop intolerable side effects or saturate the utility of the drug.

When patients are not responding as expected, monitoring plasma concentrations can distinguish between a pharmacokinetic issue (“pseudo-resistance” due to rapid metabolism) that leads to subtherapeutic plasma levels versus true clozapine resistance. For example, a non-smoking patient on 400 mg nightly with a plasma level of only 200 ng/mL may be an ultra-rapid metabolizer or non-adherent, whereas a patient with plasma levels of 500 ng/mL and no response after 3 months may require even higher plasma levels as tolerated (Dr. Cummings notes plasma concentrations may need to be titrated up to 1000 ng/mL and even up to 1400 ng/mL in very rare cases, but this is off-label, and done in a controlled setting with high monitoring and expertise) or further augmentation strategies such as ECT or adding a second antipsychotic (e.g. aripiprazole).

Augmentation and Combination For patients who are truly clozapine-resistant, confirmed by ensuring adequate plasma levels for 8 to 12 weeks and ruling out pharmacokinetic interactions, several augmentation strategies may be considered.

Addition of a Second Antipsychotic:

Although evidence supporting this strategy is limited, (Chiu et al., 2020), Tiihonen and colleagues (2019) conducted a large cohort study following over 62,000 patients for 20 years and found that patients treated with a combination of clozapine and aripiprazole had a 14% lower risk of psychiatric hospitalization compared to those on clozapine monotherapy, and that this combination was associated with the lowest hospitalization rates among all tested. However, combinations of clozapine with other antipsychotics did not significantly reduce hospitalization rates compared to clozapine alone.

*Note.* Reprinted from “Association of Antipsychotic Polypharmacy vs Monotherapy With Psychiatric Rehospitalization Among Adults With Schizophrenia”, by Tiihonen et al., 2019, *JAMA psychiatry*, *76*(5), 499–507.

When combining another antipsychotic with clozapine, it is important to choose an agent that has a complementary binding profile to clozapine. For example, clozapine’s antimuscarinic effects block the action of xanomeline, whereas antipsychotics acting on D2 receptors (such as aripiprazole) are more appropriate.

ECT augmentation

A meta-analysis by Wang et al. (2018) examined 18 RCTs, primarily conducted in China, and found that patients receiving ECT augmentation showed greater symptom improvement (effect size 1.4) and remission rates compared to those on clozapine alone. However, a more recent sham-controlled trial by Melzer-Ribeiro et al. (2024) found no significant differences in symptoms or remission rates after 20 ECT sessions. Nevertheless, ECT may be particularly useful in those with catatonic or affective features (Grover et al., 2023).

Antipsychotic Polypharmacy Without Clozapine:

For patients who are not candidates for clozapine due to intolerance or logistical barriers, combining two non-clozapine antipsychotics can be considered. Dr. Cummings notes that the goal with polypharmacy is to combine different mechanisms of action hoping for additive benefits in treatment (see also Episode 214). According to the Tiihonen et al. (2019) meta-analysis, selecting antipsychotics with complementary receptor binding profiles is a rational approach. For example, a high-affinity D2 antagonist such as haloperidol could be paired with a second-generation antipsychotic with broader receptor activity, such as olanzapine. This outcome is still inferior to clozapine’s efficacy and will expose the patient to a greater risk of EPS if both agents are used at high doses (Carnahan et al., 2006; Taipale et al., 2023).

*Note.* Reprinted from “Association of Antipsychotic Polypharmacy vs Monotherapy With Psychiatric Rehospitalization Among Adults With Schizophrenia”, by Tiihonen et al., 2019, *JAMA psychiatry*, *76*(5), 499–507.

  *Note.* Reprinted from “Association of Antipsychotic Polypharmacy vs Monotherapy With Psychiatric Rehospitalization Among Adults With Schizophrenia”, by Tiihonen et al., 2019, *JAMA psychiatry*, *76*(5), 499–507.

Monitoring and Managing Side EffectsClozapine’s side effect profile is extensive, spanning nearly every organ system. Up to 40% of patients discontinue clozapine within 2 years due to side effects or non-adherence (Dell’Osso et al., 2024; Lieberman & Stroup, 2011). However, most side effects are manageable with vigilant monitoring and targeted interventions, and despite the increased risk of severe side effects compared to other antipsychotics, all-cause mortality is lower in patients treated with clozapine (Hayes et al., 2015).

Hematologic: NeutropeniaAs discussed above, the most notorious clozapine complication is severe neutropenia, or agranulocytosis. Clozapine-induced agranulocytosis occurs in roughly 0.5-1% of patients, typically within the first six months of treatment (Myles et al., 2018). Due to mandatory blood count monitoring through REMS, the fatality rate of clozapine agranulocytosis has fallen to around 2.7–3% (much lower than the ~7–10% mortality for agranulocytosis from other causes) (Dell’Osso et al., 2024). The overall death rate from agranulocytosis in patients exposed to clozapine is less than 0.05% (Myles et al., 2018).

Known risk factors for clozapine induced neutropenia include concurrent valproate use, older age, female sex, and Asian ethnicity, as well as certain HLA genetic polymorphisms (HLA-DQB1 6672G>C [rs113332494], HLA-B38:01)(Legge et al., 2019; Konte et al., 2021). However, it should be noted that the genetics underlying clozapine-induced neutropenia are likely multifactorial and that having these genetic variants does not preclude initiation of the drug.

Management of Neutropenia: If neutropenia occurs, management depends on severity.

• Mild neutropenia (ANC 1000–1500/µL): Increase monitoring frequency to three times weekly until ANC reaches above 1500/µL.
• Moderate neutropenia (ANC 500-999/µL): Stop clozapine treatment until ANC normalizes. ANC should be checked daily until it returns to above 1000/µL, then three times weekly until ANC reaches above 1500/µL, and then weekly for an additional 4 weeks. After ANC stabilizes, a rechallenge can be initiated. A hematology consult is recommended.
• Severe neutropenia (agranulocytosis, ANC < 500/µL): Stop clozapine, consult hematology, and initiate infection precautions. ANC checks should proceed following the same protocol as moderate neutropenia (daily until above 1000/µL then 3x/week until above 1500/µL). A rechallenge is not recommended unless the prescriber determines the risks of treatment outweigh the benefits.

Augmenting Neutrophil Count Granulocyte Colony-Stimulating Factor (G-CSF, or filgrastim) can accelerate neutrophil recovery for a clozapine rechallenge. A 2023 systematic review found that clozapine rechallenge with G-CSF support can be effective regardless of initial agranulocytosis severity (Corbeil et al., 2023). In addition to G-CSF, lithium can also be used to induce granulocytosis via enhancing production of G-CSF and stimulating proliferation of pluripotent stem cells (Focosi et al., 2009).

Benign ethnic neutropenia is a genetic variant in individuals of African or Middle Eastern descent that periodically lowers baseline ANC (<1500/µL) without a concomitant increased risk of infection. Guidelines allow adjusted ANC thresholds in such cases so that clozapine is not inappropriately withheld. If suspected in a patient, consult hematology to establish the diagnosis by ruling out other potential causes and to pursue genetic testing.

Cardiovascular: Myocarditis, Cardiomyopathy, and HypotensionSerious cardiac side effects of clozapine, though rare, have garnered increased attention. Myocarditis, a potentially fatal complication, occurs in an estimated 0.02–1.2% of clozapine patients and is thought to be the result of a hypersensitivity reaction. Notably, about 50% of cases present within the first month of treatment (median onset ~2–3 weeks) and rarely occur thereafter (Bellissima et al., 2018). Vital signs (heart rate, temperature), labs (troponins and CRP), and symptoms (chest pain, fatigue) should be monitored at each weekly visit during the first 6 weeks (Segev et al., 2021). Some experts recommend a baseline echocardiogram as well.

The most common presentation is an unexplained fever with associated chest pain or malaise. However, benign fever is a common complaint, occurring in up to 20% of patients initiated on clozapine. If a patient does have a fever during the first 8 weeks, best practice is to send the patient to the ED for a workup that includes a physical exam, CBC, troponins, CRP, and imaging, if needed. If myocarditis is confirmed (e.g. via markedly elevated troponin or echocardiogram findings), clozapine must be stopped and cardiology consulted. There is no notable consensus on rechallenge after myocarditis; it has been done successfully in select cases after recovery, but only with extreme caution and perhaps a very slow titration (Manu et al., 2018).

Cardiomyopathy (dilated heart failure from long-term toxicity) is another rare complication (estimated <5% incidence), and unlike other complications of clozapine, it typically occurs after months or years of treatment. It should be suspected if a patient develops insidious dyspnea, edema, or exercise intolerance. Annual physical exams (and possibly periodic echocardiograms in high-risk individuals) are prudent to catch late cardiomyopathy. As with myocarditis, cardiomyopathy usually necessitates stopping clozapine (Murch et al., 2013).

On the benign end of the spectrum, sinus tachycardia is very common with clozapine, seen in up to 25% of patients (Dell’Osso et al., 2024). Clozapine’s anticholinergic and adrenergic effects increase heart rate. This resting tachycardia often peaks during titration and may subside over 4–6 weeks. Unless the heart rate is >120 or symptomatic, it can be monitored; if persistent, a low-dose beta blocker (e.g. atenolol 25–50 mg) can be used after the initial titration period (Dell’Osso et al., 2024). (Beta blockers should be avoided in the first 6 weeks unless absolutely needed, as they could mask early signs of myocarditis). Educating the patient about hydration and avoiding caffeine (which can worsen tachycardia) is also helpful, and determining whether the tachycardia is secondary to orthostasis is crucial.

Orthostatic hypotension frequently occurs during the first two weeks of titration due to α₁ blockade and sedation. Patients should be warned to rise slowly and stay hydrated. Most will develop tolerance by week 4. If significant dizziness or near-syncope occurs, the titration speed should be slowed or held. In severe cases, addition of midodrine or fludrocortisone can support blood pressure (Dell’Osso et al., 2024), but these are rarely needed if titration is cautious. Hypertension on clozapine is uncommon, but if it emerges later in treatment, it may relate to weight gain and metabolic changes; standard antihypertensives can be used as needed (Dell’Osso et al., 2024).

Neurologic: Seizures, Sedation, and Neuropsychiatric Effects of ClozapineSeizures: Clozapine lowers the seizure threshold in a dose-dependent manner. At doses <300 mg the risk is low (<1%), but at higher doses (600–900 mg) the risk of generalized seizures rises to around 3–5% (Dell’Osso et al., 2024). Myoclonic jerks can precede generalized seizures in some patients. Electroencephalogram (EEG) abnormalities, including generalized slowing and epileptiform discharges, are also prevalent among clozapine-treated patients, occurring in approximately 50% to 60% of cases (Hatano et al., 2023). To mitigate this risk, slow titration and using the lowest effective dose are essential (Dell’Osso et al., 2024).

If a patient has a seizure on clozapine, first ensure their clozapine level is not supra-therapeutic or rising too quickly. Typically, you would temporarily halt clozapine or reduce the dose, then add an anticonvulsant. Once stabilized, clozapine can be cautiously resumed at a lower dose alongside the anticonvulsant. “...Seizure, per se, is not a reason to stop clozapine…It’s a reason to add an antiepileptic to prevent the seizures,” says Dr. Cummings. Prophylactic valproate or lamotrigine can be considered in patients with epilepsy or EEG abnormalities before starting clozapine, or those needing very high clozapine doses (Varma et al., 2011). However, valproate can also lead to neutropenia in a dose-dependent manner and is also teratogenic in both men and women.

Sedation: Nearly all patients experience sedation on clozapine, especially during initiation. Histamine H₁ antagonism and anticholinergic effects cause drowsiness, which is often most pronounced in the first few weeks. Sedation can be dose-limiting, but concentrating the dose at night can help minimize daytime sedation. Over time, many patients develop partial tolerance to the sedative effect as H₁ receptors adapt (Dell’Osso et al., 2024). Importantly, clozapine’s sedative and sialorrhea effects make aspiration a concern at night, especially in elderly patients and those with Parkinson’s disease.

Delirium and Miscellaneous CNS effects: Clozapine’s anticholinergic properties occasionally cause a delirium, especially at higher doses, in susceptible patients (e.g. those with baseline cognitive impairment), or when abruptly stopped due to cholinergic rebound.

Rarely, clozapine can precipitate obsessive-compulsive symptoms or worsen pre-existing OCD, likely due to clozapine’s antagonism at 5-HT2A/C receptors (Moreno Tarazona et al., 2025). Management involves lowering the clozapine dose if feasible, adding an SSRI (avoid fluvoxamine or fluoxetine), or augmenting with another antipsychotic such as aripiprazole (Kim et al., 2019). If a patient does not present entirely with schizophrenia, but has a schizoaffective disorder or bipolar disorder, the option for an antidepressant while on clozapine becomes risky.

Extrapyramidal symptoms are distinctly uncommon, but clozapine can occasionally cause tremors or rigidity (often treatable by beta-blockers or anticholinergics) and very rarely neuroleptic malignant syndrome (NMS). Interestingly, if a patient has a history of NMS to another antipsychotic, about 79% will also get NMS if re-challenged with clozapine (Dell’Osso et al., 2024), so extreme caution is warranted in such scenarios. Some evidence suggests concomitant valproate might predispose to NMS with clozapine (Dell’Osso et al., 2024).

Metabolic and Endocrine: Weight Gain, Diabetes, and Lipid AbnormalitiesClozapine is the most metabolically problematic antipsychotic. Studies report that one-third to one-half of patients on clozapine gain more than 7% of their baseline body weight, driven by H₁ histamine and 5-HT2C antagonism, which increase appetite, along with increased insulin resistance and reduced activity due to sedation. Weight gain typically starts within the first six months and can progress over time to metabolic syndrome, characterized by T2DM, hyperlipidemia, and hypercholesterolemia. Up to 26% of clozapine-treated patients develop new-onset diabetes over six years, with severe cases leading to hyperosmolar coma or diabetic ketoacidosis (McGrath et al., 2022). Baseline assessment of weight, waist circumference, blood pressure, fasting glucose and HbA1c, and lipids, then follow-up at 3 months and at least annually (more frequently if changes occur) can prevent and ameliorate cardiovascular consequences (Dell’Osso et al., 2024). Managing clozapine induced metabolic syndrome requires a proactive approach, including nutritional counseling, regular exercise, and pharmacotherapy, including metformin, GLP-1 agonists, insulin and statins (see also Episode 223.)

Managing SialorrheaSialorrhea (Excessive Salivation): Paradoxically, clozapine often causes drooling (especially at night), despite having anticholinergic properties, which may be attributable to norclozapine’s partial agonist activity at M4 receptors. Up to 30–80% of patients experience sialorrhea to some degree. Dr. Cummings notes, “In many patients, that actually increases the risk of aspiration and aspiration of pneumonia. It’s one of the dangerous side effects of clozapine.”

Non-pharmacological approaches include sleeping on an incline and placing a towel over the pillow. Pharmacologically, sublingual anticholinergic drops (atropine 1% ophthalmic drops, 1–2 drops under the tongue at bedtime) often help reduce nocturnal drooling. Systemic agents like glycopyrrolate (which does not cross blood-brain barrier significantly), 1–2 mg at bedtime is a common approach that can reduce drooling with less risk of central anticholinergic side effects. Alternatively, low-dose clonidine or benztropine at night may provide some relief. Recent evidence suggests that agents from the benzamide class (such as amisulpride or metoclopramide) might also alleviate clozapine-associated sialorrhea, though this is a newer strategy and not yet widely adopted. In refractory cases, Botox injections into salivary glands have been tried. Notably, sialorrhea tends to improve over time as tolerance develops, but many patients require ongoing bedtime medication to fully control it.

Managing Constipation and Urinary RetentionConstipation and GI Hypomotility: Clozapine’s anticholinergic potency and 5-HT antagonism makes constipation the most fatal complication attributed to clozapine, as it can lead to bowel obstruction and ensuing perforation, strangulation, compartment syndrome, and sepsis (Patel et al., 2021). Importantly, hypomotility can occur regardless of treatment duration and is quite common, with some studies finding up to 30–60% of clozapine patients experience significant constipation and up to 80% experience colonic hypomotility, defined as colonic transit time greater than two standard deviations above the population mean (Every-Palmer et al., 2016). Therefore, collecting a history of baseline bowel functioning (frequency and consistency of bowel movements), performing an abdominal exam (can supplement with an abdominal X-ray), and tapering off other anticholinergic medications should be completed prior to initiating clozapine. Proactive prophylaxis is also critical: a bowel regimen with daily osmotic laxatives (polyethylene glycol) and/or stool softeners should be started at the first sign of constipation, or even preemptively in those with a history of slow bowels. Although evidence from RCTs is limited (Every-Palmer et al., 2017), many clinicians will schedule laxatives (e.g. PEG 3350 17g daily or docusate 100-250 mg QHS) for all clozapine patients to prevent severe constipation. If a patient experiences constipation and 2 days pass without bowel movement, intensify laxatives (add senna, bisacodyl if not already using, and increase docusate to max dose of 250 mg or to 125 mg BID) and monitor closely. If the patient is still constipated, perform a digital rectal exam to assess whether stool is impacted and consult GI to see if an enema or disimpaction is needed. If impacted, stop stimulant laxatives. If not impacted, consider using an intestinal secretagogue such as lubiprostone or prucalopride.

Oftentime, patients will be reluctant to use laxatives for their constipation or to disclose their symptoms, but it is important to educate patients that unlike typical constipation, this is a medication effect that must be managed daily. Clozapine-induced ileus is a medical emergency with a fatality rate of 15-28% (Cohen, 2017). If a patient on clozapine develops new abdominal pain and distension, or vomiting, an urgent evaluation (physical exam, abdominal X-ray or CT) is warranted.

Urinary retention or incontinence: Clozapine’s anticholinergic effects can also cause urinary hesitancy or retention, particularly in older men with prostate hypertrophy. If urinary retention occurs, dose reduction and urology consult (for catheterization or bethanechol, a cholinergic agent) may be needed. On the other hand, some patients experience nocturnal enuresis (bedwetting) on clozapine, possibly related to deep sedation and pelvic muscle relaxation. For enuresis, behavioral strategies (limiting evening fluids, setting an alarm to toilet at night) are first-line. If needed, desmopressin at bedtime or low-dose ephedrine/midodrine have been used in case reports to reduce enuresis (Tanzer et al., 2023).

Thromboembolism: Emerging evidence from case studies links clozapine to increased risk of venous thromboembolism (Pallares Vela et al., 2021). However, this effect may not be unique to clozapine, as sedentary behavior from sedation and weight gain are risk factors common to other antipsychotics. Clinicians should encourage mobility, manage weight, and have a high index of suspicion for symptoms like unilateral leg swelling or acute shortness of breath.

Managing Illness on ClozapinePatients who develop severe infections can present with increased clozapine levels. Although not caused by the drug itself, cytokines interleukin 6 and interleukin 8 that are produced during severe infections can inhibit the cytochrome enzymes. During periods of illness, clozapine dose distribution should be managed carefully.

ConclusionClozapine is a uniquely effective antipsychotic that offers hope for patients with the most challenging forms of schizophrenia and related disorders. Its use requires a high level of clinical diligence – from slow, careful titration and blood monitoring to the anticipation and management of numerous side effects. For the practicing psychiatrist, becoming adept with clozapine greatly expands the therapeutic toolkit for treatment-resistant illness. Key takeaways include:

• Unmatched Efficacy: Clozapine remains the only evidence-based option for true treatment-resistant schizophrenia, with proven advantages in reducing psychosis, preventing suicide (Dell’Osso et al., 2024), and improving life outcomes in patients who have failed other treatments. No combination of other antipsychotics has been shown to equal clozapine’s effectiveness in this population (Puder, 2024a).
• Complex Pharmacology: Understanding clozapine’s receptor profile (low D₂ occupancy, high 5-HT₂A antagonism, plus noradrenergic, cholinergic, and histaminergic actions) helps predict its clinical effects – minimal EPS but prominent sedation, metabolic changes, and unique benefits in conditions like catatonia (Dell’Osso et al., 2024).
• Monitoring and Side Effect Management: A structured monitoring schedule for blood counts, metabolic metrics, and cardiac symptoms is essential. Proactive side effect management (e.g. bowel regimen, exercise/diet counseling, beta blockers for tachycardia, sugar monitoring) allows most patients to remain on clozapine long-term. Severe complications like agranulocytosis and myocarditis are rare and can be mitigated by close observation during high-risk periods (Dell’Osso et al., 2024).
• Special Clinical Situations: Clozapine shows efficacy beyond psychosis, notably in mitigating catatonia (alone or with ECT) (Dell’Osso et al., 2024) and in improving tardive movement disorders and akathisia (Spivak et al., 1997). It should be considered in persistent catatonia associated with schizophrenia, and tapered carefully to avoid withdrawal catatonia (Rogers et al., 2023). Its low EPS profile makes it ideal for patients intolerant of other antipsychotics due to motor side effects.
• Emerging Uses: Ongoing research is exploring clozapine’s neurobiological impacts such as neurotrophic effects, and its potential benefits in mood disorders, personality disorders, and neurodevelopmental disorders. While these uses are off-label, they underscore clozapine’s far-reaching influence on the brain and behavior.

In treating severe psychiatric illness, clozapine often turns the tide for individuals who have suffered years of treatment failures. By combining vigilance in monitoring with an up-to-date knowledge of side effect management and adjunctive strategies, clinicians can use clozapine safely and effectively. The conversational insights of experienced clinicians like Dr. Cummings, backed by contemporary research, reinforce that clozapine therapy is both an art and a science – one that pays dividends in restored lives when done carefully. With systematic practice and patient education, psychiatrists can incorporate clozapine into clinical care as an authoritative yet compassionate treatment approach, offering patients with refractory schizophrenia a chance at remission and improved quality of life.

Additional episodes discussing clozapine

• Episode 020: The History and Use of Antipsychotics
• Episode 049: Clozapine for Treatment Resistant Schizophrenia
• Episode 127: Using Antipsychotic Plasma Levels-Therapeutic Threshold
• Episode 129: Psychosis: Management of Complex Treatment-Resistant Psychotic Disorders
• Episode 141: Psychopharmacology Mediators
• Episode 190: Schizophrenia Treatment: Clozapine, LAIs, Technology and Equity with John Kane, MD and Lauren Hanna, MD
• Episode 210: Q&A with Dr. Cummings
• Episode 211: Early Psychosis: Detection and Treatment

References:Alvir, J. M., Lieberman, J. A., Safferman, A. Z., Schwimmer, J. L., & Schaaf, J. A. (1993). Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. The New England journal of medicine, 329(3), 162–167. https://doi.org/10.1056/NEJM199307153290303

Bellissima, B. L., Tingle, M. D., Cicović, A., Alawami, M., & Kenedi, C. (2018). A systematic review of clozapine-induced myocarditis. International Journal of Cardiology, 259, 122–129. https://doi.org/10.1016/j.ijcard.2017.12.102

Blacker C. J. (2020). Clinical Issues to Consider for Clozapine Patients Who Vape: A Case Illustration. Focus (American Psychiatric Publishing), 18(1), 55–57. https://doi.org/10.1176/appi.focus.20190025

Carnahan, R. M., Lund, B. C., Perry, P. J., & Chrischilles, E. A. (2006). Increased risk of extrapyramidal side-effect treatment associated with atypical antipsychotic polytherapy. Acta psychiatrica Scandinavica, 113(2), 135–141. https://doi.org/10.1111/j.1600-0447.2005.00589.x

Chiu, Y. H., Hsu, C. Y., Lu, M. L., & Chen, C. H. (2020). Augmentation Strategies for Clozapine-Resistant Patients with Schizophrenia. Current pharmaceutical design, 26(2), 218–227. https://doi.org/10.2174/1381612826666200110102254

Cohen, D. (2017). Clozapine and Gastrointestinal Hypomotility. CNS Drugs, 31, 1083–1091. https://doi.org/10.1007/s40263-017-0481-5

Corbeil, O., Béchard, L., Fournier, É., Plante, M., Thivierge, M.-A., Lafrenière, C.-É., Huot-Lavoie, M., Brodeur, S., Essiambre, A.-M., Roy, M.-A., & Demers, M.-F. (2023). Clozapine rechallenge or continuation despite neutropenia or agranulocytosis using colony-stimulating factor: A systematic review. Journal of Psychopharmacology, 37(4), 370–377. https://doi.org/10.1177/02698811231154111

de Greef, R., Maloney, A., Olsson-Gisleskog, P., Schoemaker, J., & Panagides, J. (2011). Dopamine D2 occupancy as a biomarker for antipsychotics: quantifying the relationship with efficacy and extrapyramidal symptoms. The AAPS journal, 13(1), 121–130. https://doi.org/10.1208/s12248-010-9247-4

de Leon, J. (2005). Benztropine equivalents for antimuscarinic medication. American Journal of Psychiatry, 162(3), 627. https://doi.org/10.1176/appi.ajp.162.3.627

Dell’Osso, L., Bonelli, C., Nardi, B., Giovannoni, F., Pronestì, C., Cremone, I. M., Amatori, G., Pini, S., & Carpita, B. (2024). Rethinking Clozapine: Lights and Shadows of a Revolutionary Drug. Brain Sciences, 14(1), 103. https://doi.org/10.3390/brainsci14010103

Every-Palmer, S., Ellis, P. M., Nowitz, M., Stanley, J., Grant, E., Huthwaite, M., & Dunn, H. (2017). The Porirua Protocol in the treatment of clozapine-induced gastrointestinal hypomotility and constipation: A pre- and post-treatment study. CNS Drugs, 31, 75–85. https://doi.org/10.1007/s40263-016-0391-y

Every-Palmer, S., Nowitz, M., Stanley, J., Grant, E., Huthwaite, M., Dunn, H., & Ellis, P. M. (2016). Clozapine-treated Patients Have Marked Gastrointestinal Hypomotility, the Probable Basis of Life-threatening Gastrointestinal Complications: A Cross Sectional Study. EBioMedicine, 5, 125–134. https://doi.org/10.1016/j.ebiom.2016.02.020

Faden, J., & Citrome, L. (2024). A systematic review of clozapine for aggression and violence in patients with schizophrenia or schizoaffective disorder. Schizophrenia Research, 268, 265–281. https://doi.org/10.1016/j.schres.2023.11.008

Focosi, D., Azzarà, A., Kast, R. E., Carulli, G., & Petrini, M. (2009). Lithium and hematology: Established and proposed uses. Journal of Leukocyte Biology, 85(1), 20–28. https://doi.org/10.1189/jlb.0608388

Friedman, J.H. (2022), Clozapine Is Severely Underused in Parkinson's Disease Patients. Mov Disord Clin Pract, 9: 1021-1024. https://doi.org/10.1002/mdc3.13582

Grover, S., Sarkar, S., & Sahoo, S. (2023). Augmentation strategies for clozapine resistance: a systematic review and meta-analysis. Acta Neuropsychiatrica, 35(2), 65–75. DOI: https://doi.org/10.1017/neu.2022.30

Hägg, S., Spigset, O., Mjörndal, T., & Dahlqvist, R. (2000). Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. British Journal of Clinical Pharmacology, 49(1), 59–63. https://doi.org/10.1046/j.1365-2125.2000.00111.x

Haslemo, T., Eikeseth, P. H., Tanum, L., Molden, E., & Refsum, H. (2006). The effect of variable cigarette consumption on the interaction with clozapine and olanzapine. European Journal of Clinical Pharmacology, 62(12), 1049–1053. https://doi.org/10.1007/s00228-006-0209-9

Hatano, M., Yamada, K., Matsuzaki, H., Yokoi, R., Saito, T., & Yamada, S. (2023). Analysis of clozapine-induced seizures using the Japanese Adverse Drug Event Report database. PLoS ONE, 18(6), e0287122. https://doi.org/10.1371/journal.pone.0287122

Hayes, R. D., Downs, J., Chang, C. K., Jackson, R. G., Shetty, H., Broadbent, M., Hotopf, M., & Stewart, R. (2015). The effect of clozapine on premature mortality: an assessment of clinical monitoring and other potential confounders. Schizophrenia bulletin, 41(3), 644–655. https://doi.org/10.1093/schbul/sbu120

Howes, O. D., McCutcheon, R., Agid, O., de Bartolomeis, A., van Beveren, N. J., Birnbaum, M. L., Bloomfield, M. A., Bressan, R. A., Buchanan, R. W., Carpenter, W. T., Castle, D. J., Citrome, L., Daskalakis, Z. J., Davidson, M., Drake, R. J., Dursun, S., Ebdrup, B. H., Elkis, H., Falkai, P., Fleischhacker, W. W., … Correll, C. U. (2017). Treatment-resistant schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group consensus guidelines on diagnosis and terminology. The American Journal of Psychiatry, 174(3), 216–229. https://doi.org/10.1176/appi.ajp.2016.16050503

Kane, J., Honigfeld, G., Singer, J., & Meltzer, H. (1988). Clozapine for the treatment-resistant schizophrenic: A double-blind comparison with chlorpromazine. Archives of General Psychiatry, 45(9), 789–796. https://doi.org/10.1001/archpsyc.1988.01800330013001

Khokhar, J. Y., Henricks, A. M., Sullivan, E. D. K., & Green, A. I. (2018). Unique Effects of Clozapine: A Pharmacological Perspective. Advances in pharmacology (San Diego, Calif.), 82, 137–162. https://doi.org/10.1016/bs.apha.2017.09.009

Kim, D. D., Barr, A. M., White, R. F., Honer, W. G., & Procyshyn, R. M. (2019). Clozapine-induced obsessive–compulsive symptoms: mechanisms and treatment. Journal of psychiatry & neuroscience : JPN, 44(1), 71–72. https://doi.org/10.1503/jpn.180087

Konte, B., Walters, J. T. R., Rujescu, D., Legge, S. E., Pardiñas, A. F., Cohen, D., Pirmohamed, M., Tiihonen, J., Hartmann, A. M., Bogers, J. P., van der Weide, J., van der Weide, K., Putkonen, A., Repo-Tiihonen, E., Hallikainen, T., Silva, E., Ingimarsson, O., Sigurdsson, E., Kennedy, J. L., Sullivan, P. F., … Giegling, I. (2021). HLA-DQB1 6672G>C (rs113332494) is associated with clozapine-induced neutropenia and agranulocytosis in individuals of European ancestry. Translational psychiatry, 11(1), 214. https://doi.org/10.1038/s41398-021-01322-w

Legge, S. E., & Walters, J. T. (2019). Genetics of clozapine-associated neutropenia: recent advances, challenges and future perspective. Pharmacogenomics, 20(4), 279–290. https://doi.org/10.2217/pgs-2018-0188

Li, C. H., Stratford, R. E., Velez de Mendizabal, N., Cremers, T. I. F. H., Pollock, B. G., Mulsant, B. H., Remington, G., & Bies, R. R. (2014). Prediction of brain clozapine and norclozapine concentrations in humans from a scaled pharmacokinetic model for rat brain and plasma pharmacokinetics. Journal of Translational Medicine, 12, 203. https://doi.org/10.1186/1479-5876-12-203

Li, X.-H., Zhong, X.-M., Lu, L., Zheng, W., Wang, S.-B., Rao, W.-W., Wang, S., Ng, C. H., Ungvari, G. S., Wang, G., & Xiang, Y.-T. (2020). The prevalence of agranulocytosis and related death in clozapine-treated patients: A comprehensive meta-analysis of observational studies. Psychological Medicine, 50(4), 583–594. https://doi.org/10.1017/S0033291719000369

Lieberman, J. A., & Stroup, T. S. (2011). The NIMH-CATIE schizophrenia study: What did we learn? American Journal of Psychiatry, 168(8). https://doi.org/10.1176/appi.ajp.2011.11010039

Manu, P., Lapitskaya, Y., Shaikh, A., & Nielsen, J. (2018). Clozapine rechallenge after major adverse effects: Clinical guidelines based on 259 cases. American Journal of Therapeutics, 25(2), e218–e223. https://doi.org/10.1097/MJT.0000000000000715

McGrath, N. M., Humberstone, V., & Abraham, A. C. (2022). Diabetes mellitus prevalence in Northland New Zealand schizophrenia patients on clozapine. New Zealand Medical Journal, 135(1558), 41–45. https://nzmj.org.nz/media/pages/journal/vol-135-no-1558/8572fa6ef3-1696471165/vol-135-no-1558.pdf#page=41

Meltzer, H. Y., Alphs, L., Green, A. I., Altamura, A. C., Anand, R., Bertoldi, A., Bourgeois, M., Chouinard, G., Islam, M. Z., Kane, J., Krishnan, R., Lindenmayer, J.-P., & Potkin, S. (2003). Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Archives of General Psychiatry, 60(1), 82–91. https://doi.org/10.1001/archpsyc.60.1.82

Melzer-Ribeiro, D. L., Napolitano, I. C., Leite, S. A., Alencar de Souza, J. A., Vizzotto, A. D. B., Di Sarno, E. S., Fortes, M., Gomes, M. L., de Oliveira, G. M., Avrichir, B. S., Talib, L. L., Correll, C. U., & Elkis, H. (2024). Randomized, double-blind, sham-controlled trial to evaluate the efficacy and tolerability of electroconvulsive therapy in patients with clozapine-resistant schizophrenia. Schizophrenia Research, 268, 252–260. https://doi.org/10.1016/j.schres.2023.11.009

Montville, D. J., Lindsey, J. M., & Leung, J. G. (2021). Fluctuation between cigarette smoking and use of electronic nicotine delivery systems: Impact on clozapine concentrations and clinical effect. Mental Health Clinician, 11(6), 365-368. https://www.doi.org/10.9740/mhc.2021.11.365

Moreno Tarazona, E., Orozco Gonzalez, M., La Rosa Giron, A., Ruiz-Grosso, P., & Lazo-Porras, M. (2025). Prevalence of obsessive-compulsive symptoms in patients with schizophrenia treated with clozapine: A scoping review. BMC Psychiatry, 25, 71. https://doi.org/10.1186/s12888-024-06466-9

Murch, S., Tran, N., Liew, D., Petrakis, M., Prior, D., & Castle, D. (2013). Echocardiographic monitoring for clozapine cardiac toxicity: Lessons from real-world experience. Australasian Psychiatry, 21(3), 258–261. https://doi.org/10.1177/1039856213475684

Myles, N., Myles, H., Xia, S., Large, M., Kisely, S., Galletly, C., Bird, R., & Siskind, D. (2018). Meta-analysis examining the epidemiology of clozapine-associated neutropenia. Acta Psychiatrica Scandinavica, 138(2), 101–109. https://doi.org/10.1111/acps.12898

Nordström, A. L., Farde, L., Nyberg, S., Karlsson, P., Halldin, C., & Sedvall, G. (1995). D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients. The American journal of psychiatry, 152(10), 1444–1449. https://doi.org/10.1176/ajp.152.10.1444

Northwood, K., Pearson, E., Arnautovska, U., Kisely, S., Pawar, M., Sharma, M., Vitangcol, K., Wagner, E., Warren, N., & Siskind, D. (2023). Optimising plasma clozapine levels to improve treatment response: an individual patient data meta-analysis and receiver operating characteristic curve analysis. The British journal of psychiatry : the journal of mental science, 222(6), 241–245. https://doi.org/10.1192/bjp.2023.27

Pallares Vela, E., Dave, P., & Cancarevic, I. (2021). Clozapine-related thromboembolic events. Cureus, 13(8), e16883. https://doi.org/10.7759/cureus.16883

Patel, R. S., Veluri, N., Suchorab, A., Shah, K., & Verma, G. (2021). Clozapine-Induced Constipation: A Case Report and Review of Current Management Guidelines. Cureus, 13(5), e14846. https://doi.org/10.7759/cureus.14846

Puder, D. (Host). (2022, March 8). Psychopharmacology Mediators (No. 141) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-141-psychopharmacology-mediators?rq=141

Puder, D. (Host). (2024a, May 29). Q&A with Dr. Cummings Part 2 (No. 214) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-214-qanda-with-dr-cummings-part-2#:~:text=antagonist,treating%20me%20with%20something%20that

Puder, D. (Host). (2024,Sept. 27). Managing Weight Gain from Psychiatric Medications with Dr. Michael Cummings (No. 223) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-223-glp1-agonists-for-psych-med-induced-weight-gain

Rogers, J. P., Oldham, M. A., Fricchione, G., Northoff, G., Ellen Wilson, J., Mann, S. C., Francis, A., Wieck, A., Elizabeth Wachtel, L., Lewis, G., Grover, S., Hirjak, D., Ahuja, N., Zandi, M. S., Young, A. H., Fone, K., Andrews, S., Kessler, D., Saifee, T., Gee, S., … David, A. S. (2023). Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology. Journal of psychopharmacology (Oxford, England), 37(4), 327–369. https://doi.org/10.1177/02698811231158232

Saini, A., Begum, N., Matti, J., Ghanem, D. A., Fripp, L., Pollak, T. A., Zandi, M. S., David, A., Lewis, G., & Rogers, J. (2024). Clozapine as a treatment for catatonia: A systematic review. Schizophrenia research, 263, 275–281. https://doi.org/10.1016/j.schres.2022.09.021

Segev, A., Iqbal, E., McDonagh, T. A., Casetta, C., Oloyede, E., Piper, S., Plymen, C. M., & MacCabe, J. H. (2021). Clozapine-induced myocarditis: electronic health register analysis of incidence, timing, clinical markers and diagnostic accuracy. The British journal of psychiatry : the journal of mental science, 219(6), 644–651. https://doi.org/10.1192/bjp.2021.58

Spivak, B., Mester, R., Abesgaus, J., Wittenberg, N., Adlersberg, S., Gonen, N., & Weizman, A. (1997). Clozapine treatment for neuroleptic-induced tardive dyskinesia, parkinsonism, and chronic akathisia in schizophrenic patients. The Journal of clinical psychiatry, 58(7), 318–322. https://doi.org/10.4088/jcp.v58n0706

Stanilla, J. K., de Leon, J., & Simpson, G. M. (1997). Clozapine withdrawal resulting in delirium with psychosis: A report of three cases. The Journal of Clinical Psychiatry, 58(6), 252–255. https://doi.org/10.4088/jcp.v58n0603

Taipale, H., Tanskanen, A., & Tiihonen, J. (2023). Safety of Antipsychotic Polypharmacy Versus Monotherapy in a Nationwide Cohort of 61,889 Patients With Schizophrenia. American Journal of Psychiatry, 180(5), 377–385. https://doi.org/10.1176/appi.ajp.20220446

Tanzer, T., Warren, N., McMahon, L., Barras, M., Kisely, S., Brooks, E., & Siskind, D. (2023). Treatment strategies for clozapine-induced nocturnal enuresis and urinary incontinence: A systematic review. CNS Spectrums, 28(2), 133–144. https://doi.org/10.1017/S1092852922000050

Taylor, C., Marsh-Davies, A., Skelly, R., Archibald, N., & Jackson, S. (2022). Setting up a clozapine service for Parkinson’s psychosis. BJPsych Advances, 28(2), 90–98. DOI: https://doi.org/10.1192/bja.2021.24

Tiihonen, J., Taipale, H., Mehtälä, J., Vattulainen, P., Correll, C. U., & Tanskanen, A. (2019). Association of Antipsychotic Polypharmacy vs Monotherapy With Psychiatric Rehospitalization Among Adults With Schizophrenia. JAMA psychiatry, 76(5), 499–507. https://doi.org/10.1001/jamapsychiatry.2018.4320

Varma, S., Bishara, D., Besag, F. M., & Taylor, D. (2011). Clozapine-related EEG changes and seizures: dose and plasma-level relationships. Therapeutic advances in psychopharmacology, 1(2), 47–66. https://doi.org/10.1177/2045125311405566

Wang, G., Zheng, W., Li, X.-B., Wang, S.-B., Cai, D.-B., Yang, X.-H., Ungvari, G. S., Xiang, Y.-T., & Correll, C. U. (2018). ECT augmentation of clozapine for clozapine-resistant schizophrenia: A meta-analysis of randomized controlled trials. Journal of Psychiatric Research, 105, 23–32. https://doi.org/10.1016/j.jpsychires.2018.08.002

Zhou, S. F., Wang, B., Yang, L. P., & Liu, J. P. (2009). Structure, function, regulation and polymorphism and the clinical significance of human cytochrome P450 1A2. Drug Metabolism Reviews, 42(2), 268–354. https://doi.org/10.3109/03602530903286476

View Details

By listening to this episode, you can earn 1.25 Psychiatry CME Credits.

Other Places to listen: iTunes, Spotify

Article Authors: Awais Aftab, MD, David Puder, MD

Article review team: Joanie Burns, DNP, APRN, PMHNP-BC, Erica Vega, MD

None of the presenters or review team have any conflict of interest.

On today’s podcast, I interviewed Awais Aftab, MD is a psychiatrist in Cleveland, OH, and a Clinical Assistant Professor of Psychiatry at Case Western Reserve University. His academic, educational, and public-facing work focuses on conceptual and critical issues in psychiatry. His first book, “Conversations in Critical Psychiatry,” (2024) is an edited volume of interviews published by Oxford University Press. He writes online on his Substack newsletter Psychiatry at the Margins. I would also recommend following him on X.

Introduction To The Serotonin Hypothesis And ControversiesThere has been a recent surge in interest around the serotonin hypothesis of depression, the mechanisms of antidepressant action, and the efficacy of antidepressants. Meta-analyses and critical reviews (e.g., Moncrieff et al., 2023) have challenged the long-held assumption that depression is caused by a serotonin deficiency. While many researchers had already moved beyond this simplistic model years ago, its persistence in public discourse and pharmaceutical marketing made the critique particularly impactful. This notion became entrenched partly through pharmaceutical marketing in the 1990s. Given the popularity of the "chemical imbalance" narrative, these scientific debates have reignited public and academic debates about whether current treatments are based on flawed assumptions. Independently, there is a growing sentiment that antidepressants are being over-prescribed and there is increasing concern around historically-neglected adverse effects such as antidepressant withdrawal and sexual dysfunction (Aftab, 2024). Non-pharmacological interventions such as psychotherapy and lifestyle changes (see prior episodes on diet and exercise: 009, 010, 018, 059, 096, 131, 142, 163, 165, 179, 187, 230) are typically underutilized. Interest in newer treatments such as ketamine, psychedelics, and newer protocols of transcranial magnetic stimulation (TMS) has highlighted the limitations of first-line antidepressants. High-profile articles, books, and social media discussions have contributed to widespread public interest. These issues have become enmeshed with political developments and culture wars. In this context, clarity on what scientific literature says about serotonin abnormalities in depression, involvement of serotonergic pathways in regulation of mood and behavior, therapeutic mechanisms of antidepressants, and efficacy of antidepressants is essential.

What Is The “Serotonin Hypothesis”?Discussions on the serotonin hypothesis quickly become confusing because there is no precise articulation of what the serotonin hypothesis of depression is or what the nature of the relationship between various aspects of the serotonergic system and various aspects of depression is supposed to be. As a result, it is not evident that disproving some versions of the serotonin hypothesis means that “serotonin has nothing to do with depression.”

Here is an incomplete list of the ways in which we might understand the relationship between depression and serotonin:

• Depression is caused by low levels of serotonin in the brain or low serotonergic activity
• Depression, generally or in some subset of patients, involves alterations of the serotonin signaling system (e.g. in the distribution or sensitivity of certain sorts of serotonin receptors)
• The serotonergic system mechanistically links depressive symptoms and neurobiological dysfunctions in other aspects of brain functioning (e.g. neurogenesis or neuroplasticity)
• The serotonin system is generally involved in the regulation of mood and temperament, and there may be no specific abnormality in the serotonin system in depression, by and large, but it still provides us a target for intervention with serotonergic antidepressants.

In addition, we can also talk about whether this involvement of serotonin is considered the central or primary cause of depression or whether it exists as one causal element in a more complex causal web.

We’ve known for decades that the “serotonin deficiency” version of this hypothesis is not supported by evidence. Many researchers have believed that some alterations exist in the serotonin system, and some preliminary research findings did suggest that, but nothing conclusive has emerged that commands a strong consensus.

The significance of monoamine depletion remains to be dispelled.

In 2007, a meta-analysis by Ruhé and colleagues, published in Molecular Psychiatry, reported that acute tryptophan depletion produces depressed mood in healthy individuals with a family history of depression [Hedges’ g (95% CI) −0.56 (−1.00 to −0.13)] and in patients with depression in remission [Hedges’ g of -1.90 (-3.02 to -0.78) for individuals not on antidepressants at the time of study, and Hedges’ g of -0.49 (-0.89 to -0.10) for those on antidepressants].

A 2015 meta-analysis by Kambeitz and Howes indicated that serotonin transporter availability in depressed patients is reduced in key regions of the limbic system. Fifty (n=27 in vivo and n=25 post mortem) studies including 877 patients with depression (mean age: 42.9 years) and 968 healthy controls (mean age: 42.7 years). In vivo neuroimaging studies indicated reduced serotonin transporter binding in the striatum (g=-0.39, p=0.01), the amygdala (g=-0.37, p=0.01) and the brainstem (g=-0.31, p=0.01), including the midbrain (g=-0.27, p=0.02), but no significant alteration in the thalamus or the hippocampus. The post mortem findings were not statistically significant.

And in October 2022, after the Moncrieff and colleagues (2023) paper was published online ahead of print in July 2022, Erritzoe and colleagues (2023) published the first direct assessment of serotonin release capacity in people with depression reported a reduction in serotonin release capacity in patients experiencing a major depressive episode. 17 antidepressant-free patients with major depressive episode and 20 healthy controls underwent 90-minute dynamic [11C]Cimbi-36 PET. Following d-amphetamine administration, a change in frontal nondisplaceable binding potential (BPND), a measure of serotonin release capacity, was significantly lower in individuals with major depressive episode than the HC group (HC: 15% ± 14% vs. MDE: 6.5% ± 20%, p = .041). (It’s a small study, and the difference between groups is not that striking; thus, these findings should be interpreted cautiously and considered preliminary.)

The end result is that the presence and nature of alteration of the serotonergic system in depression, a heterogenous syndrome, are open scientific problems. Depression is a highly heterogenous and multifactorial condition, and involves a range of neurophysiological, psychological, and sociopolitical factors. Given the heterogeneity of depression, it is highly unlikely that such abnormalities of serotonin, even if they exist, will be present in most individuals with depression.

Aside from the question of serotonin alteration or dysfunction, the involvement of the serotonin system in the general regulation of mood and emotions is backed by a large body of literature from animals as well as humans (e.g., Roberts et al., 2020 and Salvan et al., 2023). Serotonin’s effects on impulsivity and negative biases are supported by convergent evidence from various studies, and appear to be related to the SSRI hypothesized effects on emotional information processing.

Antidepressants, including SSRIs, show a consistent and large effect in forced swim test in rodents. The swim test involves the scoring of active (swimming and climbing) or passive (immobility) behavior when rodents are forced to swim in a cylinder from which there is no escape (Slattery & Cryan, 2012). Reduction in passive behavior has traditionally been interpreted as an antidepressant-like effect, however, others have argued that the rodent forced swim test measures stress-coping strategy, not depression-like behavior (Commons et al., 2017). (However, animal models like the FST have significant limitations in translating directly to human depression, given the complexity and variability of depressive symptoms and underlying biology in humans.) Regardless of the behavioral interpretation of FST, it is a demonstration of the behavioral effects of serotonergic transmission. In a 2018 meta-analysis of mouse FST, fluoxetine had an effect size of 1.99 compared to the control solution (p < 0.001) (Kara et al., 2018).

Using population-level brain imaging from the Human Connectome Project (HCP), Salvan et al. (2023) identified two distinct patterns in serotonin receptor network connectivity. The first pattern correlated with impulsivity (acting impatiently or without thinking), antisocial behaviors, and aggression; the second related to negatively biased reward processing (viewing rewards as less valuable), depression, and panic symptoms. These results replicate the established division of the effects of serotonin modulation on human behavior postulated by influential theories of serotonin function.

Colwell and colleagues used a selective serotonin releasing agent, fenfluramine, which directly elevates synaptic serotonin levels, to investigate its effects on behaviors traditionally associated with serotonin function. The study (n=53 participants) demonstrated through computational modeling that increased serotonin reduced sensitivity specifically to aversive outcomes (Cohen's d = -0.57, p = 0.04), influencing how participants responded to negative feedback during reinforcement learning tasks. Additionally, increased serotonin enhanced behavioral inhibition by promoting more cautious decision-making, particularly reducing impulsivity during aversive emotional interference (e.g., fearful faces) (Cohen’s d = 1.28, p < 0.0001). (Colwell et al,, 2024). These results suggest serotonin's role in reducing impulsivity and moderating negative emotional reactivity, possibly by dampening the exaggerated negative biases seen in anxiety or depression.

Even if there is no dysfunction of serotonin in depression, the link between serotonergic mechanisms and aspects of mood/behavior allows for the possibility of effective intervention. There is nothing wrong with kidneys in chronic heart failure, but we can use diuresis as a treatment; there is nothing wrong with prostaglandin pathways in infections, but we can act on them to treat fever; etc. Serotonergic pathways appear to be mechanistically involved in regulation of mood and emotions. There may not necessarily be anything “wrong,” “dysfunctional,” or “imbalanced” in these pathways (except in an indirect sense (Aftab, 2023)) — they may be working just fine — but if they are involved in how mood/emotions are regulated, they can be intervened on to produce desired effects.

Moncrieff’s 2023 Umbrella Review Focused on Serotonin Association, Not Antidepressant EfficacyThe current iteration of public and scientific debate around the serotonin hypothesis has revolved around a 2023 Umbrella Review by Moncrieff and colleagues.

This has been particularly controversial because the review was quickly used by the authors to publicly state that this challenges the idea that antidepressant medications are effective (since there is no “serotonin imbalance” to fix) and that depression cannot be considered to be a medical condition. Additionally, the authors stated that any potential benefits of antidepressants are attributable to a general blunting effect rather than specific actions on serotonin. These claims went far and beyond the questions addressed in the review.

• They aimed to synthesize and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research.
• Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT1A receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT gene-environment interactions. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. bipolar depression) were excluded.
• 17 studies were included: 12 systematic reviews and meta-analyses, 1 collaborative meta-analysis, 1 meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic association study and 1 umbrella review.
• Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n = 1002).
• One meta-analysis of cohort studies of plasma serotonin showed no relationship with depression, and evidence that lowered serotonin concentration was associated with antidepressant use (n = 1869).
• Two meta-analyses of overlapping studies examining the 5-HT1A receptor (largest n = 561), and three meta-analyses of overlapping studies examining SERT binding (largest n = 1845) showed weak and inconsistent evidence of reduced binding in some areas.
• One meta-analysis of tryptophan depletion studies found no effect in most healthy volunteers (n = 566), but weak evidence of an effect in those with a family history of depression (n = 75).
• Another systematic review (n = 342) and a sample of ten subsequent studies (n = 407) found no effect in volunteers. The two largest and highest quality studies of the SERT gene, one genetic association study (n = 115,257) and one collaborative meta-analysis (n = 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression.
• The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations.
• Moncrieff and colleagues stated that some evidence was also consistent with the possibility that long-term antidepressant use reduces serotonin concentration.

Academic Critique Of Moncrieff’s Paper: Methodological Misrepresentation And Inappropriate ExtrapolationThe review led to a fierce set of responses from the psychiatric community. The most important among them is a commentary by Jauhar and colleagues (2023), in Molecular Psychiatry, authored by 35 distinguished scientists, a who’s who of psychiatric and psychopharmacological research, aptly titled, “A leaky umbrella has little value: evidence clearly indicates the serotonin system is implicated in depression.”

Jauhar and colleagues (2023) point out serious issues with the methodology of the umbrella review, identify compromising errors in methodological misrepresentation, and dispute the validity of the conclusions.

• They argue that multiple methodological choices (such as choosing not to synthesize the results of individual meta-analyses because they included overlapping studies, exclusion of important primary studies relevant to the serotonin-depression link, assessing quality of evidence using a “modified” version of GRADE introduced in a post-hoc protocol amendment, etc.) biased the conclusions of the review.
• The confounding effects of antidepressants were only considered if the results were positive. Jauhar and colleagues counter: “It is unclear why confounding of effects of antidepressants would not apply to all studies, i.e. not just where positive outcomes were seen: antidepressants are as likely to confound studies with negative results…” (Jauhar et al., 2023, p. 3150).
• Aside from noting the exclusion of an important clinical and molecular imaging study of tryptophan depletion, Jauhar and colleagues also dispute the Moncrieff and colleagues’ interpretation of a meta-analysis of tryptophan depletion (Ruhé et al., 2007). The meta-analysis actually showed a large effect size of tryptophan depletion on mood in depressed people not taking antidepressants.

A more accurate interpretation is that tryptophan depletion studies suggest a role for 5-HT in people vulnerable to depression and in those remitted on SSRI treatment. In contrast, by citing a series of individual negative studies in healthy participants, the authors give the impression tryptophan depletion has no effect (Jauhar et al., 2023, p. 3150).

• Several studies of circulating tryptophan concentrations were excluded from the umbrella review. L-tryptophan plasma concentrations have been shown to be decreased in major depression in small studies, including in unmedicated individuals.
• Important molecular imaging evidence was misinterpreted. Moncrieff and colleagues stated that reduced binding of serotonin 1A receptors suggests increased levels of synaptic serotonin, but reduced binding can also be because of decreased receptor density or affinity. Jauhar and colleagues appear to have mistakenly assumed that serotonin 1A receptors are exclusively presynaptic autoreceptors, but most serotonin 1A receptors are post-synaptic heteroreceptors. Diminished availability of serotonin 1A receptors in unmedicated depression is consistent with lowered serotonin transmission, and Jauhar and colleagues say that this is a replicated finding in people who were not on antidepressants.
• Moncrieff and colleagues stated that there is a lack of consistency in the brain areas in which serotonin transporter binding has been reported. Jauhar and colleagues argue that in serotonin transporter binding studies, a number of brain regions have actually been consistently implicated.
• Moncrieff and colleagues attributed the results of serotonin transporter binding studies in meta-analyses to prior antidepressant treatment, but this ignores the fact that reduced serotonin transporter findings have also been reported in drug-naive populations, and they missed the fact that 149 out of 364 people in an included meta-analysis were drug naive.
• A small study, published by Erriztoe and colleagues in 2023, employing a relatively direct assessment of serotonin release capacity, the first study of its kind, provided preliminary evidence of reduced serotonin release capacity in individuals with depression, which shows that this is still an active area of scientific inquiry and any closure is premature.
• The serotonergic system continues to be an important mechanism implicated in the effects of traditional antidepressants as well as psychedelics.
• Jauhar and colleagues (2023):

To summarise, the methodology is inconsistent with an umbrella review, with substantial bias created by the authors’ chosen quality criteria, selective reporting, and interpretation of results. There is an underappreciation of the complexities of neuroscience and neuropsychopharmacology, and it is therefore impossible for the reader to draw valid or reliable conclusions. A more accurate, constructive conclusion would be that acute tryptophan depletion and decreased plasma tryptophan in depression indicate a role for 5-HT in those vulnerable to or suffering from depression, and that molecular imaging suggests the system is perturbed. The proven efficacy of SSRIs in a proportion of people with depression lends credibility to this position (Jauhar et al., 2023, Conclusion).

Concerns about methodology and interpretation are noted in some other commentaries as well. Bartova and colleagues (2023) write:

Since [Moncrieff et al.’s] deduction is based on selected literature covering serotonin exclusively, and hence, addressing only a part of the complex understanding of depression, we argue that the authors’ conclusion, that the serotonin theory cannot be empirically substantiated, cannot be derived from the present work. A meta-analysis revealing spatial-temporal dynamics of the serotonergic neurotransmission in depression underlines the fact that serotonin represents a crucial but dynamic neurobiological underpinning of depression… (Bartova et al., 2023, para 2).

The reference cited is a meta-analysis (Gryglewski et al., 2014) of molecular imaging of serotonin transporters in major depression which revealed reductions in serotonin transporter in midbrain and amygdala. Bartova and colleagues emphasize the complex etiology of depression of which the serotonin system is a part, and say, “… the serotonin theory of depression has been substantially extended and partly modified regarding neuroplastic mechanisms rather than not empirically substantiated as suggested by the authors.”

Jacobsen (2023) comments in a response statement: “Moncrieff et al. appears unfamiliar with serotonin biology and pharmacology. The review contains factual errors, makes conclusions serotonin neurobiology may not support, and quotes the cited literature in a selective manner” (Jacobsen, 2023). Jacobsen goes on to list “the most obvious errors” pertaining to tryptophan depletion and serotonin receptor studies.

In their response to comments, Moncrieff and colleagues (2023) begin by noting that critics appear to be advancing a confusing picture of the serotonin hypothesis both long discarded and still supported, which shows Moncrieff and colleagues’ remarkable lack of appreciation of the complexity of the issues at hand, the different ways in which the serotonergic system appears to be relevant to depression, and that there is no simple, well-defined serotonin hypothesis (à la serotonin deficiency) being defended here. Moncrieff and colleagues defend their methodology and the interpretation of results, but they fail to acknowledge the significance of tryptophan and serotonin receptor studies and other limitations pointed out by critics. They also continue to promote skepticism about antidepressant efficacy and push speculative ideas about antidepressant benefits being accounted for by effects such as emotional blunting, a hypothesis they consider to be more plausible than the entire scientific literature on neurotransmitters, neuroplasticity, inflammation, or neural networks!

Their response highlights that the umbrella review findings, even if accepted at face value, acquire scientific significance only in the broader context of a universe of critical beliefs that lack widespread scientific support, beliefs including a general dismissal of the neurobiology of depression, skepticism about antidepressant efficacy, and adoption of the “drug centered model.”

It is essential to emphasize that the popularized "chemical imbalance" narrative—often simplistically communicated in patient education—never fully reflected the complexity understood by neuroscientists. Depression involves multiple neurotransmitter systems (dopamine, norepinephrine, GABA, glutamate) interacting dynamically. Thus, disproving a simplistic serotonin deficiency does not invalidate serotonin’s role altogether.

The Real Goal Of The Umbrella Review Was To Shift Public Narratives Around AntidepressantsIn retrospect, it seems clear that the goal of the Moncrieff and colleagues paper was not really scientific. Rather than seek to explicate the complicated role that the serotonergic system plays in depression, it appears to me that the authors were far more interested in refuting the popular “chemical imbalance” idea that exists in the public imagination. In order to effectively do so, and to generate provocative headlines, they needed a clean and simple conclusion with a critical hit on the serotonin-depression link. There was no room for intricacies, as that would have been a rhetorical impediment. The task of answering scientific questions by acknowledging complexities is quite different from the task of generating a public narrative with rhetorical appeal. Moncrieff and colleagues tried to hit two birds with one stone, and steamrolled over crucial scientific details in the process. Trying to score points in the psychiatric culture wars using scientific reviews is a recipe for bad science.

The validity of the "chemical imbalance" narrative has historically had little correlation with scientific findings regarding the serotonin system. Based on existing evidence from tryptophan and serotonin receptor binding studies, it does seem possible that alterations of the serotonin system play a role in depression, but the role of serotonin must be conceptualized within a whole network of other causal factors that range from molecular to cultural. None of this justifies characterizing depression as primarily a “chemical imbalance” (which is misleading at best, outright false at worst) or as fundamentally a problem of serotonin. Alterations in the serotonin system may be present in depression; however, the concept of a chemical imbalance, as commonly perceived by the public, lacks strong scientific support. Such a position may not generate headlines, but it does far more justice to the body of scientific evidence.

What do we know about how antidepressants work, especially in relationship to the serotonin system?Individuals in states of depression and anxiety often show a negativity bias in processing emotionally significant information, and they can be “stuck” in a negative cognitive and emotional state such that their usual mental flexibility is lost. People with depression and anxiety are more likely to interpret neutral or ambiguous facial expressions as negative, such as assuming someone looks sad. They also tend to focus more on negative information and remember it more easily. Additionally, they don’t respond as positively to rewards, have less motivation to seek them out, and are more sensitive to punishment. Individuals not only view the world and themselves negatively but also find it difficult to benefit from positive experiences around them. Depressed people often struggle with cognitive and emotional flexibility and are limited in their ability to switch between emotions and experience a range of emotions.

Shifts in Emotional Information ProcessingThe cognitive neuropsychological hypothesis (Godlewska & Harmer, 2020) suggests that antidepressants lead to early positive changes in emotional processing that predict later clinical improvements. Studies on healthy volunteers who take antidepressants show a shift in emotional processing tasks, such as recognizing emotions in facial expressions, within days, sometimes even after a single dose. Similar effects have subsequently been reproduced in individuals with depression and are also supported by animal studies. SSRIs seem to primarily affect the processing of negative emotions, while norepinephrine reuptake inhibitors have a better impact on how participants respond to positive or rewarding stimuli.

An important aspect of this hypothesis is that while a positive shift in emotional processing is crucial, it is not necessarily sufficient on its own. The interaction between changes in emotional processing and the environment is vital to improvement. Social interactions allowing individuals to relearn positive emotional associations play a key role. Patients in more positive environments and with stronger social supports are more likely to benefit from these early emotional changes.

In a recent study (Colwell et al., 2024) in which serotonin was directly increased in brain synapses without using SSRIs, people became less sensitive to negative outcomes with more serotonin, and their self-control improved during decision-making. That is, an increase in synaptic serotonin decreases reinforcement sensitivity to loss outcomes and enhances behavioral inhibition and impulse control.

Cognitive Flexibility and NeuroplasticityShine and colleagues (2022) hypothesize the role of serotonin as allowing for a switch between modes of “cognitive automaticity” and “cognitive flux.” If a person becomes overly reliant on recurrent, well-established behavioral patterns—behaviors that are increasingly stereotyped and inflexible (such as depressive ruminations and compulsive behaviors)—this could be conceptualized as a state of “cognitive constipation.” Increasing serotonergic activity in such a situation allows for a switch to more flexible modes of cognitive processing. [A patient of mine once described his improvement on an antidepressant as, “It is as if I mentally feel more malleable, better able to identify and move away from unhelpful thinking patterns.”]

Mechanisms of this cognitive flexibility appear to be related to both serotonergic enhancement as well as neuroplasticity. Antidepressants appear to facilitate two key processes: rapid changes in emotional processing along with molecular cascades that promote long-term neuroplasticity (Page et al., 2024). There is a decent body of literature supporting the idea that antidepressants promote neurotropic signaling, particularly by increasing brain-derived neurotrophic factor (BDNF) and activating the receptor TrkB, which enhances synapse formation and maintenance. The outcome can resemble the flexible state seen in early brain development. Studies in rodents show that environmental interventions alone don’t induce functional changes, but when combined with antidepressants, they can reverse maladaptive behaviors like aggression. Similarly, in humans, antidepressants seem to create a “window of plasticity” that allows environmental factors, such as positive experiences or psychotherapy, to reshape neural activity (Page et al., 2024).

Effects on NeuroticismSSRIs appear to reduce neuroticism (Soskin et al., 2012), a personality trait characterized by emotional instability, negative emotions, and a heightened sensitivity to stress. Neuroticism is closely linked to vulnerability to depression and anxiety, and a reduction in neuroticism appears to be a mediator of antidepressant response (Quilty et al., 2008).

The effects of neuroticism are well illustrated by Tang and colleagues in a 2009 placebo-controlled trial (n=240) that investigated the effects of an SSRI (paroxetine) on personality traits in patients with major depression. The study compared patients receiving paroxetine, a placebo, or cognitive therapy to examine whether SSRIs specifically influence these personality traits beyond simply improving depressive symptoms.

Patients who took paroxetine experienced significantly greater changes in neuroticism and extraversion compared to those who received a placebo. These personality changes were observed even after accounting for improvements in depression. Patients taking paroxetine showed much larger reductions in neuroticism (6.8 times greater) and increases in extraversion (3.5 times greater) than those on placebo, even when matched for similar depression improvements. While placebo patients experienced substantial reductions in depression, they showed minimal changes in neuroticism and extraversion. Cognitive therapy also led to notable changes in personality traits, particularly neuroticism, though the effect was less distinct once depression improvement was controlled for. In addition, a reduction in neuroticism during SSRI treatment was linked to lower relapse rates among those who responded to paroxetine, but this was not observed among those who responded to cognitive therapy.

This suggests that SSRIs have a specific pharmacological effect on neuroticism, and the effect on neuroticism contributes directly to acute and prophylactic therapeutic effects in treating depression.

Antidepressant effects on neuroticism may be linked to findings from animal models that antidepressants confer “resilience” against stress. In animal models, for example, chronic antidepressant administration can protect against the cognitive and emotional disturbances that result from chronic, unpredictable stress (Bondi et al., 2008).

Controversy Around The Efficacy Of AntidepressantsAntidepressants outperform placebo in randomized clinical trials in a manner that is statistically significant (that is, the results are unlikely to have occurred by chance alone). This was confirmed in one of the largest meta-analysis ever conducted, that included 522 clinical trials and 116K subjects: “In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89–2·41) for amitriptyline and 1·37 (1·16–1·63) for reboxetine” (Cipriani et al., 2018a, Findings). This finding has been consistently demonstrated in multiple meta-analyses and is widely accepted as robust. There is broad consensus that antidepressants exhibit statistically significant superiority over placebo.

The problem, however, is that the average difference between improvement in depressive symptoms — as measured by the most commonly used rating scale Hamilton Depression Rating Scale (HDRS) — is 2 points, or an effect size of 0.3 which is considered small. In a recent analysis of trials in the FDA database (baseline mean HDRS-17 score of 23; subjects had at least moderate severity depression on HDRS), HDRS score improved by 8 points on average in the placebo group vs 9.8 points in the antidepressant group. HDRS-17 total score ranges from 0 to 52. A difference of 2 points is not very meaningful at face-value (Stone et al., 2022).

This is the heart of the controversy: if antidepressants are clinically effective, why only a 2 point difference from placebo? How could a 2 point difference be indicative of anything but lack of clinically significant efficacy?

There are several non-mutually exclusive ways of responding to this:

1. An average different of 2 points obscures variation in treatment response and there are subgroups that display a substantial difference from placebo.
2. HDRS total score is an inappropriate measure of antidepressant efficacy; it may be sufficient to demonstrate a statistical separation from placebo, but does not appropriately quantify the magnitude of benefit.
3. Despite appearances, a 2 point HDRS average difference from placebo is indeed clinically meaningful.

1. Different trajectories of responseTraditionally, this argument has been made using “response rates” (50% reduction in symptom severity) and “remission rates” (near complete resolution of depressive symptoms). The average response to placebo in meta-analyses is around 35% compared to about 50% for antidepressants (Cipriani et al., 2018b). While clinicians find thinking in terms of response and remission rates to be more clinically meaningful than average HDRS score (for good reasons), critics have objected to such binary categorizations as arbitrary and artificially inflating efficacy. There is an argument to be made in favor of response and remission rates, but I will not dwell on that here.

Fortunately, differences in response to antidepressants can also be demonstrated without appeal to arbitrary thresholds of response rate and remission rate.

Thase and colleagues (2011) used a special statistical model to demonstrate that patient subgroups of those benefiting or not benefiting from treatment could be identified, and that about 20% of patients benefited from escitalopram but not from placebo treatment (which corresponds to a number needed to treat [NNT] of 5).

In the Stone and colleagues (2022) analysis of antidepressant trials in the FDA database, 3 trajectories of response patterns were found, with average HDRS-17 score reductions of 16.0 (large response), 8.9 (nonspecific response), and 1.7 points (minimal response). Compared to placebo, antidepressant treatment was more likely to show large responses (24.5% v 9.6%) and less likely to show minimal responses (12.2% v 21.5%). Most responses (60-70%), however, were in the non-specific category, without a prominent difference between antidepressant and placebo. The NNT for large response for antidepressant vs placebo was 6.7. (There is a case to be made that this may be an underestimate based on differences among antidepressants in the database and because of inclusion of trials with pediatric patients.)

A medication that demonstrates a large response in 25% of patients (vs 10% of those in the placebo group) and reduces the likelihood of a minimal response is by no means a medication with “marginal efficacy” and with therapeutic effects that are “clinically meaningless.” This constitutes a clear signal of efficacy in a subset of patients that is otherwise obscured by a small average difference. The NNT of 6-7 also falls well within the respectable range when it comes to treatments in general medicine. Anyone who thinks that this constitutes marginal efficacy lacks a sense of perspective of what treatment efficacy generally looks like in medicine and clinical psychology.

The efficacy certainly leaves much to be desired. It is not as high as we would like it to be. It can be nonetheless be described as, in words of Peter Kramer, “ordinarily well.” It is also notable that this is efficacy data for a single trial of antidepressant. In clinical practice, it often takes 2 or 3 trials to find an antidepressant that the patient finds to be efficacious and tolerable, and the success rates are correspondingly higher in clinical practice.

2. HDRS total score is not the right measureAnother response to the dilemma of “2 point HDRS difference from placebo” is to point out the limitations of using HDRS-17 for the purpose of evaluating antidepressant efficacy. The 17 items included in the scale represent an idiosyncratic mix. There is, for example, only one item about depressed mood, but three items about insomnia. It also includes symptoms peripherally related to depression, such as hypochondriasis, sexual symptoms, and gastrointestinal symptoms. The inclusion of sexual and gastrointestinal symptoms is particularly problematic because these are also recognized side effects of antidepressant medications, so the scale poorly discriminates between depressive symptoms and medication side effects. Furthermore, each item is given equal weight and the validity of adding these items into a single meaningful score is questioned by many.

A study by Hieronymus and colleagues (2016) provides an obvious example of the dilemma of relying on HDRS scores, as demonstrated in their patient-level post-hoc analyses of antidepressant effects on individual items of HDRS, in particular the depressed mood item. Table 3, from the article, shows an average effect size of 0.27 for HDRS total score, but 0.40 for the depressed mood item. It is also interesting to see the pattern of response among different items — there are many that change poorly. Again, emphasizing the inability of total score to illuminate the magnitude of antidepressant efficacy.

Furthermore, they also note that the depressed mood item more consistently separates active treatment from placebo at week 6:

While 18 out of 32 comparisons [56%] failed to separate active drug from placebo at week 6 with respect to reduction in HDRS-17-sum, only 3 out of 32 comparisons [9%] were negative when depressed mood was used as an effect parameter (P<0.001). The observation that 29 out of 32 comparisons detected an antidepressant signal from the tested SSRI suggests the effect of these drugs to be more consistent across trials than previously assumed (Hieronymus et al., 2016, Discussion).

Considerations, such as these, may be related to the fact that in the PANDA study in primary care patients, while the differences in the depression rating scales (PHQ-9 and BDI-II) were unimpressive (not statistically significant for PHQ-9 and only statistically significant for BDI-II at 12 weeks), a crude 1-item measure of “Feeling better (self-rated improvement)” showed prominent separation: 59% felt better with antidepressant at 12 weeks compared to 42% with placebo (Lewis et al., 2019).

3. A 2-point average difference from placebo is nonetheless meaningfulThere are different ways of supporting this point. The first relates to what we have discussed in #1 — averages can obscure subgroup differences.

A second way is to compare it to the effect of other standard treatments. In the case of depression, psychotherapy provides a meaningful comparison. A number of trials have compared antidepressant treatment to short-term manualized psychotherapy (usually CBT) and the results are pretty clear across multiple trials: both antidepressant and short-term manualized psychotherapy have equal effects on depression rating scales, and the combination of both is superior to individual treatment. This is best illustrated in a meta-analysis by Cuijpers and colleagues (2020). As a consequence, a firm commitment to the view that antidepressants are only marginally effective necessitates the acceptance that short-term manualized psychotherapy, which represents the majority of randomized controlled trial evidence for psychotherapy, is also only marginally effective in the acute treatment of depression. (There is some data to suggest that psychotherapy and combination of psychotherapy and antidepressant have more sustained long-term effects than antidepressant alone.)

A relevant comparison can be drawn with treatments in general medicine. A key reference in this context is a study by Leucht and colleagues (2012), which demonstrates that the effect size of antidepressants, relative to placebo, is comparable to that of other established medical treatments.

A third category of response makes the point that a 2-point difference from placebo group is different from a 2-point difference from no treatment. Treatment in the placebo group is not simply a dummy pill, but also involves extensive weekly evaluations with a host of built in psychosocial support and, at times, financial compensation. The improvement seen in the placebo group is likely a mixture of natural history, regression to the mean, expectancy effects, and therapeutic effects of indirect psychosocial support.

This points to a problem with the additivity of antidepressant and “placebo” effects. A robust discussion of this aspect is highlighted by Peter Kramer in Ordinarily Well. Kramer uses the example of vodka vs placebo tonic water to make the point. If we see “4 points” of intoxication/incoordination on an imaginary scale with consumption of vodka, vs “2 points” of intoxication/incoordination with placebo tonic water, the “real” effect of vodka is not vodka minus placebo. We have subtracted too much because effects of alcohol and expectancy are not additive. Vodka + placebo/expectancy (4 points + 2 points) does not equal 6 points; it is still 4 points.

In the case of depression, the antidepressant and psychotherapy effects are not additive. “[T]he common outcome in psychiatric research is, two and two do not equal four,” Kramer further elaborates:

Placebo and antidepressant effects are unlikely to be additive. Much of what medication accomplishes, it achieves on its own…. In antidepressant trials, almost certainly, full additivity does not apply—and yet our calculations, including ones for effect sizes, assume it. Virtually every formal estimate of antidepressant efficacy arises from a premise, the right to subtract, that is unproven and likely wrong. Our estimates of drug efficacy run too low (Kramer, 2017, p. 112 ).

The additivity assumption is also noted by Kirsch and colleagues (2022), who are otherwise skeptical of antidepressant efficacy: “If antidepressant drug effects and antidepressant placebo effects are not additive… then antidepressant drugs have substantial pharmacologic effects that are duplicated or masked by placebo” (Kirsch et al., 2022)

According to Kramer, this is precisely what is going on, and leads us to a certain uncomfortable conclusion:

We cannot count on additivity. This uncertainty presents a challenge for evidence-based psychiatry: Our controlled trials, conventionally analyzed, may not reflect reality. Despite our use of randomization, they are likely subject to a consistent confound, arising from a technical bias against antidepressants. We know that antidepressants work. We cannot say how well (Kramer, 2017, p 113. )

Antidepressant Efficacy and Depression SeveritySome early analyses such as by Khan and colleagues (2005) have reported the effect size of antidepressants increases with the severity of depression, such that when considering placebo vs. antidepressant effect, for the severe group there is a difference of roughly 8.3 points on HAM-D, but the overall response to antidepressant is 16.5 in this category. This is a very significant decrease in depressive symptoms.

However, subsequent analyses have re-assessed these estimates and the resulting picture is more complex.

Rabinowitz and colleagues (2016), for example, reported in their analyses of RCTs (n=10,737) that there was no significant interaction between baseline depression severity and antidepressant response (placebo vs active treatment) when using patient-level data, and a significant relationship emerged only when using trial-level data [Patient-level data is more accurate]. The drug-placebo mean difference (HDRS) was 2.04 for low baseline severity, 1.82 for medium, and 2.41 for high.

Furukawa and colleagues (2018) examined individual participant data meta-analysis of RCTs for second-generation antidepressants from Japan, and found that interaction between baseline severity and treatment was not statistically significant (coefficient = −0.04, 95% confidence interval: −0.16 to 0.08, P = 0.49). "We may expect as much benefit from antidepressant treatments for mild, moderate or severe major depression."

Hieronymus and colleagues (2019) conducted item-based patient-level, post-hoc analysis and showed that there is no relationship between baseline severity and antidepressant response as far as core symptoms of depression are concerned, but more peripheral symptoms on HDRS-17 show a more pronounced response to treatment as baseline severity increases.

*Note.* Reprinted from “Influence of baseline severity on the effects of SSRIs in depression: An item-based, patient-level post-hoc analysis”, by Hieronymus et al., 2019, *The Lancet Psychiatry, 6*(9), 745–752, Figure 2.

  *Note.* Reprinted from “Influence of baseline severity on the effects of SSRIs in depression: An item-based, patient-level post-hoc analysis”, by Hieronymus et al., 2019, *The Lancet Psychiatry, 6*(9), 745–752, Figure 4.

And finally, in an individual participant data analysis of FDA trials by Stone and colleagues (2022):

When baseline severity was used as the only covariate, improvement with drug and placebo increased with greater baseline severity. The advantage of drug over placebo increased with baseline severity by 0.09 points (95% confidence interval 0.06 to 0.12) for every one point increase in severity. The estimated difference between drug and placebo at a baseline severity of 16 points (5th centile) was 1.1 points, increasing to 2.5 points at a baseline severity of 29.6 points (95th centile) (Stone et al., 2022, p. 3)

.

From discussion:

Previous analyses of the relation between baseline severity and the efficacy of antidepressants found null to moderate (slope about 0.3) effects, and these effects might be attributable to instrument behavior rather than patient experience. We found that the effect of baseline severity was statistically significant (P<0.001) but small (slope about 0.1) (Stone et al., 2022, p. 6 ).

Therefore, it appears that the effect of antidepressants on core symptoms of depression compared to placebo is generally similar across different levels of severity, but improvements in peripheral symptoms, such as insomnia, is more pronounced at higher severity. Antidepressants are effective in cases of mild depression as well, however, given their side-effect profiles (such as gastrointestinal effects, sexual dysfunction, weight gain, and antidepressant withdrawal), the risk-benefit ratio is more favorable if mild depression is preferentially treated with psychosocial and lifestyle interventions. This is the position taken by depression practice guidelines by NICE and RANZCP as well (see also Malhi et al., 2022 for a comparison of guidelines from the UK and Australia/New Zealand, which demonstrate significant convergence in recommendations).

*Note.* Reprinted from “The management of depression: The evidence speaks for itself”, by Malhi et al., 2023, *The British Journal of Psychiatry, 222*(3), 97–99, Figure 1.

Conclusion In conclusion, the controversies surrounding the serotonin hypothesis underscore the importance of approaching depression through a nuanced and multidimensional framework. As explored throughout this paper, simplistic narratives, such as the “chemical imbalance” idea, though widely communicated to the public, have never accurately reflected the complex realities uncovered by neuroscientific and clinical research. Depression involves dynamic interactions among multiple neurotransmitter systems—not just serotonin, but dopamine, norepinephrine, glutamate, and GABA—as well as broader neurobiological factors such as neuroplasticity, stress-response dysregulation, inflammation, genetic predispositions, and psychological influences including cognitive biases and personality traits.

Critically examining Moncrieff and colleagues' (2023) umbrella review revealed significant methodological limitations and interpretative overreach, demonstrating that disproving an overly simplistic serotonin-deficiency hypothesis neither invalidates serotonin’s important role nor diminishes the relevance of antidepressants that act upon serotonergic mechanisms. Effective treatment, as discussed extensively in prior episodes of PsychiatryPodcast.com, integrates pharmacological interventions within a broader biopsychosocial context—encompassing psychotherapy, lifestyle modifications, diet, exercise, meaningful relationships, and supportive environmental factors.

Additionally, drawing upon the concept of reflective functioning (the capacity to reflect upon, understand, and interpret complex mental states in oneself and others), clinicians can move beyond oversimplified explanations and instead engage in deeper, more nuanced dialogues with patients about their depression. As clinicians and researchers, we aspire to help our patients deepen their understanding beyond the popularized but misleading “depression equals low serotonin” narrative, and toward a more holistic perspective where they value not only medication but also therapy, nutrition, exercise, and sustained lifestyle changes. Yet, this message—that meaningful improvement is not a quick fix—is less seductive. It highlights that lasting change involves deeper psychotherapy, altering daily routines, making intentional dietary choices, and maintaining consistent physical activity.

Just as patients may sometimes enter lower states of reflective function, idealizing or devaluing their early attachment figures and losing sight of relational complexities, we as healthcare providers can also find ourselves drawn to simplified, rigid narratives—idealizing certain treatments or prematurely dismissing others, especially under conditions of short visits, clinical fatigue, or burnout. Maintaining our own reflective function, along with the humility and curiosity it fosters, is essential to navigating the inherent complexity of depression and providing genuinely patient-centered care. Indeed, after years of weekly therapy—sometimes hundreds of hours spent with one patient—the deeper, more personal meanings and origins of their depression finally come to light, reinforcing that complexity, patience, and reflective understanding must remain central to our approach.

References:Aftab, A. (2023, January 6). When are we justified in calling mental disorders "brain disorders"? Psychiatry at the Margins. https://www.psychiatrymargins.com/p/when-are-we-justified-in-calling

Aftab, A. (2024, October 19). How Antidepressants Work. Psychiatry at the Margins. https://www.psychiatrymargins.com/p/how-antidepressants-work

Bartova, L., Lanzenberger, R., Rujescu, D., & Kasper, S. (2023). Reply to: “The serotonin theory of depression: A systematic umbrella review of the evidence” published by Moncrieff, J., Cooper, R. E., Stockmann, T., Amendola, S., Hengartner, M. P., & Horowitz, M. A. in Molecular Psychiatry (2022, July 20). Molecular Psychiatry, 28, 3153–3154. https://doi.org/10.1038/s41380-023-02093-0

Bondi, C. O., Rodriguez, G., Gould, G. G., Frazer, A., & Morilak, D. A. (2008). Chronic unpredictable stress induces a cognitive deficit and anxiety-like behavior in rats that is prevented by chronic antidepressant drug treatment. Neuropsychopharmacology, 33(2), 320–331. https://doi.org/10.1038/sj.npp.1301410

Cipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., Leucht, S., Ruhe, H. G., Turner, E. H., Higgins, J. P. T., Egger, M., Takeshima, N., Hayasaka, Y., Imai, H., Shinohara, K., Tajika, A., Ioannidis, J. P. A., & Geddes, J. R. (2018a). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis. The Lancet, 391(10128), 1357–1366. https://doi.org/10.1016/S0140-6736(17)32802-7

Cipriani, A., Salanti, G., Furukawa, T. A., Egger, M., Leucht, S., Ruhe, H. G., Turner, E. H., Atkinson, L. Z., Chaimani, A., Higgins, J. P. T., Ogawa, Y., Takeshima, N., Hayasaka, Y., Imai, H., Shinohara, K., Tajika, A., Ioannidis, J. P. A., & Geddes, J. R. (2018b). Antidepressants might work for people with major depression: Where do we go from here? The Lancet Psychiatry, 5(6), 461–463. https://doi.org/10.1016/S2215-0366(18)30132-2

Colwell, M. J., Tagomori, H., Shang, F., Cheng, H. I., Wigg, C. E., Browning, M., Cowen, P. J., Murphy, S. E., & Harmer, C. J. (2024). Direct serotonin release in humans shapes aversive learning and inhibition. Nature Communications, 15, 6617. https://doi.org/10.1038/s41467-024-50394-x

Commons, K. G., Cholanians, A. B., Babb, J. A., & Ehlinger, D. G. (2017). The rodent forced swim test measures stress-coping strategy, not depression-like behavior. ACS Chemical Neuroscience, 8(5), 955–960. https://doi.org/10.1021/acschemneuro.7b00042

Cuijpers, P., Noma, H., Karyotaki, E.,  Vinkers, C.H., Cipriani,  . and Furukawa, T.A. (2020), A network meta-analysis of the effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression. World Psychiatry, 19: 92-107. https://doi.org/10.1002/wps.20701

Erritzoe, D., Godlewska, B. R., Rizzo, G., Searle, G. E., Agnorelli, C., Lewis, Y., Ashok, A. H., Colasanti, A., Boura, I., Farrell, C., Parfitt, H., Howes, O., Passchier, J., Gunn, R. N., Politis, M., Nutt, D. J., Cowen, P. J., Knudsen, G. M., & Rabiner, E. A. (2023). Brain serotonin release is reduced in patients with depression: A [¹¹C]Cimbi-36 positron emission tomography study with a d-amphetamine challenge. Biological Psychiatry, 93(12), 1089–1098. https://doi.org/10.1016/j.biopsych.2022.10.012

Furukawa, T. A., Maruo, K., Noma, H., Tanaka, S., Imai, H., Shinohara, K., Ikeda, K., Yamawaki, S., Levine, S. Z., Goldberg, Y., Leucht, S., & Cipriani, A. (2018). Initial severity of major depression and efficacy of new-generation antidepressants: Individual participant data meta-analysis. Acta Psychiatrica Scandinavica, 137(6), 450–458. https://doi.org/10.1111/acps.12886

Godlewska, B. R., & Harmer, C. J. (2021). Cognitive neuropsychological theory of antidepressant action: A modern-day approach to depression and its treatment. Psychopharmacology, 238(5), 1265–1278. https://doi.org/10.1007/s00213-019-05448-0

Gryglewski, G., Lanzenberger, R., Kranz, G. S., & Cumming, P. (2014). Meta-analysis of molecular imaging of serotonin transporters in major depression. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 34(7), 1096–1103. https://doi.org/10.1038/jcbfm.2014.82

Hieronymus, F., Emilsson, J., Nilsson, S., & Eriksson, E. (2016). Consistent superiority of selective serotonin reuptake inhibitors over placebo in reducing depressed mood in patients with major depression. Molecular Psychiatry, 21(4), 523–530. https://doi.org/10.1038/mp.2015.53

Hieronymus, F., Lisinski, A., Nilsson, S., & Eriksson, E. (2019). Influence of baseline severity on the effects of SSRIs in depression: An item-based, patient-level post-hoc analysis. The Lancet Psychiatry, 6(9), 745–752. https://doi.org/10.1016/S2215-0366(19)30216-0

Jacobsen, J. P. R. (2023). Serotonin and depression—An alternative interpretation of the data in Moncrieff et al. Molecular Psychiatry, 28, 3158–3159. https://doi.org/10.1038/s41380-023-02090-3

Jauhar, S., Arnone, D., Baldwin, D. S., Bloomfield, M., Browning, M., Cleare, A. J., Corlett, P., Deakin, J. F. W., Erritzoe, D., Fu, C., Fusar-Poli, P., Goodwin, G. M., Hayes, J., Howard, R., Howes, O. D., Juruena, M. F., Lam, R. W., Lawrie, S. M., McAllister-Williams, H., Marwaha, S., ... Cowen, P. J. (2023). A leaky umbrella has little value: Evidence clearly indicates the serotonin system is implicated in depression. Molecular Psychiatry, 28(7), 3149–3152. https://doi.org/10.1038/s41380-023-02095-y

Kambeitz, J. P., & Howes, O. D. (2015). The serotonin transporter in depression: Meta-analysis of in vivo and post mortem findings and implications for understanding and treating depression. Journal of affective disorders, 186, 358–366. https://doi.org/10.1016/j.jad.2015.07.034

Kara, N. Z., Stukalin, Y., & Einat, H. (2018). Revisiting the validity of the mouse forced swim test: Systematic review and meta-analysis of the effects of prototypic antidepressants. Neuroscience & Biobehavioral Reviews, 84, 1–11. https://doi.org/10.1016/j.neubiorev.2017.11.003

Khan, A., Brodhead, A. E., Kolts, R. L., & Brown, W. A. (2005). Severity of depressive symptoms and response to antidepressants and placebo in antidepressant trials. Journal of psychiatric research, 39(2), 145–150. https://doi.org/10.1016/j.jpsychires.2004.06.005

Kirsch, I., Moore, T. J., Scoboria, A., & Nicholls, S. S. (2002). The emperor's new drugs: An analysis of antidepressant medication data submitted to the U.S. Food and Drug Administration. Prevention & Treatment, 5(1), Article 23. https://doi.org/10.1037/1522-3736.5.1.523a

Kramer, P. D. (2016). Ordinarily well: The case for antidepressants. Farrar, Straus and Giroux.

Leucht, S., Hierl, S., Kissling, W., Dold, M., & Davis, J. M. (2012). Putting the efficacy of psychiatric and general medicine medication into perspective: review of meta-analyses. British Journal of Psychiatry, 200(2), 97–106. https://doi.org/10.1192/bjp.bp.111.096594

Lewis, G., Duffy, L., Ades, A., Amos, R., Araya, R., Brabyn, S., Button, K. S., Churchill, R., Derrick, C., Dowrick, C., Gilbody, S., Fawsitt, C., Hollingworth, W., Jones, V., Kendrick, T., Kessler, D., Kounali, D., Khan, N., Lanham, P., Pervin, J., Peters, T. J., Riozzie, D., Salaminios, G., Thomas, L., Welton, N. J., Wiles, N., Woodhouse, R., & Lewis, G. (2019). The clinical effectiveness of sertraline in primary care and the role of depression severity and duration (PANDA): A pragmatic, double-blind, placebo-controlled randomised trial. The Lancet Psychiatry, 6(11), 903–914. https://doi.org/10.1016/S2215-0366(19)30366-9

Malhi, G. S., Bell, E., Bassett, D., Boyce, P., Bryant, R., Hopwood, M., Lyndon, B., Mulder, R., Porter, R., Singh, A. B., & Murray, G. (2023). The management of depression: The evidence speaks for itself. The British Journal of Psychiatry, 222(3), 97–99. https://doi.org/10.1192/bjp.2022.133

Moncrieff, J., Cooper, R. E., Stockmann, T., Amendola, S., Hengartner, M. P., & Horowitz, M. A. (2023). The serotonin theory of depression: A systematic umbrella review of the evidence. Molecular Psychiatry, 28, 3243–3256. https://doi.org/10.1038/s41380-022-01661-0

Page, C. E., Epperson, C. N., Novick, A. M., Duffy, K. A., & Thompson, S. M. (2024). Beyond the serotonin deficit hypothesis: Communicating a neuroplasticity framework of major depressive disorder. Molecular Psychiatry, 29, 3802–3813. https://doi.org/10.1038/s41380-024-02625-2

Quilty, L. C., Meusel, L.-A. C., & Bagby, R. M. (2008). Neuroticism as a mediator of treatment response to SSRIs in major depressive disorder. Journal of Affective Disorders, 111(1), 67–73. https://doi.org/10.1016/j.jad.2008.02.006

Rabinowitz, J., Werbeloff, N., Mandel, F. S., Menard, F., Marangell, L., & Kapur, S. (2016). Initial depression severity and response to antidepressants v. placebo: Patient-level data analysis from 34 randomised controlled trials. The British Journal of Psychiatry, 209(5), 427–428. https://doi.org/10.1192/bjp.bp.115.174415

Roberts, C., Sahakian, B. J., & Robbins, T. W. (2020). Psychological mechanisms and functions of 5-HT and SSRIs in potential therapeutic change: Lessons from the serotonergic modulation of action selection, learning, affect, and social cognition. Neuroscience & Biobehavioral Reviews, 119, 138–167. https://doi.org/10.1016/j.neubiorev.2020.09.001

Ruhé, H. G., Mason, N. S., & Schene, A. H. (2007). Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Molecular psychiatry, 12(4), 331–359. https://doi.org/10.1038/sj.mp.4001949

Salvan, P., Fonseca, M., Winkler, A. M., Beauchamp, A., Lerch, J. P., & Johansen-Berg, H. (2023). Serotonin regulation of behavior via large-scale neuromodulation of serotonin receptor networks. Nature Neuroscience, 26, 53–63. https://doi.org/10.1038/s41593-022-01213-3

Shine, J. M., O’Callaghan, C., Walpola, I. C., Wainstein, G., Taylor, N., Aru, J., Huebner, B., & John, Y. J. (2022). Understanding the effects of serotonin in the brain through its role in the gastrointestinal tract. Brain, 145(9), 2967–2981. https://doi.org/10.1093/brain/awac256

Slattery, D., & Cryan, J. (2012). Using the rat forced swim test to assess antidepressant-like activity in rodents. Nature Protocols, 7, 1009–1014. https://doi.org/10.1038/nprot.2012.044

Soskin, D. P., Carl, J. R., Alpert, J., & Fava, M. (2012). Antidepressant effects on emotional temperament: Toward a biobehavioral research paradigm for major depressive disorder. CNS Neuroscience & Therapeutics, 18(5), 441–451. https://doi.org/10.1111/j.1755-5949.2012.00318.x

Stone, M. B., Yaseen, Z. S., Miller, B. J., Richardville, K., Kalaria, S. N., Kirsch, I., et al. (2022). Response to acute monotherapy for major depressive disorder in randomized, placebo-controlled trials submitted to the US Food and Drug Administration: Individual participant data analysis. BMJ, 378, e067606. https://doi.org/10.1136/bmj-2021-067606

Tang, T. Z., DeRubeis, R. J., Hollon, S. D., Amsterdam, J., Shelton, R., & Schalet, B. (2009). Personality change during depression treatment: A placebo-controlled trial. Archives of General Psychiatry, 66(12), 1322–1330. https://doi.org/10.1001/archgenpsychiatry.2009.166

Thase, M. E., Larsen, K. G., & Kennedy, S. H. (2011). Assessing the 'true' effect of active antidepressant therapy v. placebo in major depressive disorder: use of a mixture model. The British journal of psychiatry : the journal of mental science, 199(6), 501–507. https://doi.org/10.1192/bjp.bp.111.093336

View Details

Podcast Host: David Puder, MD

Transcription Editing: Al-Baab Khan, Joanie Burns

Reviewer: Erika Vega, MD

By listening to this episode, you can earn 2.0 Psychiatry CME Credits.

Other Places to listen: iTunes, Spotify

Dr. Yeomans is the President of the International Society of Transference-Focused Psychotherapy (ISTFP) and is a leading figure in the development and dissemination of Transference-Focused Psychotherapy, an evidence-based psychodynamic treatment for personality disorders. He has co-authored several influential works on TFP, including:

• Transference-Focused Psychotherapy for Borderline Personality Disorder: A Clinical Guide (2015).
• A Primer on Transference-Focused Psychotherapy for the Borderline Patient

His work emphasizes the importance of understanding internalized object relations and their manifestation in the therapeutic relationship, aiming to promote personality integration and symptom reduction.

David Puder:

I thought we'd start and talk about what is, maybe for those who are less familiar and we're really speaking to an audience here of mental health professionals, people in training. They've probably heard about transference-focused psychotherapy [TFP]. I imagine they all know what transference is, but I'm hoping, in this discussion, to pull out some of the nuance of the uniqueness of the approach. On the podcast, we've talked about reflective function and how transference-focused therapy uniquely improves reflective function [see also episode 213]. So I'm wondering if you could introduce broadly transference- focused therapy and where it is today in terms of research.

Frank Yeomans:

Certainly, I'd be happy to try to do that. It might turn into a lengthy answer, but when you said that, going back to your statement, most people are familiar with transference. That's probably true. But there's also a common misperception, misunderstanding of transference, which is that it's the past being repeated in the present. That leaves out the mind, because what is actually being activated in the present when transference occurs isn't an accurate version of what happened in the past. It consists of the activation of mental images, internal representations of people, experiences, relationships that are laid down as memory traces in the mind, but often become modified and sometimes exaggerated by the processes of the mind and unconscious processes that we think about when we think about a psychoanalytic approach. Or there are fears, there are desires, or anxieties. All these have an impact on the way the memory traces are laid down into the internal representations.

So when I talk about transference in general, I'm gonna refer to the title of one of Kernberg's early works, which is Internal World and External Reality. The idea is that in the course of the development of any individual, they internalize images, as I said, representations of themselves interacting with others. These become paradigms or templates for later experiences. So transference is first of all, it's a universal phenomenon. We all transfer onto each other. Anytime I meet somebody new, my first encounter with you, there are traits, aspects of you that will activate in me, memories of, and this is largely unconscious, but you know, I'll think of, you know, “He kinda reminds me of X, Y, or Z.” So I'll project onto you characteristics that may or may not really fit who you are. The challenge in adapting to reality is taking in who the other is.

So you get a precise, an exact sense of them that might be different from your initial reaction based on some kind of images that are activated in you. So it might help at this point to give, what I think is a fairly dramatic example, and it's actually the clinical experience that convinced me to work with this approach. I had just finished my training as a psychiatrist and was working at a hospital, but also started a private practice. And one of my first patients was a man with a combination of borderline and narcissistic personality disorders. We can talk about each of those later if you'd like. But in any case, like a lot of patients with narcissistic personality disorders, he had kind of an angry, aggressive, devaluing stance toward me a lot of the time. He was kind of a tough cookie, to put it in plain English.

In any case, in one session, this guy who was usually angry and critical told me a story that's of something that happened to him when he was a kid, five, six years old. It's a very sad story, and it brought tears to my eyes, which is not what usually happens when I'm in a therapy session, but can happen anyway. So he noticed that, and he said, you have tears in your eyes. And I simply said, yes. I didn't know what else to say. Then he looked at me very closely, he kinda scrutinized me and said, in all seriousness, he said, “You are mocking me.” So that is an example of transference where the internal representation, the other who is mocking you, so prevailed over what seemed like kind of clear evidence to most people that I was sympathizing with him, that his transference onto me was what we call a paranoid transference.

“The other person doesn't like me, is critical of me, is mocking me.” And if your transferences are so strong that they prevent you from getting an accurate take on reality, then it makes it hard to adjust to life and to have success and satisfaction in life. And our patients tend to have those kind of distorted transferences where the internal image prevails over the external data that they're taking in. So in a more typical case, it's the patient who just assumes when you look at the clock to know when to end the session, that you hate them and wanna get rid of them. And that's a transference triggered by a minor external event, but leading through a massive projection.

Puder:

Can I ask you about this? So his comment, he said, “You're mocking me.” He's seen you. You're feeling emotionally distraught. So he's unable to empathize with your true experience. His reflective abilities about you and what you're really doing are off. Very off. Right. Was the paranoid transference there, the fear that you're mocking him, was that tied into the actual trauma of what happened to him when he was five years old? Like was in that five-year-old instance of him going through that conflict, was there some aggression maybe that was disavowed and now is pointed at you, his therapist?

Yeomans:

I think that's very likely the case, but it is a good point to bring up because a lot of therapies, and this is one way in which transference focused psychotherapy differs from more classical psychoanalytic psychotherapies, a lot of therapies would jump to the past and say, “Oh, in that experience, did you feel your parents (who were the people involved in the interaction, as I recall), you know, were criticizing you unfairly, putting you down, mocking you?” Then, let's try to distinguish then from now. In transference psychotherapy, we would consider that focus on the past to be an avoidance of what's happening in the here and now, because we think it's more effective therapeutically to work with what the patient is feeling in relation to you. Rather than say, “Hey, let's look at the past 30 years ago.” So you can, let's put it this way to say, “Okay, you know, you took in these ideas that people were supposed to care for you or mocking you because your parents seem to have done that.”

Yeomans:

This man is going through life on a daily basis, misperceiving others. So we do not try to correct the distortion. If it would work, I'd be happy to correct the distortion. I'd be happy to say to him, “No, please trust me. You know I'm sympathizing with you. I'm not mocking you.” But it doesn't work to say to somebody who's incapable of trust to say to them, please trust me. They're not going to. So you have to enter into the projection. You have to be able to carry the projection so that you and the patient can look at it together. So instead of saying, “No, please understand, I'm not mocking you.” My response, I mean, this was ages ago, would've been something along the lines of, “That sounds like a terrible experience to come to therapy for help and to wind up with a therapist who's mocking you. Let's think about that together. I'd like to hear more about that.” First of all, your willingness to entertain the negative projection, the negative transference usually is an implicit sign, “Maybe you're not so bad”, because anybody who's really negatively inclined to would've said, “Oh, no, no, let's not go there.” So my willingness to say, “If I'm mocking you, let's think about it”, opens up reflection.

Puder:

Okay. So, how would you feel if I pretended to be this patient? And we kind of go into this scenario right there and see what happens.

Yeomans:

We can give it a try.

Puder:

Let's give it a try. Okay. So you, you had just said to me that statement, so I'm gonna go from there. Okay.

Well yeah, I'm here. I'm paying money to be here. And like, I'm telling you this awful, awful event that happened to me when I was five. And all of a sudden, like, you're like mocking me. And I'm just like, what the heck?

Yeomans:

Well, I guess it's not just at age five, but right now your life is full of really awful events, including what's happening between us. And I can understand your depression when a helper, or a so-called helper, seems to be the opposite. It must be awfully frustrating to seek help and to encounter the opposite-- mockery.

Puder:

Well, I feel like, you know, somehow you're doing this kind of psychotherapy gymnastics around me right now, but I can't believe I caught you mocking me.

Yeomans:

So I'm trying to weasel out of what, in fact, I think of you really, which is kind of a negative critical mocking stance. So I'm trying to put the veil over that and retreat to my pretend position of sort of being a concerned caretaker. That's what's going on.

Puder:

Yeah, exactly. Like how, you know, I tried to call you and then it took like three days to hear back just the other week. And, this is just another example of this. It's like, if you really cared, you would've called me back that day. I was in absolute crisis.

Yeomans:

So it's important that this is coming out so clearly now. I guess you felt this for a while, but didn't bring it up. And again, I wanna try to sort this out because it's a pretty sad situation in life when even the person who's supposed to help turns his back on you, doesn't care enough to call back. And now it seems like the kind of mockery you see in me has broken through. One thing that's implicit in all of this is the view that I'm dishonest. You know, maybe we should think about that because you seem to feel that I'm pretending to be one thing and I'm really another. Let's open that up, please.

Puder:

Yeah, I mean, there's part of me that's like, I know a couple weeks ago I wouldn’t have, I think, I don't think I thought I saw you that way at all. I thought you were the greatest, you know, doctor ever. But somehow, all of a sudden, it seems like you're just like all the other shitheads in my life that have preceded you.

Yeomans:

Yeah, I can see that. That's confusing. And I do remember when you seemed, you know, to think I was a good guy. So therapy is about trying to figure out things that are confusing. Maybe you've figured out or decided once and for all that the good guy thing was nonsense. And that, you know, I'm like everybody else: I don't like you, reject you, internally, mock you. But on the other hand, this seems to be a little bit of that first part, which by the way, might not be the whole story either, because that seemed to be a little too good to be true. But in any case, I think you're struggling with something. It's not totally out in the open what you're struggling with. 'Cause I think it's not fully in your awareness, but at the same time that you have this negative feeling toward me, you're still coming here. So that's kind of contradictory and we should work to figure out how to sort out that confusion.

Puder:

You know, I haven't told you a dream that I had this week about you, and I think it might relate. I had a dream that we had ended a session and I had left, but the door was cracked, and I overheard a phone call with you and some colleague on the phone, and you were laughing about me with this colleague. And then when I woke up, I felt like it was so true, like it actually had happened, but that I was, I felt just absolutely betrayed. Yeah. That was the end of the dream.

Yeomans:

When did you have the dream?

Puder

Last night.

Yeomans:

Oh, just last night? Okay. Well, it seems like it's the same thing as what?

Puder:

What we're talking about.

Yeomans:

Yeah. You feel it has materialized here. Then, in spite of my, what you see as a facade of interest in you and wanting to help you, that in my mind, the honest reaction I have is to think you're kind of a pathetic human being. And you know, like I say, talk more about that.

Yeomans:

Well, lemme just say, you know, because what I'd like to do is, I'm trying to understand what in your mind would lead to my thinking, “You're a pathetic human being.”

Puder:

Oh, I mean, I think it's like a deep fear, you know? I mean, and you know, when I was, some of the early situations that I had where I felt some level of betrayal.

And I think it's a fear that I have.

Yeomans:

Being betrayed and being pathetic are not exactly the same thing. I can understand your feeling betrayed, but what I see now is a kind of feeling pathetic. Where, you know, we've seen so many instances where you disqualify yourself, attack yourself, put down an effort you've made. And I think what's happening between us, as you see it, goes on in your mind – within you – in other words, you against you– the way you see me against you right now.

Puder:

Hmm. Yeah. And so I think I'm confused because it seems like you're not against me right in this moment. You're curious about how I'm observing you.

Yeomans:

Let me just finish Yeah. That I say that is another possibility. It's very important to figure out which of the two possibilities seems more real.

Puder:

Well, I think I'm curious 'cause you've done this a lot. Like what would the patient say at this point? Would they soften, you know, in their kind of observations? Would they get more reflective? Would they dig in?

Yeomans:

I would say more often than not, no. Because defenses are very strong. When I say defenses, I mean, especially when we're talking about people with borderline level personality disorders, splitting defenses where–which we should discuss at some point–the person can't get in touch with their own aggressive feelings and sees all the aggression in the other, as this man is seeing all the aggression in me. I'm trying to get him to see there's some aggression in him. Which in fact, he turns against himself. But to answer your question about what patients usually do. Usually, they say, “Oh, you're just,” you know… what will they say? “You know, you're just running circles around me. You're just trying to use the psychobabble to cover up what I know is true.” So you can't expect every intervention to lead to increased insight, but you just have to continue with it, stay committed, and assume instances like this will happen again and again.

Yeomans:

And when you're lucky and you've accumulated enough mutual experience, one of those moments will lead to the person thinking about what you're saying and beginning to reflect and take it in. We have some research along those lines. One of our colleagues, Yogev Kivity and his other researchers published a paper about what leads to change and to the reflective functioning you mentioned. And it is what, in his paper, he calls “bids for reflection.” In the traditional TFP literature, we call it “confrontation.” A lot of people say that's not a good word– It applies to a hostile confrontation, but it really means doing what I tried to do with you in the clinical vignette. Say we've got this and we've got that, and they don't seem to fit together. How can we reflect on them? So, short answer to your question is most years the patient continues with their defensive projection, but if you keep going, eventually they begin to reflect.

Puder:

Yeah. Oh yeah. I think it's okay. So I think there's a couple things that I was trying to embody: the idealization early on in treatment and then this kind of became the devaluation, right? So I think this is a lot of what clinicians have seen. It's like, initially the patient is like, you're this all good, perfectly nurturing, you know, figure who really gets me. You truly understand me. Finally, I have a clinician that has enough expertise to help me. You know, you hear like a bunch of these strung together and you start to get a little bit worried as an experienced clinician, like, “Oh, okay. There's something deeper going on here.” Right? And then the devaluation, right? So, he's currently in the devaluation, where now you're malevolent, incompetent, cold, rejecting. And this is partly what you consider a borderline level of functioning, right? So not neurotic level of functioning. Not psychotic. Borderline level of functioning. There's a lot of this idealization – devaluation.

Object Relations Theory and What Is Behind Borderline Level of Functioning (00:22:12)Yeomans:

Yeah. But let's talk about the basic theory, because to understand what's behind idealization and devaluation, I think we have to take a little review of object relations there. Is that okay? So object relations theory is a branch of psychoanalytic theory that emphasizes the self in relation to the other [see also episodes 192 and 231]. Early Freud posited neurotic conflicts based on an internal struggle between an impulse, a drive, and a prohibition against the drive. So, you know, somebody wants to have sex, but they think it's bad and they get a symptom. And, you know, I'm simplifying, but in any case, some later analysts came along, and the one I'm thinking of in particular is Melanie Klein, who said, well, people do have drives. They have sexual drives, they have libidinal drives, and libidinal means more than sexual, it means affiliative, you know, attachment related you know, wanting to have or satisfying relations with others.

Yeomans:

So there are libidinal drives in the broad sense, and there are aggressive drives– anger, wanting to strike out, wanting to…combination to assert oneself and defend oneself. Not all aggression is bad. It can involve competitiveness and assertion and competition and creativity. Anyway, the idea is that if you have those drives, libidinal ones and aggressive ones, you don't just feel a drive, you feel a drive in relation to the object of the drive. If you're feeling you wanna connect to somebody, you have the idea of with whom you wanna connect, or if you wanna, you know, have some kind of competition with somebody, there's an object of that. So given that emphasis on the connection of the drive to the object of the drive, we can then look at infant development. And the newborn takes in a lot of experiences, and it's complicated because of neurobiology and the myelin, myelination of the brain, and so on and so forth.

Yeomans:

But, and you know, there's still a gap between the analytic theory and neurobiology. Although the gap is narrowing. So in this theory, in the early year or year and a half of life, as it is posited – experiences with the caretakers are, by the infant, seen as either perfectly satisfying or totally depriving, because there's no concept of object constancy. If you're being, you know, caressed and fed and kept warm and cozy, you're in heaven. But if you're uncomfortable, you're cold, you're hungry, you're soiled, and the caretaker isn't there, you don't have this feeling: “Oh, I know, mom will come around. You know, just give her a little time.” You don't have that object constancy. You're in pain, you're suffering, and you perceive the other as the source of the suffering. So you're either in heaven or in hell. The other is totally caring for you in an ideal way, which doesn't correspond to reality, by the way, or the other is persecuting you, not just unavailable, but persecuting you.

So, in object relations theory, the early makeup of the mind is divided between the segment of the mind that's about positive, ideal experiences and negative persecutory experiences. Interestingly, this corresponds to some neurobiology because it seems like the brain areas where positive affect is located and the brain areas of negative affect are different brain areas that require cortical intervention to bring them together. And we think therapy can help with that. So in any case, if you go through life where things are either perfect or terrible, you don't adapt well to the complexity of life because life isn't that way. So to go back to your concepts of idealization and devaluing, patients often come in projecting, “I finally found the ideal therapist –this guy knows everything. Everything's gonna be perfect.” Now, that positive side of the split internal world is just as pathological as the negative side – that's all about paranoia and rejection and harm. Because the positive side doesn't correspond to reality. You never find the perfect caretaker. No matter how much you're in love with your partner, they're not gonna be perfect. So you have to accept that. But people with splitting, when we talk about splitting, we mean the splitting between the all good and the all bad. People with splitting expect perfection. And for a while they might continue with you with the illusion that they found that, but inevitably there'll be disappointment and then it flips into the devaluing. So let's talk about what happens in successful psychological development. Oh, by the way, that split organization is called the paranoid schizoid organization. It's called schizoid because it's split. Why is it called paranoid? Because in that mental organization where aggression and libido, fondness and aggression are totally divided, the person experiencing aggression is not comfortable seeing himself or herself as the source of the aggression.

They tend to project the aggression and see it as coming from outside. So as soon as you begin to get close to somebody, you're nervous, you think something bad is gonna happen, rejection, harm, so on. So in successful psychological development, we move from the paranoid schizoid position – the radical separation of positive and negative, and the projection of anything aggressive on others – to what, interestingly, Melanie Klein called the depressive organization, which doesn't sound great. Who wants to be depressed? But it's more specific than that. If you integrate those two radical polarized extremes, two things happen. One, is you have to give up and you have to mourn your belief that you can ever find the ideal other, or that you can ever be the perfect ideal self. You have to give up on thinking anybody can be ideal, and that's kind of a sad awareness. The second thing that happens when you begin to integrate your positive and negative emotions is that you begin to have awareness and take some responsibility and consciousness for the aggressive feelings you always saw as outside of you. So it's a painful trajectory from splitting and projection to integration and mourning the ideal object and accepting that one has one's own aggression. I'd like to give you a clinical example in a minute, but does this help understand why patients come in with the idealization and then inevitably switch to devaluing when you don't meet their perfect expectation?

Puder:

Yeah, I think the thing that I would love to hear from you, kind of like how it fits into this, is the idea of identity diffusion [see also episodes 88, 170, 225, 231].

Yeomans:

Yeah.

Puder:

Can you integrate that into how you…does that fit somewhere into this?

Yeomans:

Oh, it's perfect, in fact, it's good you bring that up because in our model of the mind of personality and of personality disorders and it's treatment, identity is the core concept. Whether the identity is integrated or fragmented and diffuse. It's important when we talk about identity, to think about how we mean it. Because a lot of people, when they think about identity, think about identifications. You know, what's my gender? What's my sexual orientation? What's my ethnic affiliation? What's my nationality? What's my sports team? What are my interests? So there are all kinds of elements of identity. And when we talk about identity, that's not exactly the level at which we're talking. We are talking about identity as the ability to be in touch with and grasp and manage the full range of your internal emotional states. In other words, does your identity allow you to assume and connect with the full range of who you are as an emotional being?

That's a different level of identity. It's a very core sense of identity. Do I have an integrated identity? Means, have I gone beyond the paranoid-schizoid position where everything was polarized and fragmented so that I could not have a stable emotional existence? I was buffeted back and forth between idealization and devaluation. I don't have that core sense of emotional stability where I get it. I can be loving, I can be angry, I can adore somebody, I can be rageful with somebody. So our sense of identity integration is to be integrated emotionally, not to reject, but often project parts of your emotional self.

Puder:

Okay. Like so I've been, I've been reading thinking about identity diffusion. I was reading about this guy Salman Akhtar. Six characteristics. You know, and is this what we're talking about, the same thing? Or is that slightly different? His six characteristics were temporal discontinuity of the self, lack of authenticity, feelings of emptiness. Emptiness is kind of different from loneliness because there's a hollowness. Just feeling like, just like a shell. A lack of identity around gender, a lack of identity around sexuality. So just kind of like a diffusion beyond just like, who am I? What am I doing in the world? Is this kind of what we're talking about?

Yeomans:

Akhtar is a really brilliant guy, and I haven't read exactly what you're talking about. I would agree with the first part. I wouldn't talk as much about the second part. The emptiness. Can you mention the first three things you said? One was emptiness versus loneliness. So I wanna talk more about that.

Puder:

Like the discontinuity in the self.

Yeomans:

Yeah. And discontinuity in time. Yeah.

Puder:

So it's like a quote from him: “The past, present, and future are not integrated into a smooth continuum of remembered, felt, and expected existence for these patients” (Akhtar, 1984).

Yeomans:

Yeah.

Puder:

So that's one of them. Temporal discontinuity of the self like a chronology of how they see their life. A lack of authenticity. Here's a quote, “Act as someone else they know would act, not in a manner that is genuinely their own” (Akhtar, 1984). So they put on different faces, so to speak. Feelings of emptiness is like a hollow shell – lacks capacity to fantasize for a person or experience in the midst of, in contrast to a lonely person may fantasize for connectedness with someone. They don't have that fantasy for that other person.

Yeomans:

Yeah. Let me say I think that's a nice delineation of what we call identity diffusion. And it has to do, I'm trying to bring this all together around a concept with the development of a core sense of self. If you remain split and you're flipping back and forth: I love this person. I hate this person. Which, by the way, has internal correlates. Which is, I love myself. I hate myself. As I was trying to point out in our patient role play, he was very rejecting of himself. At the same time, he saw me as rejecting. You don't have that ballast, that core, that integrated foundation on which to build. You're just flipping back and forth between two states that never come together. That leads to emptiness. That leads to a sense of not development over time, but just time passing without development.

Dr. Kernberg has an interesting article about what he calls the destruction of time (2008). Because, if we consider time from the subjective point of view, what is our experience of going through life and the passage of time? Kernberg's idea is that we sense time as we build and grow as a self. As we enrich who we are, we add to our sense of who we are, we become more complex and we add to what we've done and what we plan to do. If you haven't yet achieved emotional integration, you can't develop because you don't know whether you're loving or hating. You can't combine the two. And if you're always jumping back and forth between two things, you don't have that foundation upon which to build. A lot of my patients say to me, “You know, the worst part of having borderline personality disorder is not the acting out when I'm maybe hurting myself or having a rage attack or something like that.”

And we should get back to the experience of aggression in the borderline patient. “The acting out isn't the worst part. The worst part are those moments when I'm sitting alone by myself and I feel totally empty.” We have to, as therapists, try to empathize with what that is like. It's pretty horrifying. Pretty scary. And a lot of the acting out is to escape from that core feeling of emptiness. And if you do have that feeling of emptiness and unclarity about who you are, then you are gonna mimic other people. You know, “I'll do what this one does. I'll do what that one does.” So, I agree a lot with what Akhtar says. I wanna invoke another title of one of Kernberg's books. He has a title called, The Inseparable Nature of Love and Aggression. And I think that relates to this concept of integration.

A lot of my patients who are stuck in that kind of naive belief that you can find the ideal, say, I know I'm getting better because I'm going out with this guy and, you know, we were having a really good time, but then I, you know, I, I don't think I can sustain it or, you know, I ruined it all because I got angry at him. I felt angry at him. And I say, well, yeah, but let's look at that. Do you feel you can really know somebody in depth, have a lot of shared experience, and it's all gonna be positive. If that's your goal, you're not gonna have any deep relationships, because in intimacy, deep connectedness is gonna include negative feelings as well as positive ones. That's a more concrete example of integration.

Puder:

In one of your YouTubes, I forgot which one, but you said something like the, the strongest identities are based off of religion, philosophy, or art. Did you say that?

[Exact quote from timecode: 33:45: “we can certainly maintain a belief in ideals, but it's better to find your ideals through spirituality or through art or through philosophy and ethics”].

Yeomans:

No, I didn't, but I'd be happy to talk about it.

Yeomans:

Well, I don't know who said that. I think you might've heard what I said about religion, philosophy, and art. Which is that that’s where you can idealize. I said, you know, when I just went over the object relations theory, where you go from the split organization, paranoid, schizoid to the integrated, more complex organization where you give up the idea of perfection and finding the ideal in another person. I wanna emphasize that I'm not totally cynical. I don't think you're not allowed to have ideal beliefs, ideal values. They might be embodied in a spiritual system, an ethical system, and artistic pursuit and aesthetic pursuit. So I think ideals are laudable, but look for them where they might exist and not in another person or oneself.

Puder:

Okay. Thank you. Thank you for that clarification. So, okay. So is someone inevitably always going to be in the depressive position? Is that where they stay forever?

Yeomans:

Well, first of all, when somebody advances to the depressive position, that really enriches life. As I said, you lose the idealization and you have to take responsibility for your aggressive feelings. But then you're in much closer contact with reality. You can really engage with others more fully. You can engage with your work, your projects more fully. So when patients make that shift to the integrated to depressive position, we help them work through the sad feelings about mourning the ideal object, and usually the guilt feelings about having their own aggression. And we try to help them see they can, what we call sublimate or direct or manage their aggression so that it can have positive applications, not negative ones. But when you mentioned the transition from the paranoid schizo split position to the integrated depressive one, unfortunately that's not a development that necessarily takes place once and for all. People like you, I assume, and me, I hope, who are in the integrated depressive level, under certain circumstances, we can regress back to splitting if we're under enough stress or if we just want the pleasure and simplicity of splitting.

Yeomans:

Because splitting allows you not to think as much. Splitting is simple, but in a way it's reassuring when your mind functions according to splitting. You know what's good, and you know what's bad. There's no ambiguity. So, if for example, you go to a, up here in the Northeast, it would be a Red Sox Yankees game for two hours. You can allow yourself to regress, to forget about all the complexity of the world. You know, your team or the good ones, the other team, or the evil ones, and you can enjoy that for two hours. The problem is that political leaders can appeal to splitting when they say, we are all good. The only problems are outside of our group, everything bad is outside. That's just like the borderline patient who says everything bad is in the other. I am, I don't have any bad traits. So I think there's a seductive splitting. You don't have to think as much, and you're told what's right and what's wrong.

Puder:

I, and I think there's a, I mean, if you look at both sides of political spectrums, it's very common that the person will adopt all of the policies of one side. Right. It's very rare to find someone who's nuanced and parses out different policies. And can see good and bad. So I think we all do kind of enjoy and revel in at times this splitting as well within our sort of tribe, right. And is that, well, a natural process?

Yeomans:

We can until the system breaks down. Because in that tribe mentality, people are not taking responsibility for themselves, but only blaming the other. And then when you get enough of that going on, somebody's gonna get into violence and it's gonna fall apart.

Puder:

Okay. So I think this is a really good aspect I like about depth therapy [see also episodes 154 and 208], is you get the person to a place of taking some responsibility. Yeah. Rather than just blaming purely all their situations they found themselves in. But do you find that there's also this kind of over exaggeration of like, all of life's issues that you have are because of the traumas that you've faced, right. And, and does this kind of like, push against transference-focused therapy, which is kind of like, “Hey, we're taking responsibility for…”?

Yeomans:

No, you're bringing up a very big issue, and a controversial one; and an area in which we sometimes get accused of being insensitive and non-empathic. So let me give you a clinical example first, and then I'll get back to that trauma question. Because, when we talk about taking responsibility for one's own aggression, we should speak for a moment about the concept of acting out. Everybody talks about acting out, but the true meaning of the term has been lost at this point. When clinicians say, “Oh, he or she acted out”, it usually kind of means they misbehaved. But the definition of acting out is to put into an action, an emotion. One cannot consciously stay with that one cannot tolerate in oneself. So you discharge the emotion through action instead of feeling it and thinking about it. So here's my example. A patient of mine came to therapy saying that even though she made a suicide attempt, she wanted me to understand she didn't have a psychiatric illness.

That all of her problems were caused by her monster husband, who made her life so miserable that any woman married to him would sometimes rather be dead. And unfortunately, that can be the case, and I, at the beginning of therapy, I had to consider that that might be an accurate description of her life. Anyway, a couple of months into therapy she comes into a session and says, “I told you how awful my husband is. Can you believe he forgot our wedding anniversary? He knows how much that means to me. He's awful. He's callous. He's cruel.” In the meantime, before that session, I had received a phone message from the husband who said, “Doctor, I don't know what to do. I forgot our anniversary. And I know that's bad. and I know that, you know, is something my wife cares a lot about. But she got so angry at me that she picked up the TV and threw it across the room at me.”

Yeomans:

So in the session, I said to my patient, “ Well, I can understand your hurt feelings and how bad it was that your husband forgot your anniversary, but he left me a message that you threw the TV at him.” You know, I said that calmly, not condemning her in any way, staying neutral. And she said, “What else could I do? I was upset.” It's different to say I was “upset” than to say I was “rageful and angry”. She felt a discomfort that I believe was rooted in her rage and anger, but she didn't wanna feel, “I'm rageful and angry. I wanna get rid of this emotion. So I'll throw the TV and then I'll sort of get it out of my system.” So if we see acting out as the discharge of something, one cannot think about, our job as therapists is first and foremost to get people to think about what's in them that is true–difficult for them to think about on their own. Now, how does that tie into trauma?

Puder:

Wait. Can I ask this sort of a side question on this? How do you feel when the family member calls you and gives you information like that? Because sometimes it can put us in a difficult position, right? Sometimes I'll get an email from a mother or father, you know, and it's like, you know, sometimes it is a little bit like, “Okay, what is reality here?” Right?

Yeomans:

Oh, very much so. But I'm glad you asked that. In TFP we're, even though we're based on psychoanalytic concepts and techniques, we are more open to contact with other persons in the patient's life. You know, classic analysis is the analyst or the therapist and the patient. That's like totally hermetically sealed. But with patients with severe personality disorders in the initial evaluation, we emphasize you have to evaluate a person and discuss what the nature of the treatment will be and what the conditions of the treatment will be. You have to have all of that in place before you begin the therapy. So anyway, part of that assessment in our practice increasingly involves bringing in the parents. If it's a young person who's very dependent on the parents or the partner, if it's somebody who's living with somebody or very close to something. And why do we do that?

We do that, because first of all, most people don't understand personality disorders. Most people, and I think this is a problem with American psychiatry, most people just think about symptom disorders. “It's a depression. It's an anxiety disorder. So there's gotta be a medication for it.” Well, you can be depressed because of the way your mind works, not because your neurons aren't firing. Right? So if we, one of our steps of beginning treatment is after our assessment to have an open discussion with the patient about our diagnostic impression. If it is a personality disorder, we say that. We explain it in simple English. We emphasize the new understanding of personality and personality disorders, that it centers around difficulties in the way one thinks about and feels about oneself and about others. That's in the alternative model of the DSM-5. And then we bring in the family with the patient present, and we have the same discussion.

Why do we do that? So first of all, they won't have unrealistic expectations that there's just a medication that hasn't been tried yet, or ECT [electroconvulsive therapy], or TMS [transcranial magnetic stimulation] or something like that. And secondly, because there's a common misconception that you can't expect much from a person with a personality disorder; and we don't find that to be true. We think you can expect a lot, but I don't mean to say this in the sense of putting a burden on the patient, but opening the patient up to their potential so they don't see themselves as medically disabled for the rest of their lives. They can get better, as many do. They can have a much more productive life.

Puder:

I think that's so important, because especially, I think people think, “Personality disorder. You have this for life.” And, and I think that a lot of people with BPD or borderline level functioning, they take on illness as a narrative about themself. And then, you know, what you're challenging is that identity of illness.

Yeomans:

Yeah.

Puder:

And like, “I am an ill person. I will always be an ill person.” Yeah. Which is why I get, I've turned so many people from bipolar to unipolar and personality disorder because it's like, “No, like there is hope.” Right? Yeah. You don't need to be on medication your whole life. If you have a personality disorder. Actually, the new standard with the APA, American Psychiatric Association, the borderline personality disorder, is not medication, isn't going to treat borderline personality disorder (APA, 2024). It may treat some of the comorbid issues, but not actually borderline personality disorder.

Yeomans:

That's the most important message from this whole discussion. I hope your viewers have stayed with us long enough to hear what you just said.

Puder:

So, go on. I'm with you. Okay. Anyway, I'm like, we're on the same team here.

Yeomans:

That's very important. Anyway, after having had this initial contact with partner or parents, whoever it may be, with a patient present, I said, “You leave it open that if those parties think there's something important to communicate to you, they can provide you that information.” The patient usually says, “you're violating my confidentiality.” And I say “No, because I'm not telling them anything. I'm just letting them know if they have a concern they think I should know about, they can tell me. And that doesn't mean I'll necessarily believe them. You know, maybe they'll say something and, you know, you'll say, that's not accurate, and maybe it'll be their issue and not yours or ours.” So anyway, that, I hope, is an answer to how we would deal with information from a third party.

Puder:

Yeah, that's good.

Yeoman

The trauma.

Puder:

We're talking about trauma. Yeah. And the reason why I'm bringing this up is because I've been thinking a lot about complex PTSD, BPD and the odds ratio when you go into like adverse childhood experiences [ACEs]. When you go into, like, when a child has four to five, the odds ratio of either one of those is like 20. It goes way up. And so, I personally see it's not enough to have a lot of ACEs to develop BPD, but it's like a part, it seems to be a part of that process [see also episodes 92, 115, 203, 204, 215, 217, & 224].

Yeomans:

Yeah. Well, it gets complicated. So first of all, let's think about what Freud called the complimentary [sic] series [complemental series]. It's a basic concept where he sees two main contributors to psychopathology. One is temperament. And the sort of emotional raw material one is born with. Some people have much more fiery and intense temperaments than others. So temperament could be the main factor in the development of a personality disorder. But the other part of the complimentary [sic] series is developmental experience. And the adverse childhood experiences you're talking about can be a good example of that. So in Freud's model, he says, you know, any individual might have their own proportion of the temperamental contribution to the pathology and the developmental. But let's go back to what you said about complex trauma and borderline personality. Let's rewind to the 1990s. I was running, I was the unit chief on an inpatient unit where we had all patients with relatively severe borderline personality disorder.

Yeomans:

And we would like to invite people who might contribute to our knowledge to come and talk to us. And at that time, and is kind of a resurgence of it now, there's a very strong emphasis on trauma as maybe the most important factor in the development of personality disorders. So Judith Herman, who writes and researches you know, trauma, a great deal along with her colleague, Bessel van der Kolk, came and spoke to us. And her work is really good. But I think she, and we are not on the same page about borderline personality disorder, because she said, “You know, you guys don't understand borderline personality disorder is a misconception. All of these patients you have are trauma patients and you should see them and treat them as trauma patients.” What is the difference there? The difference is what you said about most trauma models. I'm not saying all– because I'm not totally versed in trauma models, but they would not see any contribution of the patient's own aggressive feelings.

They would see aggression in the patient, not as the patient's innate inherent stuff. But as the result of traumatic experiences, which have been introduced into the patient's mind from outside. Mentalization based therapy is sort of a good example of this. They talk about the alien self. Their model of BPD is somewhat different from the TFP model. It's interesting 'cause both are considered psychoanalytic models, but I think TFP goes deeper in terms of looking at the core deep conflict in the mind between libidinal feelings and aggressive feelings, loving and hating. Whereas in MBT, they say, what happens is that the borderline patient has had experiences of trauma growing up, so they have in their mind an internal image of aggression that has been introduced to their mind from the outside. And that is, to use their word, colonizing their mind. And as you help them to think and reflect more clearly to mentalize their internal states and the internal states of others better, that alien aggressive element just kind of goes away.

Yeomans:

I consider that a little naive. I think that everybody, you, me, and everybody I have ever encountered, you know, part of the human nature, part of human nature is some aggression. We wouldn't have survived as a species otherwise. The problem is how in touch with that are you and how do you manage that? So I think what happens with BPD patients is, as we know, let me just give a little reference to research and then I'll get back to the clinical example. Studies have shown that about 70% of patients with BPD have had experiences of trauma. But first of all, if you look more carefully as Joel Paris, up in Montreal did, the trauma isn't all major trauma. But I think, more importantly, is to reference a study that shows that if you start by looking at the general population, and you look at the subgroup of the general population who have experienced trauma, and you study that group of trauma experiencing individuals, the majority of them do not have psychiatric conditions.

Yeomans:

So, you can't say trauma equals the development of psychopathology. We think it has to do with the way trauma is processed. And we're not saying that trauma doesn't have an impact, but let me reference a patient of mine who is a, actually a lovely young woman in her early twenties who was lovely except when she was making serious and violent suicide attempts. In a session in my office, she banged her fist on the arm of the chair and said, “I'd rather be dead than think I have anything in common with that awful abusive father of mine!” And I said,

“I think you just defined your problem beautifully. You'd rather be dead than think you have anything in common with him. Whereas, as a matter of fact, you almost undoubtedly have something in common with him because we all have some angry, aggressive feelings, part of who we are. I think your problem is that when you feel the first emergence, the slightest inkling of an aggressive feeling in you, you can't think about it, accept it, and work with it. The slightest inkling of an aggressive feeling in you activates the internal representation of a totally abusive father. And then you think you don't deserve to exist.”

So the problem is that the trauma introduces into the person's mind images of aggression that are excessive and not easy to tolerate.

Puder:

Yeah. I'm following you. I have a couple thoughts. One of the thoughts is that I've studied micro expression. So I look at small moments of flashes on the face of people as they talk to me. And often, you know, anger is given a bad rap. People don't like to think that they are angry. People don't like to imagine that they're angry. And my conception of anger has shifted over the years as I've watched people. Because they not only flash micro expressions of anger when they're frustrated at their spouse or in an argument, but they flash it as well when they're talking about what they're passionate about, a book that they're writing, an artistic endeavor. It's a passion project. And so I've reconceptualized anger as it's the energy to overcome an obstacle to move towards a goal.

And so I agree with your conceptualization that we have this drive, right, which I would say is aggressive. This aggressive drive, a drive that's maybe competitive, maybe at its worst, it's envy to a place that it doesn't allow friendships. Maybe at its best, it's a drive that allows people to accomplish worthy things, that improve society, improves your family, improves yourself. So that's my first thought on what you said.

The second thing is when I think about what we've talked about BPD on prior episodes, and we talked about some early studies by Chess, Thomas, Rutter, and Birch (1963) [see also episode 115] , they did a study of 141 children that they followed. And it was this longitudinal study where they classified people as easy, slow to warm up, and difficult. And 10% of the kids were difficult from a very young age.

And the difficult ones they described as often irregular in feeding and sleeping are slow to accept new foods, take a long time to adjust to new routines or activities, and tend to cry a great deal. And they followed these children and the difficult children accounted for the largest proportion of kids that had behavioral problems later on. And, and so it was Dr. Cummings, who has been on my podcast a number of times, he was emphasizing that a lot of the kids that potentially develop BPD have this kind of like temperamental sensitivity, higher aggressiveness. And then, if they don't go through traumas, maybe they don't develop BPD, but with a wrong environment, lack of empathy, lack of connectedness, maybe a disconnect between parenting styles, disconnect between personalities. Maybe they develop something that looks more like BPD. Maybe they, you know, we know that attachment disorganization has something to do with it. The beta's [β’s] pretty small. Emotional dysregulation and adolescence has much higher beta. I'm kind of like agreeing with you and kind of adding on this layer. And I think that with, so coming back to this idea of aggression and the positive sense of like personal responsibility taking ownership is sometimes disavowed and someone ends up in this kind of like, victim, hero, persecutor.

Yeomans:

Yeah.

Puder:

And the trauma therapy ends up in that place where the patient is always the victim. The therapist is always the hero. And the bad things in life are always the persecutor that happened earlier in life. And it's a very seductive place to live. But, it also kind of leaves them in that illness narrative, which I think keeps them stuck.

Yeomans:

Yeah. There's so much coming. First of all, I really endorse this emphasis on micro expressions. That's when a lot of what is split off and not in awareness comes through in facial expressions, nonverbal communication. Second, what was Chess’ work you're referring to? Yeah. I haven't thought about that in ages. I'm very glad to hear you refer to that because it should be given more importance in the current day. Or maybe it's just me. But you know, I haven't thought about that in a long time. But getting back to what you just said about therapist-hero, patient-victim, abuser. Outside that's where we sort of upset the apple cart, if you will. Because, we don't accept this hero role in TFP. And this is where the role of therapeutic neutrality comes in. We're often criticized these days for what we call neutrality. Can I talk about that for a minute?

Puder:

I noticed it in our back and forth. It's like you were not really overly reassuring. Right? And, you were curious. And I was almost about to like, push you on it in the role play, but I decided not to shift gears and be like, I feel like you're really distant right now. You don't really care. It looks like you're almost bored.

Yeomans:

You could be quoting a session I had yesterday. But go ahead.

Puder:

So go ahead. Tell me.

Yeomans:

That's the point. We stay neutral and that doesn't mean indifferent. We care a great deal about our patients. We react emotionally to our patients. We tend to keep our emotional reactions inside and to reflect upon them. That gets to countertransference and how one can use that. But if you're not explicitly endorsing, and I'll use the word “validating”, 'cause that's so important in DBT, the patient, often you're considered suspicious or negative, and then you just don't get this hero treatment that you would get if you said, “Yeah, it must be terrible to have had that dad who was so awful.” I mean, I wouldn't necessarily not say that. I mean, it was terrible to have that dad. But then I might say, “But if we only talk about him in the past, I think we're missing something that goes on in your current life.”

And that's when you sort of stop from totally supporting a projective defense, and you begin to be open to a deeper look inside. And that's when you're not the hero anymore, because you're saying something that connects with the patient's doubt about themself, but they had doubts about themselves before they came into your office. They just want you to reassure them. They shouldn't have any doubt. But instead of that, we're saying, what are your doubts about what is there in you that you're concerned about? Maybe if we thought about it, you could sort of get to know yourself more fully.

Puder:

What if I had said to you in that role play, “Dr. Yeomans, it's like, I feel like as you're responding to this, to me, like I sense there's so much dispassion, and I would expect you to at least react a little bit to me saying that you were making fun of me. Like it seems like you're just kind of apathetic to that accusation.”

Yeomans:

Again, I'm channeling assess…I'm trying, it's a tough position because you're being…Oh, I know. Let me let see,

Puder:

Go ahead.

Yeomans:

So essentially you’re experiencing me as a combination of indifferent and neglectful.

Puder:

Yeah. It's like, for some reason, that feels more true than you being the abuser. You know, it feels like, it feels like it's a form of abuse to just neglect me and to be apathetic.

Yeomans:

So what you would like is for me to hardly endorse the position you're taking and just say, if we could just get you beyond what your parents did to you, you know, you sort of deal with life better, be able to have better relationships, feel better about yourself. Is that the model you have in mind?

Puder:

It's like I'm talking to a, a door and I just want some…

Yeomans:

Well….

Puder:

Something other than this. I mean, it's just like even the speed at which you said that it's like lulling me into some sort of hypnosis or something. I don't know if that's like part of what you're trying to do.

Yeomans:

Well, I don't mean to be sarcastic, but the kind of thing you're asking me for. You've had a number of times over kind of long periods of therapy. So first of all…

Puder:

Yeah. And I know they were all like, I hate them all. You know? Like, they're all, well, some of them had some decent parts, but most of them were like all, you know, just quacks. They were quacky.

Yeomans:

Let's get back to here. Okay. You know, I am speaking slowly, so I'm a robot without any feeling about you. And that reflects my lack of interest, Am I getting it right?

Puder:

Yeah. I don't know. Maybe. Maybe I'm just one of a hundred patients of yours and you like, you know, it's just like, “Okay, here we go again.” You know.

Yeomans:

That I get this.

Puder:

What do you mean you get, what do you mean? What does that mean? You get it.

Yeomans:

Now? I get why it is so depressing, your life. I mean, I don't think I'd say, yeah.

Puder:

It's like you're the person who's supposed to care the most. And when I sense that you don't care at all, it's like, it's like a dagger into my heart.

Yeomans:

Well, I can understand if you feel that after coming here now for three months, twice a week, that I don't even see you. That I kind of just have this boilerplate response to the person who came before you and the person who came after you. That would leave a person pretty sad and desperate. So there I do get it.

Puder:

Yes. Thank you for that. Yes. It leaves me sad. It leaves me desolate. It leaves me feeling like, “What the heck am I doing here?”

Yeomans:

Yeah.

Puder:

Like, did I choose wrongly? Am I crazy to think that you'll be able to help me?

Yeomans:

Well, that's the question. What are you doing here? Because, like I said before, in spite of all the dissatisfaction and I guess pain you're experiencing here, you keep coming. So I just wonder if there's something else going on.

Puder:

Why, you're the person who's supposed to tell me what I'm doing here. Not me. Like, I'm not the professional.

Yeomans:

I have a hypothesis. So my hypothesis is that in spite of all surface appearances, our repeated meetings have activated some feelings in you. Negative, positive, both. But we're seeing the negative ones. We're not really seeing a whole lot of the positive ones. And yet you're coming here and continuing to do so, so just, it's something positive, but it seems really scary to you.

Puder:

And I'm embarrassed about how honest this conversation is right now. Like, this is very uncomfortable for me. I usually am not this honest.

Yeomans:

Well, do you, would you agree with me that honesty might be useful and helpful in therapy and what are? What would you usually hide? I don't think what you would usually hide would be your criticism of me. And you're saying, I'm a robot and don't care and mock you. I think what you might be hiding is that you kind of wish we had a good connection. But that's scary to think about.

Puder:

It's scary to think that you don't care.

Yeomans:

Well, but see, that's what…

Puder:

I desperately want to know that you care. Like, do you?

Yeomans:

Yeah. But I don't think I could say anything that would convince you. I think we have to continue with what you're experiencing here and what's noticeable. I think you could agree or disagree, is that you feel safer with the negative feelings than with the positive ones. And when you said you were being a little more honest here, I think it had to do with maybe communicating something positive. But that's like really going on thin ice for you. 'Cause that's not your general experience in life.

Puder:

Hmm. I think if you were to gimme a hug, I think that would convince me that you appreciated me.

Yeomans:

Well, I disagree, because you've had that kind of therapy before. And I think to ask for that is to short circuit what you're feeling right now to short circuit that tug of war in you right now. “Can I trust him? I'd like to, but I can't trust him. He's gonna hurt me.” I'd rather stick with the tug of war than try to put it to a premature close.

Yeomans:

I was gonna say, you know, that's just not something I think would be therapeutic, or be helpful, and could kind of complicate matters.

Puder:

Okay. Let's debrief. Okay. So this is like something that you experience with patients. It's like this, the neutrality kind of can engender. So Nancy McWilliams talks about, like, it's the, the tetra of the hero, the victim, the persecutor. And then she says the fourth, the uninterested observer. Right. Which the therapist can kind of get pulled into. So that's like another level of transference, right?

Yeomans:

Yeah. But the key is to being…maybe the word is too strong, but almost passionately interested in your patient. Concentrating on them, devoting your attention to them, and even in spite of your feeling as a patient that I speak slowly and without any affect. Over time, our belief is that that solid commitment to the patient is going to sink in at some level. But I also wanna say, I don't wanna portray this as simply a corrective emotional experience, but it's important to maintain that focus, that concentration, and that commitment because patients push us outta that position. Patients provoke us by provoking countertransference reactions where we can get angry at them, we can reject them, we can distance ourselves from them. It happens particularly with narcissistic patients. We haven't talked as much about narcissistic patients, but let's, for a moment. Patients with classic borderline personality disorder have almost universally an insecure attachment style as do patients with other severe personality disorders.

But there are different subtypes of insecure attachment and borderline patients. Classic borderline patients generally have what's called the preoccupied insecure, which is ruminating about the other person in the interaction. “What is he thinking about me? How did he think about the last thing I said? Does he think I'm stupid?” If the patient is worried about you and your responses, you have a ton of material to work with. So, the classic narcissistic patient has an insecure, dismissive form of attachment. You don't matter at all. I could care less about you. So what studies and clinical experience have shown is that when the therapist is subject to that dismissive attitude of the patients, most often they mirror it and they back away and they become dismissive and devaluing of themselves. That's why I say for you to maintain intense interest and commitment is not a given. A lot of therapists are derailed from that because of the countertransference reactions that are elicited in them, elicited in them from the patient.

Puder:

Interesting. Okay. So yeah, somehow their detachment as a sort of a mechanism of staying connected to mom, right? So it's like the classic picture. If mom leaves the room, there's toys, they're distressed, but they're pretending as if they're playing happily with the toys. Mom comes back and they don't even look at her, you know, but they really are in a distressed state. Their cortisol is high. So that's more of that avoidant attachment style. So you're saying that that occurring in the room when they are like that somehow that this is the way that I'm thinking of it. It's like our mirror neuron representation of that countertransferentially wants to distance ourself or become a little bit more disengaged.

Yeomans:

Yeah. Right. So anyway, to get back to whether it's a corrective experience. Emotional experience or not, your ability to stay committed, interested, and devoted to the patient, in spite of all of the storminess and the kind of negative feelings that can arise and sometimes wishes to distance herself. That in and of itself isn't enough to make the patient sort of reconsider if somebody might really care about them. Because if you take the guy who saw my tears as mockery, you have to do some interpretation before he can take in my commitment in him and interest in him, you have to help him see that he is putting in me something that exists within him. And, like I said, when we were doing or discussing the role play, the mocking person is part of his own mind towards himself that he exports to others. If we get him to see that it exists within himself, then maybe he will be less inclined to automatically see others as rejecting and be able to take in their caring about him in a way he couldn't before.

Omnipotent Control (1:19:50)Puder:

Okay. How does the kind transference of omnipotent control kind of fit into that? Like where they’re agenda setting, boundary testing?

Yeomans:

Yeah, I'm gonna refer to your notes that you sent to me about topics that might come up, because in a way that's totally understandable. You wanna talk about different types of transferences devaluing, erotic, childlike, regressive rejecting, and the controlling omnipotent. But the first thing I wanna emphasize is that given the internal fragmentation of the patient's mind, you can have rapid shifts from one transference to another. You were talking about that to some extent when you talked about going from idealization to devaluing. But you kind of talked about that as though it was like a once and for all shift. But depending on the circumstances, people can, not consciously, but just in effect, hop back and forth from one way of experiencing themselves in relation to you to another. And it can be a little bewildering until you have time to think and observe it.

So given that understanding, the transferences can shift a lot. And that's a lot of material for our reflection and engagement with the patient–the controlling or omnipotent transference makes perfect sense. It's a manifestation of the primitive defense mechanism of omnipotent control. The individual feels that usually through the way they verbally interact with the other, they have to control the interaction. Why does that make sense? If your mind is organized the way I described in the paranoid schizoid form, then by virtue of your projection of any aggressive stuff onto the other, others by definition aren't safe. They're either gonna disapprove of you or abandon you, or criticize you or hurt you. So as you get close to other people, what's the only reasonable thing to do? Control them. If in your gut you think they're a threat, you have to have control. How does this manifest in a psychotherapy session?

Can I give you an example? Because it'll take a few. So, a patient started therapy and she was such a classic example of seeing all the hostility outside of her. Everybody mistreated her–family, people she encountered, the waitress at the restaurant, the checkout person. Everybody she felt was critical and disapproving and rejecting and mean to her. Anyway, so she starts therapy and for session after session, she comes in and talks nonstop with kind of a pressured speech, which helped me understand why for many years she was diagnosed as bipolar. Pressured speech, you know, kind of a hypomanic style. Anyway, after the six or eight sessions of this, I did what is the main shift if we're considering the difference between TFP and more classic therapies perhaps in particular classic psychoanalytic therapies.

Yeomans:

I shifted from following the content of what she was saying, because all the stories were the same. “This person treated me badly. That person treated me badly.” You shift from the content to the interaction. This is something that most therapists have a hard time doing because you're taking the focus away from what they're saying to what's happening. And I said, “can we think for a minute about what's going on between us?” And she said, “You're interrupting me.”

“Yeah, I realized that, but I had something I felt might be useful to think about.”

She said, “What's wrong with you? You told me at the beginning of therapy, I was supposed to just come here and say everything on my mind. That's what I'm doing. You're interrupting me.”

So I said, “I also said that, you know, sometimes I might have an idea to think about that I like to introduce. So, you know, that's kind of what I'm trying to do now.”

She goes, “Alright, what's your stupid idea?” She was very angry and devaluing.

So this is where I'm gonna say in like three minutes, what took 20 minutes to go over with her, because you have to be so tactful. This is where you begin to challenge the patient's defenses of projecting everything on the other.

I said, ”You know, if we think back on all these sessions we had, could we agree that the kind of pattern is you come in and you talk, and there's really kind of no room for me to participate. Or, you know, my job is to sit and listen and take in.

“What's wrong with that? That's what you told me to do.”

I said, “Well, as I said, nothing's wrong with it. But we might wanna kind of understand something about it. And let's just start by describing what happens. Would you agree that, you know, your style of speech and talking, you know, without interruption, let's just say maybe that has a little bit of a controlling quality to it.”

You have to be very tactful. I was kind of surprised because she said, “Well, maybe it is a little controlling. So what?”

So I said, “well, you know, that's up to you if you wanna be controlling. You have every right to be controlling. But I think it might help to think about what motivates that and the impact it has on relations.” And in a way that surprised me, she burst into tears and she said, “if I didn't control you, you'd leave me like everybody else does.”

Perfect example of what I was saying, omnipotent control. If the other is gonna do something to you, you have to hold them in your grip. But ironically, it's the holding others in your grip that makes them run away from you. So that's an example of omnipotent control and how I might work with it with a patient.

Puder:

Wow. Oh man. Yeah. I had stirred up some stuff.

Yeomans:

I mean, the main point is I had to do what therapists have a great deal of difficulty doing it. You say, let's stop listening to what you're saying and let's look at what's going on here. For some reason, that makes therapists nervous. They don't think they have a right to do it. It made you nervous.

Puder:

No. It's just. Well, there's something about when I was a resident, I had a really good attending who was like, you know, the more you tell me about this person, it's like, she's talking at you, not with you. And so is that kind of like omnipotent control through the speech? Is that the…

Yeomans:

Yeah, and that's why, and here, I have very strong feelings. That's why a lot of psychotherapy has a real bad name within the world of psychiatry. And in the medical world, a lot of our colleagues say, “Oh, you know, psychiatry really isn’t medicine, especially if you're doing psychotherapy.” Well, that really annoys me. But when I get residents coming to me and saying, “Well, I inherited this case and she's been coming to the clinic for 20 years,” and then the resident starts presenting material and all the patient does is what my patient was doing, and she's been doing that for 20 years with one resident after another, that's a waste of a valuable medical resource–my psychiatry resident’s time. He should just be a sympathetic listener, if that's what you wanna give the patient, get her a reading group or something like that. But you know, we are trained to help people, not just to absorb, I mean, not just be a sympathetic ear. We're too highly trained and too valuable a resource. that resident should be saying, “What is it you're doing here with me that we could understand might be related to the fact that you don't have a lot of other people you're close to in your life.

Puder:

That's good, man. I feel like I want to get to some other stuff that might relate. 'Cause I feel like erotic transference can sometimes have that flavor, where it's like out of the fear they want to control. Interestingly, I've done episodes on transference here, and I've had people reach out to me by email saying like, “Hey, I find myself in this situation. I'm a patient. I have this therapist who's, you know, 50 years older than me, but for whatever reason, I feel like erotically charged towards them. And how do I make sense of this?” Sometimes I'll say things like, “Well, maybe, you know, have you told the therapist this?” But I'm curious how you have dealt with this over the years, and I know it's like something people might have interest in hearing.

Yeomans:

Oh, sure. And it's also important because you have to distinguish between the erotic transference, which is based on loving libidinal feelings and the eroticized transference, which has the look of an erotic transference, but that is perverse and destructive. We can talk about both, but basically that patient you initially referenced who says, “You know, he's 50 years older than me, but I have these loving feelings and sexual feelings. How can I understand that”–she should mention it to the therapist. And generally, those feelings are based on what we'll just go back to again and again, which is an internal representation of an idealized object that doesn't exist in reality, but that the person is projecting onto you. So when a patient, just to give you an example, a patient of mine came in and said, “You know, this has gotta be our last session.”

“Why?”

“Because I have to confess I'm in love with you, and it's hopeless because you could never feel for me the way I feel for you. And it's embarrassing and it's humiliating.”

So one approach to that is to say, “You know, I realize how uncomfortable this is, but the great thing about psychotherapy is we can talk about everything, understand things, help you move forward, nothing's gonna get acted upon.” So I said, “I know how hard and awkward it is, but you know you've been coming here for a couple of years, I'm sure you have some sense of who I am, but on the other hand, you know, since I don't talk about myself, there are probably a lot of things you don't know. And I'd like to hear more about how you imagine me and how you see me.” And she started describing somebody that was so perfect, so ideal, that even as she was listening to herself, she began to chuckle and say, “I guess that kind of person couldn't really exist.” So that's just a simple– simplification, a sort of a reduced version of how one might deal with that.

Puder:

I mean, part of me is like, well, maybe you are a great human. Here you've dedicated your life to helping people, and you've written books to help other people learn how to help other people. So like, what's reality? Maybe you are this archetypal male, right?

Yeomans:

I think that's idealization.

I'm thinking about a supervision I did last week. Maybe, I'm trying to put the focus off myself. A therapist, who's a really good therapist, was presenting a case…It had to do with the therapist being made to doubt themselves. But the reason that came to my mind is you're saying, yeah, I have written books and I have, you know, dedicated a lot of my life– certainly not all – to helping other people, but you know, I have my flaws, I have my weaknesses.

Puder:

Then why don't you tell me some of them? I mean, it would be helpful for me as a patient to know your flaws. Why don't you tell me your flaws?

Yeomans:

I'm more interested in the fact that you can't imagine them, because if I just give you a list of my flaws, you're gonna go on with this idealization and find somebody else to pin it on. So I think we'd be better off looking at how you manage to blind yourself to anything that might be less than perfect about me, and stay stuck in that perfect view. And we should also think about how important it is for you to do that. How much it means to you, how sad it would be to get beyond this idea somebody could be the way you're imagining me.

Puder:

I'm just convinced that if you don't tell me some of your imperfections, I'm just gonna inevitably not be able to un-idealize you. So I think that the only way I can get to a more balanced view is by you telling me the truth.

Yeomans:

Well, let's look at what's going on right now. Clearly, I'm not so perfect because you're having to increasingly control me to get what you want from me. So if you're putting such increasing demands on me, it sort of implies I'm not gonna give you what you want. That in and of itself is a problem, isn't it?

Puder:

Well, I think the very nature of the therapy relationship is you're not gonna be able to gimme what I want. It's gonna end some time. And our age discrepancy. At some point, you're gonna die before, you know, what if I need you 20 years from now, you know?

Yeomans:

All right, let's get back to the here and now, Not 20 years from now. You're saying to me, tell me an imperfection. If you don't tell me an imperfection, I'm gonna keep idealizing you. That's of interest to me. Because if you have to control the other to feel okay in the relationship with them, including me, what does that mean about who the other really is? I guess you're thinking that I'm not so perfect because I'm not giving you what you want. Never will. And that the only way for you to get it is to demand it and insist upon it. That doesn't seem like a very harmonious relationship.

Puder:

Touche.

Yeomans:

Okay. You always have to stick with what's going on in the here and now.

Puder:

Oh, that's good. That's good because it's that omnipotent control transference that are leaking back in, right?

Yeomans:

Yeah. And anytime you have that controlling, it implies there's no trust of the other.

Yeomans:

But let me just say one more thing. The funny thing about the erotic transference is it's harder for patients to work with than the paranoid transference or the negative transference- paranoid, negative, sort of the same. So the therapist comes into supervision, you know, it's terrible. “You know, my patient thinks I don't care about them and thinks I mock them and thinks I secretly don't like them.” And you say, “Well, you have to keep in mind, this is a very simple concept. They're not talking about you. They're talking about what they're projecting on you. They're talking about an internal element of their mind that they're sticking onto you. It's not you.”

“Oh, yeah. Well, that's perfectly logical because I'm a nice guy and I don't dislike my patients and don’t wanna get rid of them.”

Then the therapist, a year later, comes and says, “This is terrible. My patient is saying she's in love with me.”

Which we don't always get to. I'd say most cases don't get to an explicitly erotic transference. But then the therapist says, “What do I do now?” You have to say, “As I said to you, look at what they're projecting on you.” This therapist, who thought it is totally unreasonable to think the patient sees them as a bad guy. the same therapist might think, “oh, they're in love with me. That's kind of logical. I'm a nice guy.”

Puder:

Oh, man.

Yeomans:

Yeah. You have to get them to see that's not the real picture.

Puder:

Yeah.. I once had a supervisor who said it's like she was a patient at one point, and she said that she had some, you know, these kind of feelings towards her therapist. And the therapist turned to her and said, “Look, I could be a one-eyed cyclops, and you would have these feelings.”

Yeomans:

That's interesting. I wouldn't say that. You know, why?

Puder:

Why?

Yeomans:

That's telling the patient, you are wrong to have these feelings.

Puder:

I think it was more. I think the tone was more like, “These feelings that you're having towards me are more to do with the process of what's occurring in therapy than me as a person.”

Yeomans:

I could see a moment for that maybe, but I don't like…Your perception of me is wrong. Because there, like, going back to the guy- am I a friend or am I a foe? You want him to struggle with it internally instead of saying, “Your negative view of me isn't really connected to me, it's all projection.” That's saying, “You know, that's your problem. And the real problem is figuring out whether to believe in or not what you're projecting.” And I don't wanna short circuit that process by saying, “It's all you. Get over it. Problem is in you”

Puder:

You want them to be more reflective. And want to short circuit the reflectiveness of what's going on.

Yeomans:

Yeah. You wanna entertain the possibility that maybe you are an uncaring, mechanical robot who treats all his patients the same way and has no feelings for any of them. To honor that projection, as I said right at the beginning, paradoxically, is a way to increase the patient's nascent, sort of fledgling little bit of trust in you when you can say, “You know, let's think about that. Let's reflect on what you're feeling. Let's not dismiss it a priori.”

Puder:

Okay. So I think there's a couple questions we should definitely sort of hit real quick before we kind of wrap this thing up. One, would be the frame. I think a lot of the transference occurs in the frame. So I think we could probably devote two hours just to this, but attendance of therapy, reporting thoughts or feelings, the fee. How do you do contacts between session? Like what if…

Yeomans:

Can I go into an example of that? Okay. Because that's so important. Our position at TFP is that therapy takes place in the sessions and communication outside of the sessions is something we don't do. Except, for two reasons. One is practical needs like rescheduling or if you're having a true emergency. Now we can go back to what a true emergency is. But anyway, let me give you this example. A therapist comes into supervision, mid-career therapist, analytically trained, doing a kind of a typical psychodynamic therapy with a 40 something year old woman who is depressed a lot of the time, not successful in her work, and not successful in her love life. Can't get an intimate relationship going. Anyway, In the course of the therapy, the lady starts sending emails to the therapist. It begins as a trickle, but it becomes a flood.

So the therapist comes for TFP supervision and says, “You know, what do I do? I don't know what to do with all these emails.” He hadn't yet established the frame that you and I have been talking about, like limiting communication. So in the supervision, I said, “Well, I think you should say to the person, you're gonna recommend some modification in the form of therapy you're gonna do, you're gonna make it more structured. You’re gonna explain to her, you think that would have more benefit. And part of the increased structure would be that these communications between sessions stop. And as I said, only occur under two circumstances.” So that evoked, and by the way, if you wanna evoke transference, just stick to your frame of treatment. All my supervisees say, “All your patients have strong transferences to you. My patients just talk about all kinds of other stuff in their life. They don't have transferences.”

Yeomans:

You want transference? Go back to the frame. Be careful about the frame. So anyway, the therapist says, “This lady, you know, okay, so this, you know, revision in our model of treatment is that we don't have all those email contacts,” and that evoked transference. “What, you're abandoning me, you don't care about me.” And this allowed the therapist to analyze what was central to their interaction and to her pathology. She was finding in him, through her behavior, that I can send an endless number of emails to my therapist and the God-like perfect giver therapist will accept them and take them in and maybe respond to them. That was the enactment of an unrealistic internal image of the perfect provider. Why was her life a failure? Because she was going through life expecting to find a boyfriend who would be that perfectly giving. Why was she a failure at work? She expected herself to be perfect in ways that were not realistic. She was always critical of herself. So when the therapist said, “You know, we can't continue with all these emails,” that brought to the forefront what had been enacted, which was her wish for somebody perfect. And what needed to be analyzed was the fact that this wasn't gonna happen, and the way they were doing therapy was perpetuating an illusion rather than looking at it and understanding it and moving beyond it.

Puder:

Okay. That's good. Yeah, that's good.

Okay. I'm not gonna say too much on that. I just want to kind of, as we're kind of wrapping up our time. I really appreciate it, and there's a lot of things here that I think it's gonna be of great value to my audience.

And thank you so much for your time and, and thoughtfulness and everything.

But I wanted to see if there's anything else that is on your mind. That you feel like you just want to definitely talk about it. Is there anything else there?

Yeomans:

The one thing I don't think we've talked about enough, or one of a number, but the main thing is the difference between a classic narcissistic personality disorder patient and a classic borderline personality disorder patient. I refer to this a little bit when I talked about the difference in attachment style, the borderline preoccupied versus the narcissistic dismissive. But if we look at the internal structure of the narcissistic patient at the core, we find the same identity diffusion, the same kind of stew of unintegrated representations of self and other. You know, idealization, devaluing, feeling good, feeling bad, having dependency wishes, rejecting them, having fears, having desires. All that turmoil of unintegrated affects exist in the narcissistic patient, but the narcissistic patient unconsciously in their mind create a structure that seals over and hides or prevents access to that inner turmoil. We call that structure the pathological, grandiose self.

Yeomans:

It's a self story, a narrative of the self that provides a sense of unity and integration of the self, but it doesn't correspond to reality. It reassures the patient that they're okay, but it doesn't hold water. Simple example, the failure to launch young adult. The guy who finished college, because of his own self criticisms and insecurities, can't get involved in any kind of work. So he kind of retreats to the basement of, or the attic of, the parents' home and says, “I'm writing a novel.” So what sustains his self-esteem? I'm a novelist. I am writing a novel. So that's my purpose. That's what defines me. But years can go by and nothing much happens. And they’re falling far behind the curve. They hold onto their identity as the undiscovered novelist for dear life. And when they come into therapy, you have to help them move beyond their grandiose narrative and get in touch with all the painful longings and insecurities that they have, that they're defending against by this narrative that seems to reassure them, but doesn't have grounding. In reality, it's harder to work with narcissistic patients than with borderline patients.

Puder:

I think one of the things that the mentalization people said that was really kind of like was like an aha moment for me, and I think you just resaid it in a different way. But it was like, people with BPD, they crumble when there's an attachment injury. Boyfriend breaks up with them, they get suicidal. NPD, they crumble when there's a self-image injury.

Puder:

Lose a job, wake up to the reality that no one will read their novel. You know, like the incongruencies. That's kind of what you're saying or would you put some…

Yeomans:

That's interesting, I hadn't thought of it exactly that way. I think that makes sense. But in that formulation, what I don't find is what, in our model, we see as the protective, pathologically protective of the narcissistic narrative. Because the way you just formulated it, the borderline patient is gonna get in touch with all their anxiety and distress when there's a relationship failure. And the narcissistic patient will get in touch with it when there's a kind of a functioning or performance failure. But in our experience, the narcissistic patient, the very ill ones, managed to avoid those moments of crisis by an entrenchment in a narrative that can go on unabated for years. And so it's not as easy to access their distress.

Puder:

Okay. Because in the midst of losing the job, the narrative psychologically stabilizes them.

Yeomans:

Well, you know, to some degree. I give the example, first of all, if it's the kind of narcissistic patient I usually do, they don't have the job to begin with. But so they lose their job. And instead of saying, “You know, I guess there's something wrong with the way I performed there.” It's like, “You know why they fired me? Because I'm the only person there who was truly honest. They all would compromise. I would never make compromises. That's the only reason that firm makes any money. All the other people there would look the other way when something wasn't done right. I don't have that, you know, I'm above that. So, sure. They didn't like me. They didn't like me because of my level of honesty, not because there's anything wrong with them. The problem is with them and their lack of honesty and their compromising nature.” So, you see how the narrative, the narcissistic grandiose narrative repairs the injury instead of opening it up.

Puder:

Yeah. Yeah. That's really good. And it's still that, like borderline level of functioning with the splitting, the good-bad split with the identity diffusion.

Yeomans:

When you help the person see beyond their grandiose narrative, when this lady began to see, maybe it's not so simple that she's just morally superior to everybody else in the world. She begins to get in touch with longings to connect to other people, wishes for dependency that she's never been able to act on because she's too afraid of getting rejected. And the midphase of working with narcissistic patients, it's extremely painful and distressing to them. And you have to overtly empathize with that and say, you know, you're getting in touch with stuff now that's making you feel worse than when you began the therapy. I'm sorry about that, but I don't know any other way to really get better, except to get in touch with all this stuff that I think was there from the beginning, but that you were fending off.

Puder:

There's one other epiphany on narcissism. I want to kind of bring out and see what you think about it. I'm a big fan of the Big Five [see also episodes 92, 95, 97, 98, 99, 100, & 101].

Yeomans:

Oh, okay. I'm not, but let's go ahead.

Puder:

So, in this study (Samuel, et al., 2008), they looked at narcissism versus BPD and how they map on the Big Five. So borderline personality disorder had very strong links. And, if you're watching on YouTube, you'll see the slide I have on this with neuroticism. With all the facets of neuroticism. With anxiousness, with anger, hostility, anger, hostility was pretty strong. These are effect size…. Sorry, they're not correlations. So the effect size was about 0.5 for anger. Hostility for depression. Self-consciousness was 0.35. Impulsiveness, 0.34. Vulnerability 0.4. These are pretty strong effect sizes. And then for other facets in borderline personality disorder, there's some reduction in warmth and positive emotions in the extroversion domain. There's some, in the agreeableness. There's lower trust. Lower straightforwardness. Lower compliance. And in the conscientiousness domains, there's lower competence, lower dutiful, lower self-discipline, and lower deliberation.

In the narcissistic in the only neuroticism domains that are lower…. Sorry, higher. Higher, like more neurotic is the anger, hostility. . Now this is a self-reported scale. I have to say this. So this is self-perception, so it's not necessarily reality. Right. It's not like the family member did this for them. A little bit more impulsive, but not too much more. And then the other ones that are different in the narcissistic personality was the low agreeableness. Specifically, the ones that were very low were modesty and straightforwardness. Straightforwardness is, do they, questions like, can you be Machiavellian? Can you pull someone, you know, do you enjoy something like that? Modesty is, you know, how do you view yourself compared to other people? So any brief reflections on that, or is that helpful or interesting to you?

**Yeomans:**

Well, as I said, I'm not a big fan of the Big Five because I find it a little reductionist. But the way you divide it up into the subcategories is more interesting. But it's actually lucky for me that it's time to stop, because I have to. I'd be happy to look at that graph if you send it to me and have a little more time to reflect on it. But I don't have anything much off the top of my head to say about it.

Puder:

I really appreciate your time. I know we're wrapping it up here. If someone was listening to this and they were really wanting to do a training in that. What is the pathway to become someone who's a certified transference-focused therapist?

Yeomans:

Well, I hope people might wanna do that. I do find it a helpful form of therapy for many people and an interesting way to do our work. So I would direct the person to two organizations. One is a group called TFP, New York [https://www.tfpny.com/]. You can just Google that group and we can direct people towards trainings. And the other one is the International Society for Transference Focused Psychotherapy [https://istfp.org/]. The website there is istfp.org. And on that website, there's also a lot of information about trainings. But we're very eager to train people. We enjoy it, and we find the people who come for training usually find it rewarding. So I hope, and maybe you could post those websites. Okay.

Puder:

That's good. And then I think we should just say this for the record, 'cause you're gonna have a lot of people reach out to you who want you to be their therapist. Do you have openings at this point? Or if a patient was listening to this, and they were like, “I need this type of therapy,” where do they go?

Yeomans:

Yeah. First of all, I don't have any openings at this stage of my career. I'm devoting myself more to teaching and supervision than to practice. So, I'm sorry I don't have any openings, but I would go for referrals to the TFP New York website or to something I mentioned to you, David. It's a wonderful organization, part of the Department of Psychiatry here at Weill Cornell Medical Center called the Borderline Personality Disorder Resource Center. Website is [https://www.nyp.org/bpdresourcecenter]. And over the years, we have established a database of clinicians, not only in this country, but in many other countries who are trained to treat borderline personality disorder. Because even with all the advances that have been made over the last decades in understanding BPD, how to treat it, and teaching more and more therapists about it, there is not an adequate number of therapists for this patient population. So if you're looking for a referral, go to [https://www.nyp.org/bpdresourcecenter]. Or if you're looking specifically for TFP, you could go to TFP, New York.

Puder:

Awesome. Thank you so much. Appreciate you. Love to have you back on.

Yeomans:

Well, I have a feeling that could happen because you make the two hours go by very quickly with interesting questions and comments you had. So thank you.

Puder:

Alright, well thank you so much for your time.

Yeomans:

You're welcome. Bye-Bye now.

🌐 Interested in learning more about personality disorders and Transference-Focused Psychotherapy? Visit https://istfp.org/ to explore insightful resources and information.

🛠️ Are you a mental health professional seeking specialized training in Transference-Focused Psychotherapy? Discover upcoming training programs here: https://istfp.org/training/tfp-trainings/

View Details

Intro by: David Puder MD

Transcription Help: Valentina D'Annuncio, Al-Baab Khan

Peer Reviewed by: Erica Vega, Joanie Burns PMHNP-BC

Other Places to listen: iTunes, Spotify

IntroductionThis episode honors Dr. John Tarr, my late mentor, whose wisdom on ending therapy reflects what I feel now as I lose him.

I will share a lecture he gave on ending therapy—the “graduation” or “transition” that goes on in therapy. Just like in a patient’s graduation, the therapist’s voice may stay active in their mind. Dr. Tarr and I might be geographically apart, but his presence and my memories of him endure.

I am personally, therefore, both listening to him talk about this and experiencing it to be true. In my tougher moments of life, I can attune to Dr. Tarr’s voice, advice, and kindness.

Dr. John Tarr was a psychiatrist and psychotherapist who trained under Franz Alexander. He passed away on June 12th, 2023, at the age of 94, but with the mind of a young man, while globetrotting in Scotland. After his death, I had a lovely lunch with his widow of 66 years, Beverly, who shared with me that at one point Dr. Tarr wanted to be a radio host—news to me, as he refused to come on the podcast. I believe he was subjugating his earlier life desire to be exhibitionistic to his desire to be supportive of cultivating my aspirations and professional identity.

He was still seeing clients and mentoring residents at the time of his death. He was a citizen of the world—he was born in South Africa, attended boarding school in India, made trips to Venice for opera and connecting with glass-blowers, maintained ongoing relationships with English book-binders and worldwide orchestral musicians, made frequent visits to France, and had recently completed a trip to China.

He was my teacher from July 2011 to June 2014. Subsequently, we co-taught psychotherapy classes together from July 2014 till May 2023, 2-5 hours per week.

His mind was as sharp as ever when he passed. He was an obsessive, lifelong learner. He was thoughtful, encouraging, not prone to self-aggrandizement.

Through his generativity, encouragement, and wisdom he was a later life father figure to me.

In the clip, Dr. Tarr talks about how we internalize our mentors, loved ones, and therapists into us and can access them at a future time.

As a new Resident at Loma Linda University, I had almost no exposure to psychotherapy when I started the Therapeutic Alliance class with Dr. Tarr.

I remember hearing his words and thinking to myself, “What is he talking about? What? How does this work?” His language was so complex. His words were a symphony of empathic immersion into the hardships we face, reducing shame, creating a space for connection…the opening of the mind.

It is hard to describe something with which we have no framework to understand.

I am still understanding what it means to do deep psychotherapy, the type of psychotherapy that stirs up every kind of transference and countertransference possible.

Back then, I was more curious, trying to understand, trying to translate his erudite pontifications into things I could grasp.

Several months before his passing, Dr. Tarr sent an email to me detailing that he would leave me a prized book, Meditations by Marcus Areulius.

“This is yours on my demise.

There are colored inserts in addition to the gilding.

Bound by Sangorski and Sutcliffe, one of the most famous firms of book binders in the world. They bound the jeweled Omar Khayam commissioned by Widener (Harvard college library is named for him) and unfortunately sunk in the Titanic.”

I wrote back:

May 9, 2023, 5:09 AM

It will be a treasure to remember you.

I gave a book to a patient. Wrote a note. It was our last visit at Loma Linda before I left for Florida. They restarted with me. Last week she told me every time she misses me she reads a bit. I am sure it will be the same for us.

I can hear Dr. Tarr’s warmth, love and kindness in my mind. He will go with me. His last words to me two days before he passed were,

“I love and respect you.”

I wrote him back after our conversation:

Dr. Tarr,

Thank you for sharing your words. I am sorry I was a bit speechless. My words are that I have had several fathers in my life, and you are one of them. Your mentorship has allowed me to succeed in my career. But much more, your mentorship and father-ship has given me a gift of love and support and enthusiasm that often was not there from others. I have tears in my eyes. I know the way we see God is likely different, but I believe you have the fruit of the spirit—love being the main one. Please know that I am praying for you and will hope for your full recovery, and to see you in July.

David Puder

The world without him feels like a bit more lonely place. But even as I say that, he still exists, inside me, inside anyone who was his patient, student, anyone who allowed his empathic wisdom to permeate their being.

In a large part, this whole podcast is a way to carry Dr. Tarr’s spirit, erudite wisdom and prolific empathic teaching forward.

Now, let’s listen to Dr. Tarr himself as he discusses endings—how they can become transitions, and how his voice, and the voices of our mentors, truly stay with us.

The Emotional Complexity of Goodbyes: Understanding Separation, Transition, and Psychological ImpactDr. Tarr:

Goodbye is one of the most visceral things that anybody can have. And it’s experienced idiosyncratically by people in a lot of different ways. There are different separation types. The ideal one is mutually agreed on. That almost never happens. It’s almost always unilateral. Even in psychoanalysis where somebody’s been coming for three or four years, three and four times a week, it’s very seldom, mutually concurred in. It’s usually triggered by one person.

The mutually concurred in, is the easiest to handle. The one that's thrust on the patient by a rotation is the hardest. They can understand somebody dying. They can understand not going away. It's a huge feeling of abandonment, which I want to talk about. I don't like the word, as I said, “termination.” It has to do with pregnancy. I use the word “transition.” Although, sometimes I slip back into it. When it’s transitioning to another therapist or into therapy, which is a continuation of the talking therapy that goes on inside the person.

What are the emotions that get stirred up in transitioning? Seventy-five percent of patients have extreme sadness–mourning, feelings of loss. Fifty percent have rage, anger, hostility. Fifty-four percent of patients have a recurrence of their old symptoms. And about a third of patients develop new symptoms all around the issue of parting. It's a very, very potent kind of process.

The Deep Ties Between Goodbye, Self-Esteem, and Emotional AbandonmentWhy does it become so complicated for people?

For one thing, esteem and abandonment issues almost inevitably get triggered. Do you know the Cole Porter lyric:

“Everytime we say goodbye, I die a little. Everytime we say goodbye, I die a little?”

Non-consciously partings are portrayed as death. And finitude and death are the most potent emotions one can feel. But we experience much more that— the rest of the lyric is (it was a very popular song at one point in the age of the dinosaurs. Perhaps, before you were born):

“Everytime we say goodbye, I die a little. Everytime we say goodbye, I wonder why a little. Why the gods above me who must be in the know think so little of me, they allow you to go.”

What is “thinking so little of me”? That means, if they thought more of me, if I had more esteem, this parting wouldn't be happening.

So esteem, in Cole Porter's lyrics, gets portrayed in that way. It also alludes to something else that goes on non-consciously, which is that I ought to be loved forever. And that's why the god business gets triggered in there, too. The gods are involved in triggering separations, which they shouldn't be. What's the opposite of feeling “I have no esteem.” “I'm being rejected.” “I'm being abandoned,” which almost all patients feel, as a matter of fact.

Here’s another lyric by A.A. Milne:

“How lucky am I to have had something that makes saying goodbye so hard.”

That's a different meaning attribution, isn't it? “I've been so lucky to have something and it was so good that it makes saying goodbye so hard.” It's a different kind of connotation. It's very hard to do that. Some patients can, as a matter of fact. Particularly if they can feel that what has gone on is permanent. And it is permanent, as a matter of fact, in many ways. Because, many patients, if in the termination— transition phase of therapy, learn about how the permanence of a voice inside them—that they can carry with them the rest of their lives—which is the dialogue that has gone on between you, that that cannot be taken away. That the insights cannot be taken away. That they can be applied to daily situations. Does any of this sound like… Have you separated from a patient or had a separation? Does any of this feel like it is fitting what I'm saying?

The esteem component is very important because of the difference between “transitioning because it's desirable now,” and, “I count for so little that I'm being rejected now and being abandoned now.” And that's a very frequent meaning/connotation that gets detected.

The Psychology of Transition: Renunciation, Abandonment Fears, and the Power of a Fixed Ending in TherapyOkay, so we are relinquishing when we transition the patient—we are giving up protection and guidance. Is that one of the things that's being given up? We're also giving up a relationship and planning for that and preparing for it and processing it.

Okay. It stirs up giving up protection, but it stirs up abandonment threats, which are profound. Or, is one abandoning somebody or is one coming to the conclusion of a part effort? That effort being the enhancement of life and the transformation into better living patterns that one is hoping for- will take place in a continuing way and in an even more potent way after the therapy is stopped. I have conviction- the development can continue without the therapist when the therapist is stopped. That makes it easier for me to transition with patients. And if the patients believe that, that makes it easier for them too. It takes some convincing sometimes to do that. In part, it's a renunciation and having learned what in life has to be renounced and what cannot be avoided renouncing is one of the steps toward maturity. So, learning about renunciation techniques can be focused on in the end therapy.

The other thing that can make it very potent toward the end is that when one knows that there's a specific date. Now there's an incubation period between telling a person that therapy will stop at a particular time and from then on to the end of therapy. That's a little bit at odds with our conviction and every writer's conviction about it, that if a resident is starting with a patient or anybody starting with a patient where there is gonna be a fixed outcome. The patient and the therapist should know that from day one in the first session: this therapy is gonna last until June, so and so. That helps keep away from the process of becoming a permanent patient. It also helps facilitate intense focus on the here and now and urgency about change because there's a fixed known. Therapy in which a fixed date is set up in advance, numerous studies have been found to be more potent than one that's open-ended.

Embracing Transition: Opportunities for Growth, Self-Reflection, and Strengthening Self-Worth in TherapyOkay. What are some of the opportunities as transitioning to independence begins that one can do? First of all, one comes to grips with one's own feelings, how much good have I done? Could I have done more? Could the patient have done more? Dealing with the conditionality of what's been achieved so far and dealing with that explicitly with the patient. That is, what are some of the things that we wish we could have handled better? What are some of the things we wish we could have talked about? What are some of the feelings that haven't changed that you wish could be changed? And beginning with what has been accomplished and what has not been accomplished, what one is disappointed about can bring a huge amount of potency into therapy. So that the focus on in what way have I been helpful to you? In what ways have we not been helpful in our working together? What are the times when mistrust is intruded? What are the times when you felt I didn't understand what was going on? And that can be the most significant part of therapy going over the pluses and minuses of what has gone on.

How does one attempt to cope with this? First of all, I think the most important part is to try and stabilize self-esteem and the sense of self–that this is part of life. This is not a personal idiosyncratic rejection. You're not being abandoned. This is part of living. This is the part of the way it works. Everything is finite. Nothing lives forever, unfortunately. And we are going to be dealing within the limits of what we have available with as much progress as we can. We are assuming that there's narcissistic disequilibrium in the patient, that their self-worth is inevitably affected by that. And when it is, we try and help stabilize self-esteem and self-worth. That can be even more potent than in the working through part of therapy or the introductory part of therapy.

The Enduring Impact of Therapy: Attachment, Memory, and the Transition to IndependenceSo a kind of reminiscing about experiences together is one component of what is very desirable. Another is a focusing on that, you know, we can be attached even though we are geographically separated. You have memories of what we've talked about. They're inside you now. You have a version of me inside you. You have feelings that are toward me. Whether we are together or not, those feelings continue. Now, if it's a kind of patient that has had an impact on me, I will say:

“This does not stop my thinking about you. When I'm reminded of…, and I'll pick up a conflict that the patient has had. When I'm reminded of a situation in which you have been rejected in the past and felt so terrible about it, and I encounter a rejecting situation, that will probably trigger in me memories of what we've been talking about. So you will be in my mind and I will be in your mind. And my voice and the things we've said together and your voice and the things that you've said to me are part of your sense of self now.”

And that can continue short of Alzheimer's, indefinitely. And patients find that helpful, as a matter of fact. And to put it in a kind of an explicit:

“Being attached, though we are apart. Our attachment memories and our attachment representations, and your version of me and my version of you, are now part of our inner lives. And that they're there forever.”

We go a little bit away from “as we think together” and “as we've been working together” and as “you and I have been doing this,” a little more into as “you do this” and as “I do this” and change our language of “togetherness” and “we-ness” a little bit into the, “as you learn to do this” and as “I think about you” and stop using the, “we” quite as much in the collective and diminish that.

Winding Down Therapy: The Debate on Tapering, Emotional Contagion, and Lasting TransformationThere's a debate about this because there are very few patients that you see more than once a week in psychotherapeutic circles, elsewhere where there are options. There's a huge debate about whether you wind down, I'm seeing somebody three times a week. Do I go to twice a week, and once a week, and taper off or do it abruptly? I'm not for the tapering business, I'm for working as hard as possible in the number of sessions. But there are other points of view about that.

Can one be enthusiastic, genuinely, about some aspect of the patient's future as we're winding down the therapy? I find it possible to be enthusiastic with every patient about some aspect. I may have been disappointed in a diminished progress in one area, but if there's been progress in one area, and if I am fairly confident that that can continue, then I can be enthusiastic about encouraging the patient to have a new mastered strength. And, I think there's an emotional contagion that goes on between me and patients.

And I think that the mirror neurons pick that up and, and if I am genuinely pleased that something worthwhile is going to be permanently a part of a patient, I want them to know that. And I want them to think.

Another question that comes up. What about the succeeding visits with the patient? Does one leave with the understanding this is over–this is forever or with certain patients you can call me. I tend to tell patients that I will be thinking about them. And after a period of time when things are settled down, I sometimes would like to be able to call them and inquire what's going on. And I almost invariably would do that about a year later and inquire on somebody, particularly if somebody's not seeing a different therapist, that complicates it a little more.

Now, in some instances, I've invited patients to come in and done a kind of postmortem on the therapy because they're feeling more secure after having stopped it. I would to venture things more, I probably told this illustration before, but one of my earliest patients was a very distressed physician, wonderful woman, volunteered around the world AIDS programs, got addicted to pain medication while a physician, went cold turkey off it, refused even when dental extractions to have any analgesics given cuz she was afraid she'd get addicted. She was bisexual. She had commitment problems. There were issues about adopting children. And it was a very long therapy. Many years after she stopped, she came in, somewhat reluctantly, and I asked her a number of things. But one of the things that really impressed me was that she said:

“You know, Dr. Tarr, I knew that something was wrong and I knew that something had changed, but I didn't have any conviction that anything could permanently be changed in my life. And I lay there talking three or four times a week. And for the first year I was doing it mainly because you seemed so convinced that it would work and that you seemed so enthusiastic about what you were doing. And I was skeptical about that. And it took about a year before I began to feel that I was involved with that.”

Now, that was a complete surprise to me. I had no idea that she'd had that long a period of tentativeness about seeing me. It also reinforced a little bit that being together, irrespective of what the person is feeling is going on, can in some instances be rather transmuting and transforming, because she did flourish.

The Impact of Early Losses on Therapy Partings: Revisiting Trauma, Coping Strategies, and Emotional GrowthThe stages of parting resemble the stages of mourning. So they can be denial, anger, depression, and bargaining. And they can be incremental- when one tries to deal with those incrementally and take them for change.

What I want to say is because breaking up with the therapist or because leaving the therapist is a parting, it's gonna be very significantly affected by the outcome of multiple past parting experiences. Particularly, if there were profound losses in early childhood. Particularly if there was an abandonment by a spouse, at some point. And what is useful about keeping that in mind is that that can get activated in the parting dealings with parting from the therapist to re-visit, or sometimes to visit for the first time some of the most significant losses from the past. So you have potency then, when in the present there's a prescribed parting taking place to open up the forced partings that a person's had to undergo in the past. And the quality of what goes on is very largely determined by how past losses have been dealt with.

The other side of that is that one can then maturate into developing new coping patterns for dealing with losses that one hasn't been able to develop from the past. So I think that there can be strong potency in loss, survival, modulation techniques in the last days of therapy. I think a lot of countertransference gets stirred up when we think about what we intended to do and hope to do with the patient. With some patients, there's a phrase that people use, “What's the escape velocity”? Some patients have been so aggravating that some therapists really want them to have a get out of there with high escape velocity. Unfortunately, that does happen. It happens to almost everybody. Although I've been very fortunate and I'm very selective about patients. I've not had the busiest practice in the world, but I've had the most gratifying. But I've only picked people that I really wanted to live with for a long period of time.

And I have at least three patients right now that I'm gonna have to have a terrible personal struggle saying goodbye to. Because I just don't want them to leave.

David Puder:

And, do they want to?

Dr. Tarr:

No, they don't want to. And I'm feeling partially- one of them I've been probably seeing for 30 years, three times a week. And another one I've been seeing almost that long. And this new guy that I have, that is so promiscuous. He is one of the most intelligent people I've ever had. And I just love getting involved in his world, which is mastery and control in some areas of life and absolute helplessness in others. Absolute helplessness. In an intellectual sense he can argue with anybody in the world. And he's the premier person in his field and his book is the standard text in the field. But when it comes to emotions and connectedness, he's lost, absolutely lost.

Student:

What is developmentally, what do you think, would be behind that? You know, kind of one area gets strong and the other one doesn't develop?

Dr. Tarr:

There are different lines of development. Freud wrote on lines of development. There's a line of development of morality. There's a line of development of autonomy. A line of development of the superego. There's a line of intellectual mastery of the things. And he was gifted and brilliant and it worked. And he had a tyrannical grandfather he was sent to live with at a very early age. And he had a stepfather who was abusive. And he had a narcissistic mother, who was a famous politician. And he had a very complicated childhood. And he doesn't trust anyone. I'm the third or fourth therapist he's had. And what he's telling me is that he's never been involved in any relationship in which he feels as secure. And how that came about, I'm not sure. I'm not that different, much different, with him than some of the other people that have seen him in other things.

But there is an idiosyncratic chemistry with certain patients that you can't put words on- that just flows. An answer to your question, there are independent lines of development and maturation, which are not concurrent with each other and can be paralyzed in some areas and have what we used to call fixations in development. There are other people who've gone beyond that. And then they will regress and go back to the point of fixation. There's some people who've never gone beyond it. It is an actual fixation, so it's not a regression.

Okay. So just in the last couple of minutes. Earlier losses dominate whether termination occurs at favorable or difficult times in the person's life, is a big factor. If somebody's just gotten promoted versus somebody hasn't gotten promoted, stopping therapy is gonna be a very different situation depending on that.

The reactions to termination will be significantly influenced by the level of the patient's earlier capacity to achieve mastery over the separation-individuation crisis. That's the bottom line. They're gonna be influenced by the here and now, but also some significantly from the past. Okay. What are some of the coping strategies that get used? Avoiding emotions, idealizing the therapist or the patient, a negative transference, pain and grief exaggerated. Some patients deny that it's really stopping– it's gonna be going on forever. There's self-blame: if I'd been a better patient, if I'd been more interesting, he would want to continue with me. Rage for what gets perceived as abandonment or object loss. Devaluation of the therapist–very frequent. It is easier to depart from somebody whom you're reducing in value. Devaluation of the self. Return of the symptoms, which should ensure that the relationship continues. What are the main things one tries to do?

Sustaining Esteem and Positive Coping Through Therapy Termination: A Structured TransitionSustain esteem. Respect what's positive in the patient and that can continue in the future. Talk about the fact that there is permanence in the patient, in oneself.

“I've been altered by working with you. You've been altered by working with me. I will be thinking about you. You can think about what we said when stress arises. We can rehearse together how on your own you can handle the most significant losses.”

And I think perspective rehearsal in the final parts of transitioning are very helpful. Structuring it as graduation and as a new beginning and in a positive kind of way. Reinforcing over and over again that there's been an internalization of coping patterns, of insights, of emotional experiences. And that internalization can be positive and can be permanent.

In some instances, when the patience will be continuing, focusing on there is an institutional transference- even though you're not seeing me, you’re coming to the same place, the same offices, same institution. Because there are institutional transferences that can help patients get through this. I use explicit words at times. “You know, my voice can stay active in you. Things I'm saying now you can remember, you can quote them to yourself. You can have a dialogue with me even though we are not talking for it.” So, I'm saying that planning for it, and preparing for it, and processing it can be rather important.

OutroDr. Tarr with erudite wisdom expresses how ending treatment can bring up previous losses and meanings can get attached and potentially modulated in the process.

Therefore it is important to look at the meanings attached to the ending of treatment. Do they feel that if the gods cared about them, this would not happen? Do they feel “I count for so little, I am being rejected now.”

Or rather, can we look at how parts of the goodness of treatment will go with them, empowering future connectedness with life. Can we together have the conviction that the client’s development will continue without the therapist?

Dr. Tarr may no longer be with us, but his wisdom and spirit are still a part of me, and they’re a part of anyone whose life he touched.

View Details

Liam Browning, Brandon Luu, MD, Nicholas Fabiano, MD, David Puder, MD

Editor: Joanie Burns, NP

By listening to this episode, you can earn 1.5 Psychiatry CME Credits.

Other Places to listen: iTunes, Spotify

IntroductionCold exposure, a practice involving brief immersion in cold temperatures through showers, ice baths, cryotherapy, and cold-water plunges, has surged in popularity in recent years, due in part to advocates on social media such as Wim Hof.

Wim Hof (famously dubbed “The Iceman”) has built a global following with his extreme feats of cold endurance and his Wim Hof Method, which involves cold exposure with deep, rapid breathing practices. He asserts that cold immersion strengthens the immune system, helps regulate stress, and boosts mental clarity, all while training the body and mind to adapt to challenging conditions.

Other podcasters have amplified these claims and brought them into mainstream attention, often citing research on the potential for cold exposure to increase dopamine levels, improve mood, kickstart metabolism, and enhance mental toughness. To many, cold immersion is more than just a wellness trend—it’s now seen as a science-backed way to improve mental health (Czarnecki et al., 2024). In this podcast, we’ll dive into the science of cold immersion, separating fact from hype to evaluate its relevance for mental health and well-being.

Forms of Cold Exposure Available for Mental HealthThe practice of cold immersion involves cold plunges, cold showers, cold-water swimming, and cryotherapy.

• Cold water immersion: 5-15°C (40-59°F) for 2-15 minutes
• Cold showers: <15°C (<59°F)
• Cold water swimming <15°C (59°F)
• Cryotherapy: -110 to -140°C (-166 to -220°F) for 2-4 minutes

Although many people choose to take cold showers daily, the thermal conductivity, or heat-transfer coefficient, is lowest for air (0.024 W/m·K), compared with water (0.58 W/m·K) and ice (2.1 W/m·K), meaning cold water and ice are about 25x and 100x more efficient at transferring heat, respectively, compared to air. This also explains why cryotherapy temperatures need to be so low.

However, ice is less effective at cooling than water because it does not adhere to the body’s contour to maximize surface area. Water also allows for convective cooling, where the movement of water molecules constantly circulates cold water to the skin.

Compare the length of time recorded by Guinness World Records:

• Longest swim: Krzysztof Gajewski swam 3.7 miles in 1 hour and 46 minutes at 4.84°C (40.7°F)
• Longest full contact with ice: 4 hours and 2 minutes by Lukasz Szpunar

History of Cold Therapy for Physical and Mental HealthThe deliberate exposure to cold temperatures for therapeutic benefits has deep cultural and historical roots that date back to Greek and Roman times where it was used in bathhouses. It was also used medicinally during this time period, particularly by Hippocrates and Galen, the famous Roman physician who used cold water immersion for fevers and snow for bleeding. The practice has continued in Nordic countries where it remains an integral part of daily life. In Finland, for example, sauna use is sometimes paired with plunging into icy waters. This sauna-cold routine has been a cornerstone of Finnish wellness culture for centuries and has gained global recognition for its purported health benefits.

The Kuopio Ischemic Heart Disease Risk Factor (KIHD) Study (Laukkanen et al., 2018) discussed in our earlier episode on sauna (episode 221), highlights the profound health benefits of sauna practices.

The study followed thousands of Finnish men and found that almost daily sauna use is associated with reduced risks​:

• 47% lower risk of hypertension
• 62% lower risk of stroke
• 66% decreased risk of dementia
• 37% reduced risk of pneumonia
• 78% reduced risk of a psychotic disorder

While the sauna itself plays a significant role, cold exposure might have also played a role in some of these health benefits. However, this study did not describe the extent to which subjects were engaging in cold exposure, and the epidemiological data on the practice is incredibly scarce. We contacted the authors of the KIHD study in Finland, Dr. Jussi Kauhanen and Dr. Jari Laukkanen, and they said the amount of cold exposure was not measured, and likely the practices varied between winter and summer and might be hard to measure in a cohort like this.

What Happens to the Body During Cold Exposure?When the body is suddenly exposed to extreme cold, it initiates a “cold shock” response, which is essentially an acute stress response. This involves a coordinated surge of bottom-up signals from the body and top-down processing in the brain. At the core of this response are two main, interlinked systems: the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. Together, they form a recursive feedback loop that influences arousal, decision-making, and the body’s capacity to adapt to stress. Notably, these same pathways are also activated by other intense stressors, such as vigorous exercise or life-or-death scenarios.

• “Bottom up” signals from the body
• Cold is detected by thermoreceptors of the skin that are sensitive to rapid temperature drops. This activates sensory nerve fibers that synapse onto the spinal cord and signal up to the thalamus and the hypothalamus in the brain.
• The hypothalamus integrates these thermal signals and activates arousal centers in the brainstem and the spinal cord, activating the sympathetic nervous system.
• The sympathetic nervous system signals the adrenals to release epinephrine (adrenaline) and norepinephrine (noradrenaline) into the bloodstream.

• At the same time, the hypothalamus releases corticotropin releasing hormone (CRH), activating the HPA-axis and potentiating release of norepinephrine in the brain via the locus coeruleus.

• “Top-down” signals from the brain and mind (Morris et al., 2020)

• In anticipation of the cold and during immersion, our sensory cortices, prefrontal cortex (PFC), insula, and anterior cingulate cortex (ACC) constantly evaluate how much danger the cold plunge poses to us.
• These converge onto salience and anxiety centers of the brain, such as the amygdala, which excite the locus coeruleus, the brain’s primary source of norepinephrine, and the hypothalamus, which increases CRH release and HPA-axis activity.
• In turn, the increased norepinephrine and CRH heighten our arousal and narrow our attention to help us make fast decisions in the face of our perceived danger.
• While the cold immersion continues and we attempt calm ourselves, we rely on the PFC to regulate the amygdala and hypothalamus, but the high levels of norepinephrine, CRH, and cortisol bias our thinking and our decision-making towards reflexive, survival based decisions, driving us to want to get out of the cold.

The end result:

• Vasoconstriction: Blood vessels constrict to preserve core temperature, reducing blood flow to extremities.
• Nerve conduction slows due to the cold, leading to a reduction in pain and sensation.
• Heart rate: Typically increases at start, followed by a decrease. After exercise it might lead to a drop by cooling the body quickly.
• Increase in systolic and diastolic blood pressure, sometimes as much as 20-40mmHg.
• Increased respiratory rate: Breathing becomes rapid and shallow, sometimes gasping.

• This is how many die when submerging in cold water.

• Norepinephrine increases ~ 2-3 fold and remains elevated for hours.

• Cortisol increases, but this may be for the unacclimated.
• Shivering is maximal at core body temperature ~ 34–35°C (93-95°F).

Cold Water Swimming and its BenefitsCold water swimming, a practice deeply rooted in Nordic traditions, is gaining global attention for its purported health benefits. Dr. Susanna Søberg, author of Winter Swimming, highlights its potential to improve metabolism through the activation of brown adipose tissue (BAT) and its mood-enhancing effects. These effects are commonly cited by enthusiasts and researchers alike, especially as initial studies of cold water swimmers showed positive effects on the metabolism, mood, and well-being (for review, see Kunutsor et al., 2024).

Several studies have assessed the effect of cold-water swimming on mood, most notable of which is a case report of a 24-year-old woman with treatment-resistant depression who took up weekly open-water swimming off the coast of England and had complete remission of symptoms without medications (van Tulleken et al., 2018). It should be noted that this patient swam from April-September, not in the winter.

However, as with other cold immersion practices, the evidence remains limited. These initial studies lack adequate controls, sometimes lacking control groups entirely, have small sample sizes, have limited replicability, and do not account for confounding factors like physical activity, socialization, healthy user bias, and the calming effects of natural environments. Thus, to disentangle the mechanisms of cold exposure, we need to focus on passive methods of cold exposure.

Cold Therapy Improves MoodMultiple studies have shown an improvement in mood immediately after cold-exposure: * Kelly and Bird, 2021: Improved mood following a single immersion in cold water: + 42 participants stood in chest-deep 13.6°C (56.48°F) sea water in the UK in November for up to 20 minutes. + Compared to the 22 controls, the cold water group experienced small but significant improvements on all Short Form of the Profile of Mood States (POMS-SF) subscales immediately after cold water exposure. - Overall, 15 point decrease (51 to 36) for cold water vs. 2 point decrease (42 to 40) in the control group. - Vigor by 1.1, and Esteem-Related Affect by 2.2 points Tension by 2.5, Anger 1.25, Depression 2.1, Fatigue 2.2, and Confusion 2.8 points. - Control group increased in depression by 1 point. - The maximum score for these subscales ranges from 16-32.

*Note.* Reprinted from “Improved mood following a single immersion in cold water”, by Kelly, J. S. & Bird, E. (2022). *Lifestyle Medicine*, 3(1), e53.

Yankouskaya and colleagues 2023: Short-Term Head-Out Whole-Body Cold-Water Immersion Facilitates Positive Affect and Increases Interaction between Large-Scale Brain Networks:

• 33 participants sat in mildly cold 20°C (68°F) water up to their clavicles for 5 minutes
• Immediately after immersion, positive affect increased and negative affect decreased according to [the Positive and Negative Affect Schedule] PANAS by about 5 points each.
• Participants also felt more active, alert, attentive, inspired, proud, and less nervous.
• Cold water immersion correlated with brain activity changes on fMRI scans, specifically, with increased coupling of the mPFC with the anterior insula and dlPFC and decreased coupling between the mPFC and the ACC. Of note: Mechanistically, aberrant functional connectivity between these nodes has been linked to various depressive symptoms (Sheline et al., 2010).

Four connections were uniquely correlated with self-reported changes in positive affect after cold-water immersion: between DMN.MPFC; two nodes of the salience network (ACC and RPFC-L); and between FP.PPC, DAN.IPS, and Vis.Lat in the right hemisphere. Notably, a recent study identified these same regions of the salience network (dlPFC and ACC) to be larger in depressed patients compared to healthy controls (Lynch et al., 2023).

*Note.* Reprinted from “Short-Term Head-Out Whole-Body Cold-Water Immersion Facilitates Positive Affect and Increases Interaction between Large-Scale Brain Networks”, by Yankouskaya, A. et al., 2023, *Biology*, *12*(2), p. 211.

Reed and colleagues 2023: Cardiovascular and Mood Responses to an Acute Bout of Cold Water Immersion:

• Sixteen adults immersed for 15 minutes in 10°C (50°F) water up to the sternum (they did not cover with cold water the cervical sympathetic chain of the sympathetic nervous system surrounds the jugular area in the neck).
• Assessments were conducted pre-immersion, during immersion (1-minute and 15-minute time points), 30 minutes post-immersion, and 180 minutes post-immersion.
• Negative affect (assessed via PANAS) decreased significantly only 180 minutes post-immersion (p < 0.001), but not during or immediately after immersion. Positive affect did not change.

• However, for the negative affect, this may be due to one participant responding well (see box plot below)

  Note. Reprinted from “Cardiovascular and mood responses to an acute bout of cold water immersion”, by Reed, E. L. et al., 2023, Journal of thermal biology, 118, 103727.

• Serum cortisol levels did not change from 0 minutes to 30 minutes but decreased by 47% at 180 minutes (p = 0.014).

• No significant changes in β-endorphin levels were observed throughout the protocol.

Cold Exposure Increases Dopamine and Norepinephrine in the Body: The Catecholamine HypothesisThe anecdotal improvements in mood in those observed in these studies may be due to increases in catecholamines, as first demonstrated by a study in 2000 by Sramek and colleagues, Human physiological responses to immersion into water of different temperatures:

• 10 male subjects sat in a chair in different temperatures of mildly cold water for 1 hour.
• 32°C, 20°C, and 14°C (90°F, 68°F, 59°F respectively).
• Plasma norepinephrine, dopamine, epinephrine, and cortisol levels were checked sequentially at 0, 30, 60, 120 minutes.
• The coldest temperature dropped rectal temperatures from 37.3°C to 35.6°C and increased metabolic rate by 350% while also mildly increasing HR, SBP/DBP.
• Plasma peripheral (not in the brain) norepinephrine and dopamine each increased 5-fold during immersion in the coldest water, while epinephrine remained unchanged.

• Plasma cortisol decreased in each session, including in control sessions, which may suggest psychological-mediated elevations in cortisol that decreased as the participants became used to intervention.

  Note. Reprinted from “Human physiological responses to immersion into water of different temperatures”, by Šrámek, P. et al., 2000, Eur J Appl Physiol, 81, pp. 436–442.

Meanwhile, a more recent study by Eimonte and colleagues (2021) showed that norepinephrine, epinephrine, and cortisol can increase with shorter cold-plunge sessions. In this study, 12 young men sat in mildly cold 14°C (59°F) water for 10 min. Cortisol (ηp2 = 0.22), norepinephrine (ηp2 > 0.4), and epinephrine (ηp2 > 0.5) were each significantly increased and remained elevated for several hours after immersion.

*Note.* Reprinted from “Residual effects of short-term whole-body cold-water immersion on the cytokine profile, white blood cell count, and blood markers of stress”, by Eimonte, M. et al., 2021, *International Journal of Hyperthermia*, *38*(1), 696–707.

Leppäluoto and colleagues (2008) investigated the effects of repeated cold exposure over 12 weeks in 20 female participants, comparing 3x weekly cold water swimming (0–2°C for 20 seconds) and cryotherapy (-110°C for 2 minutes). The study found that plasma norepinephrine increased 2-3 fold acutely after each session for both interventions, and this effect persisted throughout the 12-week period.

In contrast, changes in epinephrine and adrenocorticotropic hormone(ACTH) levels were minimal. Cortisol levels peaked during the first two weeks of cold-water swimming before declining by week 4, indicating habituation to the stressor. It’s unclear to what extent the habituation is a result of psychological or physiological adaptation. Meanwhile, pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α remained unchanged.

*Note.* Reprinted from “Effects of long‐term whole‐body cold exposures on plasma concentrations of ACTH, beta‐endorphin, cortisol, catecholamines and cytokines in healthy females”, by Leppäluoto, J. et al., 2008, *Scandinavian Journal of Clinical and Laboratory Investigation*, *68*(2), 145–153.

This suggests that norepinephrine will likely continue to increase during cold exposure even after a person becomes cold-adapted. While the increases in norepinephrine suggest a plausible mechanism for the enhancements in mood and feelings of alertness and have been touted by social media influencers, there has only been one RCT assessing repeated cold exposure on depressive symptoms:

A Randomized Control Trial of Cold Therapy on Depressive SymptomsRymaszewska and colleagues (2020): Efficacy of the Whole-Body Cryotherapy as Add-on Therapy to Pharmacological Treatment of Depression—A Randomized Controlled Trial:

• Methods
• 92 adults (aged 20–73 years) with a diagnosis of mild-moderate depression (17 on HAM-D and 21-24 on BDI) who were receiving outpatient therapy.
• Participants were randomly allocated and exposed to cryogenic temperatures −110°C to −135°C (the experimental group (EG)) or to low, but not cryogenic temperatures −50°C [the control group (CG)].

• 10 3-minute sessions across 2 weeks (Mon-Fri).

• Results

• Both groups improved on the HAM-D and BDI.

• There were no differences between groups on either of these metrics by the end of the study.

• BDI only differed between the two groups 1 week after treatment, when the cryotherapy group scored an average of 9 points lower on BDI compared to the control group (decrease from 21.7 to 9.4 in cryotherapy group vs. 24 to 18.6 in control group).

• This effect was not maintained after 2 weeks of treatment or after 2 week follow up (cryotherapy group increased to 15.2 vs. controls 18.1).

• However, cryotherapy participants reported statistically significant improvements in several items on the BDI.

• Sadness, loss of pleasure, self-criticalness, loss of interest, and indecisiveness.

• The cryotherapy group also had significantly lower scores on the cognitive-affective dimension and the somatic dimension.

• Cryotherapy participants also improved more on quality of life and other symptoms related to pain, sleep, and self-acceptance.

• There were no changes in inflammatory markers (CRP, IL-6, IL-10, NO) or antioxidative stress.

Central vs. Peripheral Catecholamines: Does cold exposure increase levels of dopamine in the brain?Dopamine, a neuromodulator associated with mood, motivation, and reward, has garnered significant attention in discussions about cold exposure. While there is some evidence, such as the Sramek and colleagues (2000) study, suggesting a substantial increase in plasma dopamine levels following cold water immersion, it is important to note that this finding does not necessarily translate to increased dopamine activity in the central nervous system. Mechanistically, peripheral increases in dopamine do not translate into an increase in central dopamine levels. The blood-brain barrier is highly selective and restricts the passage of many substances from the bloodstream. Dopamine is relatively polar and is actively blocked by efflux transporters at the blood-brain barrier, preventing any significant entry (Abbott et al., 2010). As an example, for people with Parkinson’s Disease (low dopamine centrally), simply administering dopamine peripherally does not increase central levels. Instead, L-DOPA (levodopa), a precursor of dopamine, is used, since it can cross the blood-brain barrier (Oertel et al., 2016).

In rodents, chronic cold exposure leads to an adaptive reduction in central dopamine, likely to attenuate the dopamine system to subsequent stressors (Moore et al., 2001 & Valenti et al., 2012). Rodents exposed to acute stressors such as tail shock, foot shock or restraint exhibit marked increases in extracellular DA levels in the mPFC and moderate increases in the NAc and/or striatum (Moore et al., 2001); however, no studies exist measuring the effect of acute cold exposure on central dopamine levels or on reward-related activity in the brain. It’s unclear whether these stress-related increases in dopamine are linked to reward or represent a separate mechanism linked to aversive stimuli (Holly & Miczek. 2016). Because cold exposure in animal studies is involuntary—and, from the rodent’s perspective, likely torture—its relevance to human experiences is limited. Humans who deliberately engage in cold water immersion often view it as a personal challenge to overcome, a process that can itself elevate dopamine via a sense of reward. Thus, data from animal models of forced cold exposure may not readily translate to the human context in which belief in the health benefits could amplify–or lead to–a dopaminergic response.

Meanwhile, peripheral norepinephrine released from the adrenals is also not thought to cross the blood-brain barrier, but, unlike dopamine, peripheral norepinephrine is likely associated with increased norepinephrine in the brain in response to a stressor. This is due to the hypothalamus’s parallel actions on increasing activity of the locus coeruleus (via CRF) and the sympathetic nervous system, as well as the influence of baroreceptors on the locus coeruleus (Van Bockstaele et al., 2001). While no human studies have measured central norepinephrine in humans in response to stress, animal models show that the amount of central norepinephrine and the activity of locus coeruleus neurons increase in response to various forms of stress, including foot shock, restraint, and auditory stress (Valentino & Bockstaele, 2008). There is some evidence of chronic cold exposure (5°C [41°F] cold room for multiple days/weeks) altering locus coeruleus activity and extracellular norepinephrine in the brains of mice (Jedema et al., 2001; Buffalari & Grace, 2009), but there are no studies assessing acute cold exposure on brain norepinephrine in animals.

Notably, exercise can increase plasma norepinephrine by 1.5-6x, depending on the intensity (Zouhal et al., 2008). Meanwhile, medications such as SNRIs affect plasma concentrations less due to their selectivity for norepinephrine, serotonin, and dopamine transporters in the brain.

Cold Exposure on Inflammation and Immune FunctioningAlthough this cryotherapy study did not show a direct effect on inflammation, many proponents of cold exposure, particularly Wim Hof, argue that it improves inflammation and immune functioning. A self-report survey in 1999 by Siems suggested that cold water swimmers experience 40% less upper respiratory tract infections than those who don’t engage in cold water swimming. A study of Wim Hof and some of his followers also showed a reduced pro-inflammatory cytokine response (IL-6, TNF-alpha) to injected bacterial endotoxin (Kox et al., 2014). Wim Hof also claims cold exposure increases WBCs, and although there is a theoretical basis of the enhanced immune response (as norepinephrine and cortisol are thought to mobilize WBCs in states of sympathetic arousal in preparation for defense of microbes associated with potential bodily injury), the results of studies in winter swimmers and in those engaging in passive cold water immersion are limited. For example, some studies show an increase in pro-inflammatory plasma IL-6 concentration and monocytes in cold water swimmers (Dugué & Leppänen, 2000; Lombardi et al., 2014) and with passive cold water immersion (Janský et al., 1996; Brazaitis et al., 2021). However, these studies were small, heterogeneous, and lacked adequate controls, and the in vivo significance of these findings and whether they are clinically relevant have not been studied adequately (Tipton et al., 2017).

There are no studies, to our knowledge, that assess changes in inflammatory cytokines in participants who have elevated cytokines at baseline, which represents a possible ceiling effect observed in current studies.

The anti-inflammatory effects of cold exposure are also questionable for exercise-induced inflammation, as a recent systematic review and meta-analysis of some low-quality cold water immersion studies showed no effect on post-exercise inflammatory markers (IL-6, CRP, IL-10) and a small positive effect for reducing exercise-related delayed onset muscle soreness (DOMS) (Xiao et al., 2023). Nevertheless, as we’ll discuss later, anabolic signaling, which relies on inflammatory signaling processes, is significantly decreased by cold exposure, suggesting cold exposure could have an impact on local inflammation.

How Cold Therapy Affects the Mind: Mindfulness, Overcoming Challenges, and DissociationThere are very few studies on the topic, but a qualitative study (Østergaard et al., 2024) did identify mindfulness as a key theme expressed by Danes who were frequent cold water swimmers:

It can be quite meditative to sit there in the water. You quickly forget other things and have a strong focus on being present in the moment, because it’s challenging to think about other stuff when you’re getting hit with that cold water constantly. So, I don’t think much is happening in your head.

Sometimes it can be challenging to sit and meditate and not think about anything. But when you get into the cold water, you just can’t think about anything else. It’s like the body, with the cold and warmth just forces you to be in the moment.

From our own experience, the first seconds in the water can be profoundly overwhelming, as the shock of the cold water abruptly brings attention to the body's physiological responses. A heightened sense of panic may arise, accompanied by rapid breathing and an intense urge to escape the situation. However, by consciously regulating one’s breathing and enduring the discomfort, a state of calmness gradually emerges. This experience of pushing through the discomfort is echoed by Andrew Huberman, who advises to push through multiple of these “walls,” as this can help train willpower and resilience.

Patients with borderline personality disorder often do grounding tasks within dialectical behavioral therapy, including holding ice. For many patients, this can be something that deters self-harm behavior.

However, studies have shown that cold can increase dissociation acutely (beyond a certain temperature and duration), likely as a way to protect ourselves from the pain. A study of the cold pressor task (holding your arms under freezing water for as long as you can) showed small increases in dissociation symptoms (peritraumatic dissociative experiences scale ([PDES]; t(69) = 4.87, P < 0.01, partial η2 = 0.26), but those with high trait dissociation (>25 on dissociative experiences scale [DES]) did not experience more dissociation than those with low trait dissociation (<10 on DES). (Giesbrecht et al., 2008). A repeat similar study found that pain catastrophizing was a much stronger predictor of how much someone would dissociate during this cold pressor task, compared to anxiety sensitivity and depression symptoms (Gómez-Pérez, et al., 2013).

• Anxiety Sensitivity (AS): predicted 5% of the variance in laboratory-induced dissociation.
• Depressive Symptoms: predicted 4.4% of the variance in laboratory-induced dissociation.
• Pain Catastrophizing: predicted 18.6% of the variance in laboratory-induced dissociation, highlighting its role in how stress is appraised.

It would be interesting to have another arm of this study type where participants are told that doing this would decrease dissociation and improve mental wellbeing. Perhaps from that arm, the “meaning” would change the appraisal of the stress, and the pain would have meaning and less dissociation. This change in meaning is reminiscent of what Viktor Frankl observed as a common thread in those that suffered in the concentration camps (see episode 113):

The way in which a man accepts his fate and all the suffering it entails, the way in which he takes up his cross, gives him ample opportunity—even under the most difficult circumstances—to add a deeper meaning to his life. It may remain brave, dignified and unselfish. Or in the bitter fight for self-preservation he may forget his human dignity and become no more than an animal.

Future studies should address how cold exposure acclimatization changes the stress response and the degree of dissociation someone experiences. Furthermore, as we discussed in episode 230 in the written section titled “The Psychological Antidepressant Mechanisms of Exercise”, there is a benefit of “mastery experiences” as key sources of self-efficacy, in which enduring challenges and increasing one’s capabilities can improve how they feel about themselves. There might be an increase in self-efficacy from progressive cold exposure, which improves things like dissociation and mood.

Is Cold Exposure Just Placebo?Generally, it also needs to be considered that few studies use a control arm that could benefit from the placebo effect.

An interesting study assessed the effect of 21 days of the Wim Hof Method (30-second to 3-minute cold showers plus rapid breathing) vs. active control (warm showers and slow breathing) in 78 mildly depressed (PHQ score 10-20) women (avg age 45) (Blades et al., 2024). Both groups experienced a 20-30% reduction in depression (CES-D) and anxiety (GAD-7) symptoms but with no differences between groups. However, due to the different breathing patterns and different temperatures, it is difficult to isolate the effect of cold exposure. Also, the showers might not have been cold enough to cause a robust physiological response, potentially making the breathing a more important factor. Given both groups engaged in an intervention, the rate of spontaneous remission can’t be ruled out with the current study design.

(Depressive symptoms)

Note. Reprinted from “A randomized controlled clinical trial of a Wim Hof Method intervention in women with high depressive symptoms”, by Blades, R.et al., 2024, Comprehensive psychoneuroendocrinology, 20, 100272.

Broatch and colleagues (2014) attempted to control for the placebo effect by comparing cold water immersion to immersion in room temperature water and immersion in room temperature water with an added skin cleanser. The participants were told the skin cleanser was beneficial for improving post-exercise recovery. Results showed that only the control group without the added skin cleanser had a reduction in leg strength and subjective ratings of readiness for exercise, pain, and vigor 48 hours after completing a HIIT session.

This raises an important need for future cold immersion studies to measure and control for expectancy effects when evaluating treatment outcomes. Research in other areas of psychiatry, such as the antidepressant effects of psychedelics, has demonstrated that belief in a treatment’s efficacy can significantly moderate outcomes. For instance, psychedelics only show superiority over traditional antidepressants when participants believe in their therapeutic potential (Dutcher & Krystal, 2024).

The Theoretical Mechanism Behind Cold Therapy’s Beneficial Effects on MoodEngaging in consistent, challenging activities that elevate norepinephrine and dopamine levels—such as cold exposure and exercise—may theoretically recalibrate the signal-to-noise ratio within fear and anxiety-related neural circuits that activate the stress response, thereby reducing anxiety through bottom-up mechanisms. However, it is less clear whether these activities influence top-down cognitive processes, such as the tendency to misperceive threats or maintain negative self-perceptions. Addressing these cognitive biases appears to require targeted psychotherapeutic interventions.

Takeaways on the Antidepressant Effects of Cold Exposure* There are very few studies assessing the effect of cold exposure on depressive symptoms. * Mood improves immediately during and following cold exposure. * Norepinephrine is consistently increased during cold exposure and can persist for several hours. * Increases in cortisol during cold exposure may reflect psychological stress, as this effect decreases with repeated exposures. * Cold exposure likely has a small, undetermined effect on the immune system. * There are undoubtedly psychological mechanisms of the mood improvements of cold exposure, but not enough trials measure them or adequately account for placebo effects.

Cold Exposure Improves Post-Exercise Soreness, Power, and StrengthCurrently, the most robust evidence for cold therapy is in improving post-exercise recovery. As previously mentioned, the strongest evidence for cold-water immersion is for improving delayed onset muscle soreness (DOMs) (24 h: SMD -0.34, 95%CI [-0.65, -0.04], 7 trials) the following day, according to a meta-analysis of 7 studies. However, rates of perceived exertion were unchanged at 24 and 48 hours. There was also a small effect of improving power recovery 24 hours after cold-water immersion (24 h: SMD 4.77, 95%CI [2.12, 7.42] 4 trials) as measured by the countermovement jumps and sprints (Xiao et al., 2023). It should be noted that many studies used different protocols of cold exposure, including the exercise selection, method of cold exposure, temperature, and duration.

For cold water immersion, colder temperatures have not been shown to provide additional benefit for muscle soreness, as a recent review of 44 studies found that studies using severe cold (5-9°C) and moderate cold (10-15°C) were similarly efficacious (SMD =.99 and 1.0 respectively) when compared to control (Batista et al., 2023). Interestingly, when stratifying studies by time of immersion, only studies of short (<10 min) or medium (11-15 min) duration showed a reduction in DOMs compared to control, while longer immersions (>16 min) was not statistically significant (SMD 95% CI [-.16, 1.65], but this may be a result of publication bias.

Interestingly, the previous meta-analysis by Xiao and colleagues showed a reduction in creatine kinase and lactic acid, markers of muscle damage and metabolism, at 24 and 48 hours after cold-exposure. However, muscle damage is thought to be a key mediator of muscle growth. Cold therapy may actually dampen the anabolic response to training by limiting muscle damage and by suppressing muscle protein synthesis and mTOR signaling (Peake et al., 2020).

In a 12-week trial of 21 men, after each strength training session, participants were randomized to 10 minute cold-water immersion up to the waist (10.1°C) or 10 minute active recovery on an exercise bike. The cold-water immersion group grew significantly less muscle (d = −4.1; P < 0.001) and their muscle fibers had less myonuclei, which are thought to increase growth factor secretion in response to exercise-induced inflammatory signaling (Roberts et al., 2015).

These findings were replicated in another study by Fyfe and colleagues (2019), showing that cold-water immersion up to the sternum (15 min at 23°C) blunted muscle gains to a 7-week training program compared to controls who sat in a chair. Endurance and muscle strength were unchanged.

Meanwhile, there are only five studies assessing the effect of cryotherapy on training adaptations, with mixed but limited findings thus far (Haq et al., 2022).

Cold Exposure and Brown Fat: Separating Hype from ScienceBrown fat, or brown adipose tissue (BAT), is a subtype of fat tissue with many mitochondria that give the fat a more gray/brown hue. The mitochondria of brown fat are unique because they have an uncoupling protein that allows the brown fat to use glucose and other fat molecules to generate heat. This heat generating capability is vital for babies, as they cannot shiver.

Some studies have shown that brown fat can increase in activity in response to cold (Søberg et al., 2021), thus many advocates of cold-exposure claim that this increase in metabolic activity can be beneficial for metabolism and longevity.

However, this study by Søberg had major limitations:

• Group similarities:

• Both did around the same total physical activity/training per week, same plasma glucose, same cholesterol.

• Differences in groups:

• Total fat % was lower in the winter swimmer group (12.0% vs 18.2%).

• This means the winter swimmers at the same BMI had more muscle potentially and less fat to insulate body heat, necessitating more heat production through brown fat.

• The reported 500-calorie difference in daily resting energy expenditure is based on an extrapolation from measurements taken during a 30-minute cooling session using calorimetry. During this session, researchers observed a 10 calorie difference between the two groups. When this small difference was scaled to a full day, it resulted in the reported figures of 3,044 calories in the cold water swimmers versus 2,560 calories in the controls. However, it’s important to note that this difference in energy expenditure occurs only during the cooling period. Therefore, to achieve the reported benefits of BAT, one would need to remain cold consistently throughout the day.

• Even if the authors were able to detect a true difference in 10 calories, which itself could reflect measurement variability of their calorimetry setup, it is not tenable to assume all of these calories can be contributed to BAT. The authors themselves state “the difference in cold-induced energy expenditure could not be explained by differential glucose tracer uptake in BAT between groups, also arguing for additional contributors in cold-induced thermogenesis.”

Where these claims continue to fall short is that BAT is incredibly sparse in adults, even in cold swimmers. It may be only 50-300g (about 1 pound) in the average adult and is only detectable in less than half of people. BAT is detectable more often in the winter, in women, in younger people, and in people with less adiposity (Au-Yong et al., 2009; Saito et al., 2009). This likely correlates with the amount of time someone feels cold.

The total energy expenditure of active BAT is incredibly small, on the order of 2-5% of basal metabolic rate (van Marken Lichtenbelt & Schrauwen, 2011). Assuming a total daily energy expenditure of 2000-3000 calories, of which basal metabolic rate is about 60%, this would equate to 40-90 calories/day. This pales in comparison to the brain, which accounts for about 20% of basal metabolic rate, and to skeletal muscle. The authors state “the improved glucose clearance following cold acclimation in humans is likely mediated, at least partly, by more efficient insulin-mediated glucose uptake by the skeletal muscle.” Consider how much glucose is taken up by muscles after a meal. It’s thought that muscle takes up 80% of postprandial glucose.

Cold exposure is thought to only increase the activity in brown fat, unlike dinitrophenol (DNP), a fat loss drug used in the 1920s-30s and by some bodybuilders today, which uncouples mitochondria in all tissues. While DNP increases energy expenditure by 30-40% and leads to weight loss by about 1lb/week, it has an incredibly low therapeutic index, as you can imagine disrupting mitochondrial functioning in the heart and brain can lead to devastating consequences (Cutting et al., 1933; Ost et al., 2017). Of note, there are currently phase II clinical trials investigating different prodrugs of DNP for use in type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD).

Does Cold Water Swimming Decrease Insulin?Another frequently cited mechanism by which cold exposure improves metabolism is its potential to enhance insulin sensitivity and lower fasting insulin levels. For example, a study by Gibas-Dorna and colleagues (2016) investigated the effects of repeated cold water swimming on fasting insulin levels over seven months in non-obese female swimmers. In the cold exposure group, fasting insulin levels significantly decreased from 8.98 ± 2.29 µIU/mL in October (average water temperature 9.5°C or 49.1°F) to 6.82 ± 1.17 µIU/mL in January (1.0°C or 33.8°F), representing a reduction of 2.16 µIU/mL. By April (4.4°C or 39.9°F), insulin levels had slightly risen to 7.43 ± 1.36 µIU/mL, but they remained lower than at baseline. Conversely, the control group of indoor swimmers showed negligible changes in fasting insulin, with levels averaging around 7.00 µIU/mL from October to January.

However, before concluding that cold water swimming alone meaningfully reduces insulin, it’s important to consider this study had major limitations. First, the cold water swimming group had significantly higher baseline levels of insulin than the control group, which complicates any comparisons between the two groups. Secondly, this study was an observational study that did not control for factors such as exercise frequency, dietary habits, or other lifestyle behaviors–important influences on insulin and leptin levels. This is especially relevant considering the cold water swimming group is a self-selecting population (participants of an outdoor swimming club) that likely already believes in the health benefits of cold water swimming and therefore is more likely to make other health-conscious changes. In other studies on exercise and diet, when participants begin to change their exercise or eating habits for the better, they will typically change the other as well. Lastly, the study did not specify how often the participants engaged in cold exposure (“twice a week, or more than twice a week”), and if cold exposure alone were the key driver of lower insulin, it would be logical to see a continued decrease in insulin levels from January to March, when water temperatures are typically at their coldest; the data, however, did not clearly establish that trend.

A few small studies on passive cold exposure in diabetic patients have also reported modest effects on improved insulin sensitivity and increased metabolic rate. These effects are thought to be largely driven by cold-induced shivering, which elevates energy expenditure and glucose uptake by muscles, functioning similarly to mild exercise. When shivering is suppressed, the effects on insulin sensitivity are reduced but remain statistically significant, likely due to increased sympathetic nervous system activity or mildly elevated glucose uptake by brown adipose tissue and muscle during non-shivering thermogenesis (Remie et al., 2021). While these studies suggest short-term improvements in insulin sensitivity and energy expenditure, the changes are relatively modest, have shown limited replicability from study to study, and pale in comparison to exercise. Furthermore, there are no randomized controlled trials that have convincingly demonstrated long-term benefits of cold exposure in lowering basal insulin levels or insulin sensitivity.

Cold Exposure Acutely Decreases Processing Speed and Executive FunctioningIn a systematic review of 18 studies (eight studies of cold air exposure and 10 of cold water immersion) on cold exposure’s effects on cognitive performance, cold exposure was shown to induce an impairment in 15 out of the 18 experimental settings, both during cold exposure and in the minutes to hours after. Processing speed and executive function showed the more consistent impairment while working memory and attention showed contrasting results (Falla et al., 2021).

Safety/Precautions of Cold Exposure* Cardiovascular risks + Risk of ventricular arrhythmias with concurrent sympathetic/parasympathetic activation from the dive response (Shattock & Tipton, 2012) - Predisposing factors, such as long QT syndrome, ischemic heart disease or myocardial hypertrophy, may be necessary for fatal arrhythmias to evolve in absence of hypothermia.

• Arrhythmias due to hypothermia
• The risk is highest during the “afterdrop”

• During cold water immersion, the blood vessels in the arms and legs constrict in order to shunt blood to the core bodily organs, leaving your arms and legs much cooler. When you get out of the cold water, peripheral vasoconstriction decreases and the cold and warm blood mix, leading to a drop in core temperature as much as 4°F.

• Risk of worsening ischemia, angina

• Increased sympathetic nervous system response during cold shock may place strain on the heart, similar to exercise, which can exacerbate ischemia.

• Neurological risks

• Cerebral perfusion pressure decreases due to rapid hyperventilation from the cold shock response, increasing risk for ischemic stroke.

• Patients with autonomic dysfunction or thoracic spinal cord injury should avoid cold exposure.

• Other conditions such as asthma and Raynaud’s are relative contraindications to cold exposure, due to the respective risks of asthma exacerbation and ischemia of the fingers.

Recommendations and Future Directions: A Call for Further StudiesDespite widespread claims on social media regarding the mood-enhancing and cognitive benefits of cold exposure, there are currently very few randomized controlled trials (RCTs) on the subject. Additionally, significant heterogeneity exists among studies and the practices promoted online, making it unclear what specific protocols—such as temperature, duration, or timing—are most effective for mood enhancement, muscle recovery, or other purported benefits.

From a practical perspective, if a patient has no contraindications and finds cold exposure enjoyable, it may be reasonable to support its continued use. The benefit-to-risk ratio appears favorable, as the potential benefits, although not well-defined, likely outweigh the relatively low risks and costs associated with the practice. Furthermore, the placebo effect should not be underestimated; activities that foster a sense of energy and vitality may positively impact other facets of daily life. Psychological factors, such as the enhanced self-efficacy derived from overcoming the discomfort of cold exposure, may also contribute to mood improvements. However, to date, no studies have directly investigated these potential mediating effects.

In future studies, an ideal RCT would have the following design:

• Treatment population: 50 patients with moderate depression
• Treatment frequency and duration: 5x/Week for 8 weeks (to allow for any epigenetic impacts, similar to medications)
• Treatment arms: Cold exposure 45°F for 3-5 minutes vs. active controls who are in water that seems cold 67°F 3-5 minutes
• Outcome: Depression (HAM-D), Anxiety (GAD-7), Self-Efficacy (GSE), Treatment Expectations (TEX-Q), measured at 2, 4, 8, and 12 weeks. Cortisol, norepinephrine, dopamine, pre-post immersion once weekly.

Cold therapy offers intriguing possibilities for mental health, with evidence suggesting mood elevation and potential antidepressant effects. While physiological changes, including increasing norepinephrine levels, may underlie some of these benefits, the psychological aspect of willingly embracing discomfort aligns with logotherapy principles, promoting meaning through overcoming challenges. The research remains in its infancy, with mixed results and limitations in study designs. Nevertheless, social media influencers espouse the benefits of such interventions on enhancing resilience and treating mental health conditions, which need to be evaluated critically before clinicians can incorporate this into practice. If you are interested in collaborating to launch a study exploring these effects in psychiatry, let’s connect to bring this idea to life and study this much needed topic.

References:Abbott, N. J., Patabendige, A. A., Dolman, D. E., Yusof, S. R., & Begley, D. J. (2010). Structure and function of the blood-brain barrier. Neurobiology of disease, 37(1), 13–25. https://doi.org/10.1016/j.nbd.2009.07.030

Ancient Origins. (2016). Galen: A famous medical researcher of classical antiquity. Ancient Origins. Retrieved January 14, 2025, from https://www.ancient-origins.net/history-famous-people/galen-famous-medical-researcher-classical-antiquity-005459/

Au-Yong, I. T. H., Thorn, N., Ganatra, R., Perkins, A. C., Symonds, M. E. (2009). Brown Adipose Tissue and Seasonal Variation in Humans. Diabetes, 58(11), 2583–2587. https://doi.org/10.2337/db09-0833

Batista, N. P., de Carvalho, F. A., Machado, A. F., Micheletti, J. K., & Pastre, C. M. (2023). What Parameters Influence the Effect of Cold-Water Immersion on Muscle Soreness? An Updated Systematic Review and Meta-Analysis. Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine, 33(1), 13–25. https://doi.org/10.1097/JSM.0000000000001081

Blades, R., Mendes, W. B., Don, B. P., Mayer, S. E., Dileo, R., O'Bryan, J., Fromer, E., Guan, J. Y., Cheng, S. S., Mason, A. E., Prather, A. A., & Epel, E. S. (2024). A randomized controlled clinical trial of a Wim Hof Method intervention in women with high depressive symptoms. Comprehensive psychoneuroendocrinology, 20, 100272. https://doi.org/10.1016/j.cpnec.2024.100272

Brazaitis, M., Eimantas, N., Daniuseviciute, L., Mickeviciene, D., Steponaviciute, R., & Skurvydas, A. (2014). Two strategies for response to 14 °C cold-water immersion: is there a difference in the response of motor, cognitive, immune and stress markers?. PloS one, 9(9), e109020. https://doi.org/10.1371/journal.pone.0109020

Brenke, R. (1990). Winter swimming—an extreme form of body hardening. Therapeutikon, 4, 466-472.

Broatch, J. R., Petersen, A., & Bishop, D. J. (2014). Postexercise Cold Water Immersion Benefits Are Not Greater than the Placebo Effect. Medicine & Science in Sports & Exercise 46(11), 2139-2147. DOI: 10.1249/MSS.0000000000000348

Buffalari, D. M. & Grace, A. A. (2009). Chronic cold stress increases excitatory effects of norepinephrine on spontaneous and evoked activity of basolateral amygdala neurons, International Journal of Neuropsychopharmacology, 12(1), 95–107. https://doi.org/10.1017/S1461145708009140

Cutting W .C., Mehrtens H. G., & Tainter M.L. (1933). Actions and uses of dinitrophenol: promising metabolic applications. JAMA, 101, 193‐195. https://scholar.google.com/scholar_lookup?journal=JAMA&title=Actions%20and%20uses%20of%20dinitrophenol:%20promising%20metabolic%20applications&author=WC%20Cutting&author=HG%20Mehrtens&author=ML%20Tainter&volume=101&publication_year=1933&pages=193-195&

Czarnecki, J., Nowakowska-Domagała, K., & Mokros, Ł. (2024). Combined cold-water immersion and breathwork may be associated with improved mental health and reduction in the duration of upper respiratory tract infection - a case-control study. International journal of circumpolar health, 83(1), 2330741. https://doi.org/10.1080/22423982

Dugué, B., & Leppänen, E. (2000). Adaptation related to cytokines in man: effects of regular swimming in ice-cold water. Clinical physiology (Oxford, England), 20(2), 114–121. https://doi.org/10.1046/j.1365-2281.2000.00235.x

Dutcher, E. G., & Krystal, A. D. (2024). Treatment Expectancies and Psilocybin vs Escitalopram for Depression. JAMA psychiatry, 10.1001/jamapsychiatry.2024.4387. Advance online publication. https://doi.org/10.1001/jamapsychiatry.2024.4387

Eimonte, M., Paulauskas, H., Daniuseviciute, L., Eimantas, N., Vitkauskiene, A., Dauksaite, G., Solianik, R., & Brazaitis, M. (2021). Residual effects of short-term whole-body cold-water immersion on the cytokine profile, white blood cell count, and blood markers of stress. International Journal of Hyperthermia, 38(1), 696–707. https://doi.org/10.1080/02656736.2021.1915504

Falla, M., Micarelli, A., Hüfner, K., & Strapazzon, G. (2021). The Effect of Cold Exposure on Cognitive Performance in Healthy Adults: A Systematic Review. International journal of environmental research and public health, 18(18), 9725. https://doi.org/10.3390/ijerph18189725

Fyfe, J. J., Broatch, J. R., Trewin, A. J., Hanson, E. D., Argus, C. K., Garnham, A. P., Halson, S. L., Polman, R. C., Bishop, D. J., & Petersen, A. C. (2019). Cold water immersion attenuates anabolic signaling and skeletal muscle fiber hypertrophy, but not strength gain, following whole-body resistance training. Journal of applied physiology (Bethesda, Md. : 1985), 127(5), 1403–1418. https://doi.org/10.1152/japplphysiol.00127.2019

Gibas-Dorna, M., Checinska, Z., Korek, E., Kupsz, J., Sowinska, A., Wojciechowska, M., Krauss, H., & Piątek, J. (2016). Variations in leptin and insulin levels within one swimming season in non-obese female cold water swimmers. Scandinavian Journal of Clinical and Laboratory Investigation, 76(6), 486–491. https://doi.org/10.1080/00365513.2016.1201851

Giesbrecht, T., Smeets, T., & Merckelbach, H. (2008). Dissociative experiences on ice: Peritraumatic and trait dissociation during the cold pressor test. Psychiatry Research, 157(1–3), 115–121. https://doi.org/10.1016/j.psychres.2006.12.012

Gómez-Pérez, L., López-Martínez, A. E., & Asmundson, G. J. G. (2013). Predictors of trait dissociation and peritraumatic dissociation induced via cold pressor. Psychiatry Research, 210(3), 939–945. https://doi.org/10.1016/j.psychres.2013.08.021

Guinness World Records. (2025). Full body contact ice endurance. Retrieved January 13, 2025, from https://www.guinnessworldrecords.com/world-records/24052-full-body-contact-ice-endurance

Guinness World Records. (2025). Guinness World Records. Retrieved January 13, 2025, from https://www.guinnessworldrecords.com/

Guinness World Records. (2025). Longest distance ice swim (male). Retrieved January 13, 2025, from https://www.guinnessworldrecords.com/world-records/589877-longest-distance-ice-swim-male

Haq, A., Ribbans, W. J., Hohenauer, E., & Baross, A. W. (2022). The Effect of Repetitive Whole Body Cryotherapy Treatment on Adaptations to a Strength and Endurance Training Programme in Physically Active Males. Frontiers in sports and active living, 4, 834386. https://doi.org/10.3389/fspor.2022.834386

Holly, E.N. & Miczek, K.A. (2016). Ventral tegmental area dopamine revisited: effects of acute and repeated stress. Psychopharmacology, 233, 163–186. https://doi.org/10.1007/s00213-015-4151-3

Huberman Lab. (2024). Huberman Lab. Retrieved January 12, 2025, from https://www.hubermanlab.com/

Janský, L., Pospísilová, D., Honzová, S., Ulicný, B., Srámek, P., Zeman, V., & Kamínková, J. (1996). Immune system of cold-exposed and cold-adapted humans. European journal of applied physiology and occupational physiology, 72(5-6), 445–450. https://doi.org/10.1007/BF00242274

Jedema, H. P., Finlay, J. M., Sved, A. F., & Grace, A. A. (2001). Chronic cold exposure potentiates CRH-evoked increases in electrophysiologic activity of locus coeruleus neurons. Biological Psychiatry, 49(4), 351–359. https://doi.org/10.1016/S0006-3223(00)01054-2

Kelly, J. S., & Bird, E. (2022). Improved mood following a single immersion in cold water. Lifestyle Medicine, 3(1), e53. https://doi.org/10.1002/lim2.53

Kox, M., van Eijk, L. T., Zwaag, J., van den Wildenberg, J., Sweep, F. C., van der Hoeven, J. G., & Pickkers, P. (2014). Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans. Proceedings of the National Academy of Sciences of the United States of America, 111(20), 7379–7384. https://doi.org/10.1073/pnas.1322174111

Kunutsor, S. K., Lehoczki, A., & Laukkanen, J. A. (2024). The untapped potential of cold water therapy as part of a lifestyle intervention for promoting healthy aging. GeroScience. https://doi.org/10.1007/s11357-024-01295-w

Laukkanen, T., Kunutsor, S. K., Khan, H., Willeit, P., Zaccardi, F., & Laukkanen, J. A. (2018). Sauna bathing is associated with reduced cardiovascular mortality and improves risk prediction in men and women: a prospective cohort study. BMC medicine, 16(1), 219. https://doi.org/10.1186/s12916-018-1198-0

Leppäluoto, J., Westerlund, T., Huttunen, P., Oksa, J., Smolander, J., Dugué, B., & Mikkelsson, M. (2008). Effects of long‐term whole‐body cold exposures on plasma concentrations of ACTH, beta‐endorphin, cortisol, catecholamines and cytokines in healthy females. Scandinavian Journal of Clinical and Laboratory Investigation, 68(2), 145–153. https://doi.org/10.1080/00365510701516350

Lombardi, G., Ricci, C., & Banfi, G. (2011). Effect of winter swimming on haematological parameters. Biochemia medica, 21(1), 71–78. https://doi.org/10.11613/bm.2011.014

Lynch, C. J., Elbau, I. G., Ng, T., Ayaz, A., Zhu, S., Wolk, D., Manfredi, N., Johnson, M., Chang, M., Chou, J., Summerville, I., Ho, C., Lueckel, M., Bukhari, H., Buchanan, D., Victoria, L. W., Solomonov, N., Goldwaser, E., Moia, S., ... Liston, C. (2024). Frontostriatal salience network expansion in individuals in depression. Nature, 633, 624–633. https://doi.org/10.1038/s41586-024-07805-2

Moore, H., Rose, H., & Grace, A. (2001). Chronic cold stress reduces the spontaneous activity of ventral tegmental dopamine neurons. Neuropsychopharmacology, 24(4), 410–419. https://doi.org/10.1016/S0893-133X(00)00188-3

Morris, L. S., McCall, J. G., Charney, D. S., & Murrough, J. W. (2020). The role of the locus coeruleus in the generation of pathological anxiety. Brain and Neuroscience Advances, 4. doi:10.1177/2398212820930321

Ost, M., Keipert, S., & Klaus, S. (2017). Targeted mitochondrial uncoupling beyond UCP1 - The fine line between death and metabolic health. Biochimie, 134, 77–85. https://doi.org/10.1016/j.biochi.2016.11.013

Østergaard, E. B., Petersen, A. A., van den Hengel, L., Jensen, A. M., Jensen, N. B., Sparre, P. W., & Dahlgaard, J. (2024). Winter Bathing in Denmark: A Qualitative Case Study on Winter Bathing’s Impact on Mental Health. Healthcare, 12(20), 2076. https://doi.org/10.3390/healthcare12202076

Peake, J. M., Markworth, J. F., Cumming, K. T., Aas, S. N., Roberts, L. A., Raastad, T., Cameron-Smith, D., & Figueiredo, V. C. (2020). The Effects of Cold Water Immersion and Active Recovery on Molecular Factors That Regulate Growth and Remodeling of Skeletal Muscle After Resistance Exercise. Frontiers in physiology, 11, 737. https://doi.org/10.3389/fphys.2020.00737

Puder, D. (Host). (2024, August 30). Sauna & Heat Exposure’s Impact on Mental & Physical Health (No. 221) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-221-sauna-amp-heat-exposures-impact-on-mental-amp-physical-health

Reed, E. L., Chapman, C. L., Whittman, E. K., Park, T. E., Larson, E. A., Kaiser, B. W., Comrada, L. N., Wiedenfeld Needham, K., Halliwill, J. R., & Minson, C. T. (2023). Cardiovascular and mood responses to an acute bout of cold water immersion. Journal of thermal biology, 118, 103727. https://doi.org/10.1016/j.jtherbio.2023.103727

Remie, C. M. E., Moonen, M. P. B., Roumans, K. H. M., Nascimento, E. B. M., Gemmink, A., Havekes, B., Schaart, G., Kornips, E., Joris, P. J., Schrauwen-Hinderling, V. B., Hoeks, J., Kersten, S., Hesselink, M. K. C., Phielix, E., van Marken Lichtenbelt, W. D., & Schrauwen, P. (2021). Metabolic responses to mild cold acclimation in type 2 diabetes patients. Nature Communications, 12(1), Article 1516. https://doi.org/10.1038/s41467-021-21813-0

Roberts, L. A., Raastad, T., Markworth, J. F., Figueiredo, V. C., Egner, I. M., Shield, A., Cameron-Smith, D., Coombes, J. S., & Peake, J. M. (2015). Post-exercise cold water immersion attenuates acute anabolic signalling and long-term adaptations in muscle to strength training. The Journal of physiology, 593(18), 4285–4301. https://doi.org/10.1113/JP270570

Rymaszewska, J., Lion, K. M., Pawlik-Sobecka, L., Pawłowski, T., Szcześniak, D., Trypka, E., Rymaszewska, J. E., Zabłocka, A., & Stanczykiewicz, B. (2020). Efficacy of the Whole-Body Cryotherapy as Add-on Therapy to Pharmacological Treatment of Depression-A Randomized Controlled Trial. Frontiers in psychiatry, 11, 522. https://doi.org/10.3389/fpsyt.2020.00522

Saito, M., Okamatsu-Ogura, Y., Matsushita, M., Watanabe, K., Yoneshiro, T., Nio-Kobayashi, J., Iwanaga, T., Miyagawa, M., Kameya, T., Nakada, K., Kawai, Y., & Tsujisaki, M. (2009). High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes, 58(7), 1526–1531. https://doi.org/10.2337/db09-0530

Shattock, M. J., & Tipton, M. J. (2012). 'Autonomic conflict': a different way to die during cold water immersion?. The Journal of physiology, 590(14), 3219–3230. https://doi.org/10.1113/jphysiol.2012.229864

Sheline, Y. I., Price, J. L., Yan, Z., & Mintun, M. A. (2010). Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proceedings of the National Academy of Sciences of the United States of America, 107(24), 11020–11025. https://doi.org/10.1073/pnas.1000446107

Siems, W. G., Brenke, R., Sommerburg, O., & Grune, T. (1999). Improved antioxidative protection in winter swimmers. QJM : monthly journal of the Association of Physicians, 92(4), 193–198. https://doi.org/10.1093/qjmed/92.4.193

Søberg Institute. (2024). About us. Retrieved January 11, 2025, from https://soeberginstitute.com/pages/about

Søberg, S. (2023). Winter swimming: The Nordic way towards a healthier and happier life. Quercus Publishing. https://soeberginstitute.com/pages/winter-swimming-book

Søberg, S., Löfgren, J., Philipsen, F. E., Jensen, M., Hansen, A. E., Ahrens, E., Nystrup, K. B., Nielsen, R. D., Sølling, C., Wedell-Neergaard, A. S., Berntsen, M., Loft, A., Kjær, A., Gerhart-Hines, Z., Johannesen, H. H., Pedersen, B. K., Karstoft, K., & Scheele, C. (2021). Altered brown fat thermoregulation and enhanced cold-induced thermogenesis in young, healthy, winter-swimming men. Cell reports. Medicine, 2(10), 100408. https://doi.org/10.1016/j.xcrm.2021.100408

Šrámek, P., Šimečková, M., Janský, L. Šavlíková, J., & Vybíral, S. (2000). Human physiological responses to immersion into water of different temperatures. Eur J Appl Physiol, 81, 436–442. https://doi.org/10.1007/s004210050065

Tipton, M. J., Collier, N., Massey, H., Corbett, J., & Harper, M. (2017). Cold water immersion: kill or cure?. Experimental physiology, 102(11), 1335–1355. https://doi.org/10.1113/EP086283

Valenti, O., Gill, K. M., & Grace, A. A. (2012). Different stressors produce excitation or inhibition of mesolimbic dopamine neuron activity: Response alteration by stress pre-exposure. European Journal of Neuroscience, 35(8), 1312–1321. https://doi.org/10.1111/j.1460-9568.2012.08038.x

Valentino, R. J., & Van Bockstaele, E. (2008). Convergent regulation of locus coeruleus activity as an adaptive response to stress. European Journal of Pharmacology, 583(2-3), 194-203. https://doi.org/10.1016/j.ejphar.2007.11.062

Van Bockstaele, E. J., Bajic, D., Proudfit, H., & Valentino, R. J. (2001). Topographic architecture of stress-related pathways targeting the noradrenergic locus coeruleus. Physiology & Behavior, 73(3), 273–283. https://doi.org/10.1016/S0031-9384(01)00448-6

van Marken Lichtenbelt, W. D., & Schrauwen, P. (2011). Implications of nonshivering thermogenesis for energy balance regulation in humans. American journal of physiology. Regulatory, integrative and comparative physiology, 301(2), R285–R296. https://doi.org/10.1152/ajpregu.00652.2010

van Tulleken, C., Tipton, M., Massey, H., & Harper, C. M. (2018). Open water swimming as a treatment for major depressive disorder. BMJ case reports, 2018, bcr2018225007. https://doi.org/10.1136/bcr-2018-225007

Wim Hof Method. (2-25). Discover the method. Retrieved from https://www.wimhofmethod.com/

Xiao, F., Kabachkova, A. V., Jiao, L., Zhao, H., & Kapilevich, L. V. (2023). Effects of cold water immersion after exercise on fatigue recovery and exercise performance: A meta-analysis. Frontiers in Physiology, 14. https://doi.org/10.3389/fphys.2023.1006512

Yankouskaya, A., Williamson, R., Stacey, C., Totman, J. J., & Massey, H. (2023). Short-Term Head-Out Whole-Body Cold-Water Immersion Facilitates Positive Affect and Increases Interaction between Large-Scale Brain Networks. Biology, 12(2), 211. https://doi.org/10.3390/biology12020211

Zouhal, H., Jacob, C., Delamarche, P., & Gratas-Delamarche, A. (2008). Catecholamines and the Effects of Exercise, Training and Gender. Sports Med, 38, 401–423. https://doi.org/10.2165/00007256-200838050-00004

View Details

Audio Interview: Mark Ruffalo, David Puder

Transcript simplification and citing by: Jorge Salazar, MD, Al-Baab Khan

Editor: Joanie Burns, NP

By listening to this episode, you can earn 1.75 Psychiatry CME Credits.

Other Places to listen: iTunes, Spotify

Introduction to Burnham’s Article on Splitting in a Psychiatric Hospital 00:00:16

Puder

Welcome back to the podcast. Today, I’m joined by Mark Ruffalo. He is a person that I've become friends with, he's local to Florida. I would say he drove out to be in person for this.

I actually got to know him through the residents who were in the book club a couple times. They were big fans and said, ‘He’s the best teacher—you have to meet him!’ Later, we met on X (formally called Twitter), where I was like, ‘this guy knows a lot about BPD.’ I was also listening to some of your YouTube content and I knew we had to collaborate. Mark, I know you're a fan of the history of psychiatry, so in this episode, we’ll explore borderline personality disorder—even before it was formally called that. Would you say that’s fair to say?

Ruffalo

I think that's a pretty good description.

Puder

Specifically, we’ll discuss a paper titled The Special Problem Patient, Victim or Agent of Splitting? by Donald L. Burnham, published in 1966. For those of you listening, you might wonder, “Why a paper from 1966?” Papers aren’t written like this anymore. Mark, this is one of your favorites, right?

Ruffalo

Yes, it’s one of my favorite papers in the history of psychiatry. Burnham does such a good job describing the syndrome in a way that’s rare in today’s literature. I’m not entirely sure why, but I really love the older texts because of just how descriptive it is.

Puder

I think it's almost like the new stuff has gotten so far from the practical. You know, we look at correlations, like a 0.3 correlation between this group and that group, or we look at a lot of statistical things that are a little more esoteric or difficult to handle or understand. This is a paper about 12 women over a 10-year period at Chestnut Lodge, ages 16 to 35. Actually, there was a book written about Chestnut Lodge called, The Mental Hospital, which was published in 1954. So I was looking at that and thinking to myself, 'Okay, this is a place where people stayed for 18 months.' This is how it used to be done. You can imagine this place where you had these nurses and doctors, and you had 30, 40 people staying for a prolonged stay. The kind of data you could get out of that is so much richer than my experience of the psychiatric hospital, which was usually just three to four days for most patients with borderline personality disorder. And maybe someone stayed for six months if they were truly in a psychotic space, but that was a total exception.

Ruffalo

For those who don't know, Chestnut Lodge was one of the psychoanalytic hospitals that opened in the early part of the 20th century to treat mainly schizophrenic patients. There were a few notable hospitals that opened during this time, with Chestnut Lodge perhaps being the most famous. Others included The Menninger Clinic, which is still around, obviously; Austen Riggs Center, which is in Western Massachusetts; and a few others. These were places that specialized in the psychoanalytic treatment of severe psychopathology. Virtually all of them, except for Austen Riggs, have closed. Menninger is still around, but now it's in Texas and has changed a bit. It's definitely a different era in psychiatry now, and many major names came through Chestnut Lodge, including Harold Searles, Otto Will, and several other big names in the history of psychiatry.

Puder

And so I was thinking about, what do you get from studying people for 18 months, right? So when they talk about how they collected the data, they mention talking to all the staff members, and they have recorded sessions of these conferences. They’re narrowing in on 12 patients who evoked the most emotion and turmoil within the teams. I also love this from a team perspective. As someone who's run a partial and an IOP, I can visualize the people who split the team the best. As someone who's been in practice, I'm reading this and I'm sweating, my head is hot. I'm imagining scenarios, situations. If I had read this as a medical student, I might have been bored or slightly amused, just thinking, 'Okay, what?' But when you're reading this as someone who's in the trenches, in the deep interpersonal team dynamics, it hits differently. This week, I had a patient split me and my therapist, and you know, it happens, right?

Ruffalo

I think it's hard sometimes to truly grasp the essence of splitting unless you've experienced it firsthand. You can read all the texts and papers in the world, but unless you've experienced the extremes of idealization and devaluation right before your eyes, it's hard to really comprehend what we mean when we talk about splitting. This paper, in essence, is about staff splitting, a term that’s used all the time now. One of the best contemporary scholars on this topic is Glen Gabbard, whose writing is really quite extensive on splitting in hospitals and among staff members. But I think Burnham here is discussing this phenomenon before it was fully elaborated, making it one of the early papers on this concept.

Puder

Yeah. And I would say Glen Gabbard, one thing I didn’t know about him as I was reading his textbooks as a resident, is that he's become the go-to person for psychiatrists dealing with major boundary violations. He's essentially built his career off of this, consulting with psychiatrists, physicians, and therapists who find themselves in ethical quandaries. But here, we have a paper written about this before the term 'borderline personality disorder' was even really a word.

The Psychiatric Evolution of Borderline Personality Disorder 00:07:18

Ruffalo

So, you see, this is 1966. A bit of history on borderline personality disorder: It was John Gunderson, along with Margaret Singer in 1975, who coined the term 'borderline personality disorder.' But borderline states had been described in psychiatry as early as the 1930s, with Adolf Stern, who first described a condition existing somewhere between psychosis and psycho-neurosis. You see different terms being used—Bleuler, I think, talked about latent schizophrenia. Perhaps most notably, there was Hoch and Polatin’s concept of pseudoneurotic schizophrenia from 1949. A psychiatrist named Peterson discussed subclinical schizophrenia, and Kernberg in the 1960s described borderline personality organization, a broader concept that captures all personality disorders defined by the DSM. Then, Gunderson really described a distinct syndrome that we now call borderline personality disorder, which made its way into the DSM-III in 1980. There have been various descriptions of this condition or syndrome over the years, but it was Gunderson’s work that defined it as a distinct disorder. Another influential concept was Helene Deutsche’s 'as if' personality, which is sometimes grouped with all the historical antecedents to BPD.

Puder

Yeah. And I think, you know, it’s not like it hasn’t been around or that it was invented. People used to call it hysteria, which probably meant something similar to BPD. What do you think?

Ruffalo

Yeah, and there are some scholars, like Nancy McWilliams and Jonathan Shedler, who argue that a lot of what we call BPD is actually histrionic personality organized at the borderline level, to use Kernberg’s conceptualization. Others, like Gunderson, see it as its own syndrome. I think there’s good evidence to suggest that what we call BPD is actually a cohesive syndrome [Bohus et al. paper from 2021 supports BPD as a valid and cohesive clinical syndrome].

The symptoms tend to occur together, there's a course to the illness that begins in adolescence, and there's research on genetics. So, I do believe in BPD as a distinct psychiatric disorder. In fact, Otto Kernberg has come around to accepting this notion as well. He now incorporates BPD in his theory of personality organization.

Balancing Process and Skills in BPD Therapy 00:10:20

Puder

Yeah, this is something I’ve covered in past episodes, most recently on medications in BPD. In summary, many national societies are moving away from seeing medications as helpful for BPD itself. If there are comorbid issues, maybe you can treat those, but they’re moving away from the idea that people necessarily need to be on long-term medications.

Ruffalo

It was just a few weeks ago that the American Psychiatric Association published some new guidelines on treating BPD. They basically said psychotherapy is the treatment of choice, and while medications may be useful at times and for targeting specific symptoms, they are not advised long-term. What’s also noteworthy about the guidelines is that the APA acknowledged that psychodynamic treatments are effective, and that there isn’t one single effective psychotherapy for BPD. For years, decades now, dialectical behavior therapy has been talked about as the gold standard, and it can certainly be an effective treatment. But now, there's greater recognition that therapies like transference-focused psychotherapy [see also Episodes 130, 140, 170, and 171] , which is based on Kernberg's work; good psychiatric management, which was Gunderson’s approach and is still being taught and written about; and also mentalization-based therapy [see also Episodes 29, 115, 206, and 224], which I know you’re interested in, are also valuable.

Puder

Well, I've been covering all these topics. So, when this report came out, I was like, have I somehow influenced the APA? But probably not. We’ve been talking about this for a while. I had an episode with Feinstein where we went through five different well-studied therapies. There are studies comparing dialectical behavior therapy with transference-focused therapy, and they both show great results. In some ways, I’d argue transference-focused therapy is better, because there seems to be an improvement in reflective function. I’ve covered that topic [see also Episodes 41, 206, 213, and 224], and that has really helped my understanding of BPD and severe psychopathology in a way that’s much deeper than just saying ‘the therapeutic alliance is so important for psychotherapy.’

Puder

I used to be a huge proponent of therapeutic alliance, but I think I’ve shifted more towards the view that what we’re really trying to do is improve reflective function. Not just in our clients, but in ourselves as therapists as well. That’s a much more complex and nuanced process, and it uses things like transference and countertransference.

Okay, but I want to get into this paper because it's so good. I want to read parts of it to you guys. It starts out discussing internal splits—how the patient's experience and presentation of herself are divided. It says 'herself' because all of the clients in this cohort were female. The typical patient in this series was very poorly integrated and, in certain respects, poorly differentiated. It’s going to go through what that means palpably. I just want to point out that when we think of BPD, there are different levels of functioning, and these patients are probably more on the severe level of dysfunction. I was also thinking, do these patients become dysregulated in such an intensive setting?

Ruffalo

Sure.

Puder

And I wonder about that.

Ruffalo

Yeah. I wonder about that as well. There are certainly mixed opinions on treating BPD in the hospital setting, with some people arguing that these patients should not be admitted to general psychiatric units. I think there’s some valid reasoning behind that. The exception might be if you have a unit specializing in personality disorders, like Kernberg’s unit in New York, where it might be more appropriate to treat these patients in an inpatient setting. But, yeah, you have to wonder whether the length of stay and intensity of treatment are factors. Years ago, there was this idea of transference psychosis in borderline patients. Kernberg talks about this, and he recounts a case from early in his career where a patient saw him walking down the sidewalk in New York City and hallucinated Dr. Kernberg spitting on the ground out of contempt for the patient. The patient had a transient hallucinatory experience related to the therapy. It was noted that the intensity and frequency of classical psychoanalytic treatment—seeing the patient on the couch three, four, or five times a week—was not suitable for borderline patients, as it could trigger a transference psychosis. So, one has to wonder, when patients like this are hospitalized for long periods, whether regression occurs as a result of the hospitalization itself. In fact, hospitalization might worsen these patients, even though we might not recognize or see it in that way today. These are important considerations.

Puder

Yeah, I think when you consider most DBT tracks I've seen, they’ll have a process group once a day. So, you might be processing five days a week, but you’re not the only one sharing with one person in a dyadic way. The program I used to run was focused on psychosomatic patients, and every group was process. For some patients, it was just too much. In our program, each group had an element of process. I think that’s one reason DBT tracks focus a lot on skills-based groups. You know, they have transfer focused therapies twice a week.

Now, if you look at the papers on mentalization-based therapy, where it’s been very successful, they start with five groups a week, then go to three, and then two, for about a year and a half. By the end, patients might have had around 500 treatments. It's a lot of time and a lot of hours—500 hours of treatment. But when you think about the full spectrum of someone's life and attachments, 500 hours is just a blip in their overall life trajectory. Even 50 hours can make such an impact sometimes. In fact, 75% of people improve in just 50 hours of psychotherapy. That’s impressive. [see also Episode 144]

Ruffalo

So, I don't know for certain, but I imagine that here in the 1960s at Chestnut Lodge, a lot of these patients were seeing their psychiatrist for psychotherapy probably every single day. For 50 minutes or an hour, I would imagine that was the context. And then also group psychotherapies and attention from the nursing staff.

Symptomatology & Self-Perception00:18:01

Puder

Yeah. So when I read the book that was written about this, it mentioned— and I was specifically looking at the boundary violations—some of the staff members, especially nurses and aides, became too close to certain patients. They would spend disproportionate time attending to favored patients, sharing personal details of their own lives, and relying on the patients for emotional support. And that's the type of patient we're talking about today. Yes, they would elicit this incredible bond in the staff, and through that bond, the normal frame of how you might relate to a patient would dissipate.

Ruffalo

There's a great quote from Burnham (1966) in the article that captures this—the very essence of what you're describing. He writes, “No one could remain indifferent to or only mildly interested in the appeal. Its irresistible, gripping, insistent demand quality evoked the most intense feelings, whether of love or of hate” (p. 109).

Puder

I would say that the appeal is like this request from the patient for a special type of relationship with a particular person. They hoped to obtain the ideal self, they hoped to obtain this perfect maternal role. Right?

I want to talk about when they looked at the commonalities of patients. I want to go category by category and just kind of break this down. So, the first category was body image disturbances. This is on page 107, and it says:

She also reported such experiences as her arms swelling, her head shrinking, her body being dismembered, tenuously glued together, or suspended in midair, somehow apart from herself. Other patients spoke of feeling dead, encased in cement, and uncertain whether they still were breathing (Burnham, 1966, p.107).

Ruffalo

These are obviously symptoms that point to this historic notion that borderline personality was a schizophrenia-like syndrome. I mean, we're really talking about psychotic symptoms here. One has to wonder whether some of these patients included in the group of 12 did in fact have a psychotic illness. I've done a little bit of writing on these types of symptoms in BPD. I think they're underestimated. I think the DSM does a really poor job of appreciating the frequency and severity of these symptoms in borderline patients. I mean, in the diagnostic criteria, all we see is a reference to transient paranoia, which certainly does happen in BPD. But I think if you look a little bit closer and really do a good job evaluating the patient, you'll see brief experiences of hallucinatory phenomena, similarities in terms of how patients use logic and how they come to conclusions—similarities between BPD patients and schizophrenia patients. And other commonalities including disturbances in how one perceives one's body.

Depersonalization & Dissociation 00:21:52

Puder

When I read a lot of these, first of all, it's very visceral language. And this is why I'm saying like, no one writes like this anymore when they write about BPD. I just haven't read anything like this. To me, it's a very dissociative phenomenon that I'm reading. It's a way that I've understood a lot of the complexity of these symptoms: when you feel tenuously glued together, suspended in midair, somehow, it seems like a very dissociated state.

Let me go on to depersonalization, because that is the very definition of dissociation. It says: they felt like a stranger to themself, whose body is this, is it all mechanical and doesn't have human feeling? They refer to themselves in the second or third person. One patient referred to her eye as 'the thing one sees with,' and she strongly implied that her use of the word 'I' would be criminal misappropriation of a scarce item, which others deserved far more than she. These patients shared a pervasive doubt concerning what of themselves and others was real and what was false. They were enormously preoccupied with how to distinguish the genuine from the pretended, most obviously, in their testing of others, but fundamentally in trying to resolve their uncertainty of self-definition.

Ruffalo

Sure. This is touching on what we would say in modern object relations theory is self and object differentiation. You know, where do I end and where does the other person begin? And all sorts of disturbances here in the patient's object relations.

Puder

I think of this as dissociation, like when all the other defenses break down. Things like sublimation, rationalization, humor, denial… When those break down, it kind of ends in this more dissociated state. Do you see it differently than I do?

Ruffalo

I see it very similarly. I would say either a dissociative state or psychotic defenses at that point. So, you know, paranoid projections, hallucinations, and the like.

Puder

I've had a patient that I worked through successfully who had a dissociated transference of me. So it's not that she didn't exist, although she felt like she was often in a cloud or disconnected from her body. She went from seeing me as this kind, warm, generative figure she could bring to mind when she was distressed, to seeing me as a frightening, scary presence, as if I didn’t exist at all. Even when I was there with her in the session. It took about a year and a half—this was the most prolonged dissociative transference I’ve ever encountered with a client. It was a year and a half before we worked through it. To be vague, it required consistently showing up and being as present as I could. But even during the sessions, I started to feel dissociated. I had to ground myself, bring myself back into my body. I would sometimes feel extremely sleepy at times and needed to stand up or even pinch myself to stay grounded.

Ruffalo

What you're describing, of course, is the patient inducing a phenomenon that's very similar to their own experience. And this is the essence of countertransference. With these types of patients, we often experience intense countertransference reactions, and these reactions give us insights into the patient. I’m sure you’ve discussed this with other guests before, but it’s important. It reveals something significant about the patient, especially in cases of borderline pathology.

Puder

Yeah. It took me a while to realize this with this particular patient. I found it helpful to interpret it this way: much of her childhood was shaped by her experience with her parents. She viewed them as these ghostlike figures. And in a way, she was reprocessing that experience through me. When we worked through it, she could tolerate being around her parents more.

The Interplay of Self-Worth, Soothing, and Hypersensitivity 00:26:33

Puder

Okay, let's move to the next category:

Inside-outside uncertainty

She often perceived shifts in her feelings as drastic changes in the appearance and intentions of others. In the midst of all this inner-outer uncertainty she had little sense of autonomous control, but felt at the mercy of her environment.

One patient said, "Whose thoughts are those? They must be some- thing from a movie or a book. People have me connected up and are putting slides in my head to make me see and say what they want (Burnham, 1966, p.107).

Puder

It’s like a bunch of opposite paradoxes to some degree. Inner-outer uncertainty… She felt at the mercy of her environment and others, like where do other people end and I begin? Mentalization theory discusses this concept, calling it 'psychic equivalence mode,' where patients feel like their thoughts are reality. So when they perceive that other people are thinking something, they are actually thinking it.

It’s not just 'Dr. Puder might be angry with me,' or 'Maybe, Dr. Puder is angry with me, but I could be wrong.' No, it’s 'Dr. Puder is angry with me.' It's an absolute certainty.

Ruffalo

This also touches on Gunderson’s notion of interpersonal hypersensitivity. Patients are incredibly sensitive to what’s going on around them, often misperceiving their environment. As Harold Searles said, the borderline patient has no symptom-free moments. He pointed out that every little thing, from how you greet the patient in the waiting room to how you answer the phone when they call to change their appointment, could be vulnerable to misinterpretation.

Puder

Exactly. There’s this exquisite hypersensitivity. And it’s driven by interpersonal fear. It’s like, 'Are you and I going to be okay? Do you really care about me? Am I really your special patient? Am I someone you really care about? Am I important to you?' It’s intense fear around these questions.

I don't know if you heard my discussion with the mentalization-based guys on narcissism, but it was like an epiphany for me. I realized that the same level of fear in narcissists is tied to the question: Is this person wounding my perception of how others see me? It’s not about the relationship itself; it's about this image I have of myself, as this wonderful teacher, being wounded by this slight from this person.

Ruffalo

Yes, exactly. So, I think the deficit in narcissistic patients is in the area of self-worth. In borderline patients, it’s both in self-worth and in the ability to hold and soothe themselves. This was part of Gerald Adler's work in the 80s. He talked about a borderline-narcissistic continuum. So, we often see in borderline patients the same deficits as in narcissistic patients, but with an additional aspect of the illness when it comes to the inability to soothe and hold themselves during periods of aloneness. We could go into that idea of a continuum more if you'd like.

Puder

Yeah, help me understand that continuum. So, people with borderline personalities are really struggling to soothe themselves when they’re alone, right? And, as you know, many therapies have… when I heard Marsha Linehan talk about DBT [see also Episode 140], she would mention how borderline patients would call her. Patients with borderline traits—I'm trying to be careful about saying the 'borderline' because it labels them at the core of the disorder. I think it's the person who struggles with borderline traits. So, they would call her. I don’t have this feature in my practice, right? I think there's a different way of framing it, and the frame is very important to maintain. Therapy takes place within the session.

Ruffalo

Yeah. So, Kernberg and the transference-focused people argue that the therapy contract is essential when working with borderline patients. One of the first things that should be done is outlining the role of the patient, the role of the therapist, and maintaining the frame. Keeping the contract is vital in treating these patients. Now, Gerald Adler, whose work on BPD I really like, argued that the goal of treatment is for the patient to internalize a holding, soothing object in the form of the therapist. So, Adler recommended that when the therapist went on vacation, they should send a postcard to their patients so that the patients have something to remember them by. This might sound odd to other psychodynamic theorists, and I doubt Kernberg would agree with this approach, but Adler believed that the goal of treating borderline patients, at least the borderline segment of the pathology, was for them to internalize a soothing, holding object that could sustain them during periods of aloneness. So, they wouldn't need to reach out to others in frantic efforts to sustain themselves. This ties into his idea of evocative memory, which I find to be a very useful concept. I'd like to talk about that for a moment. Adler thought that the fundamental deficit in borderline patients was in their use of evocative memory. In healthy, normal functioning, we are able to summon a mental representation of a healthy internal object that provides us with comfort and soothes us. So, we don’t have to rely on other people to do this for us. We can do it ourselves and feel fine being alone. Adler believed that borderline patients can’t do this. They rely on self-objects, meaning they rely on other people to perform this vital psychological function for them. When these self-objects aren’t available, the patient falls apart. Adler links this idea to developmental psychopathology and developmental theory. He talks about object constancy and the formation of evocative memory in early life, somewhere between 12 months and 2 years of age. Any disturbances during that time may give rise to some of the symptoms of BPD. I think this concept of evocative memory and object constancy is really powerful for understanding why a patient becomes so frantic when their primary object is unavailable

Nature vs Nurture in BPD 00:34:46

Puder

Interesting. Two thoughts come to mind. One is from my episode on the prisons of Mesopotamia (see also Episode 172), where we discussed solitary confinement. It's actually toxic to everyone’s brain—being alone for months in solitary confinement shrinks the brain. There have been a lot of brain studies on this. It’s incredibly harmful to the brain. Afterward, everyone has worse mental health, with higher rates of psychosis and other issues. So, I think I might challenge this idea that we should be okay alone. I’m not so sure that’s always the case.

Ruffalo

I think there's nuance there.

Puder

Yeah, there’s nuance. Maybe it’s not the level of desperation or the real painful agony of separateness.

Ruffalo

I’ve had BPD patients tell me that it feels like they’re dying—like metaphorical death—when the object isn’t available.

Puder

Yeah, it’s absolute agony. It triggers a stress response in my body, just thinking about the suffering from the agony. When I read this paper, it mentions that several of the patients had been adopted, or had been cared for by a series of parent surrogates. Almost all of them had deep doubts about who their real parents were. They often developed compensatory fantasies, imagining they were descended from famous or royal figures. These were tough childhoods. Some might argue, 'I know someone with BPD who came from a really warm family, what about them?' But I’d say, 'How much do we really know about what that family was like for that child?' Was there a personality mismatch in that family? Were there messages from the parents like, 'You can’t show up emotionally, because my emotions need to be fully present and there’s no room for yours?' Or was there hostility or anger that silenced a sensitive person? I see expressions on your face that suggest you resonate with something or maybe have some memories of these things.

Ruffalo

Yes, it’s very complex. You're right, there are some patients who seem to come from fairly normal childhoods and still develop BPD. Joel Paris, who’s in Canada, talks about this and finds it quite problematic to say that all BPD cases result from trauma (Paris, 2020). I think that resonates with me. When we look at genetic research, about 40-50% of what we call BPD appears to be inherited.

Puder

That's similar to ADHD, which is more like 60%. For height, it’s about 90%. So, yes, I agree some of it is genetic. But I also want to highlight the role of adverse childhood experiences [see also Episodes 88, 92, 203, 204, 215, 217, and 224]. I recently did a deep dive into this, and as you move from one to two, three, four, five, or six different types of adverse experiences, the odds ratio for developing BPD jumps to about 25 when you hit five.

Ruffalo

Does not surprise me at all.

Puder

Exactly. While many conditions show an odds ratio of 2 (things like heart disease, diabetes, physical issues), BPD and complex PTSD have a much higher increase. It’s striking.

Ruffalo

I think psychodynamic theorists have known this for decades. I get a little frustrated when people talk about trauma as if it’s a new idea in the field. If you read historical texts, you’ll see attachment, neglect, and abuse have been discussed for a long time in psychoanalysis. It’s not a new discovery. In terms of psychogenetic factors, I think neglect is likely a more significant or relevant factor than overt abuse in BPD, though overt abuse is certainly present. Linehan and Kernberg seem to agree that neglect is a more important factor. However, there were studies in the '90s showing that 60-70% of patients with BPD had experienced sexual abuse. [This 1995 paper by Kenneth Silk et al. found that among 37 psychiatric inpatients with BPD, 76% had experienced sexual abuse.] So trauma is obviously relevant. But I worry when we go on a search for trauma in every patient’s background.

Puder

Yes, and that’s a pet peeve of mine. It’s concerning when therapists ask very leading questions, because their own journey can imprint onto their patients in the same way, which is problematic.

Ruffalo

That’s very problematic nowadays.

Puder

Yes, I’ve seen this with a religious figure in one of the towns I lived in. He seemed to think that certain types of people had certain trauma, and he became EMDR [eye movement desensitization and reprocessing] certified even though he wasn’t a therapist. That was a bad combination. I also knew a therapist who had been through sexual abuse herself, because several of her patients told me similar stories. We must be aware of our own issues and how they might affect our work.

We also need to consider disorganized attachment, which can be observed at four months of age and linked to higher rates of dissociation by age one and a half. So, there’s a link between early attachment wounds and later difficulties (see also Episodes 69, 87, 88, 194, 206, and 225). We’re not just talking about the still-face experiment, but how repeated experiences of emotional unavailability and chaos create disruptions in development. For some of my patients, their mothers were addicted to meth, alcohol, and other drugs, making them chaotic and emotionally absent. For others, their mothers had schizophrenia and were psychotic, paranoid, and erratic, often not on medication. Some of my patients were in and out of foster homes, leading to very erratic, chaotic environments. So, it’s important to recognize there are many different scenarios here. We can’t assume one path or search for the same experiences in every case.

Ruffalo

Right, exactly. Kernberg highlights this, and it’s important to note that there’s no single path to borderline personality disorder. We see trauma, abuse, neglect, as well as genetic factors, especially innate aggression and attachment pathology. BPD is complex and doesn’t have one cause. That’s why a biopsychosocial approach is crucial in understanding it, and in psychiatry overall

Identity Diffusion: Gender, Sexuality, Age & Role Dynamics 00:43:45

Puder

One section that I found interesting discussed gender and sexuality in BPD patients. It’s important to note that these issues are fluid and change from moment to moment. Sexual identity and role also were uncertain and conflictual. These patients were tormented by questions such as, "Am I woman or man, girl or boy? 'Which do I want to be? Am I like my father or my mother?" These conflicts were outwardly manifest in oscillations between masculine and feminine choices of dress, grooming, and activity interests. One patient, apparently in a determined effort to deny all femininity, sheared off her hair, smoked cigars, and wore trousers. A few weeks later, however, at a hospital party she was most decidedly feminine in a low-cut gown and evening gloves, and obviously enjoyed flirtatious exchanges with many of the men present. She, like most of the special-problem patients studied, often displayed feminine- masculine oscillations within spans of a few days or even hours.

Ruffalo

Yes, absolutely. This speaks to identity diffusion in these patients.

Puder

Exactly. I wrote down 'distinct gender identity crises in BPD.' It’s not that these individuals have always had a very concrete, fixed identity. The question is, how do we, as therapists, approach this in a nuanced way? We must avoid seeing it as monolithic and instead view it as part of a broader identity diffusion. I don’t think we talk enough about this aspect, but it’s crucial in understanding the complexities of BPD.

Ruffalo

We certainly don't talk enough about sexuality in this context. It’s a controversial territory and it’s sometimes difficult to navigate when it comes to issues of sexuality in borderline personality disorder. But going back to the '80s, Akhtar described the syndrome of identity diffusion, and one of its core symptoms is a diffusion in sexual identity. As you pointed out, it’s not just about identity confusion—it’s about the rapid and frequent changes in one’s sense of self, particularly in sexuality. These shifts can happen within days, or even hours, as noted in this paper. There’s something significant about that rapidity.

Puder

Yes, and in the next section, it mentions that age can fluctuate too.

Several claimed ages older or younger than their actual ages, and their appearances tended to fit these claims. Not infrequently, they had been encouraged to premature competence, or rather, pseudo competence, in various sectors of behavior. For example, one patient described with mixed pride and resentment how, before the age of five, she had made her way alone around the New York City subway system. —Notice it's with pride and resentment—. Others had been included in adult social activities at inappropriately young ages. Several had been recruited by their mothers as special confidantes and companions, to be leaned upon and entrusted with intimate details of the mothers' problems, including those of their marital relationships. The usual boundaries between generations had been blurred, and at times the usual independent-dependent axis of the mother-child relationship had almost been reversed. The daughter-father relationships had been similarly distorted, with frequent not-so-subtle invitations to "be a better wife to me than your mother is” (Burnham, 1966, p.108).

or as a patient has told me, 'My dad dumps all his issues on me.' There was no space for the children to express their own concerns because their parents had turned them into emotional support systems.

Ruffalo

Yes, that’s a total blurring of family dynamics. We see that all the time.

Puder

Exactly, it’s the parentification and it’s the role reversal. I think about my own kids, and while I share things with them, it’s never in a dysregulated way. But many of my patients talk about growing up with dysregulated parents—where the mother or father would rant for hours about personal issues. It’s an incredibly unhealthy dynamic.

Ruffalo

Yeah. And many of these children grow up to work in the helping professions, ironically.

Puder

Oh, absolutely. And those of us who’ve been in similar situations understand it. It often comes with this mixture of pride and resentment. It’s like, 'I had this valuable place in the family unit.' There’s a certain power in it, a special role, but at the same time, it’s suffocating for a lot of my patients. They feel this weight, like their emotional system wasn’t ready for it, but they had to deal with it. Then, they become the person that others turn to because they’re seen as a good listener. This social connection might be what they wanted or needed, but it also brings the burden of taking on other people’s emotional weight. And sometimes, they’ll come to therapy saying, 'This is the first time I’ve had a place where I can share.' But even then, they’re often afraid of burdening the therapist. I'm still afraid that it's too much. I shouldn't be sharing with you my weight or my stuff. So, it's like somehow that was imprinted and then transferentially shows up in the relationship.

Caution in the Patient & Therapist Relationship with BPD 00:50:35

Ruffalo

Yes, I think when we observe this dynamic in a therapist who was raised in such an environment, it often manifests as what is traditionally referred to as a rescue fantasy. This is the therapist's sublimated need to "rescue" a broken parent, a drive they channel into their work with patients. While this can serve as a powerful and effective motivator in therapy, it also carries significant risks. A therapist with such a strong desire to save or rescue their patient may inadvertently blur boundaries, potentially leading to ethical violations or emotional entanglements.

Puder

Absolutely. And it’s crucial to approach this dynamic with compassion and curiosity rather than judgment. For example, when working with therapists as a supervisor, I don’t adopt a punitive stance if boundaries have been crossed. Instead, I explore the underlying factors: What happened here? What led to accepting client calls at all hours of the day and night? Pulling back from these patterns can feel excruciating—not just for the therapist but also for the patient, who may perceive it as deprivation.

Ruffalo

That’s precisely why establishing a clear therapeutic frame or contract is so vital. When a therapist begins to step back and enforce boundaries, it can feel to the patient as though they’re being denied care or compassion.

Puder

When this happens, the patient can quickly shift from idealizing the therapist to devaluing them entirely. The rage that was previously directed inward—through self-harm, negative self-appraisals, or other behaviors—might now be directed at the therapist. For someone whose identity is tied to helping, this can be an exquisitely painful experience.

Ruffalo

Absolutely. It can be deeply painful and have profound effects on the therapist. Harold Searles wrote a paper in 1959 titled, “The Effort to Drive the Other Person Crazy,” which is language we wouldn’t use today. But when the patient is subjected to alternating between idealizing and devaluing patterns, it can have a profound effect on the psyche of the therapist, creating confusion: What is it that you want from me? The patient, in essence, projects disavowed aspects of themselves onto the therapist, in the attempts to induce in the therapist feelings similar to what the patient experiences.

Puder

Yeah. This is projective identification. The patient projects these feelings onto the therapist, and the therapist, depending on their own developmental history, may unconsciously identify with them. Interestingly, I used to work at a clinic that Dr. Randy Sansone did research out of, and he found higher rates of Borderline Personality Disorder in resident clinics compared to regular outpatient clinics (Sansone & Sansone, 2015).

Ruffalo

Interesting.

Puder

Yeah, and I can think of a couple of reasons why this might be the case. Having sent patients to resident clinics, I often referred patients who were really difficult to place with other therapists. Many therapists would see these patients once and decide they weren’t a good fit. However, residents were generally more open to taking on anyone. So sometimes that was the reason. But I think there’s something more to it. But yeah, I think there's something about that. Just beware, if you're a young professional listening to this.

Presentations of BPD in Literature 00:53:30

Puder

Uncertainty of Self Valuation:

The typical special-problem patient fluctuated unevenly between global good and bad self-appraisals. Once again, we’re talking about identity diffusion—the sense of self shifting so quickly. at one time regarding herself as a kind, generous near-angel, and at another as a loathsome, evil monster. She also oscillated between the opposite poles of many pairs of component attributes. Among the most salient of these were the sick-well and the dependent-independent polarities. (Burnham, 1966, p.108).

Ruffalo

Right, we’re seeing contradiction and paradox here—self-splitting. When splitting is discussed, it’s often framed as the patient viewing others as either entirely good or entirely bad. But patients also engage in self-splitting. At different points, they might see themselves as intelligent, attractive, and worthy, and at other times as foolish, unattractive, and unlovable. Self-splitting is just as significant.

Puder

Yeah. They also talked about: “Her grooming ranged from highly fastidious to totally neglectful; her eating habits from gluttony to ascetic starvation; and her communicativeness from lively conversation to muteness. Sometimes she was kind and considerate, at other times sarcastic and demanding” (Burnham, 1966, p.109).

Do you see why this paper is such a favorite?

Ruffalo

You just don't see this type of writing anymore.

Puder
It’s beautiful writing—really beautiful. It’s so delightful to read such beautiful writing, but at the same time I had a stress reaction reading it. At the same time, I’m empathizing with many patients I’ve seen over the years who struggle with these dynamics.

Ruffalo
It feels very “experience-near,” whereas much of today’s scientific writing feels “experience-far.”

Puder

It's intellectualization, creating a sense of distance—like operating on a cadaver. In the paper, they mention that terms like "mixed" and "borderline" were frequently used when attempting to place the patient in a diagnostic category. Even here, "borderline" was applied as a kind of in-between classification when they weren’t sure where she fit.

Ruffalo

As Nancy McWilliams puts it, “Too crazy to be neurotic, but not crazy enough to be psychotic.” Of course, I don’t mean “crazy” in a pejorative sense—that’s McWilliams describing the ambiguity often associated with borderline cases.

Variability of Self & Exploring BPD Relationship Dynamics 00:58:37

Puder

Okay. Here's another one:

Also filled with uncertainty were answers to vexing questions of her capacity for self-control and responsibility. At times she appeared to be a purposeful, even willful, active agent; at other times a helpless, passive victim. The variability of her behavior also spawned doubts about her sincerity and genuineness, similar to her own unsure- ness of where her masks left off and where her real self began. How to distinguish the genuine from the pretended plagued the patient and staff alike. (Burnham, 1966, p.109).

I think, as someone experienced with these cases, it’s important to avoid moralizing. I’m not trying to figure out what’s “real” or not; What are your thoughts on this?

Ruffalo

So often, borderline patients express, “I don’t know who I am. I have no idea who I am.” Burnham (1966) writes that “it’s difficult to determine where their masks end and their true self begins” (p.109 ). The variability between seeing themselves as capable and competent versus utterly helpless and victimized is striking. And yes, the concept of “victim” is significant here. When we consider the victim-victimizer dynamic, persecutory objects often play a role in their lives. At different times, therapists or psychiatrists may find themselves cast into these roles. I agree—it’s important to avoid moralizing the behavior. We can describe it and understand its phenomenology without passing judgment. But I think we run into trouble when we shy away from describing the behavior entirely. I think that some people get offended just by sort of talking about the behavior the patient engages in as if it's a bad thing to do.

Puder (01:04:31):

Right. So where does this identity diffusion come from? The struggle to form a coherent sense of self often leads to vacillating between extremes. Let’s dive into the appeal made by these patients:

It comprised requests for healing, rescue, and protection from suffering. The theme of intense need was communicated variously: "I need you... You are my lifeline… You make me alive, complete, and real…You are absolutely essential to me." Obviously, such poignant statements readily evoked wishes to help in persons who had elected healing roles. More than this, they prompted in many listeners a profound sense of being chosen as the needed person, a response which Main termed "the arousal of omnipotence” (Burnham, 1966, p. 109 ).

Ruffalo

This is one of my favorite passages in the paper because Burnham is talking about the vulnerability of therapists, doctors, and nurses to this kind of appeal. And the feelings it evokes in the other person to be needed and wanted. When a patient expresses that their survival depends on you—conveying something like, "Without you, I will fall apart. You are essential to me"—it resonates deeply, especially with those who have chosen a helping profession as their life's work. This appeal evokes a profound reaction, a sense of purpose and importance. And this is often a source of conflicts we see interpersonally. Burnham highlights how the chosen caregiver often becomes deeply invested in their role as the "needed person." There's something profoundly significant about being selected as the one who is uniquely required, and this sense of indispensability can both empower and complicate the therapeutic relationship.

Puder

“The arousal of omnipotence” (Burnham, 1966, p.109). What do you think about that phrase?

Ruffalo

I don't know exactly what Main is referring to there, but I think it refers to the sense that the therapist or caregiver believes they are the only one capable of truly understanding and helping the patient. This belief can create a "hero complex," where the helper sees themselves as the savior.

Puder

Oh yeah, it’s a hero. A type of fantasy, right? When you go back. Exactly. You mentioned victim, abuser, and hero. And this is why, when I talk about the hero's journey, I like to pose the therapist not as the hero, but as the guide, right? Yes. If anything, in the story, you're the guide which is kind of like in the hero's journey—it’s the common mythological structure. The hero ventures into a foreign land, needing to overcome obstacles. Encounters a guide to equip them in some way to overcome the obstacles they go, then separately overcome the obstacles and come up against maybe malevolence or evil, overcome it, and then go back home and bring some of the gifts that they learned along the way.

Ruffalo

That's a good metaphor. In therapy, this often plays out when the therapist assumes the role of a boundless helper or savior—believing that they can rescue the patient. The therapist might think, "It will be because of me that I save this patient." This can lead to several problems in treatment. For instance, if you're involved in psychopharmacology, you may end up prescribing medication that isn't appropriate or fail to hospitalize a patient who truly needs it because you believe you can handle everything. The mindset might be, "I'm the only one who truly understands this patient." Over time, this can lead to more significant boundary issues as well.

Puder

In the article, they talk about the origins of the appeal:

The patient's urge for a very special relationship, tantamount to rebirth into a good-mother-self union, was rooted in her conviction that herself was directly and currently shaped by proximate per- sons. In a manner typical of her faulty self-other differentiation, she experienced her good self as resulting from current contact with good persons, her bad self from contact with bad persons, and her uncertainties and variations of self-definition from the inconsistencies within and among others (Burnham, 1966, p.110).

Ruffalo

I think this is 10 or 15 years later when we see Gunderson discussing the same concept—the sensitivity of the patient to relationships with others. He defines the syndrome as an interpersonal problem at its core, explaining how the patient’s emotions are intricately tied to the dynamics of their relationships, to use Gunderson's term, with the “major object.” If they feel good today, it's because things are going well with the major object. If they feel depressed, it’s likely because there is some problem in that relationship. And their sense of goodness, or how good they are in the world, is shaped by ‘proximate persons,’ to use Burnham’s term. Their sense of self-worth, their sense of goodness, and even their will to continue living in some cases are linked to whether they feel appreciated, cared for, and loved by the ‘major object,’ (further highlighting how interconnected their self-concept is with their relationships).

Splitting: Good Objects vs. Bad Objects & How it ManifestsPuder

The paper describes how some nursing staff noticed they were perceived as the “good objects,” and they tried to encourage others to become good objects as well. Meanwhile, the patient identified other individuals as “bad objects” and tried to distance themselves from them. Additionally, the patient attempted to “purify” themselves by projecting their bad self-elements onto those defined as bad objects. Essentially, all the negativity from the patient, all of the badness, was transferred to these bad objects. This unique form of splitting creates factions within the unit. Some staff members thought, “We just need to love this person more and give them what they want,” while others believed, “This person is manipulative, lying, and taking advantage of the system. We need to be stricter.”

Ruffalo

Yes, and this dynamic often escalates. Members of the first group may accuse those in the second group of being too punitive, authoritarian, or lacking compassion. It can become quite contentious. Gabbard discusses this phenomenon extensively in his writings on staff splitting. These intense divisions can sometimes align along professional lines—for example, differences between nurses, social workers, and psychiatrists—or they may simply depend on individual personalities. Another related paper that touches on this theme is from the 1980s. It’s titled “Treating The Patient Who ‘Can’t’ Versus Treating The Patient Who ‘Won’t’”, and it explores splitting in the context of whether a patient is unwilling or unable to do something. Some staff members may assert that the patient isn’t trying hard enough, while others argue that the patient’s illness genuinely prevents them from accomplishing certain tasks. These kinds of divisions often take similar forms.

Puder

I love how you incorporate insights from other papers into this discussion—that’s so good. The paper further discusses:

The urge for an all-good self participating in all- good relationships runs counter to normal integration of both good and bad within the self and within particular relationships. These points of contrast are important in understanding the nature of the appeal(Burnham, 1966, p.111).

Ruffalo

Yes, it ties back to fundamental object relations theory. Integration—the ability to see both good and bad qualities in oneself and others—is a key part of healthy development. For example, being able to say, “This person has both good and bad qualities, but overall, they’re a decent person.” When someone hasn’t achieved that developmental milestone, we see splitting. Here, they perceive people as entirely good or entirely bad. For example, a person is seen as composed only of good qualities or only of bad ones, with no nuance. Achieving integration is a vital developmental achievement in object relations theory.

Puder

So the appeal starts often with the call from the referring agency. When I read this part, I thought, “Wow.” So you can imagine it says:

Often the initial referral was made through special channels and contained a mixed plea and warning that the patient required and deserved special treatment. The referring person would emphasize how vital it was that the patient be met by sensitive understanding lest the basis for treatment be undermined at the outset. His advance briefing would include warnings of others' failures at this task and invitations to rectify their insensitivities and mishandling of the patient. Requests for the assignment of the especially skillful and experienced therapist of a specified age and sex were common (Burnham, 1966, p.111)

Ruffalo

Yes, we still see this all the time today. I’m not sure if you follow this on social media, but I’m a member of some local groups where people post looking for referrals for certain types of patients. Often, you’ll see something like the case you just described. They’ll say, “I have a very vulnerable patient with special needs who requires particularly sensitive care.” Then, they’ll specify that the patient needs a therapist who is either a male or female of a specific age range, someone inclusive, and so on. This is exactly the kind of phenomenon Burnham was talking about over 50 years ago.

Puder

From the outset the typical problem patient engaged in a quest for persons who might fit the

good-mother, magic- helper mold (Burnham, 1966, p.112).

So, this patient is searching for this person. They're searching and I would say there's some that are just better at cultivating, and like getting this type of relationship, you know?

Poignant depiction of the theme of love- deprivation in her life was outstanding. This was conveyed by myriad subtle hints as well as by full descriptions. She avowed that her parents had been so troubled, insensitive, or otherwise preoccupied that they had neglected her needs (Burnham, 1966, p. 112).

Potentially that really did happen. So potentially... I'm like, where do I stand right now? I'm not really the magical helper, in the way I frame it.

Ruffalo

Yeah, I think that the theme of love deprivation is really interesting to me. I think clinically this often plays out when a patient comes in and starts talking about how other therapists have failed them, that no one has ever really understood them, no one has really "got" them. They've been deprived of good treatment by their past providers. Now, you and I both know there’s a lot of good therapy out there, and there’s a lot of bad therapy as well. So, you certainly can’t diagnose a patient based on this alone. But this theme of feeling deprived by all past providers or love partners is very common in borderline psychopathology.

Puder

Yeah, it’s a mixture. It’s complicated, like you said. This is where, if it's a one-off, ‘I know this provider well, I’ve had many patients with this provider,’ and this person says this, it's like, "Wow." But if it’s the 10th story about that provider, as a psychiatrist, I’ll sometimes hear the 10th story about a specific provider, it’s like, ‘Oh, take note of that too.’ But inevitably, most providers, I can kind of figure out who they work well with and who they don’t. It’s also how they cultivate certain stories about the provider, it’s like they’re splitting from the very beginning.

Ruffalo

Very often in the initial stages with this type of patient, you’ll be cast in the role of, you know, the White Knight. You know, they’ll say, "You’re the best doctor I think I’ve ever seen. You have all these great reviews on the internet, and I’m so thankful you’ve accepted me as a patient." And, you know, the idealization often begins pretty early. But as Jonathan Shedler (2022) says, “If you're cast as the White Knight in Act One, you're almost certain to be cast as a villain in Act Two” [sic]. And, of course, he’s talking about splitting and the inevitable devaluation that follows in the treatment of these patients.

Motivations of Suffering & Manipulation with BPD 01:17:33

Puder

I think it's worth going through like this one little part that talks about:

Her sufferings took on the form of intense loathing and accusations of herself using such epithets as “dirty, disgraceful thing…monster…. horrible murderer... disgusting piece of garbage.” She experienced some of these accusations as arising from within, others from outside.

Episodic self-mutilation was also frequent. Her violent hatred and rejection of parts of herself had multiple meanings, several of which will be discussed later (Burnham, 1966, p. 112).

I want to focus on the meaning of self-hatred as a form of suffering. And I would say, there is a lot of suffering in these patients. So, as we talk about this, I don’t want us to miss the heart of it, which is that we study this to help, and not over-idealize ourselves as they idealize us, or over-devalue ourselves as they devalue us. But to have some thick skin to ride through it and see ourselves with the constancy that they don’t necessarily see.

Ruffalo

I think the point about suffering in these patients is so important. When I was in graduate school and doing my internship and psychotherapy training, we certainly talked about the suffering of schizophrenic patients, those with bipolar illness, and the severely depressed patient. I believe the suffering we see in borderline personality disorder is amongst the most severe, if not the most severe, in all psychiatric illnesses. As I’ve worked with borderline patients, I think the suffering is different in some ways from how a patient with psychotic illness suffers, but it’s still profound. I think some people interpret discussing the nature and symptoms of the psychopathology as somehow missing or neglecting how much the patient suffers or what their experience is like. But I don’t see it that way. I think discussing the nature of the psychopathology is a way to understand the depth and severity of the suffering. If you don’t talk about the nature of the psychopathology, you miss it. So, there’s room for both: we can understand the pathology and also appreciate the intensity and severity of the suffering these patients endure.

Puder

I would add that, as someone who has led a team, particularly in the partial IOP that I ran, I would sometimes see the splitting. Being able to point that out to the team, put words to it, and get both sides to talk about it was some of the most important work I did. My psychodynamic understanding of transference, countertransference, and projective identification helped me in that process. When I imagine talking to you, it’s about keeping the team together as well. I imagine that as people move forward in their profession, they become team leaders, whether it’s in a small community or overseeing people who work for them. Having this ability and this paper as a tool, is important. I wonder if you could speak to this point:

The present series of patients also presented evidence of childhood experiences that taught them the power of displays of suffering and threats of self-harm to influence others. Frequently, one or both parents had used such methods of appeal or coercion in other instances. Strong self-destructive urges, while not manifesting in the parent's overt behavior, had featured prominently in their fantasies and dreams (Burnham, 1966, p.112).

Ruffalo

Yeah, I think it just makes sense that in the context of neglect, a child might learn to resort to all sorts of means to garner love, attention, and sympathy. So, I think this is often the seeds or the root of some of what we describe as manipulation. And I think this is an important way of understanding it.

Puder

And when we think of manipulation, we often think of someone manipulating us to get money, sex, or control. But this isn't necessarily what we're talking about here. We're talking about manipulation with the goal of having you as a love object, this stabilizing force internally, the soothing mother for them. This perspective helps us have more compassion for the tactics they use. A lot of this isn't conscious— they don’t realize they’re doing it. I'm also reminded of stories of sociopathy, where someone was born into a family with a father who was a conman, and they ended up doing similar things. Perhaps their parent used illness as a way of regaining connection. Maybe the mother threatened suicide when she needed something. Some of these behaviors may have been caught, not learned consciously.

It's not about shaming that, but about understanding it.

Ruffalo

Yeah, I think of somatic or hypochondriacal symptoms often developing this way. If a child's emotional needs weren’t attuned to, if they weren’t listened to emotionally, but instead a parent would bring them to a doctor at the first sign of a cough or fever, unconsciously, the child may start to exhibit physical symptoms to garner emotional attention and love. It’s a powerful idea.

Puder

Yeah. And I think the skillfulness determined how well they probably were able to achieve that. They talk about how ‘She further exemplified the care she desired by ministering to substitute objects, including live pets or cuddly toy animals. For instance, she would embrace and rock one of these, saying, ‘She is frightened and wants to be held’(Burnham, 1966, p.113).I had one attending who said, you know someone likely has borderline personality disorder if they come into the office with a stuffed animal.

Ruffalo

Yeah, I heard the same thing at Pitt. It was very commonly said, and I think there’s truth to these notions that have been around for decades.

Puder

They talked about how they described their room- one patient even tacked on the wall, pelts of pets that had died. You can think about these as transitory objects, love objects from the past.

Ruffalo

Again, to sustain the patient, right. In the failure of evocative memory, to go back to Adler, the patient needs some tangible representation of a good object. I've heard of patients who will hold on to something that reminds them of their partner when their partner is gone, to remind them that their partner still exists in the world. It could be a small gift or something they hold in their pocket—some type of souvenir that the patient can use to conjure up the mental representation of the partner in the absence of the other person. So, in this case, the pets on the wall could be something akin to that.

Puder

A staff member once commented, "Going into her room is like going inside her." The urge to create an all-good world of perfect constancy was clearly evident. The quality which she most desired in the supplies was genuineness. Again and again, she sought proof that they were real, not pretended, but her doubts never seemed quite fully allayed. Repeatedly she said explicitly and implicitly, "You don't really care. If you did, you would do something to prove it more tangibly (Burnham, 1966, p.110).

Ruffalo

Yeah. This touches on what the psychiatrist Grotstein talked about when he was describing the "black hole." He used this metaphor to describe the futility of satisfying a patient who’s plagued by this type of problem. It's sort of like pouring into a glass with no bottom—there's nothing that can be said or done that truly allays the patient's abandonment anxiety. The patient always requires more and more proof from the object that you're not going to leave them. And sometimes, this is asked explicitly in therapy. I have patients who ask me, you know, sometimes weekly, "You're not going to retire, are you? You're not going to move, or you're not going to fire me, are you?" And that may allay their concerns for a short period of time, but as Grotstein would say, it’s like a black hole phenomenon.

…01:28:52

Puder

I recently did an episode on OCD (Episode 228), and they talk about not reassuring the patient, but sitting in the doubt. I wonder if that's how we should approach that type of anxiety.

Ruffalo

That's interesting. Yeah.

Puder

It's almost like it's really distressing. I think this is what Dr. Tar would say, what he taught me. It's so distressing to think that I might leave, and I just want to sit with you in that distress. Then I'll keep reading from this article:

“If you really cared, you would give me more than talk." She spoke of many earlier experiences in which the actions of others had belied their words. Her word-wariness and seemingly insatiable desire for something more, of course, presented difficult problems in psychotherapy (Burnham, 1966, p.113).

Ruffalo

Yes. Words are not enough. You need to show me. I think that's a pervasive communication in these patients.

Puder

They go on to sharing secrets. So you can start to see where this is, where there's some slight boundary violations. There may be some places for sharing stories from your own life, but for her, the appeal was sharing secrets and receiving secrets. As Maine termed them:

…The precious little jewels of information, while telling each that this information was something she had been unable to tell anyone else, and extracting from each a promise that the secret would be revealed to no one else. Thus secrets were offered, and frequently accepted, as a valuable token of trust and esteem, creating a two-person secret society (Burnham, 1966, p.113).

This idea of secrets was later somewhat dismantled when the staff would come together in sessions and realize that multiple staff members had received the same secrets. So, it was a way of connectedness that was common.

Ruffalo

Yes. "I'm going to tell you something I've never told anybody else"—in reality, I've told multiple others this exact thing, but yes.

Puder

Another side to the patient's bestowal of secrets was her encouraging her confidants to reciprocate by confiding in her. She implied that this would go far toward proving their trust and esteem of her. She further encouraged confidences by a remarkable, though uneven, capacity for empathic reading of the inmost thoughts of others (Burnham, 1966, p.114).

These patients are often very sophisticated in reading the room, picking up on small grudges between individuals. Exploiting those grudges, gathering secrets about staff members, and potentially using those as weapons.

Ruffalo

Yes, this is what’s often referred to as triangulation. Much of it is motivated by unconscious forces, but it manifests as attempts to divide and conquer, reflecting the underlying pathology.

How BPD Bargains & Projects Unconsciously 01:32:27

Puder

The next topic is the "bargain."

A special feature of “the appeal” was “the bargain”, which as offered by the patient and accepted by the staff, was largely unspoken and perhaps largely unconscious. It involved the patient offering the implicit promise that not only that her needs were temporary and satiable, but also that if they were met, she would become well. “If you will temporarily be a good mother to me, I will then become strong and self- sufficient, even to live up to my potentialities.” (Burnham, 1966, p.114).

This dynamic becomes challenging for the provider because it demands breaking the normal frame of care. The patient conveys that colluding with her in a special type of relationship is what will be healing.

And, and this is where I think as providers, we need to be very sure that our normal way of doing things is sufficient.

Ruffalo

Exactly. What’s communicated is essentially, "I need you to bend or break the rules for me." The implication is that if you really cared about me, you’d do so. If you truly wanted to help me, you'd deviate from your established practices. Practically, this might look like texting or calling outside of sessions, meeting in non-clinical settings like parks or restaurants, or doing something outside the standard therapeutic framework. The unspoken bargain becomes, "This deviation from the norm is essential for my healing."

Puder

And I’m thinking: is it behavioral therapy to meet a patient in a park if they're anxious about going to parks? Maybe for someone with OCD, but not necessarily for this type of patient.

Ruffalo
Sure. This is why diagnosis is so important. Not every patient is treated the same way. There’s so much anti-psychiatry rhetoric out there, but this is one of the most important aspects of diagnosis in terms of psychotherapy. Treating a personality-disordered patient is very different from treating someone with other types of pathologies. I was just reading Kernberg yesterday, and he discusses how, in less severe pathologies, there’s often a blurring between psychodynamic and supportive psychotherapy. But when we're dealing with severe personality pathology, it requires a different approach.

Puder

I think one thing we may not fully address is how through this special relationship with the patient, there’s a dynamic where they can turn you against another staff member. What happens is, because of the intense self-hatred that the patient carries—the cutting, the self-harm—it needs an outlet. That inner conflict and badness have to be directed somewhere. It’s like they want you to align with them, to collude with their own anger and vitriol, and project that onto another person. So, the other staff member becomes “all bad,” in their eyes. They split, and that internal conflict manifests outwardly—through self-harm, through their interactions, and even in their dreams.

Ruffalo

Yeah, I think Gabbard has commented on how a patient's projection of their own internal conflicts can serve to alleviate those conflicts when they see them externalized—manifesting as conflict between staff members. The projection of inner turmoil onto others becomes as a mechanism for resolving unconscious forces within the self.

Puder

The paper touches on this further, particularly the concept of splitting. It discusses how team meetings became a critical tool in managing the splitting dynamic. This aligns with approaches like mentalization-based therapy and DBT. Marsha Linehan, the creator of DBT, once said at a conference that if you're not meeting as a team regularly to discuss these patients, you're not actually practicing DBT.

As leaders—because I consider all my listeners to be leaders—you're instrumental in facilitating teamwork and addressing splitting dynamics.

Provider Education on BPD & Closing Remarks 01:37:46

Puder

One of the things that stood out to me is that you may enlist colleagues to meet the patient’s needs. Your own internal regulation can reach a point where you are no longer able to meet those needs. It escalates to where you start seeking more and more support to help you regulate. I remember a colleague coming to me who was completely dysregulated after working with one of these patients. He didn’t even know she had borderline personality disorder. He had completed an entire counseling degree and had never been taught how to treat it.

Ruffalo

Such a failure of education. It's very unfortunate. Very unfortunate.

Puder

Even just saying, “This person has borderline personality disorder,” was a revelation for him. He looked at me with this expression, like, “What is that? And how do I treat it?”

Ruffalo

It's very unfortunate. Very unfortunate.

Puder

He got some books on different ways of treating it, and he’s doing good work now. It’s been several years, and the patient is thriving, at least the last time I spoke to him. So one of the things they comment towards the end of this paper was that sometimes the group meetings were not enough. And so have some compassion for yourself as a future provider, as someone who will be a part of teams.

“In outlining the benefits from these group meetings, it would be inaccurate to leave the impression that they were a sure..fire cure-all of the splitting problem. This they were not; sometimes they foundered or totally collapsed” (Burnham, 1966, p.122).

This was awesome. I feel like if we had another hour, we could do justice to the rest of the article. But you’ll have to check it out yourself. On my website, psychiatrypodcast.com, we’ll link the full article, so you can go there and read the whole thing.

Ruffalo

Definitely. I encourage your listeners to read it. It’s, you know, 49 years old now—1966, right? At first, you might think, "Oh, it’s outdated," but no, there’s real gold in this article.

Puder

Yeah. And what I appreciate about you is that you don’t neglect these older, valuable articles. I’d love to have you on again, maybe to go through more of them one at a time and really do them justice. There’s so much wisdom in these historical works. Honestly, I could see this as a great CME opportunity—you know, continuing medical education credits—because it’s so in-depth. And even though this article is 50 years old, it has timeless insights. I was thinking about how history is essential. You can’t have a philosophy or theory without grounding it in historical facts. This author and the research team did a good job summarizing the dynamics of 12 patients who effectively split the unit over a 10-year period. They captured it in a qualitative way—not with a lot of statistics, but through early qualitative research, which is the foundation of so many great papers.

Ruffalo

Absolutely. The foundation of psychiatry, psychopathology, and psychotherapy was qualitative work and case studies. If you don’t know the history, you might think you’ve invented something new, when in reality, it’s been explored for decades—sometimes even a century or more.

Puder

Exactly. That’s the “grandiose naivety,” right? It’s probably why you and I won’t create our own schools of therapy. We recognize that we’re not better than the greats who came before us. There’s just so much value in learning from them.

Okay, we’ll leave it there for today. Thank you so much for coming on—I really appreciate it. Now we’re off to enjoy some steak.

Ruffalo

Yeah. Thanks so much for having me. Been looking forward to this and appreciate the opportunity.

Puder

And I heard you’re thinking about writing a book that compiles many of these excellent papers.

Ruffalo

We're in the early stages of that right now, but yeah, I think it's gonna be an ‘essential papers’ sort of book on BPD where I write an introductory chapter and sort of try to weave all the theory together.

Puder

Let me just plug you here—you didn’t ask me to do this, but Mark L. Ruffalo. You can find him on Twitter, or X. He’s worth following to learn from the articles and insights he shares. Okay. We'll leave it there.

Ruffalo

Thanks David.

ReferencesAdler, G. (1981). The borderline-narcissistic personality disorder continuum. The American journal of psychiatry, 138(1), 46–50. https://doi.org/10.1176/ajp.138.1.46

Akhtar S. (1984). The syndrome of identity diffusion. The American journal of psychiatry, 141(11), 1381–1385. https://doi.org/10.1176/ajp.141.11.1381

Anscombe, R. (1986). Treating the Patient Who “Can’t” versus Treating the Patient Who “Won’t.” American Journal of Psychotherapy, 40(1), 26–35. https://doi.org/10.1176/appi.psychotherapy.1986.40.1.26

Asylum Projects. (2022). Chestnut Lodge Sanatarium. Retrieved from https://www.asylumprojects.org/index.php?title=Chestnut_Lodge_Sanatarium

Austen Riggs Center. (2025). Homepage. Retrieved from https://www.austenriggs.org/

Behavioral Research & Therapy Clinics. (2025). Marsha Linehan. University of Washington. Retrieved from https://depts.washington.edu/uwbrtc/our-team/marsha-linehan/

Burnham D. L. (1966). The special-problem patient: victim or agent of splitting?. Psychiatry, 29(2), 105–122. https://doi.org/10.1080/00332747.1966.11023457

D'Agostino, A., Rossi Monti, M., & Starcevic, V. (2019). Psychotic symptoms in borderline personality disorder: an update. Current opinion in psychiatry, 32(1), 22–26. https://doi.org/10.1097/YCO.0000000000000462

Gunderson, J. G., & Lyons-Ruth, K. (2008). BPD's interpersonal hypersensitivity phenotype: a gene-environment-developmental model. Journal of personality disorders, 22(1), 22–41. https://doi.org/10.1521/pedi.2008.22.1.22

Hoch, P., & Polatin, P. (1949). Pseudoneurotic forms of schizophrenia. Psychiatric Quarterly, 23, 248–276. https://doi.org/10.1007/BF01563119

Kanter, J. (2021). Otto Allen Will Jr.: A brief portrait. Psychiatry, 84(1), 16–18. https://doi.org/10.1080/00332747.2021.1889313

Keepers, G. A., Fochtmann, L. J., Anzia, J. M., Benjamin, S., Lyness, J. M., Mojtabai, R., Servis, M., Choi-Kain, L., Nelson, K. J., Oldham, J. M., Sharp, C., Degenhardt, A., Hong, S., & Medicus, J. (2024). The American Psychiatric Association practice guideline for the treatment of patients with borderline personality disorder. American Journal of Psychiatry, 181(11). https://doi.org/10.1176/appi.ajp.24181010

McGinn, L. K. (1998). Interview: Otto F. Kernberg, M.D., F.A.P.A., Developer of Object Relations Psychoanalytic Therapy for Borderline Personality Disorder. American Journal of Psychotherapy, (52)2, 125-260. https://doi.org/10.1176/appi.psychotherapy.1998.52.2.191

Menninger Clinic. (2025). Homepage. Retrieved from https://www.menningerclinic.org/

Oransky, I. (2004). Margaret Thaler Singer. The Lancet, (363)9406, 403. https://doi.org/10.1016/S0140-6736(04)15460-3

Paris, J. (2020). Treatment of borderline personality disorder: A guide to evidence-based practice (2nd ed.). Guilford Press. https://www.guilford.com/books/Treatment-of-Borderline-Personality-Disorder/Joel-Paris/9781462541935

Peralta, V., & Cuesta, M. J. (2011). Eugen Bleuler and the Schizophrenias: 100 years After. Schizophrenia Bulletin, 37(6), 1118–1120. https://doi.org/10.1093/schbul/sbr126

Peterson, D. R. (1954). The diagnosis of subclinical schizophrenia. Journal of consulting psychology, 18(3), 198–200. https://doi.org/10.1037/h0061349

Psychiatric Times. (2005, April 1). Through the times with Glen O. Gabbard, M.D. Psychiatric Times, 22(4). Retrieved from https://www.psychiatrictimes.com/view/through-times-glen-o-gabbard-md

Puder, D. (Host). (2018, September 19). What is psychodynamic theory? (No. 29) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/2018/9/19/what-is-psychodynamic-theory?rq=mentalization%20based

Puder, D. (Host). (2019, March 31). Therapeutic Alliance Part 4: What is Transference and Countertransference? (No. 41) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/strongepisode-041-strongtherapeutic-alliance-part-4-what-is-transference-and-countertransference?rq=041

Puder, D. (Host). (2019, December 11). Therapeutic Alliance Part 6: Attachment Types and Application (No. 69) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/2019/12/11/therapeutic-alliance-how-to-build-an-attachment-with-your-patient?rq=disorganized%20attachment

Puder, D. (Host). (2020, July 25). Disorganized Attachment: Fear without Solution (No. 87) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/2020/7/25/jta1s2b7mixbkkge59fio4rz1vcj3b?rq=disorganized%20attachment

Puder, D. (Host). (2020, August 8). Disorganized Attachment: Fear Without Solution Part 2 (No. 88) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/strongepisode-088-strongdisorganized-attachmentnbspfear-without-solution-part-2?rq=adverse%20childhood%20experiences

Puder, D. (Host). (2020, September 17). The Big Five: Neuroticism Part 1 (No. 92) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/strongepisode-092-strongthe-big-five-neuroticism-part-1?rq=adverse%20childhood%20experiences

Puder, D. (Host). (2021, May 13). Borderline Personality Disorder: History, Symptoms, Environment, Genetics & Brain Science (No. 115) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-115-borderline-personality-disorder-history-symptoms-environment-genetics-amp-brain-science?rq=mentalization%20based

Puder, D. (Host). (2021, November 8). Borderline Personality Disorder: Psychotherapy Schema Therapy(No. 130) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-130-borderline-personality-disorder-psychotherapy-schema-therapy?rq=130

Puder, D. (Host). (2022, February 25). Borderline Personality Disorder: Common Factors In Effective Therapies With Dr. Robert Feinstein (No. 140) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-140-borderline-personality-disorder-common-factors-in-effective-therapies-with-dr-robert-feinstein?rq=140

Puder, D. (Host). (2022, April 5). Psychodynamic Psychotherapy with Jonathan Shedler, Ph.D.

(No. 144) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-144-a-rose-by-another-name-psychodynamic-processes-in-other-therapies?rq=shedler

Puder, D. (Host). (2023, February 24). Using Transference To Improve Connection (No. 170) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-170-using-transference-to-improve-connection?rq=170

Puder, D. (Host). (2023, March 3). Nancy McWilliams on Mental Health, Transference, and Dissociation (No. 171) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-171-nancy-mcwilliams-on-mental-health-transference-and-dissociation?rq=171

Puder, D. (Host). (2023, March 10). Prisons in Ancient Mesopotamia with Nicholas Reid (No. 172) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-172-prisons-in-ancient-mesopotamia-with-nicholas-reid?rq=Mesopotamia

Puder, D. (Host). (2023, October 11). Dr. Sue Johnson: Attunement, Attachment and the Development of Emotionally Focused Therapy (No. 194) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-194-dr-sue-johnson-attunement-attachment-and-the-development-of-emotionally-focused-therapy?rq=disorganized%20attachment

Puder, D. (Host). (2024, January 19). Adverse Childhood Experiences and Their Lasting Impact on Health: A Comprehensive Guide (No. 203) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-203-adverse-childhood-experiences-and-their-lasting-impact-on-health-a-comprehensive-guide?rq=adverse%20childhood%20experiences

Puder, D. (Host). (2024, February 2). Adverse Childhood Experiences Part 2: Measurement, Impact on Future Mental Health, Dissociation, and Timing of Trauma (No. 204) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-204-adverse-childhood-experiences-part-2-measurement-impact-on-future-mental-health-dissociation-and-timing-of-trauma?rq=adverse%20childhood%20experiences

Puder, D. (Host). (2024, February 23). Mentalization Based Therapy (MBT), with Dr. Anthony W. Bateman, MA, FRCPSYCH and Dr. Peter Fonagy, PhD, FBA (No. 206) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-206-mentalization-based-therapy-mbt-with-dr-anthony-w-bateman-ma-frcpsych-and-dr-peter-fonagy-phd-fba?rq=mentalization%20based

Puder, D. (Host). (2024, May 17). Reflective Functioning: The Key to Attachment with Dr. Howard Steele (No. 213) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/reflective-functioning-the-key-to-attachment-with-dr-howard-steele?rq=213

Puder, D. (Host). (2024, June 14). Understanding Complex PTSD and Borderline Personality Disorder (No. 215) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-215-understanding-complex-ptsd-and-borderline-personality-disorder?rq=adverse%20childhood%20experiences

Puder, D. (Host). (2024, July 19). Adverse Childhood Experiences - HPA axis & Brain changes: cortisol, amygdala, hippocampus, cytokines, & epigenetics (Part 3 of ACE series) (No. 217) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-217-adverse-childhood-experiences-part-3-aces?rq=adverse%20childhood%20experiences

Puder, D. (Host). (2024, October 9). Understanding Borderline Personality Disorder (BPD) Medications & Treatment (No. 224) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/bpd-treatment-medications-and-therapy?rq=mentalization%20based

Puder, D. (Host). (2024, October 25). Psychology and Inside Out 2: A Breakdown of Adolescent Emotional Lives (No. 225) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-225-inside-out-2-adolescent-emotions-psychology-analysis?rq=disorganized%20attachment

Puder, D. (Host). (2024, December 6). Comprehensive Obsessive-Compulsive Disorder (OCD) Treatment Guide: Evidence-Based ERP Approaches and Best Practices for Clinicians (No. 228) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-228-comprehensive-ocd-treatment-guide-evidence-based-erp-and-cognitive-strategies

Sansone, R. A., & Sansone, L. A. (2015). Borderline Personality Disorder in the Medical Setting: Suggestive Behaviors, Syndromes, and Diagnoses. Innovations in clinical neuroscience, 12(7-8), 39–44. PMCID: PMC4558791 PMID: 26351624

Scharff, J. S. (2015, November 24). A tribute to Harold F. Searles, M.D. International Psychotherapy Institute. Retrieved from https://theipi.org/a-tribute-to-harold-f-searles-m-d/

Searles, H. F. (1959). The effort to drive the other person crazy: An element in the aetiology and psychotherapy of schizophrenia. British Journal of Medical Psychology, 32, 1–18. https://psycnet.apa.org/doi/10.1111/j.2044-8341.1959.tb00463.x

Shedler, J. [@JohnathanShedler]. (2022, August 16). If you audition for the role of White Knight in Act I, don't be surprised when you're cast as Villain in Act II.[X]. X (FKA Twitter). https://x.com/JonathanShedler/status/1559719049189150721?mx=2

Silk, K. R., Lee, S., Hill, E. M., & Lohr, N. E. (1995). Borderline personality disorder symptoms and severity of sexual abuse. The American journal of psychiatry, 152(7), 1059–1064. https://doi.org/10.1176/ajp.152.7.1059

Stanton, A. H. (1954). The mental hospital: A study of institutional participation in psychiatric illness and treatment. New York: Basic Books. https://archive.org/details/mentalhospitalst0000stan/page/n9/mode/2up

Stefana, A. (2015). Adolph Stern, father of term “borderline personality”. Minerva psichiatrica. (56)2. 95. https://www.researchgate.net/publication/284733558_Adolph_Stern_father_of_term_borderline_personality

Triarhou, L.C. (2022). Helene Deutsch (1884–1982). In: The Brain Masters of Vienna. Springer, Cham. https://doi.org/10.1007/978-3-031-13052-6_15

View Details

Audio Episode Host: David Puder, MD

Audio Episode Guest: Nicholas Fabiano MD, Brendon Stubbs PhD

Article Authors: Nicholas Fabiano MD, Liam Browning BA, Christopher Campbell, Brendon Stubbs PhD, David Puder MD

Article Reviewers: Erica Vega, MD, Joanie Burns DNP

Corresponding author: David Puder, MD

Psychiatry CME for listening to this activity: 1.75

Other Places to listen: iTunes, Spotify

Date Published: 12/20/2024

Conflicts of interest: Brendon Stubbs is on the Editorial Board of the Journal of Physical Activity and Health, Ageing Research Reviews, Mental Health and Physical Activity, The Journal of Evidence Based Medicine, and The Brazilian Journal of Psychiatry. Brendon has received honorarium from a co-edited book on exercise and mental illness (Elsevier), an associated education course and unrelated advisory work from ASICS and FitXR LTD.

Dr. David Puder and Dr. Nicholas Fabiano have no conflict of interests to report.

Introduction On Exercise For DepressionExercise benefits both mental and physical health. Specifically, it has demonstrated antidepressant effects, which are often compared to other first-line treatment options such as medications or therapy. In previous episodes, we have explored various aspects of exercise, including exercise as a prescription for depression/anxiety/stress (episode 010), performance enhancement (episode 012), strength training for depression (episode 018), the best exercise program for depression (episode 096), exercise as a drug for mental health and longevity (episode 142), exercise for the brain (episode 165), and the exercise & mental health 2023 update (episode 179).

In today’s episode, we are delighted to welcome two leading experts in exercise and mental health: Nicholas Fabiano, MD and Brendon Stubbs, PhD. Dr. Fabiano is a psychiatry resident at the University of Ottawa and has contributed extensively to research on exercise and mental health, as well as other innovative topics in psychiatry and medicine. Dr Stubbs is recognized as one of the world’s foremost researchers in mental health and neuroscience, ranked among the top 0.1% of researchers in the field. He has authored more than 2,500 studies, influenced global health policies through organizations such as the World Health Organization and the World Psychiatric Association, and influenced various public health campaigns. Dr. Stubbs has been an instrumental force in bringing credibility and legitimacy to the use of exercise as a valuable treatment modality. Together, Dr. Stubbs and Dr. Fabiano bring unparalleled expertise to today’s conversation on exercise and depression.

We hope you enjoy this engaging episode and encourage you to explore the work of Dr. Fabiano and Dr. Stubbs, as well as our previous episodes on exercise and mental health, for further insights into this transformative area of research.

Why Exercise: The Science Behind Its Power To Combat DepressionPhysical activity (PA) is any movement that uses energy, while exercise is a planned and structured form of PA aimed at improving fitness. PA provides many benefits for mental health. It reduces stress, improves sleep, boosts mood, enhances self-esteem, and has specific antidepressant effects (Wegner et al., 2014). Upon contraction, muscles release myokines (cytokines and peptides) that mediate communication with other organs to increase brain-derived neurotrophic factor (BDNF) (Oudbier et al., 2022). Studies have demonstrated that PA promotes neuroplasticity through this upregulation of BDNF, which is important for mood regulation (Wegner et al., 2014). There exists also a bidirectional relationship with depression—PA reduces depressive symptoms, while inactivity is associated with increased depression risk (Huang et al., 2020). Given its broad impact on mental and physical health, PA has been included in treatment guidelines for depression as a first-line therapy (Lam et al., 2024).

Public Perception Of Exercise As A Treatment For Depression (Fabiano et al., 2024)Decades ago, exercise was not a serious treatment option for depression. However, over the last 30 years, the sheer volume of research publications on physical activity, mental health, and well-being has become immense. A recent bibliometric analysis of the literature found 55,353 documents on exercise and mental health published between 1988-2021 (Sabe et al., 2022). In particular, a large-scale umbrella review (including 97 reviews [1039 trials and 128,119 participants]) found that exercise was highly beneficial for improving symptoms of depression, anxiety and distress across a wide range of adult populations, including the general population, people with diagnosed mental health disorders and people with chronic disease (Singh et al., 2023b). Although these findings are certainly valuable, the media misconstrued the evidence stating that, “[E]xercise is around 1.5 times more effective than either medication or cognitive behaviour therapy” (Singh et al., 2023a); this misleading headline has since been widely disseminated to millions across news outlets, podcasts, videos, and blogs. This claim erroneously arose through the comparison of effect sizes from “very low quality” previous systematic reviews of physical activity interventions for mental health (Singh et al., 2023b). Given the overlapping 95% confidence intervals and substantially methodologically superior systematic reviews the authors used as a comparison, they made a more accurate statement that exercise is “comparable to or slightly greater” (in mild symptoms).

It is imperative that robust science is communicated widely, but this needs to be done in the interest of science and, in this case, patients. As the media is known to play a crucial role in influencing people’s perception and behaviors, it is imperative that dissemination of scientific information is both clear and accurate. Previous research has demonstrated that subtle misinformation in news headlines, such as the claim that exercise is more effective than medication or therapy, can affect readers’ memory, inferential reasoning, and behavioral intentions (Ecker et al., 2014). Further, readers struggle to update their memory in order to correct initial misconceptions, which highlights the importance of factual messaging to the general public (Ecker et al., 2014).

This is particularly important when it is considered that there is already significant stigma surrounding the use of psychotropic medications, such as antidepressants (Sansone & Sansone, 2012). Thus, wide dissemination of the non-evidence-based claim that exercise is 1.5 times better than other first-line treatments may lead to direct harm to vulnerable patients who may delay seeking specialist support, stop taking medications, or stop attending therapy due to such headlines. Prior evidence has demonstrated that a greater delay to treatment of a depressive episode is associated with a reduced response, and may precede development of a treatment-resistant depression (Corey-Lisle et al., 2004). Further, for those already taking an antidepressant medication, abrupt discontinuation, without physician supervision, can lead to withdrawal effects characterised by dizziness, weakness, nausea, headaches, and insomnia, among others. Moreover, media claims often fail to mention that the evidence for exercise in depression lies mostly in the mild to moderate cases, therefore those with severe depression may be experiencing extreme distress warranting immediate medical attention (i.e., due to active suicidal ideation or malnutrition due to severely reduced intake).

What Does The Evidence Actually Show About Exercise And Depression?Meta-analysis of Exercise for Depression (Heissel et al., 2023) The objective of this meta-analysis was to estimate the efficacy of exercise on depressive symptoms compared with non-active control groups and to determine the moderating effects of exercise on depression and the presence of publication bias. Randomized controlled trials (RCTs) including participants aged 18 years or older with a diagnosis of major depressive disorder or those with depressive symptoms determined by validated screening measures scoring above the threshold value, investigating the effects of an exercise intervention (aerobic and/or resistance exercise) compared with a non-exercising control group were included. The authors found:

• 41 studies (2264 participants) were included.
• Twenty-one studies assessed depressive symptoms, while MDD was diagnosed in 20 studies.
• Percentage of females ranged from 26% to 100%, mean age from 18.8 to 87.9 years.
• Only non-active controls “such as usual-care, wait-list control conditions or placebo pills” were included.
• “Studies with any other exercise intervention (such as stretching or low-dose exercise) as a comparator were excluded.”

• Taking out the low-dose exercise or stretching exercises from this meta-analysis is interesting because these types of studies control for the antidepressant effect of starting an intervention or group activity, allowing for a more accurate assessment of the true effects of exercise. Using studies that compare exercise to waitlist control and non-interventional groups might inflate the effect size of exercise.

• Large effects were found in:

• All exercise interventions (standardized mean difference (SMD)=−0.946, 95% CI −1.18 to −0.71)
• Individuals with major depressive disorder (SMD=−0.998, 95% CI −1.39 to −0.61, k=20)

• Supervised exercise interventions (SMD=−1.026, 95% CI −1.28 to −0.77, k=40)

• Moderate effects were found in:

• Low risk of bias studies (SMD=−0.666, 95% CI −0.99 to −0.34, k=12, NNT=2.8 (95% CI 1.94 to 5.22)).

• Based on exercise type:

• Aerobic (SMD=−1.156) and resistance training (−1.042) as exercise types showed large effects whereas mixed aerobic and resistance training showed small effects (−0.455).

  Meta-regression:

• Shorter trials associated with larger effects (β=0.032, 95% CI 0.01 to 0.09, p=0.032, R²=0.06).

• In this study they used unstandardized beta, meaning the average number of standard deviations that the dependent variable changed for each unit change (as opposed to each standard deviation change) on the independent variable. In this example, since the unit of the independent variable is in weeks: if a study lasts 10 weeks, compared to 5 weeks, the effect size might be 0.16 units smaller (0.032 × 5 weeks).

• Higher antidepressant use by the control group was associated with smaller effects (β=−0.013, 95% CI −0.02 to −0.01, p=0.012, R²=0.28).

  Mean change and number needed to treat (NNT):

• Mean change of −4.70 points (95% CI −6.25 to −3.15, p<0.001, n=685) on the HAM-D and for the BDI of −6.49 points (95% CI −8.55 to −4.42, p<0.001, n=275).

• NNT was 2.0 (95% CI 1.68 to 2.59) for the main-analysis, and 2.8 (95% CI 1.94 to 5.22) for the low risk of bias studies.
• For MDD, only the NNT was 1.9 (95% CI 1.49 to 2.99) and 1.6 (95% CI 1.58 to 2.41) in supervision by other professionals/students.
• The authors conclude that exercise is efficacious in treating depression and depressive symptoms and should be offered as an evidence-based treatment option focusing on supervised and group exercise with moderate intensity and aerobic exercise regimes.

Network Meta-analysis: Comparing Exercise To Pharmacological Interventions For Depression (Recchia et al., 2022)The objective of this network meta-analysis was to assess the comparative effectiveness of exercise, antidepressants, and their combination for alleviating depressive symptoms in adults with non-severe depression. RCTs that examined the effectiveness of an exercise, antidepressant, or combination intervention against either treatment alone or a control/placebo condition in adults with non-severe depression were included. The authors found:

• 21 RCTs (2551 participants) were included.

• Antidepressants versus controls (n=11), exercise versus controls (n=6), combined treatments versus antidepressants (n=4) and combined treatments versus exercise (n=1).

• No differences in treatment effectiveness among the three main interventions, although all treatments were more beneficial than controls.

• Exercise vs antidepressants: SMD, −0.12; 95% CI −0.33 to 0.10
• Combination versus exercise: SMD, 0.00; 95% CI −0.33 to 0.33
• Combination vs antidepressants: SMD, −0.12; 95% CI −0.40 to 0.16

• Exercise interventions had higher drop-out rates than antidepressant interventions (RR 1.31; 95% CI 1.09 to 1.57)

• Despite the greater drop-out rates in the exercise group, the proportion of participants with adverse events was greater in the antidepressant group, with 22% reporting adverse events compared with 9% in the exercise group.

  The authors conclude that the results suggest no difference between exercise and pharmacological interventions in reducing depressive symptoms in adults with non-severe depression.

Network Meta-analysis: Optimal Exercise Dose And Modality For Treating Major Depression Compared To Psychotherapy And Antidepressants (Noetel et al., 2024)The objective of this network meta-analysis was to identify the optimal dose and modality of exercise for treating major depressive disorder, compared with psychotherapy, antidepressants, and control conditions. Any randomized trial with exercise arms for participants meeting clinical cut-offs for major depression were included. The authors found:

• 218 studies (14170 participants) were included.
• Compared with active controls “usual care, placebo tablet, stretching, educational control, and social support,” large reductions in depression were found for:
• Dance (n=107, κ=5, Hedges’ g −0.96, 95% credible interval −1.36 to −0.56)

• SMDs are usually estimated by Cohen’s d or Hedges’ g. Cohen’s d divides the difference between sample means of a continuous response by the pooled standard deviation, but is subject to non negligible bias for small sample sizes. Hedges’ g removes this bias with a correction factor.

• Compared with active controls, moderate reductions in depression were found for:

• Walking or jogging (n=1210, κ=51, g −0.63, −0.80 to −0.46)
• Yoga (n=1047, κ=33, g=−0.55, −0.73 to −0.36)
• Strength training (n=643, κ=22, g=−0.49, −0.69 to −0.29)
• Mixed aerobic exercises (n=1286, κ=51, g=−0.43, −0.61 to −0.25)

• Tai chi or qigong (n=343, κ=12, g=−0.42, −0.65 to −0.21)

• Moderate, clinically meaningful effects were also present when exercise was combined with SSRIs (n=268, κ=11, g=−0.55, −0.86 to −0.23) or aerobic exercise was combined with psychotherapy (n=404, κ=15, g=−0.54, −0.76 to −0.32).

• All these treatments were significantly stronger than the standardized minimum clinically important difference compared with active control (g=−0.20), equating to an absolute g value of −1.16.
• For acceptability, the odds of participants dropping out of the study were lower for:
• Strength training (n=247, direct evidence κ=6, odds ratio 0.55, 95% credible interval 0.31 to 0.99)

• Yoga (n=264, κ=5, 0.57, 0.35 to 0.94)

• Effects were moderate for cognitive behavior therapy alone (n=712, κ=20, g=−0.55, −0.75 to −0.37) and small for SSRIs (n=432, κ=16, g=−0.26, −0.50 to −0.01) compared with active controls.

  Across modalities, a clear dose-response curve was observed for intensity of exercise prescribed.

  Use of group exercise appeared to moderate the effects:

• Overall effects were similar for individual (g=−1.10, −1.57 to −0.64) and group exercise (g=−1.16, −1.61 to −0.73).

• Yoga was better delivered in groups.
• Strength training and mixed aerobic exercise were better delivered individually.
• The authors concluded that exercise is an effective treatment for depression, with walking or jogging, yoga, and strength training more effective than other exercises, particularly when intense.

Comparing Antidepressants and Running Therapy on Mental and Physical Health Outcomes (Verhoeven et al., 2023)The objective of this study was to examine the effects of antidepressants versus running therapy on both mental and physical health. According to a partially randomized patient preference design (compares two or more interventions among groups of patients, some of whom choose the intervention they receive), 141 patients with depression and/or anxiety disorder (mean age 38.2 years; 58.2% female; 45 participants received antidepressant medication and 96 underwent running therapy) were randomized or offered preferred 16-week treatment: antidepressant medication (escitalopram or sertraline) or group-based running therapy ≥2 per week. Baseline (T0) and post-treatment assessment at week 16 (T16) included mental (diagnosis status and symptom severity) and physical health indicators (metabolic and immune indicators, heart rate (variability), weight, lung function, hand grip strength, fitness). The authors found:

• Intention-to-treat analyses (analyzing the results of RCTs that compares groups based on their initial treatment assignment, rather than the treatment they actually received) showed that remission rates at T16 were comparable (antidepressants: 44.8 %; running: 43.3 %; p=.881)

• There was a larger decrease in anxiety symptoms after six weeks in the antidepressant group, which suggests faster improvement on especially anxiety-related symptoms

  However, the groups differed significantly on various changes in physical health:

• Weight (d=0.57; p=.001)

• Waist circumference (d=0.44; p=.011)
• Systolic (d=0.45; p=.011) and diastolic (d=0.53; p=.002) blood pressure
• Heart rate (d=0.36; p=.033) and heart rate variability (d=0.48; p=.006).
• Adherence:
• In the antidepressant group, 82.2 % (N=37) of all participants adhered to the medication treatment protocol.
• In the running therapy group, 52.1 % (N=50) of participants completed >22 sessions of exercise therapy.

• The treatment adherence was significantly higher in the antidepressant group compared to the running therapy group (p<.001).

• Limitation: A minority of the participants were willing to be randomized; the running therapy was larger due to greater preference for this intervention (out of 141 participants, 22 were willing to be randomized into the antidepressant [n=9] or the running therapy [n=13] groups, while 119 participants chose the treatment of their preference: antidepressant [n=36] or running therapy [n=83]).

• The authors conclude that while the interventions had comparable effects on mental health, running therapy outperformed antidepressants on physical health, due to both larger improvements in the running therapy group as well as larger deterioration in the antidepressant group.

Internet-Based Cognitive Behavioural Therapy Compared to Exercise for Depression (Hallgren et al., 2018)The objective of this RCT was to compare the effectiveness of exercise, internet-based cognitive behavioral therapy (ICBT), and usual care for depression. A multicentre, three-group parallel, randomized controlled trial was conducted with assessment at 3 months (post-treatment) and 12 months (primary end-point). 740 adults (mean age 43; 73% female; 56 received usual care, 49 received exercise, and 42 received ICBT) with mild to moderate depression aged 18–71 years were recruited from primary healthcare centres located throughout Sweden were included. Participants were randomly assigned to one of three 12-week interventions:

• Supervised group exercise:
• Patients in the exercise group were further randomized to one of three supervised exercise conditions: light exercise (yoga/stretching classes), moderate exercise (an intermediate aerobics class) and vigorous exercise (a higher-intensity aerobics/bodyweight strength training class).

• Patients were requested to complete three 60 min sessions per week for 12 weeks; sessions typically included 5–20 participants.

• Clinician-supported ICBT:

• Treatment involved the patient working through a self-help manual available online in the form of modules.

• Usual care by a physician:

• Standard treatment for depression administered by their primary care physician.
• In most instances, ‘usual care’ consisted of 45–60 min CBT delivered by an accredited psychologist or counselor.

The authors found:

• Mean differences in MADRS score at 12 months were 12.1 (ICBT), 11.4 (exercise) and 9.7 (usual care)

• Exercise and ICBT had equivocal effects, which were greater than treatment as usual.

  The authors conclude that the long-term treatment effects reported here suggest that prescribed exercise and clinician-supported ICBT should be considered for the treatment of mild to moderate depression in adults.

Exercise as an Add-On Therapy to Medications and CBT for Depression (Gourgouvelis et al., 2018) The objective of this study was to investigate the effects of exercise as an add-on therapy with antidepressant medication and cognitive behavioral group therapy (CBGT) on treatment outcomes in low-active MDD patients. Sixteen people were recruited; eight medicated patients performed an 8-week exercise intervention in addition to CBGT, and eight medicated patients attended the CBGT only. Twenty-two low-active, healthy participants with no history of mental health illness were also recruited to provide normal healthy values for comparison. The authors found:

• Exercise resulted in greater reduction in depression symptoms (p=0.007, d=2.06), with 75% of the patients showing either a therapeutic response or a complete remission of symptoms vs. 25% of those who did not exercise.

• Exercise was associated with greater improvements in sleep quality (p=0.046, d=1.28) and cognitive function (p=0.046, d=1.08).

  The exercise group also had a significant increase in plasma brain-derived neurotrophic factor (BDNF), p=0.003, d=6.46, that was associated with improvements in depression scores (p=0.002, R2=0.50) and sleep quality (p=0.011, R2=0.38).

• R-squared values range from 0 to 1, with 0 indicating the model doesn’t explain any variability and 1 indicating the model explains all variability.

  The authors conclude that exercise as an add-on to conventional antidepressant therapies improved the efficacy of standard treatment interventions.

Multisystem Benefits Of Exercise For Mental And Physical HealthComorbidity Between Major Depressive Disorder and Physical Diseases (Berk et al., 2023)* Those with common physical diseases (such as cardiovascular diseases, cancer and neurodegenerative disorders) experience significantly elevated rates of MDD, and those with MDD have an increased risk of numerous physical diseases. * This significant comorbidity is associated with worse outcomes, reduced treatment adherence, increased mortality, and greater health care utilization/costs. * The figure below demonstrates the association between MDD and various physical diseases according to Mendelian randomization studies. + One issue we have with this study is that it suggests a unidirectional association between type 2 diabetes mellitus and major depressive disorder. However, other studies highlight the bidirectional relationship between major depressive disorder and both type 1 and type 2 diabetes. For instance, when blood glucose levels are well-controlled, depression scores tend to improve; conversely, when blood glucose levels are poorly controlled, depression screening scores often worsen. Similarly, as major depressive disorder symptoms improve, blood glucose levels also improve, and patients are more likely to adhere to blood glucose monitoring, insulin use, and dietary modifications. By contrast, an escalation in depressive symptoms correlates with a decline in these measures (Bernstein et al., 2013; Corathers et al., 2013; Massengale, 2005; Santos et al., 2015).

Antidepressant Side Effects (Wang et al., 2018)On top of the aforementioned physical health comorbidities associated with depression, antidepressant medications have several known side effects such as:

• Cardiovascular side-effects:
• Increased resting heart rate
• Decreased heart rate variability

• Hypertension

• Gastrointestinal side effects:

• Constipation

• Metabolic:

• Weight gain

• Sleep:

• Increased rapid eye-movement (REM) sleep latency

• Insomnia

• Musculoskeletal:

• Increased risk of fractures

Therefore, although at best there is equivalence of efficacy between exercise interventions and medications or therapy, this does not mean these treatment modalities are all the same in the treatment of depression. Beyond its antidepressant effects, exercise has numerous multisystem benefits, which are often in contrast to the adverse side effects of antidepressant medications (Warburton et al., 2006). As such, exercise has the unique ability to simultaneously bolster one’s mental and physical health. Despite these beneficial multisystem effects and higher adverse events in antidepressant trials, there is a higher drop-out rate for exercise interventions (Recchia et al., 2022). This likely arises from the fact that exercise is physically demanding and more difficult to implement when compared to pharmacological interventions such as antidepressants. This places an onus of responsibility on the healthcare provider to develop an understanding of the benefits of exercise, address barriers, provide clear exercise “prescriptions,” and incorporate behavioral change techniques to increase initiation and adherence.

Optimal Amount of Exercise to Improve Depressive Symptoms (Tian et al., 2024)The objective of this systematic review and Bayesian model-based network meta-analysis of RCTs was to examine the efficacy of four major types of exercise (aerobic, resistance, mixed, and mind-body) on depression, as well as the dose-response relationship between total and specific exercise and depressive symptoms. People aged 18 years or older with a diagnosis of major depressive disorder, or a depressive symptom score above a threshold as determined by a validated screening measure, implemented one or more exercise therapy groups, and assessments of depressive symptoms at baseline and follow-up were included. The authors found:

• Forty-six RCTs (3164 people) were included.
• All exercise types improved depressive symptoms:
• Aerobic (SMD = -0.93; 95% CI: -1.25 to -0.62)
• Mind-body exercise (SMD) = -0.81; 95% CI: -1.19 to -0.42)
• Mixed (SMD = -0.77; 95% CI: -1.20 to -0.34)

• Resistance exercise (SMD = -0.76; 95% CI: -1.24 to -0.28)

• The metabolic equivalent of task (MET) is a measure of the ratio of the rate at which a person expends energy, relative to the mass of that person, while performing some specific physical activity compared to a reference, currently set by convention at an absolute 3.5 mL of oxygen per kg per minute.

  The dose-response meta-analysis showed a u-shaped curve between exercise dose and depressive symptoms.

  There were different optimal doses, depending on the type of physical activity whereby AE=aerobic, RE=resistance, ME=mixed, and MBE=mind-body.

  The minimum effective dose was estimated to be 320 metabolic equivalent (METs) -min per week and the optimal response was 860 METs-min per week.

• This is equivalent to 245 min of walking (3.5 METs-min), 140 min of moderate-intensity aerobic exercise (6 METs-min), or 215 min of yoga (4 METs-min) per week.

• The authors conclude that clinicians can carefully select the appropriate dose of exercise based on the patient’s individual characteristics and needs, in conjunction with psychological care interventions.

The Physiologic Antidepressant Mechanisms Of Exercise (Hird et al., 2024)The objective of this review was to propose a novel hypothesis for understanding the antidepressant effects of exercise, centred on motivation, across different levels of explanation. The authors found:

Depression is associated with disruptions to several closely related neural and cognitive processes, including dopamine transmission, fronto-striatal brain activity and connectivity, reward processing and motivation.

• There is also evidence to suggest that the motivational symptoms of depression are related to inflammation (Bell et al., 2017).
• Inflammation is known to reduce dopamine transmission, which, in turn, is strongly implicated in effort-based decision making for reward; however, aerobic exercise is known to decrease this systemic inflammation.
• By reducing inflammation and boosting dopamine transmission, exercise improves “interest-activity” symptoms of depression—namely anhedonia, fatigue and subjective cognitive impairment—by increasing propensity to exert effort.
• From this, cognitive impairment in depression may also be conceptualized through an effort-based decision-making framework, which may help to explain the impact of exercise on cognitive impairment.

The Psychological Antidepressant Mechanisms of ExerciseWhile the physiological mechanisms of exercise in alleviating anhedonia, fatigue, and passivity are increasingly well-characterized, its psychological mechanisms in improving cognitive and emotional symptoms of depression are no less significant.

Among the more commonly understood cognitive symptoms of depression is the persistently negative or conflicting view of the self (Montesano et al., 2017). Therefore, one of the most compelling explanations for exercise’s antidepressant effects lies in its ability to foster a sense of mastery—the belief that one can successfully accomplish tasks and achieve personal goals.

This concept is foundational to Albert Bandura’s work in self-efficacy (1977), which emphasizes the importance of mastery experiences as a key source of self-efficacy. For individuals with depression, who often feel incapable of change and struggle with helplessness, negative self-perception, and diminished agency, exercise provides an opportunity to counter these patterns through incremental and tangible achievements.

In a randomized controlled trial conducted by Craft (2005), 40 women with moderate depression were assigned to either a 9-week aerobic exercise intervention (3 sessions per week) or a control group. Each session involved 30 minutes of treadmill walking or cycling at moderate intensity. The results showed a significant improvement in coping self-efficacy—defined as the belief in one’s ability to manage depressive symptoms—among women in the exercise group compared to controls. Importantly, the coping self-efficacy was strongly correlated with reductions in depressive symptoms (r = −0.79, p < 0.05), suggesting that enhanced self-belief acted as a mediator for mood improvements.

Similarly, a 10-year longitudinal study by Harris and colleagues (2006) investigated the role of physical activity as a coping mechanism in 452 adults with depression. The authors followed this cohort and assessed their physical activity levels, coping, and depression and found that individuals who adopted regular exercise as part of their coping strategies reported greater coping efficacy and experienced significant reductions in depressive symptoms over time. The data indicated that regular exercise contributed not only to immediate self-efficacy gains but also to long-term resilience in managing stress and depressive episodes.

Importantly, constructs of the self, such as self-esteem and self-efficacy, can be viewed both as a global construct and as domain-specific. For example, domains include academic, social, physical, and emotional, within which are even more specific contexts (ability in math, science, baseball, giving a speech), and an individual’s sense of competency in these different areas depends on their prior experience. Some theorists suggest that exercise more tangibly improves physical self-efficacy, whereby these improvements do not easily generalize to improvements in global self-esteem or self-efficacy. While early research suggested minimal global changes in self-esteem following exercise, these two studies of coping efficacy highlight that improvements in self-efficacy are not entirely domain specific.

(Sonstroem & Morgan, 1989)

A meta-analysis by Spence, McGannon, and Poon (2005) lended support to the mastery hypothesis by revealing small but significant improvements in global self-esteem (effect size d = 0.23) following exercise interventions. Importantly, the effect was larger (d = 0.32) when physical fitness improved, suggesting that tangible improvements in fitness, which are probably more likely to improve physical self-efficacy, are key to improving global self-efficacy.

It may be that certain forms of exercise, such as weightlifting, running, and climbing, are particularly effective in promoting mastery because they provide objective feedback on progress. Measurable achievements reinforce the relationship between effort and reward, engaging dopaminergic pathways and further motivating continued participation.

Exercise as a Form of Behavioral ActivationThis ties closely to behavioral activation, a therapeutic approach of CBT that encourages engagement in structured, goal-directed activities to counteract the passivity and withdrawal characteristic of depression. Behavioral activation posits that progressively increasing participation in rewarding and meaningful activities provides opportunities for positive reinforcement and habit formation, which can improve mood and disrupt maladaptive cognitive patterns. Surprisingly, there has been only one study published on using exercise as an augment to behavioral activation.

Szuhany and Otto (2020) conducted a randomized pilot trial examining the effects of augmenting behavioral activation with exercise versus stretching in 31 sedentary adults with MDD. Participants completed nine sessions of BA over 12 weeks and were randomized to an additional 30-minute exercise or stretching component immediately following each session.

The exercise group was also encouraged to engage in moderate-intensity aerobic exercise (e.g., brisk walking, cycling) on their own for a total of 150 minutes per week. The stretching group performed light stretching or yoga to control for non-aerobic movement.

Both groups demonstrated significant improvements in depressive symptoms (MADRS: d=1.19; BDI-II: d=1.16), functional impairment (d=0.87), and quality of life (d=1.06) over the course of treatment. However, the exercise group showed greater improvements in perceived stress and distress intolerance, with medium-to-large effect sizes (d ≈ 0.70–1.01). Participants who engaged in more exercise (regardless of group assignment) experienced faster and larger reductions in depressive symptoms.

While the literature describing the psychological mechanism of exercise’s antidepressant effects is limited, there is plenty of reason to believe exercise can be used as a tool to challenge a patient’s understanding of themselves in a way that compliments therapy.

How To Prescribe Exercise For Depression: A Practical Guide For Clinicians (Zhou et al., 2024)Components of an Effective Physical Activity Prescription for Mental Health Prescribing physical activity involves more than simply encouraging patients to “be active.” Similar to the low adherence rates observed with psychiatric medications—where the CATIE study reported discontinuation rates as high as 74% within 18 months (Swartz et al., 2007) —we must approach physical activity recommendations utilizing an empathic and understanding approach. Building a collaborative alliance around shared goals is essential for increasing engagement. Like medication adherence, developing PA habits takes time, and patience is key to success. It can take a similar approach that a physician uses to prescribe a medication, which often includes dose, frequency, and route of administration. For PA, a structured approach based on the FITT framework—Frequency, Intensity, Time, and Type—ensures that PA is both effective and sustainable.

Frequency—how often one is participating in PA. For optimal outcomes, patients should participate in PA three to five times per week. Regular, consistent activity is key to maximizing the antidepressant effects. For patients unfamiliar with PA or who struggle with motivation, reducing sedentary behaviors (e.g., sitting, watching TV, using a computer) or aiming for even lower PA frequency, such as once a week, can still provide benefits and serve as a starting point. Ultimately, any PA is better than none.

Intensity—How Much Energy is Expended During PA. The “talk test” is a practical way for patients to measure PA intensity, which is separated into three groups: (1) low intensity (you can talk and sing during the activity), (2) moderate intensity (you can talk but not sing during the activity), and (3) vigorous intensity (you cannot say more than a few words during the activity). Moderate- to vigorous-intensity PA is recommended for treating depression in adults. However, the patient’s baseline fitness level and preferences help to determine the initial plan. Additionally, intensity influences affect during physical activity (PA) and plays a key role in planning. For individuals with severe depressive symptoms or older adults, starting with low-intensity activities like walking or yoga may be more suitable and still provide mental health benefits. As patients become more comfortable with PA, they can gradually increase the intensity.

Time—how long PA sessions are. Sessions of 45 to 60 minutes are most effective for improving mood and reducing depressive symptoms. However, shorter durations—such as 10- to 30-minute bouts—can still provide meaningful benefits. The emphasis should be on starting with manageable/realistic goals and gradually increasing the duration as patients gain confidence.

Type—aerobic, resistance, or mind-body. All three PA types (and their combinations) have been shown to reduce depressive symptoms. Aerobic activities include walking, swimming, and cycling; resistance training activities include weightlifting or bodyweight exercises; while mind-body activities include yoga, tai chi, and qigong. As people with depression are characterized by strong affective responses, clinicians should encourage patients to select enjoyable activities, leading to greater adherence and long-term success.

Supervision and Support for Enhancing Exercise Benefits Supervised PA enhances adherence and amplifies the antidepressant effects of physical activity, particularly in the early stages. Structured group-based PA or individual sessions with an exercise professional, such as a kinesiologist or health coach, provide accountability and motivation, which are particularly important for individuals with depression, who may struggle with fatigue or low motivation. When supervision is not feasible, clinicians can recommend online exercise programs, fitness apps, or community resources that provide structure.

Social interaction during PA can further enhance its mental health benefits. Group activities or buddy systems can reduce feelings of isolation, which are common in depression (particularly among older individuals), and promote a sense of community. For patients who prefer individual activities, encouraging them to engage in outdoor PA may also boost mood and adherence, as exposure to nature has additional benefits for mental health (Bettmann et al., 2024).

Overcoming Barriers To Physical ActivityBarriers such as low energy, lack of motivation, low income, comorbidities, inexperience with PA, and time constraints are common among individuals with depression and can hinder engagement in PA. Particularly, green space availability is significantly lower in neighbourhoods with increased poverty, limiting access to outdoor physical activity. A scoping review identified these as key obstacles but also highlighted that social support and enjoyable activities can facilitate adherence. One useful strategy is the “commit 10” approach, where patients commit to just 10 minutes of PA, with the option to continue if they feel capable. Further, engaging in small bouts of activity (such as walking the stairs instead of taking the elevator) or setting daily step goals can make PA more feasible for those with limited time. Although these recommendations fall short of the optimal PA threshold according to the FITT framework, they provide manageable/realistic starting points that can reduce the psychological barriers to beginning a new activity, fostering positive associations with PA for patients.

Gradual progression in both the intensity and duration of PA is essential to prevent patients from feeling overwhelmed. Starting with small, achievable goals allows individuals to build confidence and gradually incorporate more PA into their routines. Clinicians can emphasize that any amount of physical activity (PA) is beneficial and that setbacks or missed sessions are not failures. It is important to maintain the therapeutic alliance when making recommendations, especially to avoid evoking feelings of shame if goals are not met. At the same time, motivational interviewing techniques can be used, where the clinician encourages the patient to express their reasons for change, reflects these reasons back to them, and emphasizes previous successful habits that supported adherence to change.

Patient Involvement in Decision-Making Enhances Exercise Adherence Involving patients in the decision-making process is crucial for long-term adherence. Patients are likely to be more motivated and maintain a PA plan when they have a say in their activity–inventory patient preferences, whether they enjoy indoor or outdoor activities, and whether they prefer activities alone or in groups.

Flexibility in Exercise Regimen Supports Adherence Approaching physical activity (PA) for depression with flexibility is important. Patients with depression often experience fluctuations in mood and energy levels, and rigid activity goals may not always be achievable. Clinicians can encourage patients to view PA as a flexible, adaptive process and remind them that even small amounts provide benefits. This approach helps foster a positive mindset toward PA, supporting long-term adherence.

ConclusionDepression is a complex mental illness with devastating impacts. As such, it is vital for clinicians to consider and utilize all available treatment approaches. Exercise stands out as a unique and evidence-based intervention that addresses both mental and physical health needs simultaneously. As highlighted in today’s episode, research demonstrates that exercise is effective both as a standalone treatment and in conjunction with antidepressant medications and psychotherapy.

When prescribing exercise, clinicians should prioritize aerobic and resistance exercises, which are associated with the best outcomes. Moreover, an optimal exercise dose is approximately 860 MET-minutes/week (e.g., 245 minutes of walking or 140 minutes of moderate-intensity exercise). Tailoring exercise to the patient’s needs using the FITT framework (Frequency, Intensity, Time, and Type), flexibility in exercise regimens, supervised exercise programs, and strategies like the “commit 10” approach can further enhance adherence and long-term success. Ultimately, by integrating exercise into a patient’s treatment regimen for depression, clinicians can promote an effective, patient-centered approach to psychiatric care that has broad benefits for both mind and body.

Previous Episodes To Explore: Sensorium Part 3: Exercise as a Prescription for Depression, Anxiety, Chronic Stress (like Diabetes) and Sensorium (episode 010): Exercise, especially strength training, improves cognitive function, mental health, and overall resilience. It reduces depressive symptoms, enhances brain plasticity, lowers the risk of dementia, and counteracts stress while also improving physical health markers like muscle strength, insulin sensitivity, and cardiovascular health. High-intensity training shows particularly strong benefits for mood, vitality, and cognitive function. * Performance Enhancement with Dr. MaryEllen Eller (episode 012): A discussion about the benefits of learning how to consciously modulate your internal sympathetic state as the key to unlocking optimal performance. * Prescribing Strength Training for Depression (episode 018): A discussion about how strength training can decrease depression and help people deal with anger and develop confidence and assertiveness. Resources are provided to help formulate a simple strength training program. * The Best Exercise Program For Depression (episode 096): A review of recent studies on strength training, exercise, and depression, highlighting the effectiveness of strength training both as a treatment for depression and as a protective measure against its onset. Also discussed: how aerobic training compares with high-intensity interval training (HIIT) in addressing depressive symptoms and practical ways to incorporate these findings into clinical practice. * Exercise as a Drug for Mental Health and Longevity (episode 142): Dr. Puder speaks with Dr. Stephen Seiler about the connection between mental health and physical activity. Physical activity has been shown to reduce stress reactivity and reduce all cause mortality. Physical activity also results in decreased psychosocial stress. * Exercise for the Brain (episode 165): A deep dive into the pathophysiology behind positive effects of exercise and the concept of contracting skeletal muscle behaving as an endocrine organ. * Exercise & Mental Health 2023 Update (episode 179): An in depth discussion on the extensive research available on the benefits of exercise for the brain and pathophysiology as it pertains to dementia, skeletal muscle mass, exercise as a mental health treatment, and cardiorespiratory fitness and its relationship to all-cause mortality. * 5 Factors and Domains of Psychiatric Care* (episode 207): The 5-factor approach to holistic, patient-centered psychiatric care recognizes each individual’s unique physiological and psychological makeup. It focuses on four modifiable environmental factors—therapy, sleep, activity, and nutrition—to enhance well-being, with the option of adding medication as a fifth factor.

References:Bandura, A. (1977). Self-efficacy: Toward a unifying theory of behavioral change. Psychological Review, 84(2), 191–215. https://doi.org/10.1037/0033-295X.84.2.19 1

Bell, J. A., Kivimäki, M., Bullmore, E. T., Steptoe, A., MRC ImmunoPsychiatry Consortium, & Carvalho, L. A. (2017). Repeated exposure to systemic inflammation and risk of new depressive symptoms among older adults. Transl Psychiatry 7, e1208. https://doi.org/10.1038/tp.2017.155

Berk, M., Köhler-Forsberg, O., Turner, M., Penninx, B.W.J.H., Wrobel, A., Firth, J., Loughman, A., Reavley, N.J., McGrath, J.J., Momen, N.C., Plana-Ripoll, O., O'Neil, A., Siskind, D., Williams, L.J., Carvalho, A.F., Schmaal, L., Walker, A.J., Dean, O., Walder, K., Berk, L., Dodd, S., Yung, A.R., & Marx, W. (2023). Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management. World Psychiatry, 22: 366-387. https://doi.org/10.1002/wps.21110

Bettmann, J. E., Speelman, E., Blumenthal, E., Couch, S., & Schmalz, D. L. (2024). Nature Exposure, Even as Little as 10 Minutes, is Likely to Yield Short-Term Benefits for Adults with Mental Illness: A Meta Analysis. Ecopsychology. https://doi.org/10.1089/eco.2023.0063

Bernstein, C. M., Stockwell, M. S., Gallagher, M. P., Rosenthal, S. L., & Soren, K. (2013). Mental health issues in adolescents and young adults with type 1 diabetes: prevalence and impact on glycemic control. Clinical pediatrics, 52(1), 10–15. https://doi.org/10.1177/0009922812459950

Corathers, S. D., Kichler, J., Jones, N. H., Houchen, A., Jolly, M., Morwessel, N., Crawford, P., Dolan, L. M., & Hood, K. K. (2013). Improving depression screening for adolescents with type 1 diabetes. Pediatrics, 132(5), e1395–e1402. https://doi.org/10.1542/peds.2013-0681

Corey-Lisle, P. K., Nash, R., Stang, P., Swindle, R. (2004). Response, Partial Response, and Nonresponse in Primary Care Treatment of Depression. Arch Intern Med. 164(11):1197–1204. https://doi:10.1001/archinte.164.11.1197

Craft, L. L. (2005). Exercise and clinical depression: Examining two psychological mechanisms. Psychology of Sport and Exercise, 6(2), 151–171. https://doi.org/10.1016/j.psychsport.2003.11.003

Ecker, U. K. H., Lewandowsky, S., Chang, E. P., & Pillai, R. (2014). The effects of subtle misinformation in news headlines. Journal of Experimental Psychology: Applied, 20(4), 323–335. https://doi.org/10.1037/xap0000028

Fabiano, N., Puder, D., & Stubbs, B. (2024). The Evidence Is Clear, Exercise Is Not Better Than Antidepressants or Therapy: It Is Crucial to Communicate Science Honestly. Journal of Physical Activity and Health (published online ahead of print 2024). Retrieved Dec. 13, 2024, from https://doi.org/10.1123/jpah.2024-0743

Gourgouvelis, J., Yielder, P., Clarke, S. T., Behbahani, H., & Murphy, B. A. (2018). Exercise leads to better clinical outcomes in those receiving medication plus cognitive behavioral therapy for major depressive disorder. Frontiers in Psychiatry, 9. https://doi.org/10.3389/fpsyt.2018.00037

Hallgren, M., Helgadóttir, B., Herring, M. P., Zeebari, Z., Lindefors, N., Kaldo, V., Öjehagen, A., & Forsell, Y. (2016). Exercise and internet-based cognitive–behavioural therapy for depression: multicentre randomised controlled trial with 12-month follow-up. British Journal of Psychiatry, 209(5), 414–420. doi:10.1192/bjp.bp.115.177576

Harris, A. H., Cronkite, R., & Moos, R. (2006). Physical activity, exercise coping, and depression in a 10-year cohort study of depressed patients. Journal of affective disorders, 93(1-3), 79–85. https://doi.org/10.1016/j.jad.2006.02.013

Heissel, A., Teismann, T., Kahl, K. G., Puschmann, A. K., Sutter, L., Schuch, F. B., Stubbs, B., & Vancampfort, D. (2023). Exercise as medicine for depressive symptoms? A systematic review and meta-analysis with meta-regression. British Journal of Sports Medicine, 57(16), 1049–1057. https://doi.org/10.1136/bjsports-2022-106282

Hird, E.J., Slanina-Davies, A., Lewis, G. Hamer, M., & Rosier, J. P. (2024). From movement to motivation: a proposed framework to understand the antidepressant effect of exercise. Transl Psychiatry 14, 273. https://doi.org/10.1038/s41398-024-02922-y

Huang, Y., Li, L., Gan, Y., Wang, C., Jiang, H., Cao, S., & Lu, Z. (2020). Sedentary behaviors and risk of depression: a meta-analysis of prospective studies. Translational psychiatry, 10(1), 26. https://doi.org/10.1038/s41398-020-0715-z

Lam, R. W., Kennedy, S. H., Adams, C., Bahji, A., Beaulieu, S., Bhat, V., Blier, P., Blumberger, D. M., Brietzke, E., Chakrabarty, T., Do, A., Frey, B. N., Giacobbe, P., Gratzer, D., Grigoriadis, S., Habert, J., Ishrat Husain, M., Ismail, Z., McGirr, A., McIntyre, R. S., … Milev, R. V. (2024). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults: Réseau canadien pour les traitements de l'humeur et de l'anxiété (CANMAT) 2023 : Mise à jour des lignes directrices cliniques pour la prise en charge du trouble dépressif majeur chez les adultes. Canadian journal of psychiatry. Revue canadienne de psychiatrie, 69(9), 641–687. https://doi.org/10.1177/07067437241245384

Massengale J. (2005). Depression and the adolescent with type 1 diabetes: the covert comorbidity. Issues in mental health nursing, 26(2), 137–148. https://doi.org/10.1080/01612840590901590

Montesano, A., Feixas, G., Caspar, F., & Winter, D. (2017). Depression and identity: Are self-constructions negative or conflictual? Frontiers in Psychology, 8, 877. https://doi.org/10.3389/fpsyg.2017.00877

Noetel, M., Sanders, T., Gallardo-Gómez, D., Taylor, P., del Pozo Cruz, B., van den Hoek, D., Smith, J. J., Mahoney, J., Spathis, J., Moresi, M., Pagano, R., Pagano, L., Vasconcellos, R., Arnott, H., Varley, B., Parker, P., Biddle, S., & Lonsdale, C. (2024). Effect of exercise for depression: systematic review and network meta-analysis of randomised controlled trials BMJ, 384:e075847. https://doi.org/10.1136/bmj-2023-075847

Oudbier, S. J., Goh, J., Looijaard, S. M. L. M., Reijnierse, E. M., Meskers, C. G. M., & Maier, A. B. (2022). Pathophysiological Mechanisms Explaining the Association Between Low Skeletal Muscle Mass and Cognitive Function. The journals of gerontology. Series A, Biological sciences and medical sciences, 77(10), 1959–1968. https://doi.org/10.1093/gerona/glac121

Puder, D. (Host). (2018, March 22). Sensorium Part 3: Exercise as a Prescription for Depression, Anxiety, Chronic Stress (like Diabetes) and Sensorium (No. 10) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-10-sensorium-part-3-exercise-as-a-prescription-for-depression-anxiety-chronic-stress

Puder, D. (Host). (2018, April 16). Performance Enhancement with Dr. MaryEllen Eller (No. 12) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/performance-enhancement-breathing-maryellen-eller?rq=012

Puder, D. (Host). (2018, May 18). Prescribing Strength Training for Depression (No. 18) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/prescribing-strength-training-depression-treatment

Puder, D. (Host). (2020, Sept. 30). The Best Exercise Program For Depression (No. 96) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/the-best-exercise-program-for-depression

Puder, D. (Host). (2022, March 15). Exercise as a Drug for Mental Health and Longevity(No. 142) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-142-exercise-as-a-drug-for-mental-health-and-longevity

Puder, D. (Host). (2022, Dec. 9). Exercise for the Brain (No. 165) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-165-exercise-for-the-brain

Puder, D. (Host). (2023, May 12). Exercise & Mental Health 2023 Update (No. 179) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-179-exercise-amp-mental-health-2023-update

Puder, D. (Host). (2024, May 4). 5 Factors and Domains of Psychiatric Care (No. 207) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection.https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-207-5-factors-and-domains-of-psychiatric-care?rq=207

Recchia, F., Leung, C. K., Chin, E. C., Fong, D. Y., Montero, D., Cheng, C. P., Yau, S. Y., & Siu, P. M. (2022). Comparative effectiveness of exercise, antidepressants, and their combination in treating non-severe depression: A systematic review and network meta-analysis of randomised controlled trials. British Journal of Sports Medicine, 56(23), 1375–1380. https://doi.org/10.1136/bjsports-2022-105964

Sabe, M., Chen, C., Sentissi, O., Deenik, J., Vancampfort, D., Firth, J., Smith, L., Stubbs, B., Rosenbaum, S., Schuch, F. B., & Solmi, M. (2022). Thirty years of research on physical activity, mental health, and wellbeing: A scientometric analysis of hotspots and trends. Frontiers in Public Health, 10. https://doi.org/10.3389/fpubh.2022.943435

Sansone, R. A., & Sansone, L. A. (2012). Antidepressant adherence: are patients taking their medications?. Innovations in clinical neuroscience, 9(5-6), 41–46. https://pmc.ncbi.nlm.nih.gov/articles/PMC3398686/

Santos, F. R., Sigulem, D., Areco, K. C., Gabbay, M. A., Dib, S. A., & Bernardo, V. (2015). Hope matters to the glycemic control of adolescents and young adults with type 1 diabetes. Journal of health psychology, 20(5), 681–689. https://doi.org/10.1177/1359105315573429

Singh, B., Maher, C., & Brinsley, J. (2023a, March 1). Exercise is even more effective than counselling or medication for depression. But how much do you need? The Guardian.Retrieved from https://www.theguardian.com/lifeandstyle/2023/mar/02/exercise-is-even-more-effective-than-counselling-or-medication-for-depression-but-how-much-do-you-need

Singh, B., Olds, T., Curtis, R., Dumuid, D., Virgara, R., Watson, A., Szeto, K., O’Connor, E., Eglitis, E., Ferguson, T., Miatke, A., Simpson, C. E. M., Maher, C. (2023b).Effectiveness of physical activity interventions for improving depression, anxiety and distress: an overview of systematic reviews. British Journal of Sports Medicine, 57,1203-1209. https://doi.org/10.1136/bjsports-2022-106195

Sonstroem, R. J., & Morgan, W. P. (1989). Exercise and self-esteem: rationale and model. Medicine and science in sports and exercise, 21(3), 329–337. https://pubmed.ncbi.nlm.nih.gov/2659918/

Spence, J. C., McGannon, K. R., & Poon, P. (2005). The Effect of Exercise on Global Self-Esteem: A Quantitative Review. Journal of Sport and Exercise Psychology, 27(3), 311-334. Retrieved Dec 20, 2024, from https://doi.org/10.1123/jsep.27.3.311

Swartz, M. S., Perkins, D. O., Stroup, T. S., Davis, S. M., Capuano, G., Rosenheck, R. A., Reimherr, F., McGee, M. F., Keefe, R. S., McEvoy, J. P., Hsiao, J. K., Lieberman, J. A., & CATIE Investigators (2007). Effects of antipsychotic medications on psychosocial functioning in patients with chronic schizophrenia: findings from the NIMH CATIE study. The American journal of psychiatry, 164(3), 428–436. https://doi.org/10.1176/ajp.2007.164.3.428

Szuhany, K. L., & Otto, M. W. (2020). Efficacy evaluation of exercise as an augmentation strategy to brief behavioral activation treatment for depression: A randomized pilot trial. Cognitive Behaviour Therapy, 49(3), 228–241. https://doi.org/10.1080/16506073.2019.1641145

Tian, S., Liang, Z., Qui, F., Yu, Y., Wang, C., Zhang, M., & Wang, X. (2024). Optimal exercise modality and dose to improve depressive symptoms in adults with major depressive disorder: A systematic review and Bayesian model-based network meta-analysis of RCTs. Journal of Psychiatric Research, 176, 384–392. https://doi.org/10.1016/j.jpsychires.2024.06.031

Verhoeven, J. E., Han, L. K. M., Lever-van Milligen, B. A., Hu, M. X., Révész, D., Hoogendoorn, A. W., Batelaan, N. M., van Schaik, D. J. F., van Balkom, A. J. L. M., van Oppen, P., & Penninx, B. W. J. H. (2023). Antidepressants or running therapy: Comparing effects on mental and physical health in patients with depression and anxiety disorders. Journal of Affective Disorders, 329, 19–29. https://doi.org/10.1016/j.jad.2023.02.064

Wang, S.-M., Han, C., Bahk, W.-M., Lee, S.-J., Patkar, A. A., Masand, P. S., & Pae, C.-U. (2018). Addressing the side effects of contemporary antidepressant drugs: A comprehensive review. Chonnam Medical Journal, 54(2), 101–112. https://doi.org/10.4068/cmj.2018.54.2.101

Warburton, D. E. R., Nicol, C. W., & Bredin, S. S. D. (2006). Health benefits of physical activity: The evidence. CMAJ, 174(6), 801–809. https://doi.org/10.1503/cmaj.051351

Wegner, M., Helmich, I., Machado, S., Nardi, A. E., Arias-Carrion, O., & Budde, H. (2014). Effects of exercise on anxiety and depression disorders: review of meta- analyses and neurobiological mechanisms. CNS & neurological disorders drug targets, 13(6), 1002–1014. https://doi.org/10.2174/1871527313666140612102841

Zhou, C., Puder, D., & Fabiano, N. (2024). How to prescribe physical activity for depression. Sports Psychiatry, 0(0). https://doi.org/10.1024/2674-0052/a000099

View Details

By listening to this episode, you can earn 1.25 Psychiatry CME Credits.

Other Places to listen: iTunes, Spotify

Article Author: Stijn Vanheule, PhD

Podcast Host: David Puder, MD

Podcast guest: Stijn Vanheule, PhD

Stijn Vanheule, PhD, is a professor of clinical psychology and psychoanalysis at Ghent University (Belgium), where he chairs the Department of Psychoanalysis. He has published extensively on psychosis and other mental health-related topics, as well as Lacanian psychoanalysis. He is also a practicing psychoanalyst in Belgium. An overview of his publications, which include 7 monographs and 220 peer-reviewed papers in academic journals, can be found here.

In September of 2024, Other Press published my new book, Why Psychosis Is Not So Crazy. This nonfiction work is written for mental health care professionals, patients and their families, and anyone curious about psychosis, psychology, and creativity.

Why Psychosis Feels Strange—Yet Is More Common Than You ThinkThe idea of experiencing psychosis might seem abnormal and strange. However, I explore how psychosis-like experiences are more common than many might think. Research shows that about 15% of the general population has had short-lived or isolated psychosis-like experiences (Verdoux & van Os, 2002) , such as holding strong irrational beliefs, seeing a ghost, or witnessing paranormal phenomena (Monshouwer et al., 2023). For 7% of the population, these experiences can be classified as “psychotic,” (van Os & Reininghaus, 2016) and in 3% of cases (Perälä et al., 2007), the situation may become severe enough to require psychiatric intervention.

Challenging Stereotypes: The Real-Life Course of PsychosisWhen people think about psychosis, dramatic portrayals often dominate—decline, danger, and unpredictable behavior. But through my research and writing, I offer a different perspective. Evidence shows that most individuals who experience a psychotic episode recover well (van Os. et al., 2012). For example, 15% of cases involve one or two brief episodes with no lingering clinical symptoms. In 30% of cases, the course is episodic, with multiple episodes throughout life but no residual symptoms in between. Another 40% of cases are episodic as well, though with mild symptoms persisting between episodes. Only 15% of cases have a poor outcome, with ongoing symptoms and significant impairment.

Through this book, I hope to challenge misconceptions and provide a deeper understanding of psychosis—not as something to fear, but as an experience that can be understood, addressed, and often overcome. I argue that contemporary mental health care’s approach to psychotic experiences—as mere signs of illness that require management—is limited, because it overlooks their psychological meaning. Rooted in psychoanalysis, I suggest that psychotic symptoms are subjective expressions of serious existential challenges. The model discussed in Why Psychosis Is Not So Crazy connects psychosis to language use and the difficulties individuals face in interpreting life’s events within common-sense narratives.

How Our Minds Work: Primary-Process vs. Secondary-Process Thinking in PsychosisIn my view, psychotic outbreaks occur when common ways of making sense of reality break down, leading to discrete psychotic experiences. These experiences are subtle disturbances in a person’s sense of self and perception of reality, often causing confusion and disorientation. Unlike full-blown psychotic episodes, discrete psychotic experiences are more fragmented. They may manifest as trivial events demanding excessive attention, a loss of control over thoughts and language, strange bodily sensations, impulsive actions, or feelings of detachment from oneself. During these moments, narrative organization and a sense of agency are lost. Instead, consciousness becomes dominated by associative, primary-process thinking, which is experienced passively.

Freud described primary-process thinking as the fundamental mode of thought that operates at the level of unconscious mental functioning, characterized by a free and associative flow of ideas. It differs from secondary-process thinking, which is guided by logic, order, and rational connections, and governs conscious, waking thought. According to Freud, primary-process thinking becomes dominant in dream states and in conditions where the unconscious surfaces, such as during psychotic episodes. It organizes thoughts based on associative links, such as visual or auditory similarities, rather than logical connections. In these states, language and imagery connect freely, producing a surreal and often chaotic experience, much like the free association seen in dreams.

The book elaborates that during psychotic experiences, the dominance of primary-process thinking disrupts the coherence typically provided by secondary-process thinking, leading to a breakdown in logical structuring of thoughts. This results in bewilderment and despair. Hallucinations and delusions further intensify the process, adding a sense of intrusion: strange communications from the outside world seem to haunt the individual.

Breaking Points: Traumatic Events, Existential Struggles, and the Onset of PsychosisIn my view, psychotic experiences are deeply tied to how individuals confront challenging and disruptive events, as well as existential struggles. These experiences often arise when individuals face situations that destabilize their sense of reality. Traumatic events such as conflicts, losses, or major life transitions—like the birth of a child, relationship difficulties, unemployment, or the death of a loved one—can overwhelm a person’s ability to organize their thoughts coherently, resulting in psychotic episodes.

In these moments, the normal frameworks people rely on—such as language and narrative structures—can fail, leading to a collapse of the sense of self and reality. I suggest that when individuals cannot symbolically frame or comprehend these disruptive events, their experiences may become so intense and vivid that they overwhelm the mind, creating a chaotic and disorienting state. Furthermore, these psychotic experiences often express profound, subjective truths related to the existential challenges individuals are grappling with. In this sense, psychosis serves as a manifestation of the struggle to find meaning or stability in the face of life’s uncertainties and existential voids.

The Power of Empathic Listening: Supporting Individuals Through PsychosisTaking this into account, I emphasize the importance of a specific listening approach to help patients overcome these difficulties. A calm, receptive, and dialogical stance is crucial when engaging with individuals experiencing psychosis. I argue against displays of power or anxiety-driven reactions, as these only heighten fear and create distance. Instead, establishing a trusting and supportive environment is essential. Connecting through conversation helps the person articulate their concerns and experiences, enabling them to begin to re-establish their grip on reality.

This listening approach also involves accepting the fragmented and allusive nature of psychotic speech. Rather than dismissing these expressions as nonsensical, I encourage mental health professionals to approach delusions and hallucinations as symbolic references to the issues the person struggles to articulate coherently. Through this perspective, professionals can better support individuals in navigating their experiences and finding meaning amid the disorientation of psychosis.

On page 165, I characterize this as follows:

“If I look at a sculpture by Yayoi Kusama or step into the cinematic world of David Lynch, I do not fully understand everything that I am seeing. Even so, I am still captivated by their work. Their art stimulates new ideas and sensations that go beyond what I ordinarily experience. They take me out of my comfort zone and force me to view reality from a different perspective. This helps me (as it can help all of us) to escape from the force of habit. Art—and, in particular, “unpolished” art that is rough around the edges—gives expression to things we cannot say.

Psychoses have this same expressive status, with the difference that in a psychotic universe everything is wilder and more unbridled than in the creative work of an ordinary artist. And it is precisely there that the challenge is to be found. Like contemporary modern art, psychotic experiences stimulate dialogue and interaction. As soon as we are prepared to regard these experiences as expressive acts, we can come into meaningful contact with them—just as the visitor to an art gallery does with a sculpture or a cinema-goer does with a film. If we can do this, psychosis is no longer a defect, but rather an invitation to listen to a new language full of allusions and to be open to how someone deals with the groundlessness of his existence.”

The book argues that to help people recover from disruptive events and existential struggles in psychosis, mental health care should focus on creating supportive, inclusive, and dialogical environments. I emphasize the importance of not solely relying on medication, as it is not a cure and may not be effective for everyone. Instead, the focus should be on building meaningful connections and understanding the subjective nature of psychotic experiences​.

Key strategies include:

1. Fostering dialogue and connectedness: Mental health professionals should provide space for open dialogue, enabling individuals to express and work through their experiences. This involves engaging patients and their support networks (family, friends) in conversation to address the underlying social and emotional issues revealed during psychotic episodes​.
2. Creating safe and welcoming environments: Establishing safe, unforced environments where individuals can freely explore their experiences and interests is crucial.
3. Offering therapies that foster expression: Approaches that allow individuals to express their experiences creatively (e.g., art, music, storytelling) help in making sense of their psychotic episodes. Such methods are vital for reconnecting with reality and developing a coherent sense of self​.

In making the latter point, I refer to Annie Rogers, a psychoanalyst, clinical psychologist, and professor known for her work in the field of psychoanalysis and trauma, particularly focusing on the experiences of psychosis. She has integrated her own personal experiences with psychosis into her professional and academic work, offering insights into how individuals can navigate and make sense of psychotic experiences. Rogers emphasizes that overcoming psychosis involves finding a new language that resonates with the individual’s own voice and experiences. This process allows for the expression of previously unimaginable thoughts and feelings, creating a space where the illogical aspects of one’s experience can be articulated. In this way, aspects of primary-process thinking are articulated in terms of secondary-process thought. Rogers discovered her new language through psychoanalytic therapy, which provided her with the space to explore her experiences creatively.

However, Rogers suggests that not all primary-process thinking that occurs in the context of psychosis can be expressed in terms of secondary-process memories and narratives. In her view, a “nub of nonsense” will always remain present. This remainder also deserves expression, which can be achieved by playing with forms, images, or even sounds that match the associative nature of someone’s psychotic experiences. For example, she experimented with drawing, printmaking, poetry, and photography, embracing absurdity and whimsy. She used this approach to give expression to elements that remained elusive, accepting that some aspects of her experience would defy logical understanding yet still hold meaning in a symbolic or aesthetic sense.

Jung’s Path to Meaning: Using Creativity to Translate Psychosis into Psychological TheoryAnother example discussed in Why Psychosis Is Not So Crazy concerns Carl Jung, who began experiencing acute psychotic episodes shortly after his rupture with Sigmund Freud. Jung's relationship with Freud started as a promising partnership in advancing psychoanalytic theory but ultimately unraveled due to conflicting theoretical perspectives. Freud viewed Jung as a potential successor, partly because of Jung's respected academic background and non-Jewish identity, which Freud hoped could mitigate some of the anti-Semitism facing psychoanalysis. However, their differing views on the unconscious, sexuality, and spirituality created a divide, leading to a painful separation. This split left Jung in an existential crisis, during which he experienced psychotic episodes marked by powerful, often terrifying visions and auditory hallucinations. These psychotic experiences seemed to erupt as his mental anchors, previously supported by his friendship with Freud, were shaken.

Interestingly, in response to these disruptive experiences, Jung began making notes and drawings to document what he was going through, thus embarking on what he called a “spiritual journey” recorded in The Red Book, an illuminated manuscript blending calligraphic text, esoteric paintings, and mandalas. Jung saw this work as a personal myth-making process, helping him integrate and express his internal chaos. The manuscript includes symbols and imagery that reflect the depth of his visionary experiences. Over time, he translated these experiences into foundational concepts in psychology, such as the animus and anima, introversion and extraversion, and even the idea of a midlife crisis. By recording and reflecting on these visions, Jung managed to integrate the unconscious insights of his primary process into his conscious self through secondary-process thinking, thereby developing theories that bridged personal and collective unconscious elements.

Later in his life, Carl Jung began constructing Bollingen Tower on Lake Zürich—a small, medieval-inspired castle that he designed as a sanctuary for self-reflection and solitude. He saw the tower as a symbol of rebirth and a concrete expression of his psychic life, describing it as a representation of the maternal womb. In Why Psychosis Is Not So Crazy, I draw a parallel between Jung’s use of Bollingen Tower and Annie Rogers’s concept of working with what she calls the “nub of nonsense.” For both, this involves giving form and expression to elusive, illogical elements that resist conventional understanding. Jung’s Bollingen Tower became a personal sanctuary where he could immerse himself in mysticism, allowing primary-process thoughts—marked by symbolic and illogical elements—to exist within a structured physical space. Within the architectural confines of the tower, his “madness” found a safe realm for irrationality and self-expression.

Both Carl Jung and Annie Rogers employed creativity inspired by primary-process thinking not only as a personal outlet but also as a way to break through the isolation of their psychotic experiences and connect with a broader audience. Jung externalized his chaotic, symbolic visions through The Red Book and the construction of Bollingen Tower, translating his internal struggles into tangible, aesthetic forms. This creative process served as a bridge between his inner world and the external world, fostering connections with others who could see the psychological and spiritual value in his insights. Similarly, Annie Rogers used her art to transform her once-isolated experiences into something that could resonate with others. By sharing her work, she invited others to engage with and appreciate her subjective reality.

In both cases, their creative expressions became powerful mediums for building social connections, validating their psychotic experiences, and offering others a way to understand the misunderstood and deeply personal nature of psychosis. Through their work, they opened doors for audiences to explore the richness and complexity of psychotic experiences from a place of empathy and engagement.

Together, Jung’s and Rogers’s methods illustrate that therapeutic work with psychosis can benefit from embracing both primary and secondary process thinking. This dual approach allows patients to express and integrate their fragmented thoughts and experiences in a constructive way. By combining psychoanalytic therapy with active support for creative expression, patients can find coherence and meaning. This, in turn, reduces isolation and provides them with tools to reconnect with reality and others.

Holding Space for Complexity: The Power of Presence in Psychotherapy for PsychosisEffective therapeutic work with individuals suffering from psychosis also requires therapists who can skillfully manage both their own and their patients’ anxiety. This is crucial because psychotic experiences are often deeply overwhelming and disruptive—not only for the individuals experiencing them but also for those providing care. For therapists, this means maintaining a calm, composed presence that allows them to stay engaged and receptive without becoming overwhelmed by the chaos or fear that psychosis can provoke. Moreover, I believe therapists should approach psychotic experiences with creativity, exploring the meanings and paradoxes embedded in such episodes. By providing space for unconventional expressions—whether through symbols, metaphors, or other forms of primary-process thinking—therapists can help patients give voice to experiences and thoughts that might otherwise feel unmanageable.

This creative engagement enables patients to construct a narrative or symbolic language that bridges their fragmented internal experiences with a more coherent reality, paving the way toward recovery. In essence, this therapeutic approach requires flexibility, openness to the surreal and illogical, and a willingness to engage with each patient’s unique symbolic expressions. By doing so, psychotic experiences can be integrated constructively rather than suppressed, allowing for a healing process that respects the individual’s subjective reality.

To illustrate the importance of openness and flexibility in therapeutic work with patients suffering from psychosis, I discuss my therapeutic work with Mario in Why Psychosis Is Not So Crazy. Mario was a young man with Down syndrome who experienced severe psychotic episodes, which led him to withdraw almost entirely from his surroundings. Isolated in his attic room, Mario became locked in an imaginary world, engaging in conversations with an invisible companion. This disrupted his contact with reality and made it difficult for him to connect with those around him.

As a junior clinical psychologist at the time, I observed that a fruitful transference relationship with Mario was only possible when a genuine encounter occurred—one that was not obstructed by my own ego or ambitions:

“One rainy day, about three months after I started visiting him, I arrived at his house for a new session. Afterward, I was scheduled to attend an important meeting, and, with this in mind, I was wearing my best suit, hoping to make a good impression. With my thoughts already half on the meeting, I got out of my car and walked quickly up the garden path toward Mario’s front door, forgetting that this path was covered with moss that had now been made super slippery by the recent downpour. I felt my feet slowly sliding away from under me and, notwithstanding my best efforts to maintain my balance, soon found myself lying flat on my back in the grass, wet and spattered with mud! Mario had witnessed this whole unedifying episode from the loneliness of his attic room. As I struggled to get back to my feet, cursing my stupidity, he opened the front door and called out, “You okay?” Once I was finally inside, he disappeared for a few seconds and returned with a towel, which he pressed to my chest. “Here, clean yourself up.”

Suddenly, he was no longer the one with the problem: it was me! This turned out to be an important breakthrough. Many young professionals, which I was at that time, hold rigid views about their role as a professional. They strive to be seen as an expert and impose their own agenda onto their patients. Or, even worse, they want to be a savior or act as if they are the patient’s closest confidant. In my case, I probably tried to be the clever and heroic therapist who would achieve a breakthrough. However, to my surprise, significant changes were not achieved through my earnest efforts, but rather when I let go of my desire to be the hero and instead focused on being present and attentive for Mario.

Being present and attentive in the moment may sound easy but is very difficult. In daily life, we are often preoccupied with our own thoughts and miss what others are saying. However, if therapists remain deaf like this, they make a serious mistake. Regardless of their level of education or professional experience, all mental health care workers have blind spots they should be aware of. It is part of their job to examine their own attitudes and behaviors. Through discussing this event with my own psychoanalyst, I came to realize that the secret fantasy of being the smart savior was one of my blind spots. It was only by recognizing and acknowledging the caricature of the savior in myself that I was able to let it go.

(…) A key lesson I have learned is that to be effective as a therapist, one must set aside any personal agenda and strive to be fully receptive to what patients are expressing, both verbally and through their symptomatic behaviors. Understanding these expressions can be difficult, as speech may be chaotic, patients’ experiences may be far from reality, and silences can be overwhelming. While this can be frustrating, it becomes less so when you accept that it is inherently difficult to truly comprehend the subtle meanings another person is communicating. Even with detailed attention to an individual’s problems, a missing link will always be present in our understanding. It is by accepting this lack and taking it as our starting point that a true encounter is possible.”

References:Jung, C. G. (2009). The Red Book: Liber Novus (S. Shamdasani, Ed., M. Kyburz, J. Peck, & S. Shamdasani, Trans.). W. W. Norton & Company.

Monshouwer, K., ten Have, M., Tuithof, M., van Dorsselaer, S., Bak, M., Gunter, N., Delespaul, P., van Os, J., & de Graaf, R. (2023). Prevalence, incidence, and persistence of psychotic experiences in the general population: Results of a 9-year follow-up study. Psychological Medicine, 53(8), 3750-3761. DOI: https://doi.org/10.1017/s0033291722002690

Perälä, J., Suvisaari, J., Saarni, S. I., Kuoppasalmi, K., Isometsä, E., Pirkola, S., Partonen, T., Tuulio-Henriksson, A., Hintikka, J., Kieseppä, T., Härkänen, T., Koskinen, S., & Lönnqvist, J. (2007). Lifetime prevalence of psychotic and bipolar I disorders in a general population. Archives of General Psychiatry, 64(1), 19-28. DOI: https://doi.org/10.1001/archpsyc.64.1.19

Vanheule, S. (2024). Why psychosis is not so crazy: A road map to hope and recovery for families and caregivers. Other Press.

van Os, J., & Reininghaus, U. (2016). Psychosis as a transdiagnostic and extended phenotype in the general population. World Psychiatry, 15(2), 118-124. DOI: https://doi.org/10.1002/wps.20310

van Os, J., Murray, R. M., & First, M. B. (2012). Course and outcome of schizophrenia. In J. A. Lieberman & R. M. Murray (Eds.), Comprehensive care of schizophrenia: A textbook of clinical management (2nd ed., pp. 1–16). Oxford University Press.

Verdoux, H., & van Os, J. (2002). Psychotic symptoms in non-clinical populations and the continuum of psychosis. Schizophrenia Research, 54(1–2), 59-65. DOI: https://doi.org/10.1016/s0920-9964(01)00352-8

View Details

Writers: Al-Baab Khan, Liam Browning, Joanie Burns DNP, Christopher Campbell, David Puder, M.D.

Audio Episode Host: David Puder, MD

Audio Episode Guest: Fred Penzel, PhD

Corresponding author: David Puder, MD

By listening to this episode, you can earn 1.25 Psychiatry CME Credits.

Other Places to listen: iTunes, Spotify

Date Published: 12/6/2024

In today’s episode, we have the pleasure of talking once again with one of the preeminent OCD experts, Dr. Fred Penzel, who brings over 43 years of experience in treating OCD. Early in his career, Dr. Penzel had a professor say that OCD was simply “too hard to treat.” This challenge motivated Dr. Penzel to dedicate a significant portion of his career to finding effective solutions for treating OCD. In this episode, we will explore the nuances of OCD and the treatment approaches that prove most effective. In previous episodes, we have explored additional aspects of OCD, including a general overview (episode 119), psychotherapy for OCD (episode 126), and the immune-related obsessive-compulsive symptoms associated with PANS and PANDAS (episode 147). We encourage listeners to visit or revisit our prior episodes for additional detail and context on this complex subject. By listening, you’ll not only gain valuable clinical insights but also have the opportunity to earn 1.25 psychiatry CME credits to advance your professional development in mental healthcare.

Introduction To Obsessive-Compulsive Disorder (OCD) Obsessive-compulsive disorder (OCD) is a complex and often debilitating condition, defined by intrusive thoughts and repetitive behaviors that vary widely in severity. OCD affects approximately 1.2% of adults in the United States annually and has an overall lifetime prevalence of 2.3% (National Institute of Mental Health, 2023). Notably, the average age of onset is approximately 19 years old, with up to one third of patients first experiencing symptoms in childhood (Anxiety and Depression Association of America, 2022).

Clinical Definition of Obsessions and Compulsions Obsessions:1. Intrusive, persistent thoughts, images, or urges that are experienced as distressing or unwanted, often eliciting significant anxiety or emotional discomfort. 2. These thoughts or impulses are resisted or managed through avoidance, suppression, or engagement in compensatory actions (e.g., compulsions).

Compulsions:1. Repeated actions (e.g., excessive cleaning, checking, or organizing) or mental rituals (e.g., counting, repeating phrases, praying) performed to neutralize obsessions and/or accompanying anxiety, or adhere to strict internal rules. 2. These behaviors aim to alleviate emotional distress or prevent feared outcomes, but are typically excessive or disconnected from the perceived threat.

Clinical Significance:* Obsessions and/or compulsions are disruptive enough to occupy over an hour per day or significantly impair functioning across social, professional, or personal domains. * The presenting symptoms cannot be fully accounted for by another psychiatric condition, ensuring accurate differential diagnosis.

The above definitions and clinical significance of OCD are drawn from the DSM-V (APA, 2013) and the Substance Abuse and Mental Health Services Administration (SAMHSA, 2016).

How OCD Turns Doubt Into An ObsessionObsessive-compulsive disorder is often termed the “doubting disease” due to its hallmark feature: an inability to tolerate uncertainty, resulting in repetitive obsessions and compulsions. These behaviors stem from the brain’s misinterpretation of fear signals and a disrupted confidence in memory and decision making. While OCD sufferers generally exhibit intact cognitive abilities, their excessive need for certainty drives compulsive behaviors that aim to mitigate perceived threats, but paradoxically intensify anxiety over time (Grant & Chamberlain, 2023; Song et al., 2022). As Dr. Fred Penzel describes, “Doubt is the central characteristic of OCD—it is what sets the disorder apart from everyday anxiety. OCD sufferers cannot accept even a reasonable degree of certainty in their lives.”

Breaking The OCD Cycle: Stop The CompulsionsDr. Penzel explains that in OCD, compulsions are performed to alleviate the anxiety caused by obsessions. Therefore, effective treatment focuses on stopping compulsions, which, over time, diminishes the intensity and frequency of the obsessions themselves.

There is a common misunderstanding among patients and providers that the obsession itself is the primary problem, leading to the belief that eliminating obsessive thoughts will reduce anxiety and stop compulsive behaviors. In reality, compulsions occur because the individual feels compelled to act on the obsession in an attempt to gain certainty or relief (e.g., a patient may have an intrusive thought that they forgot to lock their front door, triggering a compulsion to repeatedly check the lock). However, this cycle fails to provide the desired certainty or relief and instead strengthens both the compulsion and the obsession over time.

Performing the compulsion directly reinforces the behavior by providing temporary relief from the anxiety caused by the obsession. This relief serves as negative reinforcement, making it more likely that the compulsion will be repeated in the future. Simultaneously, acting on the compulsion indirectly reinforces the obsession by validating its perceived importance or danger, keeping it prominent in the individual’s mind.

The goal of OCD treatment is not to eliminate the obsession. Instead, it is to help the patient tolerate the discomfort and anxiety caused by intrusive thoughts without resorting to compulsive behaviors. By resisting compulsions, the patient can break the reinforcement cycle that sustains both the compulsions and the obsessions. Over time, they will learn that these intrusive thoughts naturally subside without intervention.

This process of habituation, fundamental to exposure and response prevention (ERP) therapy, requires repeated exposure to distressing thoughts while refraining from compulsive responses. It is not something a patient can simply “think themselves out of”; rather, it is akin to training a muscle. OCD can be conceptualized as a disorder of deeply entrenched habits, and overcoming it takes time, consistent practice, and the willingness to endure discomfort in order to build healthier, more adaptive responses.

The Role Of Ambiguity In OCD One specific feature of OCD is that obsessions can manifest from even the most ambiguous situations. For example, Dr. Penzel describes a driver obsessing about having killed someone on the road. A speed bump, which triggered the intrusive thought, can create an obsessive-compulsive cycle resulting in the driver going back to the speed bump, checking the roads, calling hospitals, and watching the news to seek certainty that they did not hit anyone. The individual may even avoid driving cars to prevent making the obsession a reality.

Although thoughts associated with safely operating a vehicle and staying vigilant are appropriate, one of the distinctions between appropriate behavior and OCD lies in the ambiguity of the trigger. A speed bump to the average driver, through context cues and reassurance, may not cause much concern. A speed bump to a driver with OCD would trigger a cycle of doubt and uncertainty that will never be resolved (see also Driven To Distraction: “Hit And Run OCD”).

“The problem with OCD lies not in the content of the obsession, but in how the brain misinterprets these thoughts as dangerous, necessitating action.”

-Penzel, 2019

Pathway To OCD RecoveryFirst Steps for OCD TherapyWhen considering the hallmarks of good therapy, Dr. Penzel demonstrates that the first step in OCD treatment is psychoeducation, where he teaches patients about the nature of OCD, what to expect from the illness, and why certain treatment methods are required to get better. This is critical as it encourages patients to be partners in their treatment.

The psychoeducation component of treatment is supplemented with Dr. Penzel’s article 25 Tips for Succeeding with OCD Treatment, which provides key principles of understanding OCD and the treatment path. This guide offers clinicians and patients the same information to start their therapy, keeping the standard of care consistent and reliable. Although the guide shares many critical tips for starting, succeeding, and maintaining OCD treatment, a few of the key tips are highlighted below that are especially important for reshaping the philosophical basis of the disorder.

1. Try not to be a black-and-white, all-or-nothing thinker.
2. When you have a choice, always go toward the anxiety, never away from it.
3. Don’t be sidetracked by perfectionism.
4. It is sometimes possible for OCD to try to make you doubtful about your homework.
5. Overall, never forget that OCD is very paradoxical and rarely makes much sense.
6. When faced with two possible choices of what to confront, choose the more difficult of the two whenever possible.
7. When faced with a challenging assignment or an unexpected challenging situation, try to look at it as a positive.
8. Remember that in OCD, the problem is not the anxiety—the problem is the compulsions.
9. Give your homework your full attention, focus on what you are doing, and let yourself feel the anxiety.

These tips address the reality of OCD while providing meaningful insights on how to manage challenges in treatment objectively without creating opportunities to regress.

OCD Homework for Effective TreatmentThese three homework assignments listed below aim to desensitize the patient to the anxiety, control their compulsions, and instill a sense of trust in themselves.

1. Gradually agree with the obsessive thought.
2. Sit with the anxiety of the obsessive thought without analyzing it or acting on it.
3. Refrain from seeking reassurance for the obsessive thought.

The foundation for this homework is in guiding OCD patients to agree with their obsessive thoughts, and to do so gradually so as to not push the patient too far past their comfort zone. Gradual acceptance of the intrusive thought, from acknowledging the presence of the obsession in the periphery to fully agreeing with the obsession for oneself, paves the path to desensitization that is integral for the rest of treatment. For example, if a patient fears that they would kill a civilian while driving, therapy would begin by helping the patient to progressively accept the following thoughts:

1. People in this world have killed others while driving.
2. Some people around me have killed others in car accidents.
3. It is possible that I could kill someone while driving.
4. I likely have killed someone while driving.
5. I have killed someone while driving.

By agreeing with the obsessions gradually, patients are able to tolerate the discomfort at each step and work towards breaking the cycle of compulsion when not acting on the anxiety.

In addition to accepting the obsession, it is arguable that the most crucial component of treatment is not providing reassurance. Reassurance can reinforce the obsession by challenging the doubt, thus encouraging the individual to act compulsively, thereby fueling the cycle. Dr. Penzel emphasizes that his patients and their loved ones refrain from reassurance—even from the therapist—as they navigate treatment.

Effective OCD Treatments & PhilosophyExposure and Response Prevention (ERP)ERP remains a cornerstone of OCD treatment. As Dr. Penzel has noted, “You can’t fight OCD with logic, because OCD isn’t logical. It’s emotional.” ERP aligns with this principle by focusing on retraining the brain’s response to distressing stimuli. To achieve this, ERP guides patients to confront their fears without engaging in compulsions. The goal is not to satisfy the obsession, but rather teach patients how to live with their thoughts and uncertainty.

Efficacy of ERP Therapy:Meta-analyses show that ERP results in significant symptom reduction for 60-70% of patients, with effects often sustained long after treatment. ERP is effective across many OCD subtypes, including contamination, harm-related, and existential OCD (Ferrando & Selai, 2021; Song et al., 2022).

Furthermore, ERP is considered widely applicable to various patient populations and settings (Hezel & Simpson, 2019). This speaks to its ability to be effective in both highly structured and real world environments, which makes it ideal for the majority of patients.

Supplementing ERP with additional therapies can also prove beneficial for some individuals in OCD treatment. For example, One study found that this combination led to greater symptom reduction across all main presentations of OCD, with patients achieving clinically significant improvements compared to ERP alone (Rector et al., 2018). Additionally, a review by Hezel and Simpson (2019) saw that patients who took medication (e.g., d-cycloserine) before starting ERP experienced a faster rate of symptom improvement in the first few weeks of therapy.

Cognitive RestructuringCognitive restructuring is a core component of cognitive behavioral therapy and can be used to help patients identify negative thought patterns and replace them with more realistic or positive ones. Cognitive restructuring, when used alongside ERP, helps address the distorted beliefs that drive obsessions. A major focus of this is on Thought-Action Fusion (TAF):

• Likelihood Thought-Action Fusion: The belief that thinking about an event increases its probability.
• Moral Thought-Action Fusion: The belief that having a thought is morally equivalent to acting on it.

“OCD’s distortions often involve an exaggerated sense of responsibility and moral accountability. Cognitive therapy helps patients understand that thoughts do not equal actions” (Penzel, 2000).

For example, someone with violent intrusive thoughts might believe they are at risk of harming others simply because the thought occurred. Restructuring these beliefs—by identifying and challenging their validity—has shown to reduce obsessional thinking (Van Noppen et al., 2021).

Embracing UncertaintyFor individuals with OCD, the obsession with finding certainty is not the solution, but the very trap that keeps them stuck. Treatment strategies focus on breaking this cycle by embracing uncertainty rather than eliminating it.

1. Agreeing with intrusions: Techniques like leaning into feared outcomes, as Penzel advocates, encourage patients to make peace with uncertainty. For instance, a patient with moral obsessions might practice affirmations like, “Maybe I am bad, and that’s okay,” as part of their therapy.
2. Sitting with doubt: Sitting with the bodily sensation of anxiety is critical to desensitizing the patient to their obsessions. Dr. Puder’s patients might describe this as tightness or heaviness in their chest, tightness in their throat, or a nauseated feeling of wanting to vomit. Often, patients confuse such discomfort with danger. However, despite this anxiety being uncomfortable, there is no threat or danger to the patient or anyone around them. When this happens in session, we sit with them, without reassuring them, creating a safe space for them to experience such sensations through giving them our calm presence.

Cognitive Mechanisms Shaping OCDNeurological and Cognitive DriversResearch highlights that OCD involves intolerance of uncertainty and a tendency to over interpret ambiguous situations as threatening. Computational models suggest that OCD sufferers disproportionately weigh new information over previous knowledge, driving repetitive checking and reassurance-seeking behaviors (Rigoux et al., 2024). As Dr. Penzel elaborates, “For those with OCD, ‘not knowing’ is the equivalent of danger. This drives their need to constantly check or seek reassurance.”

Misinterpretation of Risks & Lack of TrustIndividuals with OCD often overestimate risks and misinterpret benign events as dangers, driven by what Dr. Penzel describes as an “inflated sense of responsibility” and a “need to prevent harm at all costs.” This distorted perception of risk creates a feedback loop where compulsions, intended to reduce uncertainty, paradoxically intensify it. Dr. Penzel explains that the temporary relief provided by compulsive actions strengthens the belief that the compulsion was necessary, thereby reinforcing the behavior (see also How to Defeat OCD by Surrendering).

For instance, someone repeatedly checking if a door is locked may feel more uncertain after each attempt because, as Dr. Penzel points out, the act of checking undermines trust in their memory and their initial decision. This cycle perpetuates a “failure to trust oneself,” further entrenching the compulsion. He likens this to a vicious cycle: “The more you do it, the less sure you are, and the less sure you are, the more you feel you must do it.” By feeding this cycle, compulsions not only fail to provide lasting relief but also deepen the sense of doubt that defines OCD.

Advanced OCD Therapies & Novel InterventionsNarrative Scriptwriting and Imaginal Exposure for OCDFor existential or abstract fears, scriptwriting involves crafting a vivid, detailed narrative of the worst-case scenario and repeatedly exposing oneself to it. This technique leverages the principle of habituation, which Dr. Fred Penzel highlights as a crucial element in reducing the emotional salience of intrusive thoughts. Penzel notes that scriptwriting for existential OCD allows patients to confront their deepest fears—whether about the meaning of life, the universe, or their moral character—without attempting to resolve them. “By sitting with the discomfort,” he explains, “patients gradually desensitize themselves to the anxiety these thoughts provoke, breaking the cycle of avoidance and compulsive analysis.”

Dr. Penzel has observed that this method is particularly effective for moral or existential OCD because it directly challenges the obsessive need for certainty or resolution. He emphasizes that the narrative should be revisited repeatedly and without seeking reassurance, as this helps retrain the brain to tolerate ambiguity and distress. For instance, someone struggling with existential OCD might write and reflect on a script exploring the possibility that life has no inherent meaning, allowing them to embrace the uncertainty rather than fear it (see also “To Be or Not to Be. That is the Obsession: Existential and Philosophical Obsessions”).

Audio Recordings for OCDSimilar to narrative exposure, Dr. Penzel highlights the efficacy of using audio recordings to treat OCD. Effective audio recordings include details of triggering events to activate obsessions and anxieties, which the patient must then overcome. When listening to these recordings repeatedly, patients are activating more memories and details, which are then then built into new recordings and listened to again. The goal is for the patient to strengthen their tolerance to the discomfort from the obsession over time.

The methodology for the recordings is to increase the intensity of the obsession by listening to more detailed and morbid audios until the patient no longer has a reaction to it, or considers it “boring.” During this therapy, the patient is preparing their mind and building tools to address their OCD response. However, if residual obsessions or anxieties are still left, patients will continue listening to recordings and the therapy persists.

Personalized ERP ProtocolsDr. Penzel underscores the importance of tailoring ERP to match the obsessions and compulsions unique to each OCD subtype and patient, emphasizing that “no two cases of OCD are exactly alike.” Customizing exposures enhances treatment efficacy by addressing the specific fears driving the disorder, as illustrated below:

• Contamination OCD: Patients might perform tasks such as touching “contaminated” objects like public door handles and resisting the urge to wash their hands. Dr. Penzel notes that gradual exposure, starting with less distressing stimuli, helps build tolerance to anxiety while fostering confidence in the treatment process (see also “Stronger Than Dirt–OCD and Contamination”).
• Harm OCD: Exposure tasks often involve handling feared objects, such as knives, while confronting the irrational belief that simply holding them might cause harm. Penzel advises that therapists create a safe environment for these exposures, gradually dismantling the association between intrusive thoughts and danger (see also “Morbid Obsessions: Thought of Harming Others”).

By targeting the specific fears underlying each OCD presentation, personalized ERP allows patients to confront their obsessions systematically and build resilience against uncertainty.

Augmenting ERP with TechnologyDigital tools such as virtual reality (VR) and mobile apps are being explored to simulate exposures in a controlled, repeatable manner. For example, VR scenarios can replicate real-world triggers, making ERP more accessible and tailored (Javaherirenani et al., 2022).

Predictors Of Treatment SuccessEarly EngagementA meta-analysis revealed that patients who actively engage in ERP early in treatment achieve better outcomes, as success depends on the willingness to confront discomfort. Dr. Penzel stresses the importance of building trust between the therapist and patient during this critical initial phase. According to Penzel, “Patients often come into therapy feeling overwhelmed and hopeless. Helping them take that first step into exposure work, no matter how small, sets the stage for future success.” Early victories, even with less challenging exposures, can boost confidence and reinforce the therapy’s effectiveness.

Penzel also emphasizes the value of psychoeducation during this stage, explaining the mechanisms of OCD and how ERP works to counteract them. As mentioned earlier, when patients understand why they are being asked to endure distress without compulsions, they are more likely to engage actively and maintain commitment to the process. He states, “The more patients understand their enemy, the more empowered they are to fight it.”

Inhibitory LearningThe inhibitory learning model teaches patients to tolerate distress and uncertainty by experiencing anxiety without performing compulsions, gradually weakening the obsession-compulsion cycle. Dr. Penzel emphasizes creating a “library of new experiences” to counteract OCD fears, such as a contamination OCD patient touching feared objects without becoming ill, which rewrites catastrophic associations.

Penzel highlights the importance of varied exposures, cautioning against rigid repetition that leads to habituation. He advises diversifying tasks to “surprise the OCD,” helping patients generalize tolerance for uncertainty across different areas. Mindfulness techniques also reinforce inhibitory learning by fostering nonjudgmental awareness, reducing emotional reactivity to intrusive thoughts, and teaching that anxiety, while uncomfortable, is not dangerous and fades without compulsions.

By combining early engagement, psychoeducation, and inhibitory learning principles, Penzel’s approach enhances evidence-based OCD treatments, boosting long-term recovery prospects.

Social Support One of the most important pillars of treatment success, especially in OCD, is a consistent and reliable support system. Dr. Penzel mentions this is especially crucial when patients are instructed to not seek out reassurance for their obsessions. When discussing the nature of the disorder to support systems, Dr. Penzel says, “I explain how harmful [reassurance] is and how enabling it is…” to illustrate how families can help or hinder the treatment for the patient. The role of a loved one in a patient’s obsessions also play a critical role in treatment of their OCD (see also “Living With Your Loved One’s OCD: Some Advice for Significant Others”).

For instance, one of Dr. Penzel’s patients received therapy for obsessions he had about killing his girlfriend. In addition to Penzel’s guidance, the girlfriend also played an active role in the treatment plan. She participated in the homework, understood her partner’s obsessions, and would sit next to him while he was holding a big knife* in his hand saying, “Please don’t kill me.” This type of support helped the treatment by forcing the patient to confront his fear in every possible situation where harm could have occured, without reassuring his thoughts.

*We recommend not trying this one without consulting an OCD specialist!

OCD & ComorbiditiesOCD can present with other mental illnesses, which, when considering treatment, may require a different approach. Specifically, such cases of comorbidity require identification of the additional mental illness that may be present, and may require treatment of the non-OCD mental illness first.

For example, OCD is one of the most common comorbidities associated with bipolar disorder. During manic or mixed episodes in patients with both OCD and bipolar disorder, the treatment of mood symptoms often takes precedence over the treatment of OCD (Kazhungil, F. & Mohandas, E., 2016). Thus, as Dr. Penzel suggests, managing the bipolar disorder first would offer the necessary stability required to address the OCD. Such approaches are similar to those with comorbid OCD and schizophrenia as well, where managing the more severe illness first gives way to effectively treat the obsessions-compulsions.

On the topic of personality disorders, Dr. Penzel believes that they can be difficult to address in psychiatry, which can make it difficult to identify as a comorbidity with OCD. However, the approach is similar. Patients who present with borderline personality disorder (BPD), or who have trouble regulating emotions, should receive DBT treatment before moving forward with OCD therapy.

Eating Disorders & Body Dysmorphic Disorders Dr. Penzel discusses the connections between obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD), and eating disorders, highlighting both their overlapping features and their important distinctions.

BDD, for instance, is classified within the OCD spectrum in the DSM-V due to shared elements, such as intrusive thoughts and compulsive behaviors. However, BDD is unique in its focus on perceived physical flaws, which drive behaviors like mirror checking or skin picking aimed at “fixing” these flaws (see also “Body Dysmorphic Disorder (BDD) Fact Sheet,” “Eating Disorders are Not the Same as Body Dysmorphic Disorder (And Why It Matters),” “Are Eating Disorders Obsessive Compulsive Disorder? Let Us Discuss,” “Treatment of OCD with Comorbid Eating Disorders,” and “Eating Disorders and OCD: Part of the Spectrum”).

Eating disorders, while they may share some similarities with BDD (such as body image concerns), are distinct conditions. As such, they involve broader psychological and behavioral dimensions and cannot be treated solely through OCD-based methods. Instead, specialized eating disorder therapies are required, though elements of cognitive behavioral therapy (CBT) for BDD, like body image work and exposure therapy, might provide useful tools.

Trauma & Post-Traumatic Stress DisorderAn additional area for exploration is the relationship between trauma and OCD. Although it is possible for obsessions to center around trauma, Dr. Penzel advises that professional judgement is necessary for determining which condition to prioritize for treatment. If the patient’s post-traumatic stress disorder (PTSD) is severe, addressing it first may help the patient effectively engage in their treatment for OCD. Furthermore, treatments for OCD may also be utilized in addressing trauma (i.e., exposure therapy via recordings). By engaging in such exposure, patients are able to build tolerance to their respective PTSD triggers, which can build the foundation to effectively treat the OCD. However, overlapping features of these conditions, such as intrusive thoughts and avoidance behaviors, can often complicate diagnosis.

For example, consider a case in which a patient has been sexually assaulted. This individual may develop a persistent fear of being assaulted again, which can evolve into intrusive, obsessive thoughts about personal safety and lead to compulsive behaviors (e.g., excessive checking of locks). In these cases of trauma, it is critical to determine whether a patient’s symptoms stem from PTSD, OCD, or a combination of both, to develop an effective treatment plan.

Trichotillomania & Skin PickingTrichotillomania (i.e., hair pulling disorder) or excoriation disorder (i.e., skin picking disorder) are part of body-focused repetitive behaviors (BFRBs), and can have a variety of motivations or inputs. Specifically, it can develop from cognitive, sensory, environmental, or emotional symptoms. Although these disorders are on the spectrum of OCD, Dr. Penzel notes that the treatment for these disorders has to be more comprehensive, as each patient can have a different motivation for their disorder.

For example, a treatment can address the cognitive component for one patient, but a combination of sensory and environmental for another (see also “Comprehensive Behavioral (ComB) Treatment for Skin Picking and Hair Pulling Disorders,” “Excoriation (Skin Picking Disorder) Fact Sheet,” “Skin-Picking and Nail-Biting - Related Disorders,” and “Trichotillomania (Hair Pulling Disorder) Fact Sheet”).

OCD Recovery: After & BeyondThe goal for OCD treatment is to build an individual’s tolerance to their obsessions and anxieties. When thinking about what that looks like, or what the measure of recovery would be, Dr. Penzels explains, “[It’s] when we cannot come up with any more homework assignments to get your anxiety going anymore…[when] the thoughts no longer have an impact on you.”

Through a comprehensive approach, Dr. Penzel is able to illustrate that by requiring the patient to sit with and through the discomfort of their obsessions without engaging in compulsion, they can build the resilience necessary to overcome their OCD. Ultimately, patients will accept their thoughts as exactly that—just thoughts. Dr. Penzel notes that the first half of the treatment involves regaining control over one’s symptoms, and the latter half of treatment involves the maintenance of long-term control over one’s symptoms. Such insight serves as a cautionary note that patient’s must remain vigilant even after they achieve symptom remission in order to guard against future relapse.

The Strain of OCD on Support SystemsOften when patients with OCD struggle, their families struggle as well. Just as the patient loses time doing the obsessions, family time and connection can be lost in the midst of the illness. Attempts to disrupt compulsive routines can sometimes lead to heightened emotions or frustration within the family. Due to the nature of certain compulsions, families as a whole may be limited or restricted from normal activities to avoid triggers. The International OCD Foundation (IOCDF) offers an extensive network of resources and guidance for the families and support persons of patients with OCD.

How to Emotionally Heal from OCDWhen a patient is in recovery, they may reach a point where feelings of guilt and depression begin to arise in the midst of seeing the impact of their illness on their loved ones. While these feelings can be challenging, they present an opportunity for patients to begin the process of self-forgiveness and healing. Patients must understand that they did not choose their illness. As such, forgiveness and acceptance of their past, as well as themselves, is a necessary first step in committing to getting better. Through self-forgiveness and embracing their past experiences (which may be explored via techniques such as therapy, journaling, mindfulness, among others), patients can embrace their new, optimistic future ahead of them and implement their new strategies to live in the present. This process ultimately helps patients build trust and security with their support system each day (see also “Coming to Terms With the Lost Years” and “What Do You Say After You Say You're Sorry?”).

Neurobiological Underpinnings of OCDThe roots of obsessions and compulsions in OCD lie in dysregulated brain activity. Historically, early Positron Emission Tomography (PET) imaging studies identified hyperactivity in the orbitofrontal cortex (OFC) and subcortical regions, primarily the basal ganglia (Baxter et al., 1987).

The basal ganglia are a group of deep brain structures, including the dorsal striatum (putamen and caudate), ventral striatum (nucleus accumbens), pallidum, and subthalamic nucleus. Together, they act as a central hub that filters and refines signals between the cortex, thalamus, and other brain regions, regulating movement, habits, and some emotional and decision-making processes. While early imaging studies lacked the resolution to fully map the complex interactions of these regions, they provided foundational evidence linking basal ganglia dysfunction to OCD.

Volumetric & Structural Differences in OCDAdvances in Magnetic Resonance Imaging (MRI) have enabled researchers to investigate structural abnormalities with more precision. A meta-analysis by Del Casale et al. (2024) synthesized data from over 3,000 subjects and revealed:

• Increased gray matter volume in the basal ganglia, thalamus, left parietal cortex, and cerebellum.
• Decreased gray matter volume in cortical regions such as the medial and superior frontal gyri, as well as subcortical areas like the hippocampus and caudate.

While these findings highlighted structural differences in OCD, most volumetric studies, including this meta-analysis, do not account for confounding variables like comorbid psychiatric conditions, socioeconomic factors, or childhood trauma—all of which are independently associated with brain morphology changes.

Fouche et al. (2022) controlled for some of these factors, including medication use and comorbid depression and anxiety, and found no significant structural differences overall. However, among OCD patients with comorbid anxiety or depression, they observed an increased surface area of the pallidum and a decreased surface area of the caudate, suggesting that structural differences might vary with clinical comorbidity.

Importantly, volumetric differences, while informative, do not necessarily correlate with symptoms (Radua and Mataix-Cols, 2009; Tang et al., 2013) or brain function.

Functional Connectivity and NetworksBecause structural studies provide only snapshots of the brain, it is important to examine changes in how parts of the brain interact with each other. Resting-state functional MRI (rs-fMRI) explores the dynamic communication between brain regions while a person is at rest.

Given the findings on the basal ganglia and its potential implication in OCD, initial studies hypothesized there would be connectivity changes between it and other brain regions. Early studies did suggest disrupted connectivity between the striatum and both the PFC and the thalamus (Liu et al., 2023). These findings contributed to the development of the corticostriatal-thalamocortical (CSTC) model, which explains OCD symptoms as arising from dysfunction in these interconnected brain circuits. According to this model, the cortex (OFC and ACC) of a patient with OCD is hyperactive and more likely to produce perceptions of threat or anxiety. This cortical hyperactivity is theorized to be a result of hyperactivity in the thalamus, which relays sensory information to the cortex, and that this thalamic hyperactivity is due to dysfunction of the striatum. However, many of the findings that generated this model were limited by small sample sizes, study heterogeneity, and publication bias, and other studies have suggested that there are other dysfunctional circuits at play.

For example, a recent mega-analysis by the ENIGMA-OCD consortium (Bruin et al., 2023) combined data from 1,024 OCD patients and 1,028 healthy controls across 28 independent studies across the globe using standardized imaging methods. Key findings included:

• No significant differences in connectivity between the striatum and PFC, challenging the CSTC models.
• Hyperconnectivity between the thalamus and sensorimotor regions, particularly in patients with more severe symptoms.
• Sensorimotor hypo-connectivity, suggesting a role for disrupted sensory and motor integration in OCD symptoms.

Interestingly, machine-learning algorithms trained on these connectivity patterns could not reliably classify OCD patients from controls, achieving accuracy only slightly above chance. However, such algorithms performed better in distinguishing medicated versus unmedicated individuals, suggesting medication may be more highly associated with consistent functional connectivity changes than OCD, per se. This may be due to the various ways in which OCD manifests or due to the fact that OCD patients were simply sitting in the MRI machine and not actively experiencing symptoms.

Task-Based fMRI: Inducing OCD Symptoms in Real-TimeTask-based fMRI studies that elicit symptoms of OCD provide a better lens to assess the brains of patients with OCD. Unfortunately, there are relatively few studies that employ this technique because the different symptom triggers associated with each person’s OCD are likely associated with differential brain activity, making these protocols hard to standardize and replicate (Thatikonda et al., 2024 [pre-print]; Viol et al., 2019).

Nevertheless, symptom provocation tasks consistently demonstrate differences in brain regions associated with cognitive control and performance monitoring (e.g., ACC, hippocampus, PFC, amygdala) (De Nadai et al., 2023; Viol et al., 2019).

ERP Therapy & Brain ConnectivityExposure and response prevention (ERP), the gold standard for OCD treatment, targets the cycle of obsessions and compulsions. Two studies, Moody et al. (2017) and Becker et al. (2024), examined its effects on brain connectivity. Both reported changes in neural networks following ERP, including increased activity in the frontoparietal network and default mode network. However, these changes were not consistently correlated with symptom improvement as measured by the Yale-Brown Obsessive Compulsive Scale (YBOCS).

Insights from Deep Brain Stimulation (DBS) for OCDWhile the neurobiology of OCD is not yet fully understood, the disorder is increasingly seen as one of disrupted network dynamics rather than isolated regional dysfunction. Current research supports the notion that OCD reflects over-stimulation of habitual thoughts and compulsions. The anxiety triggered by intrusive thoughts leads to behaviors that provide temporary relief but reinforce maladaptive cycles, likely through aberrant activity in the basal ganglia and reward circuits.

Deep brain stimulation (DBS) targeting areas such as the anterior limb of the internal capsule, which contains a large portion of axons in the CSTC circuit, and nucleus accumbens offers clues about the implicated circuits and holds promise as an intervention for severe cases (Mar-Barrutia et al., 2021).

ConclusionOCD’s defining feature—chronic doubt—creates unique challenges, but also opportunities for effective intervention. Through evidence-based strategies like ERP, cognitive restructuring, and acceptance of uncertainty, patients can regain control and reduce compulsions. These approaches emphasize that intrusive thoughts are neither reflective of intent nor moral character, but rather byproducts of a misfiring brain. Dr. Penzel poignantly notes, “Recovery begins when sufferers stop fighting their thoughts and instead work on tolerating them, allowing uncertainty to become part of life.” By shifting the focus from eliminating doubt to tolerating it, OCD treatment fosters resilience and long-term recovery, ultimately allowing patients to once again engage fully in all aspects of their life.

ReferencesAhmari, S. (2018). Post-mortem Brain Research Holds Potential for Discovery of New OCD Treatments.OCD Newsletter. Retrieved from https://iocdf.org/expert-opinions/post-mortem-brain-research/

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596

Anxiety and Depression Association of America (ADAA). (2022, October 28). Anxiety disorders - facts & statistics.Retrieved from https://adaa.org/understanding-anxiety/facts-statistics

Baxter, L. R., Jr, Phelps, M. E., Mazziotta, J. C., Guze, B. H., Schwartz, J. M., & Selin, C. E. (1987). Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls. Archives of general psychiatry, 44(3), 211–218. https://doi.org/10.1001/archpsyc.1987.01800150017003

Becker, H. C., Beltz, A. M., Himle, J. A., Abelson, J. L., Block, S. R., Taylor, S. F., & Fitzgerald, K. D. (2024). Changes in Brain Network Connections After Exposure and Response Prevention Therapy for Obsessive-Compulsive Disorder in Adolescents and Adults. Biological psychiatry. Cognitive neuroscience and neuroimaging, 9(1), 70-79. doi:10.1016/j.bpsc.2023.09.009

Bruin, W. B., Abe, Yoshinari, A., Alonso, P., Anticevic, A., Backhausen, L. L., Balachander, S., Bargallo, N., Batistuzzo, M. C., Benedetti, F., Triquell, S. B., Brem, S., Calesella, F., Couto, B., Denys, D. A. J. P., Echevarria, M. A. N., Eng, G. K., Ferreira, S., Feusner, J. D., Grazioplene, R. G…van Wingen, G. A. (2023). The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium. Molecular psychiatry, 28(10), 4307–4319. https://doi.org/10.1038/s41380-023-02077-0

Del Casale, A., Ferracuti, S., Barbetti, A. S., Bargagna, P., Zega, P., Iannuccelli, A., Caggese, F., Zoppi, T., De Luca, G. P., Parmigiani, G., Berardelli, I., & Pompili, M. (2022). Grey Matter Volume Reductions of the Left Hippocampus and Amygdala in PTSD: A Coordinate-Based Meta-Analysis of Magnetic Resonance Imaging Studies. Neuropsychobiology, 81(4), 257–264. https://doi.org/10.1159/000522003

Del Casale, A., Ferracuti, S., Mancino, S., Arena, J. F., Bilotta, I., Alcibiade, A., Romano, A., Bozzao, A., & Pompili, M. (2024). A coordinate-based meta-analysis of grey matter volume differences between adults with obsessive-compulsive disorder (OCD) and healthy controls. Psychiatry research. Neuroimaging, 345, 111908. https://doi.org/10.1016/j.pscychresns.2024.111908

De Nadai, A. S., Fitzgerald, K. D., Norman, L. J., Russman Block, S. R., Mannella, K. A., Himle, J. A., & Taylor, S. F. (2023). Defining brain-based OCD patient profiles using task-based fMRI and unsupervised machine learning. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology, 48(2), 402–409. https://doi.org/10.1038/s41386-022-01353-x

Fama, J. M. (n.d.) Excoriation (Skin Picking Disorder) Fact Sheet. International OCD Foundation. Retrieved from https://iocdf.org/wp-content/uploads/2014/09/ExcoriationSkin-Picking.pdf

Ferrando, C., & Selai, C. (2021). A systematic review and meta-analysis on the effectiveness of exposure and response prevention therapy in the treatment of obsessive-compulsive disorder. Journal of Obsessive-Compulsive and Related Disorders, 31, 100684. https://doi.org/10.1016/j.jocrd.2021.100684

Fisher, E., Neziroglu, F., & Feusner, J. (2023). Eating Disorders are Not the Same as Body Dysmorphic Disorder (And Why It Matters). OCD Newsletter. Retrieved from https://iocdf.org/expert-opinions/eating-disorders-not-the-same-as-bdd/

Fouche, J.P., Groenewold, N. A., Sevenoaks, T., Heany, S., Lochner, C., Alonso, P., Batistuzzo, M. C., Cardoner, N., Ching, C. R. K., de Wit, S. J., Gutman, B., Hoexter, M. Q., Jahanshad, N., Kim, M., Kwon, J. S., Mataix-Cols, D., Menchon, J. M., Miguel E. C., Nakamae, T., Phillips, M. L,…Stein, D. J. (2022). Shape analysis of subcortical structures in obsessive‐compulsive disorder and the relationship with comorbid anxiety, depression, and medication use: A meta‐analysis by the OCD Brain Imaging Consortium. Brain and behavior, 12(10), e2755 doi:10.1002/brb3.2755

Grant, J. E., & Chamberlain, S. R. (2023). Impaired cognitive flexibility across psychiatric disorders. CNS Spectrums, 28(6), 688–692. doi:10.1017/S1092852923002237

Harris, E., Horn, P., Kirschner, A., & Xiang, J. (2019). Measuring Brain Waves Can Help Detect OCD Symptoms in Youth. OCD Newsletter. Retrieved from https://iocdf.org/expert-opinions/measuring-brain-waves-can-help-detect-ocd-symptoms-in-youth/

Hazari, N., Narayanaswamy, J. C., & Venkatasubramanian, G. (2019). Neuroimaging findings in obsessive-compulsive disorder: A narrative review to elucidate neurobiological underpinnings. Indian journal of psychiatry, 61(Suppl 1), S9–S29. https://doi.org/10.4103/psychiatry.IndianJPsychiatry_525_18

Hezel, D. M. & Simpson, H. B. (2019). “Exposure and response prevention for obsessive-compulsive disorder: A review and new directions.” Indian journal of psychiatry. 61(Suppl 1): S85-S92. doi:10.4103/psychiatry.IndianJPsychiatry_516_18

Hoffman, J., Franklin, D., Mickolus, C., & Padron, M. (2022). Are Eating Disorders Obsessive Compulsive Disorder? Let Us Discuss. OCD Newsletter. Retrieved from https://iocdf.org/expert-opinions/are-eating-disorders-ocd/

International OCD Foundation (IOCDF). (n.d.). Homepage. Retrieved from https://iocdf.org/

Javaherirenani, R., Mortazavi, S. S., Shalbafan, M., Ashouri, A., & Farani, A. R. (2022). Virtual reality exposure and response prevention in the treatment of obsessive-compulsive disorder in patients with contamination subtype in comparison with in vivo exposure therapy: a randomized clinical controlled trial. BMC psychiatry, 22(1), 740. https://doi.org/10.1186/s12888-022-04402-3

Kazhungil, F., Mohandas, E. (2016). Management of obsessive-compulsive disorder comorbid with bipolar disorder. Indian journal of psychiatry, 58(3), 259–269. https://doi.org/10.4103/0019-5545.192001

Leonard, R. C., & Riemann, B. C. (2013). Treatment of Obsessive-Compulsive Disorder with Comorbid Eating Disorders. OCD Newsletter. Retrieved from https://iocdf.org/expert-opinions/treatment-of-obsessive-compulsive-disorder-with-comorbid-eating-disorders/

Liu, Y., Sun, J., Jiang, J., Wan, K., Tang, Y., Zhang, M., Chen, L., Hua, Q., Fang, W., Zhu, C., & Wang, K. (2023). Brain functional specialization in obsessive-compulsive disorder associated with neurotransmitter profiles. Journal of Affective Disorders, 329, 477–482. https://doi.org/10.1016/j.jad.2023.02.146

Maia, T. V., Cooney, R. E., & Peterson, B. S. (2008). The neural bases of obsessive-compulsive disorder in children and adults. Development and psychopathology, 20(4), 1251–1283. https://doi.org/10.1017/S0954579408000606

Mansueto, C. S. & Golomb, R. G. (2019) Comprehensive Behavioral (ComB) Treatment for Skin Picking and Hair Pulling Disorders. OCD Newsletter. Retrieved from https://iocdf.org/expert-opinions/comprehensive-behavioral-comb-treatment-for-skin-picking-and-hair-pulling-disorders/

Mar-Barrutia, L., Real, E., Segalás, C., Bertolín, S., Menchón, J. M., & Alonso, P. (2021). Deep brain stimulation for obsessive-compulsive disorder: A systematic review of worldwide experience after 20 years. World journal of psychiatry, 11(9), 659–680. https://doi.org/10.5498/wjp.v11.i9.659

Moody, T. D., Morfini, F., Cheng, G., Sheen, C., Tadayonnejad, R., Reggente, N., O'Neill, J., & Feusner, J. D. (2017). Mechanisms of cognitive-behavioral therapy for obsessive-compulsive disorder involve robust and extensive increases in brain network connectivity. Translational psychiatry, 7(9), e1230. https://doi.org/10.1038/tp.2017.192

National Institute of Mental Health (NIMH). (2023). Obsessive-Compulsive Disorder (OCD). Retrieved from https://www.nimh.nih.gov/health/statistics/obsessive-compulsive-disorder-ocd

Neziroglu, F. & Sandler, J. (2009). Eating Disorders and OCD: Part of the Spectrum. OCD Newsletter. Retrieved from https://iocdf.org/expert-opinions/expert-opinion-eating-disorders-and-ocd/

Neziroglu, F. & Slavin, J. C. (n.d.). Body Dysmorphic Disorder (BDD) Fact Sheet. International OCD Foundation. Retreived from https://iocdf.org/wp-content/uploads/2014/09/BDD-1.pdf

Penzel, F. (n.d.). Coming to Terms With the Lost Years. Western Suffolk Psychological Services. Retrieved from https://www.wsps.info/articles/coming-to-terms-with-the-lost-years

Penzel, F. (n.d.). How to Defeat OCD by Surrendering. Western Suffolk Psychological Services. Retrieved from https://www.wsps.info/articles/how-to-defeat-ocd-by-surrendering-1

Penzel, F. (n.d.). Living With Your Loved One’s OCD: Some Advice for Significant Others. Western Suffolk Psychological Services. Retrieved from https://www.wsps.info/articles/living-with-your-loved-ones-ocd-some-advice-for-significant-others-1

Penzel, F. (n.d.). Morbid Obsessions: Thought of Harming Others. Western Suffolk Psychological Services. Retrieved from https://www.wsps.info/articles/morbid-obsessions-thought-of-harming-others

Penzel, F. (n.d.). Skin-Picking and Nail-Biting - Related Disorders. Western Suffolk Psychological Services. Retrieved from https://www.wsps.info/articles/skin-picking-and-nail-biting-related-disorders

Penzel, F. (n.d.). Stronger Than Dirt–OCD and Contamination. Western Suffolk Psychological Services. Retrieved from https://www.wsps.info/articles/stronger-than-dirt-ocd-and-contamination

Penzel, F. (n.d.) To Be or Not to Be. That is the Obsession: Existential and Philosophical Obsessions. Western Suffolk Psychological Services. Retrieved from https://www.wsps.info/articles/to-be-or-not-to-be-that-is-the-obsession-existential-and-philosophical-obsessions

Penzel, F. (n.d.). What Do You Say After You Say You're Sorry? (Coming to terms after you recover from OCD. Western Suffolk Psychological Services. Retrieved from https://www.wsps.info/articles/what-do-you-say-after-you-say-youre-sorry-coming-to-terms-after-you-recover-from-ocd-1

Penzel, F. (2000). Obsessive-compulsive disorders: A complete guide to getting well and staying well. Oxford University Press.

Penzel, F. (2014). 25 Tips for Succeeding with OCD Treatment. OCD Newsletter. Retrieved from https://iocdf.org/expert-opinions/25-tips-for-ocd-treatment/

Penzel, F. (2015). Driven To Distraction: “Hit And Run OCD”. OCD Newsletter. Retrieved from https://iocdf.org/expert-opinions/driven-to-distraction-hit-and-run-ocd/

Puder, D. (Host). (2021, June 23). Obsessive Compulsive Disorder (OCD) (No. 119) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-119-obsessive-compulsive-disorder-ocd?rq=119

Puder, D. (Host). (2021, Sept. 28). Psychotherapy for Obsessive-Compulsive Disorder (No. 126) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-126-psychotherapy-for-obsessive-compulsive-disorder

Puder, D. (Host). (2022, May 22). PANS & PANDAS (No. 147) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-147-pans-and-pandas

Puder, D. (Host). (2023, Sept. 8). Body Dysmorphic Disorder: A Guide for Therapists and Mental Health Professionals with Dr. Katharine Phillips (No. 191) [Audio podcast episode]. In Psychiatry & Psychotherapy Podcast. Emotion Connection. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-191-body-dysmorphic-disorder-with-dr-katharine-phillips?utm_source=chatgpt.com

Radua, J., & Mataix-Cols, D. (2009). Voxel-wise meta-analysis of grey matter changes in obsessive-compulsive disorder. The British journal of psychiatry : the journal of mental science, 195(5), 393–402. https://doi.org/10.1192/bjp.bp.108.055046

Rector, N. A., Richter, M. A., Katz, D. & Leybman, M. (2018). Does the addition of cognitive therapy to exposure and response prevention for obsessive compulsive disorder enhance clinical efficacy? A randomized controlled trial in a community setting. British Journal of Clinical Psychology. 58(1): 1-18. https://doi.org/10.1111/bjc.12188.

Rigoux, L., Stephan, K. E., & Petzschner, F.H. (2024). Beliefs, compulsive behavior and reduced confidence in control. PLoS Comput Biol 20(6): e1012207. https://doi.org/10.1371/journal.pcbi.1012207

Song, Y., Li, D., Zhang, S., Jin, Z., Zhen, Y., Su, Y., Zhang, M., Lu, L., Xue, X., Luo, J., Liang, M., & Li, X. (2022). The effect of exposure and response prevention therapy on obsessive-compulsive disorder: A systematic review and meta-analysis. Psychiatry Research, 317, 114861. https://doi.org/10.1016/j.psychres.2022.114861

Substance Abuse and Mental Health Services Administration. (2016). Table 3.13, DSM-IV to DSM-5 Obsessive-Compulsive Disorder Comparison. Nih.gov; Substance Abuse and Mental Health Services Administration (US). https://www.ncbi.nlm.nih.gov/books/NBK519704/table/ch3.t13/

Tang, W., Li, B., Huang, X., Jiang, X., Li, F., Wang, L., Chen, T., Wang, J., Gong, Q., & Yang, Y. (2013). Morphometric brain characterization of refractory obsessive-compulsive disorder: diffeomorphic anatomic registration using exponentiated Lie algebra. Progress in neuro-psychopharmacology & biological psychiatry, 46, 126–131. https://doi.org/10.1016/j.pnpbp.2013.07.011

Thatikonda, N. S., Narayanaswamy, J. C., Venkatasubramanian, G., Reddy, J. Y. C., & Arumugham, S. S. (2024). Differential connectivity of frontolimbic circuit induced by individualized disorder-specific stimuli in distinct symptom profiles of obsessive-compulsive disorder. medRxiv. https://doi.org/10.1101/2024.02.16.24302954 (PREPRINT)

Van Noppen, B., Sassano-Higgins, S., Appasani, R., & Sapp, F. (2021). Cognitive-behavioral therapy for obsessive-compulsive disorder: 2021 update. FOCUS, 19(4). https://doi.org/10.1176/appi.focus.2021001

Viol, K., Aas, B., Kastinger, A., Kronbichler, M., Schöller, H., Reiter, E. M., Said-Yürekli, S., Kronbichler, L., Kravanja-Spannberger, B., Stöger-Schmidinger, B., Aichhorn, W., & Schiepek, G. (2019). Individual OCD-provoking stimuli activate disorder-related and self-related neuronal networks in fMRI. Psychiatry research. Neuroimaging, 283, 135–144. https://doi.org/10.1016/j.pscychresns.2018.12.008

Zasio, R. (n.d.). Trichotillomania (Hair Pulling Disorder) Fact Sheet. International OCD Foundation. Retrieved from https://iocdf.org/wp-content/uploads/2014/09/Trichotillomania.pdf

Zhu, Y., Fan, Q., Zhang, H., Qiu, J., Tan, L., Xiao, Z., Tong, S., Chen, J., & Li, Y. (2016). Altered intrinsic insular activity predicts symptom severity in unmedicated obsessive-compulsive disorder patients: a resting state functional magnetic resonance imaging study. BMC psychiatry, 16, 104. https://doi.org/10.1186/s12888-016-0806-9

How to Earn Psychiatry CME Credits for This Episode

To earn 1.25 psychiatry CME credits for listening to this episode, simply follow these steps:

1. Listen to the entire episode: Spotify, iTunes, YouTube
2. Complete the corresponding 4 question brief CME post-episode quiz

View Details

Authors: David Puder, M.D., Joanie Burns, Robert Drozek, LICSW

Presentors: Robert P. Drozek, LICSW, Brandon T. Unruh, M.D., Anthony Bateman, M.A., FRCPsych, David Puder, M.D.

Date Published: 11/15/2024

IntroductionThis week, I am joined by some of the world’s leading experts in treating pathological narcissism and personality disorders: Robert P. Drozek, Dr. Brandon Unruh, and Dr. Anthony Bateman.

Robert P. Drozek is a distinguished psychotherapist specializing in personality disorders, trauma, dissociative disorders, and addiction. He serves as the clinical director of the Mentalization-Based Treatment (MBT) Clinic at McLean Hospital and as a staff psychotherapist in the Gunderson Outpatient Program at McLean. He is a trainer and supervisor in MBT through the Anna Freud Centre in London and holds a teaching associate position in the Department of Psychiatry at Harvard Medical School. Robert Drozek is a co-founder and co-director of MBT Boston, an organization dedicated to providing training and supervision in mentalization-based treatment. He has authored multiple publications, including the book, Psychoanalysis as an Ethical Process, which explores the role of ethics in psychoanalytic practice. Additionally, Mr. Drozek is the lead developer of mentalization-based treatment for pathological narcissism, co-authoring a comprehensive handbook on the subject.

Brandon Unruh, M.D., is an instructor in psychiatry at Harvard Medical School and the medical director of the Gunderson Residence of McLean Hospital, a specialized residential program for individuals with severe personality disorders. He is also the founding director of McLean’s insurance-based outpatient mentalization-based treatment clinic for personality disorders. His clinical approach is anchored in the integration of evidence-based treatments for personality disorder such as dialectical behavior therapy (DBT), mentalization-based treatment (MBT), transference-focused psychotherapy (TFP), and general/good psychiatric management (GPM). He is an MBT trainer and supervisor through the Anna Freud Centre in London and one of the original cohort of GPM trainers established by John Gunderson. He has published on a variety of topics including suicide, personality disorders, spirituality, medical ethics, general hospital psychiatry, and literature and medicine. He is co-investigator with Mary Zanarini on a randomized-controlled trial studying an MBT group intervention developed to promote flourishing and character virtues in individuals with borderline personality disorder. His academic interests also include the treatment of pathological narcissism, and the relationships between mental health and spirituality and religiosity in both pathological and healthy forms. He is a co-developer of Mentalization-Based Treatment for Pathological Narcissism (MBT-N) along with Robert Drozek and Dr. Anthony Bateman, with whom he co-authored the treatment manual Mentalization-Based Treatment for Pathological Narcissism: A Practical Guide (Oxford, 2023) and with whom he regularly teaches and supervises clinicians and systems implementing this model. He co-edited Borderline Personality Disorder: A Case-Based Approach(Springer, 2018), a generalist guide for clinicians learning to manage BPD.

Dr. Anthony Bateman, M.A., FRCPsych, is a renowned psychiatrist and psychotherapist recognized for co-developing mentalization-based treatment (MBT) alongside Peter Fonagy. MBT is an integrative form of psychotherapy that combines elements from psychodynamic, cognitive-behavioral, systemic, and ecological approaches, primarily designed for individuals with borderline personality disorder (BPD). Dr. Bateman serves as the Director of Psychotherapy Services and Research Lead for personality disorder at St. Ann’s Hospital in North London. His contributions to the field include co-authoring several seminal works, such as Psychotherapy for Borderline Personality Disorder: Mentalization-Based Treatment and Mentalization-Based Treatment for Personality Disorders: A Practical Guide. These publications provide comprehensive insights into the application of MBT for treating personality disorders.

Narcissistic Personality Disorder (NPD): Prevalence, Epidemiology, and Distinction Between Vulnerable and Grandiose NarcissismNarcissistic personality disorder (NPD) affects an estimated 1-6% of the general population, with significantly higher prevalence observed in psychiatric settings.

There are 2 main types of narcissism:

• Grandiose Narcissism: Individuals with grandiose narcissism display overt self-importance, entitlement, and a significant lack of empathy. They often present themselves as charismatic, confident, and assertive, attracting admiration through their external charm. However, beneath this outward facade, their sense of self-esteem remains fragile and heavily dependent on external validation. This external validation is vital for maintaining their exaggerated self-image. While they may appear self-assured, their emotional reactions are often disproportionate, particularly when they feel slighted or challenged. Their emotional responses, such as anger or aggression, stem from a need to protect their inflated sense of superiority. Those with grandiose narcissism often come to treatment not by their own choice, but because of external pressures, such as family or others urging them to seek help. This often makes them less likely to seek therapy voluntarily compared to people with vulnerable narcissism.
• Vulnerable Narcissism: Vulnerable narcissism, in contrast, tends to be less obvious. These individuals often present as introverted, anxious, or hypersensitive. They struggle with deep insecurity and their self-worth is fragile, often fluctuating dramatically based on external validation. While they still maintain a narcissistic self-focus, they tend to exhibit greater emotional instability, with their mood swinging based on how well they perceive they are being validated or admired. For instance, their self-esteem can rise when they receive positive feedback but can plummet with rejection or criticism. Individuals with vulnerable NPD often experience intense shame and self-doubt, which can lead to outbursts of anger when they feel rejected or unappreciated. The heightened emotional instability seen in vulnerable narcissism mirrors the emotional dysregulation in borderline personality disorder (BPD), leading to potential diagnostic confusion.

Just as individuals with BPD may experience decompensation after relational conflicts, those with NPD can face a significant breakdown when their self-image is threatened. For individuals with NPD, these moments can trigger intense emotional distress, rage, or withdrawal as they struggle to protect their fragile sense of self. Their sense of existence is validated by external perceptions and achievements, so any perceived threat to these external sources can feel devastating. Potential triggers include receiving negative feedback, being rejected or ignored, not being the center of attention, experiencing failure or public embarrassment, being outperformed by a peer, losing social status or prestige, being challenged by subordinates or family members, perceived disrespect from authority figures, being compared unfavorably to others, or social media criticism and lack of engagement.

Problems in Mentalizing Associated with Pathological NarcissismPathological narcissism is closely linked with significant impairments in mentalizing, the capacity to understand and interpret one’s own and others’ mental states. These impairments can manifest in various ways, especially within therapeutic contexts, impacting self-reflection, empathy, and relational stability.

Diminished Emotional Awareness and Alexithymia Individuals with NPD frequently experience alexithymia—the difficulty in identifying and describing their emotions, particularly vulnerable ones like sadness, shame, and insecurity. This blunted emotional awareness often leads to a defensive posture, where they mask vulnerability with anger, superiority, or a detached demeanor. Narcissistic individuals may describe external scenarios but struggle to reflect on their emotional states, making it difficult for them to access or express feelings of vulnerability. This lack of emotional insight hinders authentic self-reflection, impeding their capacity to engage deeply in therapeutic work and develop genuine empathy for others.

Overconfidence in Perspective-Taking in NPDIndividuals with NPD often overestimate their ability to understand others’ perspectives. They believe they can accurately interpret others’ thoughts and emotions, but this overconfidence leads to misinterpretations and assumptions. These individuals may experience “psychic equivalence mode,” where they view their perceptions as absolute truths, reinforcing their belief that they understand others perfectly. This can lead to rigid certainty about their perspective, making it difficult for them to entertain or consider alternative viewpoints. In therapy and relationships, this results in a lack of genuine exploration of others’ perspectives, as they focus on justifying their own beliefs rather than seeking to understand others. Their inability to challenge these assumptions causes misunderstandings and conflicts, as they view situations through a self-centered lens, often reacting defensively when their assumptions are questioned. This further isolates the individual, as their view of others becomes increasingly distorted and self-focused.

How Envy Drives Pathological Narcissism: Understanding Its Impact on Self-Esteem and TherapyEnvy exposes a deep sense of inadequacy beneath the inflated self-image. Rather than motivating self-improvement, envy in narcissistic personality disorder (NPD) triggers defensiveness and resentment. These individuals may react to feelings of envy by devaluing others or exaggerating their own achievements to protect their unstable sense-of-self. For instance, in the role play, Dr. Puder lamented, “My best friend got in everywhere and to all the graduate programs that I didn’t get into. We studied together, took the same classes, were in the same research lab—pretty much identical in terms of grades and extracurriculars. Yet he gets in everywhere, and I don’t get in anywhere. What the heck?” This reflects a painful awareness of being outperformed despite feeling equally deserving. Envy challenges their self-worth and highlights their perceived lack of something essential, as seen when a patient exclaims in frustration, “How could they not see how awesome I would be?”

Rather than using envy as a catalyst for growth, it exacerbates their feelings of inferiority, leading them to externalize blame or feel victimized by perceived injustices. The inability to tolerate feelings of envy often leads them to react defensively or aggressively, rather than using the emotion constructively. For example, in the role play, Dr. Puder directed envy toward the therapist by stating, “I don’t think there’s any way that you could know how this feels because you have obtained the pinnacle of success.” This demonstrates how envy can manifest as comparisons to the therapist, making it difficult for the individual to accept feedback or reflect on their own vulnerabilities. Instead of introspection, envy triggers a need to dismiss or surpass others, reinforcing narcissistic behaviors.

This unresolved envy ultimately impairs emotional growth and interpersonal connection, further reinforcing narcissistic patterns and hindering progress in therapy. A patient might even question the value of therapy itself, saying, “Therapy feels so painful, others seem to enjoy it, but it is so hard for me… I question if I should even do this,” reflecting how envy of others’ perceived happiness can lead to despair and withdrawal from the connection going on in therapy. To move through envy constructively, patients must first acknowledge the feeling without judgment and explore what it reveals about their own unmet desires, transforming it into a tool for self-reflection rather than a source of resentment. This can be followed by identifying small, actionable steps toward their own goals, while simultaneously learning to appreciate and celebrate another person’s unique hero’s journey. The inability to sit with envy and process it in a healthy way blocks emotional development, as it turns potentially constructive emotions into barriers that prevent meaningful change.

Impaired Empathy in Narcissistic Personality DisorderIndividuals with NPD often struggle with empathy, despite believing they understand others’ emotions. However, their understanding is typically self-serving, shaped by envy or an inflated sense of superiority. In the role play, Dr. Puder demonstrates impaired empathy by saying, “Are you laughing at my comment here? I’m trying to pour out my heart, and I feel like you’re making light of this.” This reveals an inability to consider the therapist’s benign intent, instead interpreting the situation through a self-focused lens. When envious, they find it difficult to celebrate or feel excited for others’ victories, as their envy clouds their ability to appreciate others’ success. Similarly, when overly confident in their own perspective, they lack the curiosity necessary to explore what they may be missing about others’ experiences. This inability to acknowledge others’ emotions or intentions was evident when Dr. Puder fixated on his own perception of being misunderstood, disregarding the therapist’s genuine efforts to connect. This failure to step outside their own viewpoint or feel joy for others reinforces relational difficulties and emotional isolation.

Black-and-White Thinking in Narcissistic Personality Disorder: Difficulty Tolerating Ambiguity and Rigidity in PerceptionIndividuals with NPD often struggle to tolerate ambiguity in relationships, leading to rigid, black-and-white thinking. They may idealize or devalue others based on minor changes in behavior, causing them to oscillate between admiration and devaluation. This pattern frequently disrupts therapeutic alliances, as they may interpret the therapist’s actions in polarized terms, vacillating between idealization and mistrust. For example, in the role play, Dr. Puder quickly shifts to devaluation with comments like, “Is this what I’m getting from Harvard? Is this what I’m getting?” and “Are you laughing at my comment here? I’m trying to pour out my heart, and I feel like you’re making light of this.” Such statements illustrate how even minor misinterpretations can be perceived as betrayals. Additionally, the patient dismisses the therapist’s empathy with, “I don’t think there’s any way that you could know how this feels because you have obtained the pinnacle of success.” These responses reflect how perceived threats to self-esteem or attachment needs activate defensive mental states that disrupt mentalizing, making it difficult for them to accept feedback or reflect on their own vulnerabilities.

Externalizing Blame in Narcissistic Personality Disorder: How the Teleological Mode Undermines Self-GrowthIndividuals with NPD often externalize blame, attributing their failures or challenges to external factors rather than acknowledging their own role in the issue. This defense mechanism serves to protect their fragile self-esteem and preserve their grandiose self-image. Instead of reflecting on their own vulnerabilities or mistakes, they shift the responsibility elsewhere, which allows them to avoid confronting the deeper emotional insecurities tied to their sense of self. This externalization is partly rooted in the teleological mode, where individuals focus excessively on external achievements (e.g., success, status, appearance) to define their self-worth. In this mode, self-esteem becomes contingent on measurable, external indicators rather than a realistic, internally grounded sense-of-self. When these external markers are threatened or questioned, they externalize blame to preserve their fragile self-worth. This mode prevents them from developing a solid sense-of-self, which, according to Nancy McWilliams, ideally comes from emotional regulation, self-reflection, and integration of both successes and setbacks. By avoiding responsibility and focusing on external validation, individuals with NPD reinforce their reliance on distorted self-concepts and prevent meaningful emotional growth.

Self-Esteem Triggered Mentalizing FailuresMentalizing difficulties in NPD are often heightened when self-esteem is challenged. When individuals perceive a threat to their self-worth or attachment security, they may shift into defensive, non-mentalizing modes, resulting in behaviors like devaluation or idealization of others to protect their self-image. Potential triggers for such responses include:

• Losing a prestigious job or title, which undermines their sense of status and competence.
• Aging or changes in physical appearance, which may threaten their self-image tied to attractiveness.
• Public criticism or negative feedback, especially in front of others, leading to feelings of humiliation.
• Social comparisons where peers achieve greater success, status, or recognition.
• Financial setbacks or losing material possessions that were symbols of their success.
• A loved one or close friend succeeding in areas they feel insecure about, triggering envy and self-doubt.
• Social exclusion, like not being invited to important events or gatherings.
• Failing to meet personal or professional goals, leading to intense feelings of inadequacy.
• Loss of admiration or attention from others, especially on social media platforms.

These experiences would be challenging for anyone, but for someone without a strong, stable sense-of-self, they can become truly tragic. This protective response to perceived threats can manifest as entitlement, blame-shifting, or withdrawal in relationships, making it difficult to maintain consistent engagement in therapy. By externalizing blame and focusing on external validation, individuals with NPD prevent themselves from engaging in self-reflection and emotional growth.

Implications for Therapy and Reflective FunctioningThese mentalizing impairments are thought to play a role in the developmental pathway of narcissistic pathology. In therapy, enhancing reflective functioning—a core skill within mentalization—has shown promise in improving outcomes for individuals with personality disorders, including NPD. By helping individuals recognize the subjectivity of their perspectives and the potential bias in their interpretations, therapy can support patients in moving away from rigid self-perceptions and developing more flexible, empathetic ways of relating to others.

In sum, the impairments in mentalizing associated with NPD contribute to a self-centered, defensive orientation that challenges therapeutic progress. Addressing these mentalizing deficits, particularly by targeting reflective functioning, enables individuals with NPD to cultivate a more nuanced understanding of themselves and others, fostering greater relational stability and personal growth.

Aims and Treatment Strategies in the Development of the Mentalization-Based Treatment (MBT) Model for NarcissismThe development of MBT for pathological narcissism (PN) emerged from a need to address the distinctive challenges posed by narcissistic pathology. Built on the foundation of mentalizing theory, MBT for pathological narcissism was adapted to focus specifically on issues like self-esteem regulation and defensive structures that obstruct mentalization (Drozek & Unruh, 2020; Drozek et al., 2023). Clinical observations revealed that patients with pathological narcissism benefit significantly from structured mentalization exercises, which help them build emotional awareness and relational stability. The introduction of MBT groups for narcissism creates a controlled setting for practicing these skills, allowing participants to engage in real-time mentalization with peers facing similar challenges.

This approach counters the misconception that individuals with pathological narcissism are “untreatable” or resistant to change. Positive outcomes from MBT groups have shown that, with consistent intervention, patients with pathological narcissism can experience meaningful growth in emotional regulation, impulse control, and empathy. These encouraging results are documented in a published paper and an accompanying manual, which now provide clinicians with guidance on implementing MBT for narcissism.

Primary Aims of MBT for NarcissismThe primary aim of MBT for narcissism is to enhance the capacity to mentalize across three domains—content, context, and process—which are central to achieving self-awareness and relational resilience:

1. Content Domain: This domain focuses on increasing awareness of internal states, such as emotions, thoughts, and intentions. Structured interventions encourage patients to explore their inner experiences and examine how these experiences influence interactions with others. By starting with less emotionally charged content, therapists build a foundation that allows patients to engage with more complex, vulnerable emotions over time.
2. Context Domain: The context domain emphasizes situational awareness, helping patients recognize the specific triggers that activate narcissistic processes. By reflecting on how context influences their reactions, patients begin to understand the conditional nature of their responses and can gradually work toward modifying maladaptive patterns. This exploration supports insight into how relationships and self-esteem are influenced by situational factors, providing a basis for more adaptive responses.
3. Process Domain: This domain addresses the relational dynamics that shape a patient’s thoughts and feelings in the moment. By examining these interactions in real time, patients learn to approach relationships with increased flexibility and reduced defensiveness. The goal is to help them recognize and reflect rather than react impulsively, fostering healthier relational dynamics and greater resilience in social situations.

Key Treatment Strategies in MBT for NarcissismMBT for narcissism employs several specific strategies to support these aims: Structured Emotional Regulation: A structured approach to emotional regulation enables patients to stabilize their emotional responses, an essential step before deeper mentalizing work can occur. This focus on managing impulsivity and regulating emotions helps patients build continuity in therapy. * Scaffolded, Stepwise Approach: MBT utilizes a stepwise approach, beginning with less emotionally intense topics to establish a secure foundation. This method allows patients to feel safer before exploring more vulnerable emotional areas, promoting gradual engagement with complex emotions. * Empathy and Perspective-Taking: Strengthening empathy and perspective-taking skills is essential for helping patients understand the impact of their behavior on others. Therapists work with patients to distinguish between intention and impact, fostering a nuanced understanding of interpersonal dynamics. * Contingent and Marked Validation: Therapists employ contingent validation to acknowledge patients’ emotions without reinforcing narcissistic self-enhancement. This technique involves validating the patient’s feelings while subtly challenging underlying assumptions, promoting curiosity and alternative perspectives. * “Reflect, Not React”: A core strategy in MBT is teaching patients to “reflect, not react.” This approach encourages patients to pause and consider their thoughts and emotions rather than responding impulsively. This skill is especially important for managing tendencies like perfectionism and attention-seeking. * Educational Component on Narcissistic Traits*: An educational aspect is incorporated to help patients understand the roots and impacts of their narcissistic traits. By contextualizing their symptoms, patients can reduce self-stigma, facilitating better engagement with mentalizing exercises.

By targeting these three domains—content, context, and process—MBT for narcissism aims to cultivate a balanced and resilient self-concept. This structured, reflective approach enables patients with PN to improve their self-awareness, interpersonal empathy, and emotional regulation, fostering lasting change in their relationships and sense-of-self.

Role of Group Psychotherapy in the Treatment of NarcissismGroup psychotherapy plays a critical role in MBT for narcissism, providing an interactive space where individuals can observe, reflect on, and engage with others in a structured setting. Group members have opportunities to receive immediate feedback and witness the mental and emotional states of others, which supports the development of empathy. This format is particularly valuable for individuals with pathological narcissism, as it allows them to engage in real-time interpersonal exchanges that challenge their usual relational patterns.

In MBT groups, the focus on mentalizing within a peer environment fosters a deeper understanding of one’s own and others’ perspectives, which is essential for improving relational stability. Over time, participants gain the ability to maintain a more balanced view of themselves and others, cultivating resilience against shame-driven responses and enhancing their capacity for empathy. This group dynamic has proven effective in helping individuals with pathological narcissism achieve substantial and lasting interpersonal growth.

Abstract Discussion and the Need for Concrete ClarificationPatients with NPD often engage in therapy through abstract discussions. They might speak in generalizations or offer broad insights about themselves or others, such as “I am the sort of person who always strives for perfection,” or “Her problem is that she is too codependent.” While these statements provide some self-perception, they can avoid deeper emotional engagement and maintain a self-enhanced image.

What to Say Next: Facilitating Concrete ExplorationTo move beyond abstract discourse, it is essential to guide the patient toward concrete experiences and specific events. This involves asking open-ended questions that encourage the patient to describe actual situations and their behaviors within them. For example:

• “Can you walk me through what happened during that interaction?”
• “What did you say to her when she expressed her feelings?”
• “How did you feel in that moment when she responded to you?”

These questions help ground the conversation in reality, allowing both the therapist and the patient to explore the nuances of their experiences.

How to Say It: Emphasizing Empathy and Non-JudgmentWhen prompting the patient for more detailed information, it is crucial to maintain a stance of curiosity and empathy. The therapist should avoid judgmental tones or leading questions that might provoke defensiveness. Instead, use a gentle and supportive approach:

• “I'm interested in understanding more about that situation.”
• “It might help to look at what specifically happened so we can explore it together.”
• “Let's consider how that interaction unfolded from both perspectives.”

This manner of communication fosters a safe therapeutic environment where the patient feels heard and validated, reducing the need to rely on defenses.

Applying Reflective Function to Enhance MentalizingThe goal of these interventions is to strengthen the patient’s reflective functioning—their ability to understand and interpret their own and others’ mental states. By focusing on factual clarification before delving into feelings (“facts before feelings”), the therapist helps the patient build a more accurate and less distorted narrative of events.

Once the concrete details are established, the therapist can guide the patient toward reflecting on their internal experiences and the perspectives of others involved:

• “What was going through your mind when that happened?”
• “How do you think she might have felt in that situation?”
• “What does this interaction tell us about your relationship with her?”

This process encourages the patient to consider multiple viewpoints and recognize the complexity of interpersonal dynamics, which is often a challenge for individuals with PN due to their self-focused orientation.

Outcome: Building a More Balanced Self-PerceptionBy integrating reflective function into therapy, patients begin to articulate a picture of reality that is less dictated by their needs for self-enhancement. They develop greater self-awareness and empathy, which are critical for improving interpersonal relationships and reducing narcissistic processes. Over time, this approach can lead to meaningful changes in behavior and emotional regulation, supporting the overall goals of treatment for pathological narcissism.

Prevalence of Anger-Related Emotions in Pathological Narcissism and Expanding Emotional AwarenessMany individuals with pathological narcissism display anger as a predominant emotion within their narratives. This often accompanies behaviors of self-enhancement, such as devaluing others, emphasizing personal strengths, or recounting instances of being mistreated, casting others as the problem. These tendencies help the individual maintain a sense of superiority and protect them from feelings of vulnerability.

Response: Using the Affect Elaboration Pathway in MBTIn response to this prevalent anger, MBT introduces the affect elaboration pathway specifically tailored for pathological narcissism. This approach encourages individuals to broaden their emotional awareness, moving beyond anger to consider a wider range of feelings, including more vulnerable emotions like sadness, insecurity, or desires for connection.

Therapists initiate this process by asking questions that prompt exploration of underlying feelings. For example:

• “So, when he called you a ‘loser,’ what emotions did that bring up for you?”
• “How did that make you feel about yourself?”

These questions facilitate a deeper examination of the emotional response, helping patients acknowledge feelings they might otherwise suppress or overlook. This approach supports the patient in recognizing the layered emotions beneath their anger, fostering a richer emotional awareness that can improve self-understanding and interpersonal relationships.

Reflective functioning (RF) refers to the ability to recognize and interpret mental states, both in oneself and others, with nuance and depth. When assessing RF, low ratings typically indicate responses that are self-centered, simplistic, or lacking in complexity, while higher ratings reflect a sophisticated understanding of the interplay between thoughts, feelings, and behaviors.

For an individual with NPD who solely expresses anger, their RF will be rated low. This type of response often reflects a rigid, concrete mental state that overlooks alternative emotions or perspectives. Self-focused expressions that include self-enhancing or other-devaluing statements often indicate limited mentalization, revealing a minimal capacity to reflect on more vulnerable feelings, such as hurt or insecurity, that might underlie the anger. These responses can seem rote or one-dimensional, with little explicit reference to the mental states of others, consistent with descriptors of low RF in the manual.

In contrast, a response that integrates a range of emotions—such as shame, disgust, guilt, sadness, and insecurity—demonstrates a more advanced RF. For example, if the individual acknowledges feeling insulted but also considers whether their anger masked a sense of inadequacy, this would reflect higher RF. Such a response shows an awareness of the complexity of mental states, an understanding of the defensive nature of certain emotions, and consideration of how these feelings influence their perceptions and actions. This type of nuanced reflection aligns with higher RF ratings, where respondents show an effort to “tease out mental states underlying behavior” and recognize diverse perspectives.

Encouraging individuals with pathological narcissism to explore these underlying emotions facilitates mentalization by fostering a more balanced self-concept, ultimately strengthening reflective function.

Disconnection from Self and Others: The Role of Pretend Mode in Pathological NarcissismIn pathological narcissism, patients frequently exhibit a disconnection from their authentic emotions and desires, often engaging in therapy from a cognitive, detached stance rather than an emotionally grounded one. This phenomenon, referred to in MBT as “pretend mode,” presents a significant barrier to therapeutic progress. In pretend mode, patients intellectualize or theorize about their experiences without genuine emotional involvement, reinforcing defensive structures and limiting opportunities for self-reflection. This detachment hinders the patient’s capacity to form meaningful connections with others and undermines the potential for true mentalization—the ability to understand oneself and others in terms of mental states.

The Reflective Functioning (RF) Manual provides valuable insights into the characteristics of low RF, which closely align with the features of pretend mode. Low RF responses tend to be superficial, self-focused, and lacking in emotional complexity. A patient in pretend mode may discuss events abstractly, often omitting references to their own emotional responses or personal vulnerabilities. According to the RF Manual, such responses lack depth and fail to recognize the range of internal experiences, thus meriting a low RF rating. They reflect a limited capacity for mentalization, as the patient often disregards the mental states of themselves and others, focusing instead on external, intellectualized narratives.

Interventions to Disrupt Pretend Mode and Reconnect with Authentic EmotionsTo counteract pretend mode, MBT utilizes a range of interventions that aim to re-establish an emotional connection and facilitate higher RF. Rather than engaging with the patient’s intellectualized narrative—which often perpetuates pretend mode—therapists guide the conversation toward the patient’s immediate experiences and emotions. These techniques are consistent with the RF Manual’s criteria for moderate to high RF, which involve recognizing multiple mental states, conflicting emotions, and situational influences.

Effective interventions include:

• Moving from general to specific: By asking patients to provide concrete examples (e.g., “Can you give me a recent example of this?”), therapists help them ground their narratives in real-life events, thereby promoting a more authentic exploration of emotions. This shift away from abstraction encourages patients to connect with their actual experiences, fostering a richer understanding of their emotional responses.
• Directing attention to present affect: Encouraging patients to articulate their immediate feelings or desires (e.g., “Could you try to put words onto what you are wanting right now?”) interrupts the intellectualized discourse and directs attention to current emotional states. This focus on the present helps patients break away from detached reflections and re-engage with genuine emotions.
• Naming what is absent: Pointing out missing emotional content—such as saying, “You’re sharing a lot of insights, but I can’t tell what you’re feeling as you sit here with me”—raises awareness of the emotional gaps in the patient’s narrative. This prompts the patient to consider their lived emotional experience, enhancing the capacity for self-reflection and mentalization.
• Directly challenging pretend mode: In MBT, a “challenge” is a surprising, irreverent, often provocative comment that has the effect of “waking patients up” to more authentically access their own emotional states, or to consider the mental states of the therapist. This can involve the therapist self-disclosing their own emotions (“I am feeling a vague sense of dread right now”), making a humorous comment, saying something bizarre or strange (“I am not really in the room right now”), directly contradicting patients’ perspective; or highlighting an aspect of reality that patients are ignoring or minimizing (“I know you’re extremely hopeful that you will get back together with your ex. Do you ever think about the fact that she’s actively dating other people?”).

These interventions work collectively to “pop the bubble” of pretend mode, reconnecting patients to their authentic selves and enabling genuine therapeutic work. The RF Manual emphasizes that high RF is marked by an awareness of emotional complexity, conflicting feelings, and the mental states of both self and others. By guiding patients in pretend mode to reconnect with their immediate affective experiences, MBT supports the development of higher RF, promoting a balanced and cohesive sense-of-self. This progress is essential in treating PN, as true mentalization—and, consequently, the ability to form meaningful relationships—requires an emotionally engaged and reflective stance.

What is psychic equivalence and how does it emerge?Psychic equivalence is a phenomenon in which individuals equate their internal experiences and beliefs with external reality, perceiving their subjective emotions as objective truths. This cognitive distortion is common in personality disorders like borderline personality disorder (BPD) and is particularly prominent in narcissistic personality disorder (NPD), where rigid self-focused beliefs can lead to the devaluation of others. Research on mentalization and attachment theory provides insight into several key factors that contribute to the emergence of psychic equivalence:

1. Attachment and early development: Secure attachment experiences in early development are foundational to the capacity for mentalization—the ability to understand oneself and others in terms of mental states. However, individuals with insecure attachment histories often struggle with this skill. When caregivers provide inconsistent, dismissive, or intrusive responses, children may lack sufficient experiences of having their emotions accurately mirrored. This deficit in reflective interaction leads them to experience thoughts and feelings as undifferentiated from reality, resulting in psychic equivalence. For example, a child who feels anger but lacks validation may grow up assuming that their anger reflects others’ intentions, rather than merely their perception​.
2. Developmental factors and the failure to mentalize: Psychic equivalence is part of what MBT describes as prementalistic modes of functioning—modes of cognition that antedate full mentalizing abilities. In these modes, thoughts and feelings are either overly concrete (psychic equivalence), detached and hypothetical (pretend mode), or understood only in terms of physical actions (teleological mode). These modes can emerge when an individual’s mentalizing capacity is compromised, often due to developmental delays in achieving self-other differentiation. Consequently, under stress or emotional arousal, they revert to perceiving their subjective states as tangible truths.
3. Trauma and emotional dysregulation: Trauma, particularly early in life, has a profound impact on mentalization. Emotional arousal during traumatic experiences can reinforce the association of feelings with absolute truth, as trauma often disrupts the ability to distinguish between inner states and the external world. This heightened emotional reactivity contributes to psychic equivalence by making intense emotions, such as fear or anger, seem like reliable indicators of external threat or hostility. Studies show that trauma survivors, particularly those with BPD, may interpret strong emotions as direct reflections of others’ intentions, without questioning the subjectivity of these feelings​.

In summary, psychic equivalence is rooted in developmental experiences that limit the capacity for mentalization. Secure attachment, emotional validation, and the opportunity to reflect on one’s inner world are critical in preventing this rigid mode of thinking.

Devaluation of Others and the Role of Psychic Equivalence in NPDIn narcissistic personality disorder (NPD), patients often maintain rigid, devaluing views of others, frequently emphasizing their own superiority. This tendency to view others through a fixed, critical lens reflects the MBT concept of psychic equivalence. For individuals with NPD, this mode of thinking results in equating their negative evaluations of others with objective reality, leaving little room for alternative interpretations. This cognitive rigidity and conflation of subjective experience with fact hinder reflective function, demonstrating a minimal capacity for self-reflection or empathy toward others’ mental states.

Psychic equivalence, by encouraging a single, unchanging view of others, blocks the development of mentalization—the ability to understand oneself and others in terms of mental states—and reinforces maladaptive structures. Individuals in this mode may find it difficult to consider that others could have intentions or feelings different from their own perceptions. This limits flexibility and empathy in relationships, as they are often unwilling or unable to see beyond their own perspective.

Response: Interventions to Disrupt Psychic Equivalence and Foster Reflective FunctionTo address this rigidity and encourage a shift toward mentalizing mode, MBT employs a trajectory of interventions designed to gradually introduce nuance, empathy, and self-reflection. Each intervention corresponds with the RF Manual’s criteria for higher RF, which involve recognizing multiple perspectives, exploring the underlying motivations for rigid views, and appreciating the complexity of relationships.

1. Empathic validation: Beginning with empathic statements, such as, “It sounds like this was a really challenging interaction,” helps build rapport and reduces defensiveness. This approach establishes a safe space where the patient feels understood, enabling them to consider alternative perspectives without feeling criticized. It also models for the patient an alternative way of engaging with emotions and conflicts, fostering an environment where flexibility in thinking is more possible.
2. Inviting articulation of their process: By asking patients to describe how they reached their rigid views (e.g., “What clues you in that she was trying to humiliate you?”), therapists encourage patients to reflect on the assumptions underlying their certainty. This exploration aligns with the RF Manual’s moderate RF levels, where individuals begin to acknowledge that their perceptions are influenced by internal states and may not always reflect objective reality. This process disrupts the equivalence between perception and fact, nudging the patient toward seeing their beliefs as interpretations rather than absolute truths.
3. Examining the impact of certainty: Encouraging patients to reflect on how their rigid views affect them (e.g., “How does it affect you when you focus so much on her deficiencies?”) helps them see the broader consequences of psychic equivalence. This reflection can illuminate the negative emotional and relational impacts of their beliefs, potentially motivating them to reconsider their approach. As the RF Manual notes, awareness of how one’s own mental states affect behavior and relationships is central to higher RF, as it fosters insight into the role of these beliefs in perpetuating conflict or dissatisfaction.
4. Encouraging nuance: Introducing questions that invite complexity, such as, “Is she always so critical of you, or are there times when she treats you more positively?” helps patients expand their perspective. This intervention challenges black-and-white thinking and opens the possibility that others might have mixed or variable intentions. This greater flexibility is a hallmark of moderate to high RF, where individuals demonstrate an ability to hold multiple, sometimes conflicting views about others.
5. Offering a therapeutic perspective: Finally, sharing an observation, such as, “I know you see her as treating you poorly, but sometimes it has struck me that you can be a bit aggressive to her as well,” encourages the patient to consider how their actions and demeanor influence their relationships. This feedback invites the patient to reflect on the interaction from a more relational perspective, a characteristic of high RF that requires recognizing the impact of one’s own behavior on others’ responses.

Fostering Higher RF and Moving Toward Mentalizing ModeTogether, these interventions aim to disrupt psychic equivalence by fostering a more balanced, flexible, and empathetic approach to relationships. In shifting from a fixed, self-focused stance to a mentalizing mode, patients with NPD can begin to appreciate the diversity of mental states in themselves and others, achieving higher levels of RF. This process is essential for effective therapy, as it allows individuals to replace defensive, devaluing patterns with genuine self-reflection and connection. By enhancing reflective function, MBT enables patients to form more meaningful interpersonal relationships and to develop a more integrated sense-of-self that embraces complexity and change.

External Standards for Self-Worth: The Role of Teleological Self-EsteemIn some individuals, self-worth and self-esteem are closely tied to external standards, leading to significant self-criticism when they fail to meet these standards. This phenomenon, described in MBT for narcissism as teleological self-esteem, occurs when a person’s sense of self-worth is dependent on achieving specific external goals or maintaining particular roles (Drozek et al., 2023). For example, a patient might believe, “I am worthless because I lost that job,” interpreting the external failure as a direct reflection of their intrinsic value. This mode of thinking is rigid and can prevent a more balanced and internalized sense of self-worth, leaving the individual vulnerable to significant emotional distress when external achievements or validations are lacking.

Teleological self-esteem aligns with teleological mode, one of the prementalistic modes of functioning in MBT. When in teleological mode, individuals require tangible, external evidence to validate their internal feelings or self-concept. When applied to self-esteem, this results in a dependency on external achievements to feel worthwhile, undermining the ability to maintain a stable self-concept independent of circumstances. Research indicates that such externalized standards are often associated with low RF, as described in the Reflective Functioning Manual, where responses tend to be concrete and overly reliant on external markers without introspective reflection.

Interventions to Encourage Internalized and Reflective Self-WorthTo address teleological self-esteem, MBT interventions focus on promoting reflection and helping patients question the perceived necessity of external validation for self-worth. These techniques are aimed at fostering a more balanced and internally grounded sense-of-self, aligning with higher RF, which emphasizes awareness of the subjective nature of mental states.

1. Empathic validation: By validating the patient’s experience (e.g., “So at this point, you feel like you absolutely need to get your old job back.”), the therapist acknowledges the importance the patient places on the external standard. This step creates a supportive environment in which the patient feels understood, laying the foundation for further exploration of their beliefs.
2. Exploring emotional meaning: Encouraging the patient to examine what the external factor represents emotionally (e.g., “This sounds so important. Can you tell me more about what makes this the perfect job for you?”) allows them to explore underlying motivations and feelings. This approach aligns with higher RF, as it prompts the patient to move beyond surface-level interpretations and consider the deeper significance of their goals and standards.
3. Examining the impact of externalized standards: Helping patients reflect on the consequences of tying self-worth to external achievements (e.g., “How does this impact you—to not have the only thing that would make you feel good about yourself?”) fosters insight into how teleological self-esteem may be limiting or damaging. This intervention encourages patients to consider how this dependency might affect their overall well-being and stability.
4. Explicating the link between external achievements and self-worth: By explicitly linking the external factor to the patient’s sense of self-worth (e.g., “So for you, your old job [external factor] was literally the source of your self-worth [internal process]—without it, you have nothing, and you are nothing.”), the therapist helps make this dependency more conscious. This awareness can motivate the patient to explore alternative sources of self-worth.
5. Questioning the permanence of external validation: Inquiring about the sustainability of external achievements as a source of self-esteem (e.g., “So if you were to get your job back, would it make you feel good about yourself permanently, once and for all?”) challenges the patient’s assumption that external validation can provide lasting self-worth. This prompts reflection on whether an internalized sense-of-self might offer more stability.
6. Gently offering an alternative perspective: Carefully sharing an alternative viewpoint (e.g., “I am hearing that, for you, that job is the only way for you to have a sense of self-worth. While you may be right about that, personally, there’s something that just doesn’t feel right about the idea that your only value comes from your professional achievements.”) introduces the possibility of developing a more balanced, intrinsic sense of self-worth. This approach aligns with high RF by promoting awareness of mental states as subjective and encouraging flexibility in self-concept.

Integrating Reflective Functioning and Teleological Self-EsteemThe Reflective Functioning Manual suggests that higher RF involves the capacity to reflect on the subjective and provisional nature of one’s own beliefs, rather than seeing them as absolute truths. By helping patients question the rigid link between external factors and self-worth, MBT supports the development of higher RF, fostering a more resilient and internalized sense-of-self. These interventions enable patients to gradually replace teleological self-esteem with a stable, reflective self-concept that can endure regardless of external achievements or failures. This shift is crucial for achieving therapeutic progress, as it allows patients to maintain self-worth independently, facilitating healthier and more balanced interpersonal relationships.

Introduction to the Role Play: Exploring Mentalization in Narcissistic PatientsThis section delves into a role play exercise designed to demonstrate how mentalization-based treatment (MBT) can be effectively used with patients exhibiting narcissistic traits. The therapists, Dr. Puder and Mr. Drozek, simulate a session to highlight the common challenges of working with individuals who maintain rigid, black-and-white views about their relationships. Narcissistic patients often present with a sense of certainty and negative judgment toward others, which can serve as a defense against underlying feelings of inadequacy and vulnerability.

In the role play, Dr. Puder portrays a patient struggling with intense anger and resentment towards his wife, whom he perceives as unfairly critical despite his efforts. Mr. Drozek, in the role of the therapist, utilizes MBT techniques to explore the patient’s rigid perspective without directly challenging it. By staying attuned to the patient’s experience and gently guiding him to reflect on moments of connection in his relationship, the therapist aims to introduce subtle uncertainty into the patient’s narrative. This approach helps to expand the patient’s mentalizing capacity, encouraging him to move beyond his defensive certainty and consider alternative perspectives.

The role play illustrates key principles of MBT, such as the importance of empathic validation, the use of a non-confrontational stance, and the gradual exploration of the patient's subjective experience. This technique fosters a therapeutic environment where the patient feels understood, allowing for deeper emotional exploration and the potential for meaningful change.

Drozek:
Okay, so this approach really stems from Anthony’s formulations about treating personality disorders more generally. We didn’t do anything entirely new here. The most common form of certainty you’ll see in many individuals with narcissism involves a negative judgment of the other person. For example, “My wife is too critical of me.” That’s often the kind of negative judgment we encounter. In MBT, we wouldn’t challenge that perspective immediately; instead, we would start by saying, “Okay, tell me more. In what ways is she so critical?” You guide them to build their case and then explore the impact on the patient. For instance, “Wow, so when she treats you that way, how does that affect you? What feelings does that bring up for you?” We don't challenge it at first because the goal is to align with their perspective. But if we only do that, we're not truly helping patients to develop a more flexible outlook. So, we have to take it further, which is what Anthony has envisioned.

Puder:
Okay, let’s jump into this. I’ll be the narcissist here, alright?

Drozek:
Cool.

Puder:
Well, it brings up rage for me, Bob. Absolute rage.

Drozek:
Okay. Tell me more. What’s the rage about?

Puder:
It feels so disrespectful, you know?

Drozek:
Yeah, yeah.

Puder:
I’m working my butt off, you know? I do the dishes, and then I hear criticism. It’s like, “Hey, I’m doing a lot here.”

Drozek:
Absolutely. So you’re working really hard, putting in so much effort, and it’s enraging that she would speak to you that way.

Puder:
Yeah, exactly what I said, Bob. Good—you’re repeating back to me exactly what I’m saying.

Drozek:
(Laughs) I know.

Puder:
Is this what I’m getting from Harvard? Is this what I’m getting?

Drozek:
Well, that’s fair. I’m just curious—has she always been this way?

Puder:
Wait, are you laughing at my comment here? I’m trying to pour out my heart, Bob, and I feel like you’re making light of this.

Drozek:
I’m sorry, I apologize. I thought you were joking with the Harvard comment. I appreciate that.

Puder:
No, I was joking (laughs).

Drozek:
Okay, just to be clear—let’s keep going. Has she always been this way?

Puder:
No, I mean, in the beginning—maybe the first six months—she was very supportive. Then something flipped.

Drozek:
I see. And when she was more supportive, how did she treat you?

Puder:
Oh, everything was positive, warm, and full of gratitude.

Drozek:
Now I’m curious—this past week, were there any days when she was better, maybe kinder, than usual?

Puder:
Yeah, maybe.

Drozek:
Okay. What did she do on that day?

Puder:
She greeted me with a hug. That was nice.

Drozek:
Yeah? What was that like?

Puder:
I don’t know. It was... nice, you know?

Drozek:
It sounds nice. I appreciate you putting words to it because it seems like you work incredibly hard, and it doesn’t feel fair that she’s critical. Yet, there are these moments where she’s kinder, warmer, and you see a different side of her. That must be confusing.

Feedback and AnalysisUnruh:
What we just saw was Bob responding to you, David, without challenging or questioning your initial perspective. That’s a core principle in MBT, particularly when treating narcissism. It’s important to start by aligning with the patient’s subjective experience. Bob did not question or criticize but instead asked clarifying questions to explore how you arrived at your perception of your wife as critical.

Unruh:
Even though Bob might have thought, “This sounds overly certain or rigid,” he didn’t press on that immediately. Instead, he used reflective questioning to introduce some nuance, asking about moments when your wife was supportive. The aim here is to slowly shift the patient from a position of certainty to one of curiosity—getting them to see that maybe things aren’t always black and white. That’s where mentalizing begins, by opening up space for different perspectives.

Bateman:
Exactly. The goal is to expand the patient’s field of discovery. You start with a very narrow focus—“My wife is critical”—and gently expand it by exploring other moments and experiences. This is done from a not-knowing stance, where you accept the patient’s perspective without challenging its validity. It’s about creating space for exploration, not dismantling their views outright.

Reflection on the Role-PlayThis role play exercise demonstrates how MBT can be a powerful tool in working with narcissistic patients who are entrenched in rigid, defensive patterns. By adopting a stance of empathic validation and non-confrontational curiosity, the therapist begins to gently unravel the patient’s certainty and defensive posturing. This approach is crucial in treating individuals with narcissistic traits, who often struggle with a disconnection from their authentic emotions, as highlighted earlier in the document.

The technique of mentalization—exploring the patient’s feelings without immediately challenging their narrative—aligns with the broader theme of helping patients move beyond pretend mode. Narcissistic individuals often intellectualize their experiences to avoid confronting deeper vulnerabilities, keeping them trapped in self-reinforcing cycles of blame and resentment. By shifting the focus from an externalized, black-and-white perspective to a more nuanced exploration of internal states, MBT helps patients reconnect with their genuine emotional experiences.

Ultimately, this role play underscores a central theme of the document: the importance of creating a therapeutic space that allows for the gradual development of reflective functioning. In doing so, patients can begin to recognize and tolerate a wider range of emotions, fostering a more cohesive and resilient sense-of-self. This shift is essential not only for reducing pathological narcissistic defenses but also for building the capacity for meaningful interpersonal relationships, which are often compromised in individuals with narcissistic pathology.

Resources:Bateman, A., & Fonagy, P. (2013). Mentalization-Based Treatment. Psychoanalytic Inquiry, 33(6), 595–613. https://doi.org/10.1080/07351690.2013.835170

Bateman, A., Fonagy, P., Campbell, C., Luyten, P., & Debbané, M. (2023). Cambridge guide to mentalization-based treatment (MBT). Cambridge University Press. https://a.co/d/3UAQ98X

Drozek, R. P., & Unruh, B. T. (2020). Mentalization-based treatment for pathological

narcissism. Journal of Personality Disorders, 34(Supplement), 177-203. https://doi.org/10.1521/pedi.2020.34.supp.177

Drozek, R. P., Unruh, B. T., & Bateman, A. W. (2023). Mentalization-based treatment for pathological narcissism: A handbook. Oxford. https://global.oup.com/academic/product/mentalization-based-treatment-for-pathological-narcissism-9780192866134?cc=us⟨=en&

Fonagy, P., Target, M., Steele, H., & Steele, M. (n.d.). Reflective-functioning manual: Version 5 for application to Adult Attachment Interviews. University College London, Sub-Department of Clinical Health Psychology.

Upcoming trainings/conferences on MBT for narcissism featuring Bob Drozek, Brandon Unruh, and Anthony Bateman:Understanding Narcissism: From Healthy to Disordered

Offered virtually through Harvard Medical School

Thursday 1/30/2025 through Friday 1/31/2025

Registration: https://cmecatalog.hms.harvard.edu/course/understanding-narcissism-healthy-disordered

Mentalization-based treatment (MBT) for Narcissism Training

Offered virtually through the Anna Freud Centre in London

Wednesday 2/5/2025, Friday 2/7/2025, and Saturday 2/8/2025

Registration:

https://bookings.annafreud.org/s/event/a4VQ5000000Nok5MAC/mentalizationbased-treatment-mbt-and-narcissism-training?filters&chatterGroupId&utm_source&utm_medium&utm_campaign&sort=Asc

View Details

David Puder, MD

Burnout in healthcare professionals often shows up as depersonalization, an emotional detachment that allows clinicians to shield themselves from the overwhelming trauma they witness on a daily basis. Depersonalization falls into the broader category of dissociation, where a clinician becomes emotionally numb and detached from their patients. It acts as a protective mechanism to shield against overwhelming emotions, but is also something we must actively work through to regain emotional connection.

Dr. Jessi Gold, a psychiatrist and Chief Wellness Officer of the University of Tennessee System, sheds light on these experiences through her work, highlighting the toll burnout takes and offering practical solutions for how healthcare providers can reconnect with their emotional lives.

What Does Depersonalization Look Like In Healthcare Workers?Depersonalization doesn’t happen all at once—it builds gradually as clinicians overexpose themselves to trauma without sufficient emotional processing. As a patient of Dr. Gold explains, it’s a protective mechanism: “Not feeling anything is protective in the job, for sure, and I think it’s good sometimes, but maybe it isn’t good all the time” (How Do You Feel?, p. 56).

When depersonalization occurs, healthcare professionals may feel as though they’re going through the motions, seeing patients as tasks to complete rather than individuals in need of care. This is captured in a common set of experiences that align with the depersonalization domain of the Maslach Burnout inventory, such as:

• “I feel I look after certain patients/clients impersonally, as if they are objects.”
• “I really don’t care about what happens to some of my patients/clients.”
• “I have become more insensitive to people since I’ve been working.”
• “I’m afraid that this job is making me uncaring.”

These statements reflect the emotional distancing that comes with burnout, as clinicians become detached from the empathy that once motivated them. Dr. Gold shares a story about a clinician noticing their own experience with emotional detachment: “...like once at a family dinner when someone asked me about work, I told them about one shift where a bunch of family had died in a car accident, a lot of them kids, and everyone looked so surprised. Some even teared up. And, then there’s me just telling the story like I was ordering a cheeseburger. I didn’t even stop eating dinner” (How Do You Feel?, p. 55).

This numbness isn’t necessarily deliberate—it’s often a way to cope with the relentless exposure to suffering. As one patient describes: “It feels like I’m not processing things like a human” (How Do You Feel?, p. 56). Over time, this lack of emotional processing can lead to deeper feelings of alienation, where healthcare workers feel like they are merely going through the motions, both professionally and personally.

Depersonalization And Dissociation As A Unified ExperienceIn Dr. Gold’s work, the concepts of depersonalization and dissociation often blend together. When clinicians begin to dissociate, the broader category that depersonalization fits into, they are emotionally disconnecting from their environment. As this emotional detachment deepens, clinicians may lose their ability to feel empathy for their patients—and sometimes, even for themselves.

“I used to be able to go into work and see the roses through all of the thorns, but now I only see the thorns. Are there still any roses?” (How Do You Feel?, p. 54). This poignant metaphor illustrates the gradual erosion of joy and meaning in work as depersonalization takes hold.

At its most severe, this process leads to clinicians feeling like they are no longer fully human—just cogs in a broken healthcare machine. As Dr. Gold describes, We healthcare workers regularly see trauma and tragedy in ways that slowly desensitize us... It’s the system that needs fixing, not just us.

The Role Of AlexithymiaOne of the consequences of prolonged depersonalization and dissociation is alexithymia, the inability to recognize or describe one’s own emotions. This can be particularly dangerous for healthcare providers, who rely on their ability to empathize with patients and process their own emotional responses to trauma. Over time, clinicians may lose touch with their emotional states altogether.

Alexithymia often goes hand-in-hand with burnout. A patient of Dr. Gold’s describes how the culture of medical training sometimes discourages the display of emotions: “I remember, in medical school, receiving what were basically subjective evaluations of my personality, in which my supervisors said things like I ‘made faces,’ and I ‘didn’t take my job seriously’ when I acted like myself around patients and supervisors…” (How Do You Feel?, p. 68). Through mentors, we may learn or be encouraged to hide our emotions.

Solutions For Overcoming Depersonalization And AlexithymiaDr. Gold offers several strategies for healthcare professionals to overcome depersonalization, dissociation, and the emotional detachment that accompanies burnout. These solutions are not just about "fixing" the clinician, but also about recognizing the systemic issues that contribute to burnout.

1. Recognizing and Addressing Burnout Early

Dr. Gold emphasizes the importance of catching burnout early, before depersonalization and dissociation become entrenched. “By the time someone shows up in my office, I’m often thinking, ‘I wish you’d come months or even years earlier.’” Recognizing the early warning signs—like feeling other burnout symptoms such as emotional exhaustion or a decreased sense of meaning and purpose at work, can help you catch burnout early.

2. Seeking Therapy to Process Emotions

Therapy is a vital tool for healthcare workers, offering a space to process difficult emotions and reconnect with oneself. Dr. Gold says in the episode, “I would always want a therapist who sees a therapist. I think it’s healthy to admit that our job affects us too”. For clinicians experiencing alexithymia, therapy can help them regain the ability to recognize and describe their emotions, which is essential for both their personal and professional lives.

3. Creating Emotional Boundaries While Staying Connected

While emotional boundaries are necessary for protecting against burnout, Dr. Gold emphasizes that healthcare workers need to find a balance between protecting themselves and staying connected to their patients. “Not feeling anything is protective in the job, for sure, and I think it’s good sometimes, but maybe it isn’t good all the time” (How Do You Feel?, p. 56). Therapy, mindfulness, and regular check-ins with colleagues can help maintain this balance.

4. Challenging Systemic Burnout Causes

Individual solutions are not enough to tackle burnout on their own. Dr. Gold advocates for addressing the systemic issues that drive clinicians to depersonalization in the first place. Sometimes the system says, “You fix you”, instead of fixing itself. That’s what the resiliency conversations have become, and it misses the point—changing the system is what really helps. Institutional change is crucial to preventing burnout, whether through reducing workloads, increasing support staff, or creating environments where healthcare workers feel valued and supported.

5. Reconnecting with the Meaning in the Work

One of the key steps in overcoming depersonalization is rediscovering the meaning in the work. Finding ways to reconnect with the reason you entered the profession—whether through peer support, mindfulness, or creative outlets—can reignite a sense of purpose.

Empathy For Healthcare Providers In BurnoutBurnout is not a personal failing—it’s a response to overwhelming systemic pressures. Dr. Gold’s work offers empathy and understanding for clinicians who find themselves emotionally disconnected from their patients and themselves. She reminds us that it’s not uncommon for healthcare workers to feel numb or disconnected after years of exposure to trauma.

For those struggling with burnout, it’s important to remember that seeking help is not a sign of weakness, but of strength. As Dr. Gold so aptly puts it: “Your story is your story. Tell it when you’re ready, but just know, if a place rejects you for being honest, you probably wouldn’t have fit there anyway.”

By addressing depersonalization, dissociation, and alexithymia head on, healthcare providers can begin to heal, as well as help create a healthier, more sustainable system for everyone.

Further reading:How Do You Feel by Jessi Gold

Connect with Dr. Gold on social media (Instagram, Tiktok, X): @drjessigold and her website drjessigold.com.

View Details

David Puder, MD

Note: Contains spoilers

David Puder, Rachel Blackston and Eric Bender have no conflicts of interest to report.

IntroductionIn this write-up, I reflect on and expand upon insights that emerged from our podcast episode on Inside Out 2. The podcast guests are Rachel Blackston, mother of three and co-owner of a thriving group practice with over 20 therapists in Orlando, and Eric Bender, a psychiatrist who works with adolescents in the San Francisco area and previously joined me in discussing “The Shrink Next Door.”

In Inside Out 2, Riley transitions from childhood into adolescence. The movie introduces new emotions, representing the turbulence and heightened self-consciousness that many teenagers face during this pivotal stage of development.

Setting the Stage: Adolescence and Emotional Transitions in Inside Out 2One of the central themes of Inside Out 2 is the emotional upheaval that accompanies adolescence. As Riley transitions from childhood to her teenage years, we witness the introduction of new emotions—Anxiety, Envy, Embarrassment, and Ennui (Boredom)—which reflect the increasingly complex emotional landscape teens must navigate. This emotional expansion is chaotic but essential to development of internal reflectiveness.

Rachel Blackston shared her personal experience of adolescence within her family, illustrating how accurately the film captures this transition:

“I felt it. A wrecking ball comes into the scene and starts dismantling and disrupting, and that’s sort of what it’s felt like in my household. It’s like Family Island, that used to be the center of everything, gets pushed into the background as Friend Island takes over. Suddenly, as a parent, you’re not the central figure anymore, and that’s a really disorienting experience.”

Family Island—once stable and reliable—begins to fade in importance as Riley’s relationships with peers grow. The metaphor of islands shrinking or growing reflects the real-world shift in a teenager’s priorities as they move through adolescence. A secure attachment with parents provides the emotional foundation needed for teenagers to confidently explore new friendships and navigate the shifting priorities of adolescence.

Adolescence is all about the evolution of identity. The new emotions—Anxiety, Envy, and Embarrassment—are particularly powerful because they represent a teenager’s increasing awareness of how they’re perceived by others. For example, the anxiety Riley feels about how she fits in with her friends and the envy that arises when she sees others doing better or fitting in more easily. These emotions aren’t just disruptions—they’re signs that her self-concept is shifting and expanding.

Dr. Eric Bender added a clinical perspective, connecting these emotional changes to adolescent mental health:

“I see this all the time with my patients. Anxiety especially starts to ramp up as kids hit adolescence. It’s not just that they’re suddenly more emotional—it’s that they’re beginning to realize how others see them, and that’s a massive shift. The fear of not fitting in, of not being good enough, becomes a driving force in their emotional lives. Envy is another big one. It’s natural to compare yourself to your peers, but it can spiral into something destructive if it’s not balanced with a healthy sense-of-self. What I love about Inside Out 2 is that it doesn’t shy away from showing how complicated these feelings can be, especially during this crucial stage of development.” — Dr. Eric Bender

Through these reflections, we see that Inside Out 2 effectively externalizes the complex emotional journey of adolescence, making it easier to visualize and understand.

The Transition To Puberty In Inside Out 2At the beginning of the film, Joy introduces a machine designed to throw bad memories to the back of Riley’s brain (representing the unconscious) as a way to protect her from negative emotions. Joy’s mantra was, “Keep the best, toss the rest.” Now 13 years old, Riley is transitioning to a new school and early in the movie she learns that her friends, Brie and Grace, won’t be attending the same school as her. This revelation shakes her world, marking a significant emotional challenge as she navigates the complexities of adolescence.

Then, the puberty team arrives and causes chaos in headquarters, destroying Joy’s new machine in the process. Riley begins grappling with attachment fears: “I’m not going to be with my friends. What’s going to happen?” A new set of emotions, including Anxiety, enter the scene, adding to her turmoil.

As difficult as this process is for parents—often bringing a sense of grief—it’s essential for them to remain stable through the storm. This development is a crucial part of a child’s sense-of-self and formation of a separate identity from their parents. Without it, kids can become emotionally “stuck.” Parents may long for the days of Inside Out 1, when Riley’s core memories—centered on family moments like ice skating with her parents—were at the forefront, but these memories naturally fade to the background as she grows and new priorities emerge.

The concept of a "sense-of-self" is introduced in Inside Out 2. Before puberty and the Anxiety takes over, Riley’s sense-of-self is built from Joy’s carefully selected memories—all positive, reinforcing the idea that she is a good friend and a good person.

It’s essential for everyone to recognize their inherent worth and value, while maintaining a balanced, reality-based understanding of the unique contributions they bring to relationships—whether as a friend, daughter, or son. These beliefs form the foundation of who we are and how we engage with the world. Because Riley’s childhood was largely positive, her core beliefs and sense-of-self remain stable as she navigates new challenges.

However, not all individuals are as fortunate as Riley in developing a stable sense-of-self. In psychodynamic literature, identity diffusion refers to the difficulty in forming a cohesive and consistent identity, often rooted in early attachment disruptions or unresolved emotional challenges. When this foundational development is interrupted—whether due to trauma, neglect, or inconsistent caregiving—individuals may struggle with a fragmented sense of who they are. Instead of having a stable core identity, they might experience fluctuating self-images, rely heavily on external validation, or feel chronically unsure about their roles, values, or relationships. This lack of a clear identity can lead to emotional instability, poor boundaries, and difficulties in forming meaningful connections. In adolescence, this struggle becomes particularly pronounced, as the natural developmental task of solidifying one’s identity clashes with unresolved emotional wounds from the past.

How Inside Out 2 Could Explore Emotional Trauma and Adverse Childhood ExperiencesMany adults and children have not had the opportunity to properly develop emotionally due to experiencing adverse childhood events (ACEs)—including physical, sexual, or emotional abuse, neglect, domestic violence, or witnessing substance abuse. Research shows that these experiences can lead to long-term changes in the brain and body, such as dysregulation of the HPA axis, heightened amygdala reactivity, and epigenetic changes. These physiological shifts often contribute to emotional and psychological difficulties later in life, including identity diffusion, emotional dysregulation, and challenges in forming healthy relationships (Puder, 2024).

In contrast, Riley from Inside Out does not face significant trauma. Her emotional development follows a normal path, allowing her to form a stable sense-of-self. This is evident in the film, where she successfully navigates early developmental tasks, supported by positive role models and a secure attachment with her parents. As a result, Riley’s core sense-of-self remains intact, and she avoids the deep internal struggles around self-worth and identity that are common among children who experience trauma. In children who have faced early abuse or neglect, thoughts like “I am bad” or “I am worthless” often become deeply ingrained, especially if they enter adolescence without stable role models to help them develop their core identity.

Children who experience disorganized attachment—often due to caregivers who are inconsistent, frightening, or unable to provide reliable comfort—are particularly vulnerable to identity diffusion. Without a secure foundation, these children struggle to form a cohesive sense-of-self and may develop disorganized attachment patterns. As they grow, this can lead to emotional fragmentation, where they lack a stable internal framework to manage their emotions or maintain relationships. This disorganization can result in identity diffusion, where the child feels unsure of who they are, fluctuating between different self-images and relying on external validation to define themselves. Over time, this can manifest as emotional dysregulation, identity disturbance, and dissociative states (Episode 087, Episode 088).

If Inside Out 2 were to explore a character with a high ACE score or disorganized attachment, the emotional landscape would be markedly different from Riley’s. Rather than having a well-developed sense-of-self, a child with a history of trauma would likely experience fragmented emotions, identity confusion, and chronic feelings of emptiness. These symptoms are often seen in individuals with borderline personality disorder (BPD), where identity diffusion leads to unstable emotions, chaotic inner conflicts, and impulsive behaviors as coping mechanisms. This character’s inner world would be far more turbulent, reflecting the complex interplay of trauma, attachment issues, and emotional dysregulation. Where Riley’s emotions are able to coexist and integrate, a traumatized child might find their emotions at odds, leading to inner chaos and difficulty navigating the social and emotional challenges of adolescence (Episode 115).

Exploring such a character would highlight the profound effects of early trauma on emotional development and identity formation, offering a more nuanced portrayal of the struggles faced by children who grow up without the secure attachments and positive experiences that Riley had. It could also provide an opportunity to examine how healing and growth occur, perhaps depicting the character developing resilience through therapeutic relationships, mentorship, or other supportive interventions that help foster a more cohesive sense-of-self.

How Inside Out 2 Depicts Anxiety And Emotional Fragmentation During AdolescenceBy the end of Inside Out, the theme of emotional integration is fully realized as different emotions coexist and contribute to Riley’s sense-of-self. This mirrors real life, where core beliefs like “I’m a good person” and “I’m not good enough” often sit side by side. In Riley’s case, her anxiety inadvertently leads to the emergence of a new critical belief: “I’m not good enough.” These conflicting beliefs coexist within all of us, shaping our identity. The tension between positive and negative self-perceptions is a normal part of emotional development, especially during adolescence when identity formation becomes more complex.

In contrast, individuals who haven’t developed positive core beliefs often experience an imbalance in their self-concept. Instead of holding a mix of positive and negative beliefs, they may internalize a single, dominant thought: “I am bad.” This is particularly common in children who experience neglect or inconsistent caregiving. According to Bowlby’s attachment theory, when children feel abandoned or unworthy due to caregiver neglect, they often internalize a deep sense of shame and inadequacy, believing they are inherently unworthy of love. This can lead to chronic low self-esteem and difficulties in forming secure relationships later in life.

Additionally, as Kohut often emphasized, the absence of empathetic validation from caregivers can result in a fragmented sense-of-self. Children who do not experience emotional attunement may come to believe, “I must need too much” or “I’m overwhelming,” as a way of rationalizing why their needs weren’t met. Without positive role models or emotional support, this narrative of unworthiness can dominate their internal world, setting the stage for emotional dysfunction and relational difficulties in adulthood.

Riley’s sense-of-self, initially rooted in positive core memories, is shaped by Joy’s efforts to maintain her emotional balance. However, as Anxiety enters the picture, Riley’s focus shifts away from her past experiences, and her emotional landscape becomes dominated by fear of the future. Anxiety’s attempt to “build a better Riley”—as seen when she launches Riley’s core sense-of-self to the back of her mind—illustrates the dangers of allowing anxious thoughts to reshape one’s identity. As Nancy McWilliams has often pointed out, anxiety can distort the self-concept, leading individuals to construct identities based on external pressures rather than authentic desires and values. This mirrors how Riley’s authentic self is pushed aside in favor of a version more focused on social acceptance and external validation.

Erik Erikson’s theory of psychosocial development highlights adolescence as a critical period for identity formation, where the conflict between identity and role confusion is central. Adolescents, like Riley, are tasked with forming a stable sense-of-self while navigating external pressures from peers and society. When anxiety takes control, as it does for Riley, it can lead to identity confusion—a state where the individual prioritizes social conformity over personal authenticity. Rather than exploring her true desires, Riley’s anxiety shifts her focus toward constructing an identity shaped by fear and the need for social acceptance, ultimately disrupting the healthy process of identity formation.

This act of emotional suppression fragments Riley’s identity, leaving her disconnected from her authentic self. It serves as a powerful metaphor for how unresolved emotions, especially those driven by anxiety, can take control of our internal landscape, leading to inner turmoil. Anxiety often distorts one’s sense-of-self by introducing fears of inadequacy and a need for external validation, as we see in Riley’s struggle. By prioritizing social acceptance over personal authenticity, her sense-of-self begins to fracture, resulting in emotional confusion and insecurity.

We witness Riley’s emotional fragmentation most clearly when her core memories—representing key aspects of her identity—are literally sent to the back of her mind. This displacement reflects her vulnerability as she tries to navigate new peer relationships without a fully integrated self-concept. Inside Out 2 powerfully illustrates a common experience of adolescence, where shifting social dynamics and increasing self-awareness create internal conflicts that can destabilize one’s identity. The process of forming a cohesive sense of self is complicated by these emotional upheavals, but also represents the essential developmental task of adolescence: integrating these conflicting emotions and experiences into a stable, authentic identity.

Inside Out 2: How Joy’s Anxiety Foreshadows Riley’s Emotional StrugglesInterestingly, before Anxiety officially takes control, Joy’s actions already reveal underlying anxiety. By using a machine to eject bad memories, Joy attempts to protect Riley from negative emotions, but this, in itself, is an anxious response. Joy fears what will happen if Riley retains these difficult memories, reflecting a common human tendency to suppress negative experiences in hopes of securing a better future. This behavior mirrors broader societal pressures to prioritize happiness and avoid discomfort, highlighting the cultural tendency to reject emotional complexity. Joy’s anxious actions foreshadow Anxiety’s role, which centers on planning for and controlling the future to protect Riley from potential pain.

When Anxiety takes over, she believes that Riley can secure her place in social circles, avoid rejection, and ultimately thrive by being overly cautious and strategic in her relationships. Anxiety fixates on ensuring Riley has friends and social acceptance, assuming that by planning and worrying, she can secure Riley’s future success.

In life, we often “send memories to the back” when they feel too overwhelming to confront. These memories, when labeled as negative or painful, can become dissociated or denied, pushed deep into the subconscious. While suppression and denial may work as short-term strategies to cope with overwhelming emotions, these defenses prevent emotional integration, leaving unresolved feelings to resurface in maladaptive ways. They don’t disappear; they resurface in dreams, slips of the tongue, or intense emotional reactions. Inside Out 2 vividly illustrates this process when Anxiety, in an effort to protect Riley from future pain, launches her sense-of-self to the back of her mind. Anxiety’s plan, driven by fear, is to create a “better” Riley—one that is more socially accepted and successful. As Anxiety states, “We build her a new sense-of-self, a brand new her.”

This act of emotional suppression fragments Riley’s identity, leaving her disconnected from her authentic self. As Freud suggested, suppressed memories don’t vanish; they continue to influence behavior from the unconscious. In Riley’s case, the anxiety that pushes her core memories aside reflects a defense mechanism leading to deeper emotional conflict. Nancy McWilliams would argue that anxiety distorts Riley’s self-concept, shifting her focus toward external validation rather than authentic self-expression. Erik Erikson’s theory highlights that adolescence is a time when external social pressures, such as fitting in with peers, exacerbate identity confusion—exactly what we see in Riley’s journey, as her anxiety shifts her focus from personal authenticity to social acceptance.

Winnicott’s concept of the True Self vs. False Self is evident in Anxiety’s attempt to build a “better” version of Riley. By pushing her True Self to the background, Riley becomes disconnected from her emotional core, increasing her vulnerability to instability. Ultimately, the film shows that emotional growth is not about avoiding or erasing painful memories, but about integrating them into a cohesive sense-of-self. As Erikson and Winnicott suggest, emotional resilience comes from embracing all aspects of our experience—both joyful and painful—and learning to live authentically within this complexity.

How Inside Out 2 Shows Parents Unintentionally Suppressing Adolescent Emotions: Lessons In Emotional ExpressionAs parents, there’s often a temptation to rescue our children from difficult emotions or to push for them to always be happy and well-adjusted. In doing so, we might unknowingly encourage emotional suppression—the conscious avoidance of uncomfortable feelings—in an attempt to protect them. This is illustrated in Inside Out 2, where Riley expresses fear about hockey camp, saying, “I’m never gonna make this team. I’m not gonna do well.” Her parents respond, “Don’t think that way,” instead of allowing her to sit with and express her worry. This instinct to soothe or fix emotions is natural but can inadvertently teach children to suppress, rather than confront, their feelings.

While suppression may seem helpful in the short term, if these emotions are never addressed, it can lead to more primitive defenses like denial, where children unconsciously reject their emotions altogether. Over time, instead of simply avoiding difficult feelings, they may lose touch with them, acting as though those emotions don’t exist. In extreme cases, they might develop defenses like projection (blaming others for their feelings) or splitting (seeing situations as entirely good or bad). Helping children acknowledge and process their emotions is essential to prevent the slide into these more primitive, maladaptive defenses.

As therapists, we understand the importance of helping our patients sit with difficult emotions and work through them. But when it comes to our own children, we’re more deeply invested, which makes it harder to follow this same approach. Parents tend to shield their children from discomfort, wanting to reassure them or fix their emotional struggles. However, avoiding these emotions or disavowing them can cause long-term emotional suppression, complicating their ability to process feelings later on.

In a previous episode with Paul Wachtel on disavowed emotions, he explained, “Disavowed emotions do not disappear. They get expressed in ways that are often more destructive than if they were acknowledged and addressed directly.” When parents inadvertently teach their children to suppress or disavow their emotions, those feelings don’t go away—they show up in indirect or harmful ways, such as anxiety, outbursts, or emotional withdrawal.

In Inside Out 2, Riley’s parents unintentionally disavow some of her darker emotions as she navigates adolescence, which fragments her developing sense-of-self. Without a space to express these emotions, Riley begins to internalize that certain feelings are unacceptable or must be hidden. This fragmentation of her emotional experience illustrates how suppressed emotions can resurface in less healthy forms, complicating her emotional development.

There’s a powerful scene in Inside Out 2 when Riley arrives at camp and learns that her friends Brie and Grace won’t be attending the same school as her. The emotions in her head initially urge her to “keep it together,” reflecting the common pressure to suppress sadness and maintain composure. But eventually, her emotions allow Sadness to have a moment to express herself, demonstrating the importance of acknowledging difficult feelings rather than bottling them up.

This scene highlights the psychological truth that if we don’t express our emotions when they arise, they don’t simply disappear—they come out in other, often less healthy ways. It’s like trying to hold a beach ball underwater: the more you push it down, the more forcefully it pops up, often in unexpected and disruptive directions. By not addressing her sadness directly, Riley risks having those unacknowledged feelings manifest in ways that could negatively affect her emotional well-being.

Naming and honoring emotions reduces their power over us. This concept is mirrored in Harry Potter, where Dumbledore encourages Harry to stop calling Voldemort “He Who Must Not Be Named,” saying, “Will you stop that? Just, just name it. Otherwise, it has too much power over you.” The same is true of our emotions: when we refuse to name or acknowledge them, they gain control over us. But when we name and confront our emotions, we take the first step toward processing them in a healthy way.

How Anxiety Hijacks Creativity: Lessons From Inside Out 2 And A Beautiful MindThe character of Anxiety is intentionally uncomfortable and difficult to watch, reflecting how distressing real-life anxiety can be. As Anxiety takes over more of Riley’s mind, the more unsettling it becomes for both Riley and the audience, mirroring the way anxiety feels overwhelming in real life. Watching Anxiety on screen mirrors the frustration and discomfort many people with anxiety experience—constantly wondering, “When can I stop worrying? When will this calm down?” At one point, Joy asks anxiously, “How do we get rid of anxiety?” followed by the somber realization, “Maybe we can't.” This simple yet profound exchange captures a truth at the core of anxiety: it’s not always about eliminating the worry, but learning to live with it.

In the movie, Riley’s mind leads Joy, Sadness, and Disgust to the Imagination Station, a place that symbolizes her creative powers. However, as they enter, they realize that Anxiety has taken over this space, using Riley’s imagination to spin endless fear scenarios—just as anxiety hijacks our thoughts, making us obsess over potential threats and mistakes. Anxiety, standing in front of a large screen and a group of workers, commands, “Great! We need to help Riley prepare. Now is the time to send up every possible thing that could go wrong. We are looking to the future. Every possible mistake she could make…” Riley misses an open goal, and the coach writes about it in her notebook. “Yes! More like that.” The workers, driven by Anxiety, begin churning out these worst-case scenarios, one after another, while Riley, caught in the grip of these imagined fears, tosses and turns in bed, her face showing mounting distress.

It’s a vivid depiction of how anxiety dominates our mental space, often overshadowing other emotions. Anxiety can hold joy, sadness, and other feelings hostage, leaving us focused entirely on what could go wrong. The Imagination Station is turned completely orange—the color of Anxiety in the film.

As I reflected on the Imagination Station scene, it resonated deeply with my own experience of anxiety taking control of my imagination. In the movie, Anxiety hijacks Riley’s creative powers to churn out endless worst-case scenarios, and I know firsthand what that feels like. When anxiety takes over, your mind becomes a factory of potential bad outcomes, constantly spinning up fear scenarios and trying to plan or predict how to handle them. It’s like being your own worst prosecutor—your imagination, once a powerful creative force, turns against you, and it feels as if there is no way to turn it off. You wake up in the middle of the night or early in the morning with your mind relentlessly churning out all the ways things could go wrong. That’s what happens to Riley when the Imagination Station is overtaken by Anxiety—her powers of creativity are completely enveloped by fear and worry, making it difficult to focus on anything else.

In the 2001 film A Beautiful Mind, the highly intelligent protagonist, John Nash, suffers from schizophrenia, creating paranoia that is both nuanced and believable due to his intelligence. His delusions, like working for the Department of Defense to crack secret codes, are so detailed that even he cannot distinguish them from reality. This reflects what we see in highly intelligent individuals with anxiety or psychosis—their imaginative and intellectual abilities make their fears more sophisticated and harder to detect. Nash’s “internal prosecutor” is powerful, as his mind turns against him, weaving intricate, convincing narratives, much like the brutal impact of imagination turned inward in many clients I have seen. His hallucinations and delusions echo the complexities of mental health struggles, where intelligence amplifies the believability of one’s fears.

As Anxiety takes over the Imagination Station, Joy grabs a pen and tries to counter it by drawing positive scenarios for Riley’s future. She imagines Riley scoring the winning goal, surrounded by cheers and celebration. Disgust adds her own flair, sketching Riley painting her nails to match her jersey, making her the trendsetter everyone wants to copy. Fear, ever cautious, shows Riley wearing knee pads for protection, while Anger, in a rare gesture of kindness, draws Riley buying flowers for the losing team as a show of sportsmanship.

Meanwhile, frustrated by Fear’s growing agitation, Embarrassment throws a button away and presses another, causing Riley to focus on these lighter, imaginative scenarios. Joy then rallies the workers to keep creating positive futures, and as the room fills with hopeful images, a pillow fight breaks out. The playful scene finally allows Riley to relax and fall asleep, her mind soothed by the shift away from anxiety-driven fears.

During periods in my life where I wake up at 4 a.m., with my "Imagination Station" running on overdrive, I’ve learned to manage the anxiety by fully waking up my mind and body. Sometimes, I’ll do this with exercise or a cold plunge, a shock to the system that helps me reset. Over the years, I’ve also developed mental “tools” to deal with these moments. I use cognitive therapy techniques, identifying and challenging any cognitive distortions that might be feeding my anxiety. I might lean on logotherapy, refocusing on my deeper meanings and values, or invite my spiritual side into these negative moments to find calm. Sometimes, I distract myself by sublimating my anxiety into meaningful work—taking advantage of the early hours to focus on productivity, perhaps related to the anxiety. On occasion, I’ll reach out to mentors by email, asking for their thoughts, reflections, or prayers, seeking perspective and connection to ground myself.

Examples Of Microexpressions In Inside Out 2: Adolescence and Self-DoubtIn Inside Out 2, the film vividly portrays the self-doubt that begins to emerge during adolescence, often triggered by anxiety and social pressures. Riley’s sense-of-self glows when she’s around her friends, showing how secure and confident she feels in those moments. For example, when she helps Grace pick up pennies, her sense-of-self blossoms, reminding us that being her authentic self strengthens her friendships. However, as she navigates adolescence, self-doubt starts to creep in—something typical of this developmental stage, where kids question their identity and their place in social groups. Adolescents often need reminders that their friendships originally formed because they were true to themselves. As Dr. Bender suggests, a helpful reminder for teens could be, “You made these friends by being yourself. Maybe it’s worth trying to be yourself again—some people might not like you, and that’s okay.”

Microexpressions: Subtle Emotional Cues in AdolescenceThe film also highlights how adolescents internalize self-doubt through subtle emotional cues, specifically microexpressions. As Riley’s friends begin to look uncertain, Riley instinctively picks up on their facial expressions (a microexpression of fear, eyebrows going up and together with tension) before they even verbalize their decision not to attend the same school as her. This is an excellent example of microexpressions in action—quick, subconscious flashes of emotion that last for only a fraction of a second. Long-time listeners of this podcast will remember previous episodes on microexpressions, which are 1/10th-of-a-second glimpses of emotion that appear on someone’s face. Inside Out 2 visually captures this moment as Riley’s mind zooms in on her friends’ faces, revealing slow-motion flashes of fear. These microexpressions suggest that Riley sensed what was happening before she fully realized it consciously.

Mentalizing and Misreading Emotional CuesMentalizing—the ability to understand and interpret others’ emotions and thoughts based on their facial expressions and actions—can be particularly difficult for individuals with borderline personality disorder (BPD). People with BPD often struggle with mismentalizing, misinterpreting others’ emotional cues, especially when their fear of abandonment is triggered. They may overread microexpressions, perceiving neutral or ambiguous expressions as negative or rejecting. Anxiety can heighten this hyperawareness, causing them to constantly try to “read” others, often resulting in misjudgments.

In therapy, part of the process involves helping patients reduce the intensity of hyper-mentalizing and teaching them to interpret emotional cues more accurately without projecting their fears. In Inside Out 2, we see a more adaptive approach in Riley’s response to her friends’ expressions, as her concern prompts her to ask more questions rather than jumping to conclusions. However, if Riley had a history of neglect or trauma, she might misread expressions more frequently, perceiving rejection or disapproval in situations where none exists.

The Normalization Of Self-Reflection And Emotional IntegrationAdolescence brings significant changes in the brain, including maturation of the prefrontal cortex, which enhances self-reflection and emotional regulation. At the same time, heightened activity in the limbic system increases sensitivity to social and emotional cues, contributing to social anxiety. Inside Out 2 normalizes these changes, showing that the internal turbulence of adolescence is universal. In today’s TikTok culture, where self-diagnosis is common, there is a tendency to pathologize normal developmental experiences. Yet, as the movie illustrates, self-reflection and emotional integration are natural parts of growing up.

Our sense-of-self is at its most authentic when we can simply be ourselves. This authenticity

fosters deeper connections with others and strengthens relationships. However, as the film shows, anxiety can often overshadow this authenticity, acting like a blanket that smothers everything, making it difficult to truly connect.

One of the film’s most powerful moments occurs when Riley experiences a panic attack in the penalty box. As she holds her hockey stick and focuses on sensory details—the sunlight, the sounds of the ice—she begins to ground herself. This moment marks the integration of her shadow side, where she allows the return of negative memories and confronts the complexity of her self-image. Riley begins to reconcile conflicting beliefs about herself: “I am a good person, and sometimes I’m selfish”; “I am good enough, and sometimes I’m not.” This emotional integration is further deepened through her repair with Grace and Brie, leading to a resurgence of Joy, not just as an emotion, but as a sense of self-compassion. It is in this moment of self-acceptance that Riley’s sense-of-self returns, allowing her to feel joy and connection once more.

When things calm down, true emotional integration occurs. Riley realizes that she doesn’t need to cling to her old sense-of-self, as Joy had desperately tried to do. Instead, she can embrace the complexities of her emotions—her anxiety, her moments of self-doubt, and her moments of confidence. This recognition—that we can hold multiple, sometimes contradictory, feelings—is part of what it means to be human. While emotional integration takes much longer than a three-day hockey camp in real life, Pixar’s magic reminds us that growth and self-compassion are within reach.

Ennui: The French Art Of BoredomIn Inside Out 2, a new emotion, Ennui, is introduced, perfectly embodying the teenage struggle with boredom and disillusionment. Ennui, too cool for school, lounges on the couch, glued to her iPhone, showing little interest in anything around her. Her indifference only breaks when she loses her phone, and she’s half-heartedly dressed, with one sock barely on, illustrating a complete disengagement from life. Ennui reflects the pressure teens often face to appear aloof and indifferent as a way to fit in with the “cool” crowd.

As adolescents grow, they begin to notice social cues from their peers, learning what is deemed “cool” or “acceptable,” and this creates tension between being authentic and adopting superficial identities. In Inside Out 2, Riley faces this tension directly in a scene where she must decide whether to help someone who drops their coins or ignore them to maintain her cool status. The voices in her head reflect the struggle: one urges her to prioritize her social image, while the other encourages her to help. When Riley chooses to help, it becomes a defining moment for her. The act reinforces her sense-of-self, built on kindness and authenticity, and deepens her connection with others.

This scene underscores a critical lesson for adolescence: while peer pressure may tempt teens to adopt a detached, “too cool” persona, true growth and self-development happen when they stay grounded in their values. Riley’s decision to help shows that embracing authenticity and kindness leads to stronger relationships and a deeper sense-of-self—an important contrast to the apathetic Ennui.

The Split In The Adolescent MindThroughout Inside Out 2, there are moments when Riley lies to fit in with her new group of friends. Every time Riley lies to fit in, an earthquake creates a chasm in her Deep Mind, symbolizing the growing gap between her core emotions and sense of self. This crack, labeled 'sarcasm,' distorts communication between her authentic feelings and outward behavior. When Joy shouts, “You guys are the best crew ever,” the workers on the other side misinterpret her words as sarcastic. This visual metaphor represents Riley’s growing difficulty in staying true to herself, as the divide between her authentic emotions and her outward behavior widens.

This chasm of sarcasm symbolizes the growing tendency for adolescents to hide their true selves in social situations. As Riley distances herself from her core identity, we see how lying to fit in gradually disconnects her from her authentic self. Anxiety pushes her to conform, while her inner self—a reflection of who she has been up until now—reminds her of what she values. It is common during adolescence to experience this inner conflict, where old interests, like Riley’s affection for boy bands, now seem embarrassing or childish. This split reflects the pressure adolescents face to leave behind what once brought them joy, to appear more mature or fit in with peers.

In adolescence, this kind of internal splitting is normal, but it doesn't have to mean completely losing one’s authentic self. Adolescents often feel the need to justify or hide what is meaningful to them in order to be accepted by others. It’s important for them to realize that it’s okay to still like what they used to love, even if it’s no longer “cool.” Encouraging teens to embrace their true interests, rather than disavow them for the sake of fitting in, can strengthen their self-confidence and sense of identity.

For many parents, this split is observable on a daily basis. Adolescents can shift between their “cool” social persona at school and their authentic, silly selves at home, where they feel safer to express who they really are. Providing this safe space for teens allows them to explore both sides of their identity—the part of them that conforms to fit in and the part of them that feels true to who they are. It’s a back-and-forth crossing of the chasm, one that happens even daily, and as parents, it’s essential to champion their authentic selves during these moments.

Adolescents And The Development Of Social VeneersEven if the side of themselves that our kids display when coming home from school isn’t always their silly side—it might be their unpleasant side—in a way, this is complementary to us as parents because it suggests that they believe we can handle them and shows they are not worried about us crumbling if they aren’t the perfect, nicest kid. They have been trying to hold it together all day and there are many different ways they can show up as their true selves at home, allowing themselves to feel things that they wouldn’t want to share with others.

On the other hand, something to acknowledge is that individuals with different degrees of reflective functioning may find it more or less challenging to navigate these various social contexts. Mentalization, or the capacity to understand and interpret others' emotions and thoughts, plays a key role in how adolescents shift between environments. Individuals with autism spectrum disorder (ASD), for instance, often struggle with this theory of mind, making it difficult for them to read social cues or adapt their behavior to fit different settings. They may not have the capacity to discern what might be appropriate or how their “audience” could interpret certain information.

In this same way, how our kids respond to their friends might not be the same way they respond to a teacher, which might not be the same way they talk to a parent. It’s almost like code-switching, testing how they can be themselves in various settings. Adolescents with a strong sense of theory of mind will learn to adapt their presentation based on context, while those who struggle with reflective functioning might reveal too much or fail to understand how their behavior affects others. For example, children with ASD may share facts without emotional context, a behavior that requires focused therapeutic work to help them understand and navigate social expectations.

As therapists, we often coach our patients on how to gate or filter aspects of their emotional experiences in different environments to help them achieve their goals. Others may need encouragement to be more vulnerable in relationships. Either approach can be beneficial, depending on the individual’s context and needs. Therapy often fosters reflective functioning by helping patients evaluate how their behavior might be interpreted by others, allowing them to manage social situations more effectively.

Techniques For Managing Panic Attacks Seen In the FilmMoving through the film, Riley gets to the point where she is so overcome with anxiety that she experiences a panic attack in the penalty box at her hockey game. We can witness, as she's coming out of the panic attack, this moment of integration of herself. This isn’t necessarily typical for someone to feel in the middle of a panic attack, but for the purposes of the film, we can see how it is illustrated that she has a coming together of the competing sides of herself— “I can be anxious. I can be good. I can feel bad about myself and I can feel good about myself.” All of that coming together helps her panic subside.

A method they also portray Riley using is the 3-3-3 rule in treatment for panic attacks, which is about observing three things—touch three different things or move three different body parts, etc. We can see Riley actually hearing the skates on the ice and we see a picture of a skate. She observes that she is touching the side rail in the penalty box. This is a grounding technique that helps her come back to the present and realize she is going to be ok. She becomes able to sit with the fact that she hasn’t been good to her friends at hockey camp. She's also doing some great relaxation breathing, inhaling through her nose and exhaling twice as long through her mouth. These are common techniques used to calm panic.

Tying this situation back into the importance of the secure sense-of-self, it is so helpful that Riley had that to draw on during this time of utter panic. Her inner world became so hijacked that she had to go to her outer world to calm down, and the faces of her secure relationships, her friends with whom she had such history, helped remind her of who she was. Mirror neurons, which allow us to resonate with and mirror the emotional states of others, play a significant role in this process of co-regulation. Riley’s ability to ground herself is likely reinforced by the calming, empathic presence of her friends, whose emotional states help reflect a sense of calm and safety back to her.

The film could have shown more of the impact of co-regulation, depicting her interacting with another person’s mind and influencing her during that moment, because we know that our minds are not fully independent. The role of mirror neurons in empathy is part of how this connection works. We can imagine a picture of how the softness of a friend’s love for her helps calm her flying amygdala, displaying the incredible power of co-regulation during such a moment.

She is able to reconnect with the realization that these are her friends, they genuinely care about her, and she can be honest with them. At first, Riley tries to tell her friends that she’s okay, but soon admits that she isn’t, revealing her vulnerability and showing a part of her true self. This moment of honesty allows her to let go of the facade she’s been maintaining, leading to a deeper, more authentic reconnection with her friends. By acknowledging her emotional state and sharing it with them, Riley strengthens her bond with her friends, demonstrating the healing power of vulnerability and authenticity in relationships.

Treating Panic In A Therapy SettingThe sequence of events was accurate, too, in that she really needed to connect to her own body and become grounded before she was able to receive from her friends. In life, we cannot simply look to other people to solve our problems. With patients, we want them to learn both. In instances of working with suicidal patients, we will make a plan where they will first attempt a specific pleasurable activity, and then they will call a friend, then they will get some exercise. It’s really a progression of things that are positive that they could do in the midst of the panic.

If Riley was a patient of ours and she was talking about this panic attack later, we might start by just asking her what it was like, acknowledging that it sounds like a horrible moment, and have her go through it. As she tells her experience, and relives it to some degree, she can walk through it again feeling that she wasn't alone with it—that she actually has somebody else with her who understands this, as we bear witness to her experience and offer empathy through voice and facial expressions. She was so isolated in her own head once anxiety flooded her that it really disconnected her. Resuming some of the disconnected attachment (connection) in the therapy room is the absolute starting place. This can speak to any disavowed part of the experience, as well. If she feels guilty about something, for perhaps pushing her friend over while she was trying to make a shot, or for hogging the ball, we can make room for normalizing those experiences.

Anxiety is often really tricky. It masks other hard feelings, so we can wonder what else is being experienced or repressed in Riley (or a patient). Some of those feelings might be anger, sadness, guilt, embarrassment. If we can recognize that, we can get to what was underneath of it. Maybe she did feel guilty. She ran into Grace and didn't have any remorse on the ice. Or maybe she was so worried about being accepted and felt like she needed to score, as Anxiety kept telling her to do. So we could back up and examine what other emotions were going on previous to the culminating moment of panic. “What were you feeling? What else was in there?” And going from there to understand more and say, “It sounds like that was really hard to feel and it came out in this way. I wonder if there's a way for it to come out differently. Can you tell yourself, ‘I'm really worried I'm not going to be accepted. I'm really worried I'm not going to make the team.” We can help them start putting the feelings into words that allow for expression of the feeling so it doesn't have to build to an uncontrollable moment.

The more Riley’s panic subsides, we see a shift towards her finding meaning in the suffering of what she went through and what she experienced. That can be the place where she comes to terms with the fact that she lost sight of herself in some places in her friendships at the cost of trying to make the team and fit in, and maybe it’s a sadness that she had hurt her friend. Ultimately, it all started with the grief of losing her friends to another school and grew from there.

ConclusionThe final scenes of Inside Out 2 show Anxiety settling into a special chair, complete with a foot massager and a cup of tea—a humorous yet poignant reminder that anxiety, too, has its rightful place. Anxiety can serve a purpose: helping us plan, protect, and prepare for the future. Yet it’s crucial to ensure that anxiety stays within bounds, not overwhelming other emotions or distorting our sense of self. This is an ongoing task, not only for our patients but for ourselves. As mental health professionals, we help our clients find balance, while we ourselves rely on community, supervision, quiet time in nature, and even creative outlets to stay grounded.

Pixar ties up the movie with a hopeful resolution, yet it subtly hints at the ongoing, messy nature of human experience. Emotions like anxiety, embarrassment, and ennui are constants in life. They can challenge us, but also teach us when integrated into a balanced sense of self. For Riley, navigating adolescence meant experiencing and expressing a full range of emotions, learning how lying or performing for others can fracture the self, and realizing how microexpressions and the reactions of others play into her self-concept. Her ability to connect authentically with her friends, largely through empathy and mirror neurons, offers a window into the power of shared emotional resonance.

This visual portrayal of complex themes offers a valuable reminder for therapists, parents, and adolescents alike: all emotions have value, and each part of the self deserves acknowledgment. By maintaining awareness of our own internal “dashboard,” we create a space where we, too, can observe, accept, and integrate all parts of our experience. For viewers young and old, it’s validating to see that emotions—no matter how contradictory or uncomfortable—are universal. Art, like Pixar’s work, reminds us that understanding and embracing our full emotional lives can lead to healing, resilience, and, ultimately, connection with ourselves and others.

View Details

Liam Browning, Christopher Campbell, Mark Ruffalo, Nicholas Fabiano, Joanie Burns, Michael Cummings, David Puder

Borderline Personality Disorder (BPD) is often considered challenging to manage from a clinician's perspective. Many clinicians may feel apprehensive about treating patients struggling with BPD, given the complexity and intensity of symptoms. In previous episodes, we’ve explored various aspects of BPD, including a general overview of the disorder (episode 115), schema therapies (episode 130), commonalities to effective treatment approaches (episode 140), and how to distinguish BPD from complex PTSD (episode 215).

Psychotherapy is widely regarded as the most effective treatment modality for managing BPD and remains the cornerstone for BPD treatment. However, important questions still arise: What role, if any, do medications play in the treatment of BPD? What medications should be avoided? What special considerations are necessary when prescribing? How should comorbid conditions be managed with pharmacotherapy?

In this episode, we aim to address these questions comprehensively. Our goal is for clinicians to feel more confident in understanding when and how to use medications for BPD. We also hope to provide valuable information regarding additional treatment modalities, such as exercise, omega-3 fatty acids, Transcranial Magnetic Stimulation (TMS), and esketamine for managing BPD.

Etiology And Causes Of Borderline Personality Disorder (BPD)Role of Temperament in BPD DevelopmentMany individuals with BPD exhibit behavioral and temperamental differences from an early age, suggesting that temperament plays a crucial role in the development of the disorder. The New York Longitudinal Study (1956-1988) provides a foundational understanding of how early temperament influences later behavioral problems. Of the 141 infants evaluated, researchers categorized them into three temperament types:

• Easy (40%): Generally cheerful, quick to adapt to routines, and less emotionally reactive to new stimuli.
• Slow to warm up (15%): More reserved in activity and hesitant with new experiences but eventually adaptable.
• Difficult (10%): Highly reactive, irregular in daily routines, slow to accept changes, and prone to distress.

This study found that children classified as "difficult" were more likely to develop behavioral problems, with 70% of the difficult children showing such issues later in life (Chess et al., 1963). These findings emphasize the role of inherent temperament in shaping interpersonal relationships and emotional regulation, which are central challenges for individuals with BPD. Some psychodynamic theorists, such as Kernberg and colleagues (1989), have highlighted innate aggression as a key factor contributing to borderline psychopathology. However, temperament alone cannot account for the disorder’s full complexity; it interacts with genetic predispositions and environmental influences to shape the trajectory of personality development.

Heritability and Genetic Factors in BPD Research into the genetic underpinnings of Borderline Personality Disorder (BPD) reveals a moderate but significant genetic contribution to the disorder. A large-scale population-based family study in Sweden, involving over 1.8 million individuals, identified 11,665 individuals clinically diagnosed with BPD (Skoglund et al., 2021). The study found that the heritability of BPD was estimated at 46% (95% CI = 39–53), meaning that approximately half of the variance in BPD traits can be attributed to genetic factors, while the remaining variance is influenced by environmental factors.

This study also highlighted the concordance rates across different types of familial relationships, demonstrating how genetic relatedness impacts the likelihood of developing BPD:

• Monozygotic (MZ) twins had a concordance rate of 7.4%.
• Dizygotic (DZ) twins showed a concordance rate of 4.2%.
• Full siblings had a concordance rate of 2.5%.
• Maternal half-siblings had a concordance rate of 2.7%.
• Paternal half-siblings had a concordance rate of 2.0%.

These findings suggest a moderate genetic component compared to other psychiatric and physical conditions. For instance, schizophrenia shows a heritability of 73%, with 33% concordance in MZ twins and 7% in DZ twins (Hilker et al., 2018), while bipolar disorder has a heritability of 60% (Johansson et al., 2019). In contrast, traits like height are highly heritable, with estimates between 89% and 93% (Silventoinen, 2003), and ADHD has a heritability of 71-73% (Nikolas & Burt, 2010).

Although the genetic contribution to BPD is significant, it is notably lower than these other conditions, suggesting a strong interplay between genetic predispositions and environmental influences. The moderate heritability indicates that while genetic factors confer risk, they do not fully account for the disorder's development. This leaves substantial room for environmental stressors, such as adverse childhood experiences (ACEs), to interact with genetic vulnerability and shape the trajectory of the disorder.

Impact of Adverse Childhood Experiences (ACEs) on BPDAdverse childhood experiences (ACEs-covered in episodes 203, 204, 217), such as abuse and neglect, are also highly associated with the disorder, suggesting a combination of genetic susceptibilities and environmental stressors creates a fertile ground for the emergence of BPD. A meta-analysis conducted by Porter and colleagues (2020), involving 97 primarily cross-sectional studies, found that individuals with borderline personality disorder (BPD) were 13.91 times more likely (CI 11.11-17.43; p<0.001) to have experienced some form of adversity compared to participants without BPD, including those with other mental health conditions. Specifically, 71.1% of BPD patients reported at least one adverse childhood experience, with emotional abuse (OR 38.11), neglect (OR 17.73), and sexual abuse (OR 5.96) being particularly strongly associated​.

Comorbidities in BPDUp to 85% of patients with BPD have at least one additional mental disorder (Lenzenweger et al., 2007). High rates of specific comorbidities include:

• Major depressive disorder: at least 70%
• Post-traumatic stress disorder: 30-50%
• Substance use: 58-84%

Additionally, 16-40% of patients demonstrate other comorbid disorders such as anxiety, panic disorder, eating disorders, and more (Johnson et al., 2003). These comorbidities add layers of complexity to treatment, particularly when considering pharmacotherapy, and necessitate careful management of overlapping symptoms.

Current Treatment Guidelines Of BPDGiven the limited evidence supporting the effectiveness of medications for treating borderline personality disorder (BPD), national treatment guidelines vary between nations. Some countries recommend medications primarily for managing symptoms associated with BPD, such as mood instability or impulsivity, while others discourage the use of medications altogether, emphasizing psychotherapy as the cornerstone of treatment. Notably, most national guidelines are in agreement that it is appropriate to use medications for the treatment of comorbid mental disorders in patients with BPD. This is an important consideration, as up to 85% of patients with BPD have at least one additional mental disorder (Lenzenweger et al., 2007).

American Psychiatric Association Borderline Personality Disorder Guidelines: Past (2001) and Future (draft; coming 2025):

The 2001 APA guidelines for treating BPD emphasized pharmacotherapy for acute decompensation and for chronic “trait vulnerabilities,” such as affective dysregulation, impulsive-behavioral dyscontrol, and cognitive-perceptual symptoms (Oldham, 2005). On a relatively limited amount of evidence, these guidelines suggested trials of SSRIs for affective dysregulation and impulsivity symptoms, stating a “reasonable trial of an SSRI for treatment of patients with borderline personality disorder is at least 12 weeks,” and that “if affective dysregulation appears as anxiety, an SSRI may be insufficient. At this point, the use of a benzodiazepine should be considered, although there is little systematic research on the use of these medications in patients with borderline personality disorder.”

The APA guidelines are currently being restructured to incorporate extensive research from the past two decades on pharmacotherapy for BPD. A recently published draft of the upcoming 2025 APA guidelines illustrates some proposed updates, though it must be noted that this draft remains tentative and does not represent the current APA standards of care. The draft anticipates recommending that psychotropic medication for BPD be time-limited, targeted to specific measurable symptoms, and used only as an adjunct to psychotherapy. The proposed guidelines emphasize the importance of informing patients that medications will not address core BPD features and warn against over-reliance on them for emotional regulation. Additionally, short-term medication use may be appropriate for managing crises, such as severe agitation or psychosis, but frequent dose changes or prolonged use are discouraged. Medications for managing co-occurring conditions (e.g., depression, OCD) may be considered, but they should be prescribed cautiously, considering risks like toxicity or misuse.

United Kingdom’s National Institute for Health and Care Excellence (NICE) clinical practice guidelines 2015:

The United Kingdom’s NICE guidelines advise that pharmaceuticals should not be used for either the treatment of BPD specifically or for the treatment of particular BPD-related symptoms or behaviors. The guidelines emphasize that if sedative or antipsychotic medications are utilized for initial stabilization in the acute setting, they should be used cautiously and with consent from the patient, and should not be utilized for durations longer than 1 week. The guidelines specifically recommend against the use of antipsychotic medications for medium- to long-term treatment of BPD. Lastly, the NICE guidelines do suggest that medications can be considered for treatment of comorbidities in patients with BPD (NICE, 2009).

“Drug treatment should not be used specifically for borderline personality disorder or for the individual symptoms or behaviour associated with the disorder (for example, repeated self-harm, marked emotional instability, risk-taking behaviour and transient psychotic symptoms).”

“Antipsychotic drugs should not be used for the medium- and long-term treatment of borderline personality disorder.”

“​​Drug treatment may be considered in the overall treatment of comorbid conditions.”

“Short-term use of sedative medication may be considered cautiously as part of the overall treatment plan for people with borderline personality disorder in a crisis.”

European guidelines for personality disorders: past, present and future:

A recent 2019 study analyzing the various European guidelines for treatment of personality disorders found that most European nations advise against the use of medications as a first-line treatment for BPD; however, there are notable exceptions. Switzerland, Finland, and the Netherlands all recommend that medications may be considered for targeting specific symptoms or behaviors associated with BPD (Simonsen et al., 2019).

"Finally, recommendations on pharmacological treatment are in overall agreement that, based on sparse trial evidence, medication should not be considered the primary intervention for PD, but should be used mainly for treating comorbid disorders and in some cases used briefly during times of crisis (see Table 4). The Swiss, Finnish and Dutch guidelines suggest that medication may be used to reduce specific dimensions of BPD such as anger, impulsivity or negative mood. However, these specific recommendations are not consistent and are somewhat at odds with the more general recommendation of being cautious with the use of medications."

BPD is Best Treated with PsychotherapyInstead, BPD symptoms should be targeted by therapies, such as dialectical behavioral therapy (DBT), cognitive behavioral therapy (CBT), mentalization-based therapy, transference-focused therapy, general psychodynamic psychotherapy, or schema-focused therapy. These therapies focus on helping patients manage intense emotions without turning to destructive or risky impulsive coping strategies, while also promoting the integration of raw emotional experiences into a coherent narrative through promoting reflective functioning. Object relations approaches help patients develop greater integration in their sense of self and other, so that they can approach situations in more appropriate and nuanced ways without resorting to the characteristic defenses of splitting, projection, and projective identification (Kernberg et al., 1989).

Gunderson, whose work in the 1970s helped to identify BPD as a distinct psychiatric disorder, developed an approach for BPD called Handbook of Good Psychiatric Management for Borderline Personality Disorder (Gunderson & Links, 2014), which can be utilized by psychiatrists and clinicians without specific training or supervision in the treatment of BPD patients.

Reflective Function and BPDReflective function (RF) is assessed using the Adult Attachment Interview (AAI) and is scored on a scale from -1 to 9, where higher scores reflect a greater ability to understand and interpret mental states in oneself and others. In the Cassel Hospital Study, the average RF score for patients with Borderline Personality Disorder (BPD) was 2.7, indicating a lower capacity for mentalization. Notably, a study on Transference-Focused Psychotherapy (TFP) showed that RF scores significantly increased from 2.86 to 4.11 after one year of treatment (Fonagy et al., 1998; Levy et al., 2006) (see also episode 213).

8 Years of Mentalization-Based Therapy Improved BPD Symptoms and Reduced Need for Psychiatric MedicationsBateman et al. (2008) (see also episode 206) showed that432 hours of therapy (72 hr of individual mentalization-based therapy [MBT], 216 hr of group MBT, 144 hr of expressive therapy and community meeting) over 1.5 years and an optional booster of 2 hours/week (144 hr) of group MBT for 18 months lead to significant improvements in BPD symptoms (d =1.80), suicide attempts (d = 1.4), hospitalizations (d = 1.50), employment (d = 0.94), and decreased use of antidepressants (d =1.10), antipsychotics (d = 2.04), and mood stabilizers (d = 1.17) at assessment five years after discharge.

**Current Use of Psychiatric Medications in BPD** Overview of Medications for BPDIn 2015, Zanarini and colleagues (2015) reported on a cohort of 290 inpatients with BPD followed over 16 years (avg age 26 at baseline and 42 at follow up) and found at baseline in 1999:

• 79.7% were taking antidepressants (67.9% SSRI, 31.7% atypical)
• 43.1% benzodiazepines
• 38.6% antipsychotics (37.5% FGA, 6.2% SGA)
• 35.9% mood stabilizer (22.1% anticonvulsant, 25.9% lithium [only 3.9%] at 16 yr FU])
• Polypharmacy was also common, with almost 19% of patients taking four or more psychotropic drugs.
• Over time, the rate of antipsychotic and mood stabilizer use remained stable, but with FGA use decreasing and SGA use increasing. Antidepressant and benzodiazepine use decreased.

These findings were mirrored by those of a twenty-year observational study in Spain. Pascual and colleagues (2021) tracked pharmacotherapy trends in 620 patients presenting to an outpatient BPD clinic and showed:

• Antidepressant use remained stable (74%)
• Benzodiazepine use decreased (77% to 36%)
• SGA use increased (15% to 32%)

Despite these high use rates of psychiatric medications in this patient population, a recent Cochrane Review and meta-analysis showed that nearly all classes of medications are ineffective for treating the core symptoms of the disorder (Stoffers-Winterling et al., 2022).

General Clinical Considerations for Pharmacotherapy in BPD (Pascual et al., 2023)* Due to high comorbidity of BPD with addictive disorders, use of substances with high dependence potential should be avoided if possible. * The use of unsafe drugs with risk of overdose (tricyclic antidepressants [TCAs], monoamine oxidase inhibitors [MAOIs]) should be avoided. Even a one week supply of amitriptyline is comparable to the drug’s median lethal dose (LD50) – the dose at which a substance is lethal for 50% of tested subjects.

“There are no clinical trials directly comparing a symptom-targeted approach with other approaches to pharmacotherapy for personality disorders” (Skodol, 2022)

Antipsychotics In The Treatment Of BPDIn clinical practice, low doses of antipsychotics are used for management of BPD-related impulsivity, agitation, aggression, and psychosis. In the inpatient setting, patients are most commonly treated with quetiapine and aripiprazole (Riffer et al., 2019).

According to the Cochrane Review (see below), antipsychotics did not show greater benefit to overall BPD symptoms, suicide, self-harm, impulsivity, or psychosocial functioning compared to placebo. However, there were small but significant improvements in anger and affective instability (with olanzapine, primarily).

Antipsychotics Are Not Effective For Treating BPD SymptomsRandomized controlled trials (RCTs) from cochrane review and meta-analysis (Stoffers-Winterling et al., 2022):

Zanarini et al., 2011: A dose comparison of olanzapine for the treatment of borderline personality disorder: a 12-week randomized, double-blind, placebo-controlled study

• 451 outpatients with moderate BPD symptoms randomized to 12 weeks of treatment with olanzapine 2.5 mg/day vs. 5-10 mg/day vs. placebo.
• Only 5-10 mg olanzapine was associated with significantly greater mean change from baseline to endpoint in Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) total score relative to placebo (-8.5 vs -6.8, respectively; P = .010; effect size = 0.29; 95% CI, 0.06-0.52).
• Patients treated with olanzapine were more likely to report adverse effects such as somnolence, fatigue, increased appetite, and weight gain.
• Black et al., 2014: Comparison of Low and Moderate Dosages of Extended-Release Quetiapine in Borderline Personality Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial
• 95 outpatients with BPD, randomized to 8 weeks of “low dose” quetiapine (150 mg) vs “high dose” quetiapine (300 mg) vs placebo.
• 82% in the low-dosage quetiapine group were rated as “responders,” compared with 74% in the moderate-dosage group and 48% in the placebo group.
• The difference in improvement on the Zanarini scale between the low-dosage quetiapine group and the placebo group was statistically significant (d=−0.79, p=0.031); the difference between the moderate-dosage quetiapine group and the placebo group was not (d=−0.41, p=0.265).

• The overall completion rate for the 8-week double-blind treatment phase was 67% (67% for the low-dosage quetiapine group, 58% for the moderate-dosage quetiapine group, and 79% for the placebo group). Participants who experienced sedation were more likely to drop out.

• Grant et al., 2022: A Double-Blind, Placebo-Controlled Study of Brexpiprazole in the Treatment of Borderline Personality Disorder

• 80 outpatients randomized to 13 weeks of 2 mg/day brexpiprazole vs placebo.

• There was a significant difference in BPD symptoms, but only for the last visit, and no effect size was reported.

  Antidepressants Do Not Reduce Borderline Personality Disorder SymptomsThe Cochrane Review (see above) noted that antidepressants did not significantly reduce overall BPD severity or improve impulsivity and suicidal behavior, with fluoxetine even associated with an increase in suicidal ideation. Fluvoxamine showed a slight improvement in affective instability, but there were no notable effects on self-harm, feelings of emptiness, or anger. Amitriptyline was the only antidepressant found to significantly reduce depressive symptoms; however, amitriptyline should be avoided in patients with BPD due to the increased lethality associated with overdose.

Lamotrigine (Lamictal) For BPDBPD Symptom Treatment with Lamotrigine (Lamictal) Only two studies have directly assessed the effect of lamictal on BPD symptoms (both used the ZAN-BPD)

• Small preliminary study (N=28) suggested lamotrigine (flexible dosing) may have an effect on impulsivity, anger, and behavioral dyscontrol in BPD (Reich et al., 2009).
• However, the large (N = 276) randomized clinical trial carried out by Crawford and colleagues (2018) in patients with BPD found no evidence to support the use of lamotrigine (400 mg/day) for the treatment of BPD symptoms.

Depersonalization/Derealization Treatment with Lamotrigine (Lamictal)There are multiple case reports on using lamotrigine for depersonalization/derealization disorder (Sierra et al., 2006) and only two RCTs:

• [Retracted due to plagiarism] Aliyev 2011: 80 Azerbaijani outpatients (mean age 37.7, 0% female), lamotrigine (25–300 mg/day) vs placebo for 12 weeks. The lamotrigine therapy group saw greater improvement on the Cambridge Depersonalization Scale (CDS) than the placebo group.
• Sierra et al. 2003: Cross-over study of 9 UK outpatients with depersonalization/derealization disorder (mean age 35.2), lamotrigine (25–250 mg/day), vs placebo for 12 weeks. Lamotrigine had no significant advantage over placebo.

Do Benzodiazepines Worsen BPD?Previous studies have linked benzodiazepine use to paradoxical increases in impulsivity and violent aggression in patients with BPD (Gardner & Cowdry, 1985). Benzodiazepines are also associated with an increased risk of suicide in patients with BPD and also in other disorders (Dodds, 2021). This effect may be linked to benzodiazepines reducing prefrontal cortex (PFC) activity through GABA signaling, which can lead to disinhibition and impulsivity, similar to the effects observed with alcohol.

Lieslehto and colleagues (2023) assessed risk of suicide attempt or completed suicide by following 22,601 BPD patients for 16 years and found:

• Decreased risk of suicide attempt or completed suicide in patients taking ADHD medications (HR, 0.83; 95% CI, 0.73-0.95)
• Null findings for mood stabilizers (HR, 0.97; 95% CI, 0.87-1.08)
• Increased risk for antidepressants (HR, 1.38; 95% CI, 1.25-1.53), antipsychotics (HR, 1.18; 95% CI, 1.07-1.30), and benzodiazepines (HR, 1.61; 95% CI, 1.45-1.78)

To address reverse causality (the possibility that more severely ill patients, who are at higher risk of self-harm or suicide, are more likely to be prescribed benzodiazepines, antipsychotics, etc.), the authors attempted to control for this by excluding the first two months of treatment from their analysis, operating under the assumption that the drug’s effects would have manifested after this period. However, benzodiazepines, SSRIs, or antipsychotics have not been shown to reduce BPD symptoms or the risk of suicide in BPD patients in prior studies, making the assumption that their impact would only begin after two months problematic. Therefore, this study may overestimate the risks associated with benzodiazepine use in this population, and more studies are needed to identify how benzodiazepines influence BPD symptoms.

Nevertheless, the association of benzodiazepines with increased risk of suicide in other disorders does raise concerns about the risks of their long-term use. For example, Tiihonen and colleagues (2012) demonstrated in a cohort study of 2588 hospitalized patients with a first-time diagnosis of schizophrenia that benzodiazepine use was associated with an increased risk of all-cause mortality (HR, 1.91; 95% CI, 1.13-3.22) and suicidal death (HR, 3.83; 95% CI, 1.45-10.12) while antidepressants did not increase risk for mortality and decreased risk for suicidal death (HR, 0.15; 95% CI, 0.03-0.77).

Use of ADHD medications for ADHD in patients with BPD may improves impulsivity There are few studies assessing the use of stimulants in patients with comorbid ADHD and BPD (Matthies & Phillipsen, 2014). A naturalistic study suggests that methylphenidate may improve impulsivity and reduce self-injurious behavior in individuals with comorbid BPD and ADHD, particularly when combined with intensive DBT. In methylphenidate- (MPH-) treated patients, impulsivity showed a 15.87% reduction compared to 4.96% in the non-treated group. Additionally, depression severity improved by 54.25% in MPH-treated patients versus 29.95% in the non-treated group, and state anger decreased by 28.92% compared to 16.68% in those not receiving MPH. These findings were observed in a naturalistic setting and focused on patients with comorbid ADHD, not in a randomized controlled trial, which limits the ability to establish causal relationships (Prada et al., 2015).

Additional Treatment Modalities For BPDOmega-3 Fatty Acid Supplementation May Reduce Impulsivity and Depressive Symptoms in BPD According to a recent meta-analysis by Kelaiditis and colleagues (2023), omega-3 supplementation has shown potential benefit in treating depression and anxiety, particularly with EPA-enriched formulas. Studies suggest that EPA doses between 1 and 2 grams per day may help reduce depressive symptoms, and recent APA major depressive disorder (MDD) guidelines suggest supplementation may be helpful as an adjunct. The evidence for anxiety is less clear.

The therapeutic mechanism of omega-3 supplementation is unclear but may be related to its effects on reducing inflammation or on regulating neuronal membrane fluidity, allowing for greater neurotransmitter receptor availability. BPD patients may have elevated levels of inflammatory cytokines, possibly linked to early life stress or adverse childhood experiences (see also episode 217), therefore, omega-3 supplementation could help alleviate some symptoms of BPD, such as mood instability and aggression.

A meta-analysis by Karaszewska and colleagues (2021) reviewed four small randomized controlled trials evaluating the effects of omega-3 supplementation on symptoms related to BPD. The analysis found a significant reduction in depressive symptoms (referred to as “affective instability” by the authors) with a standardized mean difference (SMD) of 0.74, and a decrease in impulsivity (SMD = 0.45). Three of the studies compared clinically-dosed EPA (700-1220 mg) and DHA (480-908 mg) to placebo. Only one study directly measured BPD symptoms using a validated scale. Bellino and colleagues (2014) found that 12 weeks of treatment with 1200 mg EPA and 800 mg DHA, combined with 50-100 µg of valproic acid, did not significantly reduce overall BPD symptoms (BPD severity index scale) compared to valproic acid alone. However, small improvements were noted on subscales related to anger and impulsivity.

Although more studies are needed to fully understand the effect of omega-3s on BPD, this intervention offers a low-risk, well-tolerated adjunct to treatment with the added potential for cardiovascular and cognitive benefits.

Borderline Personality Disorder & ExerciseThere is limited research into exercise and BPD. However, exercise has been consistently shown to have a positive effect on mood, anxiety, and overall mental health (seealso episode 179). Numerous studies across various populations and conditions have highlighted the benefits of physical activity for improving emotional well-being and reducing symptoms of mood disorders, implying there may be a role for exercise for treating BPD. Skeletal muscle acts as a neuroendocrine tissue, releasing myokines during contraction that influence various bodily systems, including the brain. Certain myokines, such as cathepsin-B and irisin, can cross the blood–brain barrier, where they subsequently influence an indirect increase in BDNF, resulting in downstream contributions to improved cognition and neuroprotection (Oudbier et al., 2022).

People with BPD are known to be at a higher risk of self-harm and suicide attempt compared to the general population. The majority of suicide attempts are characterized impulsivity and low-lethality (Lopez-Castroman et al., 2016). Previous systematic reviews have demonstrated that exercise significantly decreases suicide attempts in those with mental disorders (Fabiano et al., 2023 & Fabiano et al., 2024). As exercise is known to reduce emotional-impulsivity, it is hypothesized that regular exercise may serve as a protective factor against suicide attempts (Javelle et al., 2022), however further research is required specifically within the BPD population.

St-Amour and colleagues (2022) conducted a small RCT looking at the effect of physical exercise on negative affect in patients with BPD. They randomly assigned 28 participants with BPD to a 20-minute single session of stationary bicycle or a control condition (emotionally neutral video) then watched a short video clip simulating negative mood induction (Silence of the Lambs). Following the negative mood induction, both conditions decreased the level of negative affect with a medium effect size, but there was no significant difference between them (St-Amour et al., 2022).

Apart from this study, there are no other studies investigating the therapeutic effects of exercise for adults with BPD (St-Amour et al., 2021). However, exercise is known to reduce emotional dysregulation, which is a prominent symptom in those with BPD (Berstein et al., 2019). Further, BPD is known to be highly comorbid with other mental disorders (such as depression and anxiety) and physical health conditions (such as metabolic syndrome and cardiovascular diseases), for which exercise has proven efficacy (Doering et al., 2019). In particular, cardiovascular and endocrine diseases account for nearly one third of deaths among people with cluster B personality disorders (Cailhol et al., 2017). As such, although further research is required, exercise may be a promising intervention for those with BPD to reduce emotional dysregulation, treat comorbid mental disorders, and improve overall physical health.

What is Known about Ketamine and Esketamine and BPD?Given BPD is associated with quasi-psychotic and dissociative symptoms, symptoms which ketamine can induce, there is concern that patients with BPD may not tolerate ketamine, or that it could exacerbate their symptoms.

A recent RCT pilot trial attempted to address this question, finding the dissociative effects of ketamine were transient. However, the six ketamine-group participants with history of

dissociative experiences had higher mid-infusion dissociative (Clinician administered dissociative state scale [CADSS]) and positive psychotic symptom (BPRS) scale scores than the four ketamine-group participants without history of dissociation (Fineberg et al., 2023).

The study did not find statistically significant improvements in suicidality or BPD symptoms (ZAN-BPD), but it was likely too underpowered to address these.

Aside from several case reports (Nandan et al., 2023), the only other study assessing ketamine’s effects on BPD symptoms was by Danayan and colleagues (2023):

Real world effectiveness of repeated ketamine infusions for treatment-resistant depression with comorbid borderline personality disorder:

• Methods

• 50 outpatients with depression and moderate-to-severe BPD symptoms (measured by Borderline Symptom List 23-item [BSL-23]) and 50 outpatients with only depression received four doses of intravenous ketamine (0.5-0.75 mg/kg over 40 minutes) over two weeks.

• Results

  After three infusions, the BPD group’s BPD symptoms had improved significantly (p<0.0001; η2=0.44)

• Both groups also improved in depressive symptoms (QIDS-SR16) (p<0.0001; η2 = 0.185), suicidality single item on QIDS-SR16) (p< 0.0001; η2 = 0.076) and anxiety single item on QIDS-SR16) (p<.0001; η2 = 0.15), with no significant differences between the two groups following four infusions.

• Ketamine increased dissociation symptoms (CADSS-6) in both groups, but not more in the BPD group.
• Limitations
• There was no placebo or active control condition.
• This analysis is post-hoc, meaning it was not a randomized trial.
• BSL-23 scores are correlated with depression severity and were not reported in the “BPD-negative” group. This means the BPD-negative group might have had improvements in their BSL-23 scores that the authors did not report.

While the initial results are encouraging, further randomized controlled trials are needed. These studies should incorporate long-term follow up monitoring using appropriate tools that assess dissociation, depersonalization, identity disturbances, and affective instability, in order to evaluate whether patients with BPD are at a greater risk of destabilization.

Dr. Craig Heacock, a psychiatrist with extensive experience prescribing ketamine therapy to many patients, weighed in on its use for BPD (personal correspondence):

“I think lower dose oral ketamine can potentially be helpful in the context of ketamine assisted therapy, but it must be used cautiously and judiciously and only after a strong and trusting therapeutic relationship has developed. Ketamine can light transference on fire, it can trigger self harm and suicidal thoughts in BPD, and it can exacerbate the fragmented sense of self—all of which are major challenges for the therapist and patient. The higher psychedelic doses of ketamine are generally contraindicated for BPD, given the risk of destabilization.”

Initial TMS Studies Show Potential to Treat BPD SymptomsThere have been three pilot studies using transcranial magnetic stimulation (TMS) to target BPD symptoms (see review: Konstantinou et al., 2021) that have each shown small but positive effects on BPD symptoms or BPD-related symptoms, such as impulsivity, anger, and fear of abandonment.

Cailhol and colleagues (2014) conducted a randomized, controlled study with 10 BPD patients, dividing them into 10 20-minute sessions of active rTMS (n=5) and sham (n=5) groups. Active treatment targeted the right Dorsolateral Prefrontal Cortex with 10 Hz rTMS over two weeks. Results indicated a >30% reduction in BPD Symptom Severity Index (BPDSI) in two of five patients in the treatment group and one of four in the sham group.

Reyes-Lopez and colleagues (2018) found similar reductions in BPD symptoms in 29 patients randomized to 15 sessions of 1Hz or 5Hz rTMS to the Dorsolateral Prefrontal Cortex, especially impulsiveness and emotional instability, with no significant side effects across their cohort.

Calderon-Moctezuma and colleagues (2020) also observed improvements in 14 patients randomized to sham or 15 sessions of 5Hz rTMS over the Dorsomedial Prefrontal Cortex. Only the active group improved on total CGI-BPD scores (p = 0.028).

Does ECT have a Role for Treating BPD?

Electroconvulsive therapy (ECT) has been shown to be particularly helpful for patients with treatment-resistant depression, catatonia and psychosis, which could be present in patients with BPD, but it does not treat BPD symptoms specifically. However, there are no published studies on its use for BPD symptoms (Zou et al., 2023).

“There were no ECT studies evaluating BPD symptom outcomes; however, studies of ECT in patients with comorbid BPD and depression suggested that depressive symptoms were less responsive to ECT compared with depression-only patients.”

Partial and therapy are more highly recommended than ECT. Also, consideration of memory issues might dissuade one from doing ECT. Historically, the presence of borderline psychopathology was widely considered a contraindication for ECT.

We asked our colleague Darcy Trenkle, MD, a psychiatrist who ran an ECT program for a number of years, to comment on this:

“I agree that ECT does not directly treat symptoms related to Borderline Personality Disorder (BPD). However, ECT can be highly effective for severe depression and/or catatonia when co-morbid with BPD. Given this, the clinical interview, collateral information, and informed consent process are critical when considering ECT for a patient with co-morbid BPD.

In my evaluations, I always ensured that all non-ECT treatment options had been thoroughly explored before considering ECT. If a patient had participated in PHP, adhered to medications, etc., I would consider ECT but was very clear that we would limit it to a maximum of 9–12 sessions (3x/week), followed by a rapid taper. For patients with BPD, the goal was never to rely on maintenance ECT, as this could potentially do more harm than good.

When I started my ECT practice, I inherited a few patients with BPD who had become dependent on the "experience" of ECT to maintain stability. There was often unconscious secondary gain from long-term maintenance ECT. These patients had developed close relationships with ECT staff, and the entire process—requiring a support person to accompany them—became an ingrained part of their routine. Whenever I tried to space out their sessions, they reported worsening symptoms. Few patients were able to stop ECT without decompensating, as it had become an entrenched part of their identity after 3–4 years. Many were willing to tolerate side effects from monthly ECT sessions out of fear of what life would be like without it.

Overall, I did my best to avoid starting ECT in patients with BPD and had direct conversations explaining my rationale. It was crucial that patients understood the risks, benefits, and alternatives (r/b/a) clearly. If ECT was initiated, I set very clear expectations (e.g., 3x/week for one month followed by an aggressive taper, with the goal of stopping or reducing to no more than quarterly sessions).

It was my genuine belief that in most cases, starting ECT for patients with BPD would do more harm than good. It’s essential to identify the exact symptoms we’re treating and to acknowledge that while ECT is incredibly effective for depression, in BPD, depressive episodes are often part of a more complex symptom profile. Whether depression is 20% or 80% of the acute issues is unclear, and using ECT for what might only be 10-15% of the problem poses a significant risk for limited benefit. Additionally, the nurturing environment that comes with being an ECT patient can inadvertently improve symptoms, which complicates the clinical picture.”

ConclusionPsychotherapy remains the first-line treatment modality for BPD. While medications are commonly prescribed in BPD, their role differs significantly from that in primary mood, anxiety, or psychotic disorders. Medications should primarily be used to address comorbid conditions, such as depression and anxiety, and not as a direct treatment for BPD symptoms. National guidelines suggest avoiding long-term use of medications to manage BPD directly, though sedatives or antipsychotics may be considered for short-term stabilization in cases of severe agitation or psychosis.

High-risk medications, including those with high addictive potential (e.g., benzodiazepines) and those with increased lethality in the setting of overdose (e.g., TCAs or MAOIs), should be avoided given the increased rates of addictive behaviors and suicidality in BPD patients. Additionally, exercise and omega-3 supplementation can be considered as a low-risk intervention that may help reduce impulsivity and depressive symptoms, while also offering physical health benefits. While novel neuromodulation treatments like esketamine and TMS show potential for BPD, they are not yet approved for this use, and more research is needed.

Ultimately, effective treatment of BPD requires a holistic approach, with psychotherapy as the foundation, supported by judicious use of medications and the consideration of integrative interventions like exercise and omega-3 supplementation. Together, these approaches can help patients achieve greater stability, improved emotional regulation, and enhanced quality of life.

Connect with trusted providers in Dr. Puder’s team: here

REFERENCES/RESOURCESAliyev, N. A., & Aliyev, Z. N. (2011). Lamotrigine in the immediate treatment of outpatients with depersonalization disorder without psychiatric comorbidity: randomized, double-blind, placebo-controlled study. Journal of clinical psychopharmacology, 31(1), 61–65. https://doi.org/10.1097/JCP.0b013e31820428e1 (Retraction published J Clin Psychopharmacol. 2014 Dec;34(6):671. doi: 10.1097/JCP.0000000000000243)

Bateman, A., & Fonagy, P. (2008). 8-year follow-up of patients treated for borderline personality disorder: mentalization-based treatment versus treatment as usual. The American journal of psychiatry, 165(5), 631–638. https://doi.org/10.1176/appi.ajp.2007.07040636

Bellino, S., Bozzatello, P., Rocca, G., & Bogetto, F. (2014). Efficacy of omega-3 fatty acids in the treatment of borderline personality disorder: a study of the association with valproic acid. Journal of psychopharmacology (Oxford, England), 28(2), 125–132. https://doi.org/10.1177/0269881113510072

Black, D. W., Zanarini, M. C., Romine, A., Shaw, M., Allen, J., & Schulz, S. C. (2014). Comparison of low and moderate dosages of extended-release quetiapine in borderline personality disorder: a randomized, double-blind, placebo-controlled trial. The American journal of psychiatry, 171(11), 1174–1182. https://doi.org/10.1176/appi.ajp.2014.13101348

Cailhol, L., Roussignol, B., Klein, R., Bousquet, B., Simonetta-Moreau, M., Schmitt, L., Thalamas, C., Tap, G., & Birmes, P. (2014). Borderline personality disorder and rTMS: a pilot trial. Psychiatry research, 216(1), 155–157. https://doi.org/10.1016/j.psychres.2014.01.030

Calderón-Moctezuma, A. R., Reyes-López, J. V., Rodríguez-Valdés, R., Barbosa-Luna, M., Ricardo-Garcell, J., Espino-Cortés, M., Hernández-Chan, N., García-Noguez, L., Roque-Roque, G., Trejo-Cruz, G., Cañizares-Gómez, S., & Hernández-Montiel, H. (2021). Improvement in borderline personality disorder symptomatology after repetitive transcranial magnetic stimulation of the dorsomedial prefrontal cortex: preliminary results. Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999), 43(1), 65–69. https://doi.org/10.1590/1516-4446-2019-0591

Chess, S., Thomas, A., Rutter, M., & Birch, H. G. (1963). Interaction of temperament and environment in the production of behavioral disturbances in children. The American journal of psychiatry, 120, 142–148. https://doi.org/10.1176/ajp.120.2.142

Crawford, M. J., Sanatinia, R., Barrett, B., Cunningham, G., Dale, O., Ganguli, P., Lawrence-Smith, G., Leeson, V. C., Lemonsky, F., Lykomitrou-Matthews, G., Montgomery, A., Morriss, R., Munjiza, J., Paton, C., Skorodzien, I., Singh, V., Tan, W., Tyrer, P., & Reilly, J. G. (2018). Lamotrigine for people with borderline personality disorder: a RCT. Health technology assessment (Winchester, England), 22(17), 1–68. https://doi.org/10.3310/hta22170

Danayan, K., Chisamore, N., Rodrigues, N. B., Vincenzo, J. D. D., Meshkat, S., Doyle, Z., Mansur, R., Phan, L., Fancy, F., Chau, E., Tabassum, A., Kratiuk, K., Arekapudi, A., Teopiz, K. M., McIntyre, R. S., & Rosenblat, J. D. (2023). Real world effectiveness of repeated ketamine infusions for treatment-resistant depression with comorbid borderline personality disorder. Psychiatry research, 323, 115133. https://doi.org/10.1016/j.psychres.2023.115133

Dodds T. J. (2017). Prescribed Benzodiazepines and Suicide Risk: A Review of the Literature. The primary care companion for CNS disorders, 19(2), 10.4088/PCC.16r02037. https://doi.org/10.4088/PCC.16r02037

Fineberg, S. K., Choi, E. Y., Shapiro-Thompson, R., Dhaliwal, K., Neustadter, E., Sakheim, M., Null, K., Trujillo-Diaz, D., Rondeau, J., Pittaro, G. F., Peters, J. R., Corlett, P. R., & Krystal, J. H. (2023). A pilot randomized controlled trial of ketamine in Borderline Personality Disorder. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 48(7), 991–999. https://doi.org/10.1038/s41386-023-01540-4

Fonagy, P., Target, M., Steele, H., & Steele, M. (1998). REFLECTIVE-FUNCTIONING MANUAL Version 5 FOR APPLICATION TO ADULT ATTACHMENT INTERVIEWS. 5.

Gardner, D. L., & Cowdry, R. W. (1985). Alprazolam-induced dyscontrol in borderline personality disorder. The American journal of psychiatry, 142(1), 98–100. https://doi.org/10.1176/ajp.142.1.98

Grant, J. E., Valle, S., Chesivoir, E., Ehsan, D., & Chamberlain, S. R. (2021). A double-blind placebo-controlled study of brexpiprazole for the treatment of borderline personality disorder. The British journal of psychiatry : the journal of mental science, 220(2), 1–6. Advance online publication. https://doi.org/10.1192/bjp.2021.159

Gunderson, J. G., & Links, P. (2014). Handbook of good psychiatric management for borderline personality disorder. American Psychiatric Association Publishing.

Hilker, R., Helenius, D., Fagerlund, B., Skytthe, A., Christensen, K., Werge, T. M., Nordentoft, M., & Glenthøj, B. (2018). Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register. Biological psychiatry, 83(6), 492–498. https://doi.org/10.1016/j.biopsych.2017.08.017

Johansson, V., Kuja-Halkola, R., Cannon, T. D., Hultman, C. M., & Hedman, A. M. (2019). A population-based heritability estimate of bipolar disorder - In a Swedish twin sample. Psychiatry research, 278, 180–187. https://doi.org/10.1016/j.psychres.2019.06.010

Johnson, D. M., Shea, M. Tracie., Yen, S., Battle, C. L., Zlotnick, C., Sanislow, C. A., Grilo, C. M., Skodol, A. E., Bender, D. S., McGlashan, T. H., Gunderson, J. G., & Zanarini, M. C. (2003). Gender differences in borderline personality disorder: findings from the collaborative longitudinal personality disorders study. Comprehensive Psychiatry, 44(4), 284–292. https://doi.org/10.1016/s0010-440x(03)00090-7

Karaszewska, D. M., Ingenhoven, T., & Mocking, R. J. T. (2021). Marine omega-3 fatty acid supplementation for borderline personality disorder: A meta-analysis. The Journal of Clinical Psychiatry, 82(3), Article 21m13814. https://doi.org/10.4088/JCP.21m13814

Kelaiditis, C. F., Gibson, E. L., & Dyall, S. C. (2023). Effects of long-chain omega-3 polyunsaturated fatty acids on reducing anxiety and/or depression in adults; A systematic review and meta-analysis of randomised controlled trials. Prostaglandins, leukotrienes, and essential fatty acids, 192, 102572. https://doi.org/10.1016/j.plefa.2023.102572

Kernberg, O. F., Selzer, M. A., Koenigsberg, H. W., Carr A. C., & Applebaum A. H. (1989). Psychodynamic psychotherapy of borderline patients. Basic Books.

Konstantinou, G. N., Trevizol, A. P., Downar, J., McMain, S. F., Vila-Rodriguez, F., Daskalakis, Z. J., & Blumberger, D. M. (2021). Repetitive transcranial magnetic stimulation in patients with borderline personality disorder: A systematic review. Psychiatry research, 304, 114145. https://doi.org/10.1016/j.psychres.2021.114145

Lenzenweger, M. F., Lane, M. C., Loranger, A. W., & Kessler, R. C. (2007). DSM-IV Personality Disorders in the National Comorbidity Survey Replication. Biological Psychiatry, 62(6), 553–564. https://doi.org/10.1016/j.biopsych.2006.09.019

Levy, K. N., Meehan, K. B., Kelly, K. M., Reynoso, J. S., Weber, M., Clarkin, J. F., & Kernberg, O. F. (2006). Change in attachment patterns and reflective function in a randomized control trial of transference-focused psychotherapy for borderline personality disorder. Journal of Consulting and Clinical Psychology, 74(6), 1027–1040. https://doi.org/10.1037/0022-006x.74.6.1027

Lieslehto, J., Tiihonen, J., Lähteenvuo, M., Mittendorfer-Rutz, E., Tanskanen, A., & Taipale, H. (2023). Comparative Effectiveness of Pharmacotherapies for the Risk of Attempted or Completed Suicide Among Persons With Borderline Personality Disorder. JAMA network open, 6(6), e2317130. https://doi.org/10.1001/jamanetworkopen.2023.17130

Linehan, M. M. (1993). Cognitive-behavioral treatment of borderline personality disorder. Guilford Press.

Matthies, S. D., & Philipsen, A. (2014). Common ground in Attention Deficit Hyperactivity Disorder (ADHD) and Borderline Personality Disorder (BPD)-review of recent findings. Borderline personality disorder and emotion dysregulation, 1, 3. https://doi.org/10.1186/2051-6673-1-3

Nandan, N. K., Soni, P. K., Parsaik, A., & Hashmi, A. (2022). "Esketamine" in Borderline Personality Disorder: A Look Beyond Suicidality. Cureus, 14(4), e24632. https://doi.org/10.7759/cureus.24632

National Institute for Health and Care Excellence (NICE). (2009, January 28). Recommendations | Borderline personality disorder: recognition and management | Guidance | NICE. Www.nice.org.uk. https://www.nice.org.uk/guidance/cg78/chapter/Recommendations

Nikolas, M. A., & Burt, S. A. (2010). Genetic and environmental influences on ADHD symptom dimensions of inattention and hyperactivity: a meta-analysis. Journal of abnormal psychology, 119(1), 1–17. https://doi.org/10.1037/a0018010

Oldham, J. (2005). Guideline Watch for the Practice Guideline for the Treatment of Patients With Borderline Personality Disorder 1 GUIDELINE WATCH: PRACTICE GUIDELINE FOR THE TREATMENT OF PATIENTS WITH BORDERLINE PERSONALITY DISORDER DEFINITION, DIAGNOSTIC STABILITY, AND LONGITUDINAL COURSE Definition. American Psychiatric Association. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/bpd-watch-1410457064610.pdf

Oudbier, S. J., Goh, J., Looijaard, S. M. L. M., Reijnierse, E. M., Meskers, C. G. M., & Maier, A. B. (2022). Pathophysiological Mechanisms Explaining the Association Between Low Skeletal Muscle Mass and Cognitive Function. The journals of gerontology. Series A, Biological sciences and medical sciences, 77(10), 1959–1968. https://doi.org/10.1093/gerona/glac121

Paris, J. (2008). Treatment of borderline personality disorder: A guide to evidence-based practice. Guilford Press.

Pascual, J. C., Arias, L., & Soler, J. (2023). Pharmacological Management of Borderline Personality Disorder and Common Comorbidities. CNS drugs, 37(6), 489–497. https://doi.org/10.1007/s40263-023-01015-6

Pascual, J. C., Martín-Blanco, A., & Soler, J. (2021). Twenty-Year Trends in the Psychopharmacological Treatment of Outpatients with Borderline Personality Disorder: A Cross-Sectional Naturalistic Study in Spain. CNS drugs, 35(9), 1023–1032. https://doi.org/10.1007/s40263-021-00852-7

Porter, C., Palmier‐Claus, J., Branitsky, A., Mansell, W., Warwick, H., & Varese, F. (2019). Childhood adversity and borderline personality disorder: a meta‐analysis. Acta Psychiatrica Scandinavica, 141(1), 6–20. https://doi.org/10.1111/acps.13118

Prada, P., Nicastro, R., Zimmermann, J., Hasler, R., Aubry, J. M., & Perroud, N. (2015). Addition of methylphenidate to intensive dialectical behaviour therapy for patients suffering from comorbid borderline personality disorder and ADHD: a naturalistic study. Attention deficit and hyperactivity disorders, 7(3), 199–209. https://doi.org/10.1007/s12402-015-0165-2

Puder, D. (Host). (2018-current). Psychiatry & Psychotherapy Podcast [Audio podcast]. Emotion Connection, LLC. https://www.psychiatrypodcast.com/

Reich, D. B., Zanarini, M. C., & Bieri, K. A. (2009). A preliminary study of lamotrigine in the treatment of affective instability in borderline personality disorder. International clinical psychopharmacology, 24(5), 270–275. https://doi.org/10.1097/YIC.0b013e32832d6c2f

Reyes-López, J., Ricardo-Garcell, J., Armas-Castañeda, G., García-Anaya, M., Arango-De Montis, I., González-Olvera, J. J., & Pellicer, F. (2018). Clinical improvement in patients with borderline personality disorder after treatment with repetitive transcranial magnetic stimulation: preliminary results. Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999), 40(1), 97–104. https://doi.org/10.1590/1516-4446-2016-2112

Riffer, F., Farkas, M., Streibl, L., Kaiser, E., & Sprung, M. (2019). Psychopharmacological treatment of patients with borderline personality disorder: comparing data from routine clinical care with recommended guidelines. International journal of psychiatry in clinical practice, 23(3), 178–188. https://doi.org/10.1080/13651501.2019.1576904

Sierra, M., Baker, D., Medford, N., Lawrence, E., Patel, M., Phillips, M. L., & David, A. S. (2006). Lamotrigine as an add-on treatment for depersonalization disorder: a retrospective study of 32 cases. Clinical neuropharmacology, 29(5), 253–258. https://doi.org/10.1097/01.WNF.0000228368.17970.DA

Sierra, M., Phillips, M. L., Ivin, G., Krystal, J., & David, A. S. (2003). A placebo-controlled, cross-over trial of lamotrigine in depersonalization disorder. Journal of psychopharmacology (Oxford, England), 17(1), 103–105. https://doi.org/10.1177/0269881103017001712

Silventoinen, K. (2003). Determinants of variation in adult body height. Journal of biosocial science, 35(2), 263–285. https://doi.org/10.1017/s0021932003002633

Simonsen, S., Bateman, A., Bohus, M., Dalewijk, H. J., Doering, S., Kaera, A., Moran, P., Renneberg, B., Ribaudi, J. S., Taubner, S., Wilberg, T., & Mehlum, L. (2019). European guidelines for personality disorders: past, present and future. Borderline Personality Disorder and Emotion Dysregulation, 6(1). https://doi.org/10.1186/s40479-019-0106-3

Skodol, A. (2022) Borderline personality disorder: Treatment overview. UpToDate. Retrieved October 3, 2024, from https://www.uptodate.com/contents/borderline-personality-disorder-treatment-overview

Skoglund, C., Tiger, A., Rück, C., Petrovic, P., Asherson, P., Hellner, C., Mataix-Cols, D., & Kuja-Halkola, R. (2021). Familial risk and heritability of diagnosed borderline personality disorder: a register study of the Swedish population. Molecular psychiatry, 26(3), 999–1008. https://doi.org/10.1038/s41380-019-0442-0

St-Amour, S., Cailhol, L., Ruocco, A. C., & Bernard, P. (2022). Acute Effect of Physical Exercise on Negative Affect in Borderline Personality Disorder: A Pilot Study. Clinical psychology in Europe, 4(2), e7495. https://doi.org/10.32872/cpe.7495

Stoffers-Winterling, J. M., Storebø, O. J., Pereira Ribeiro, J., Kongerslev, M. T., Völlm, B. A., Mattivi, J. T., Faltinsen, E., Todorovac, A., Jørgensen, M. S., Callesen, H. E., Sales, C. P., Schaug, J. P., Simonsen, E., & Lieb, K. (2022). Pharmacological interventions for people with borderline personality disorder. The Cochrane Database of Systematic Reviews (CDSR), 11(11), CD012956. https://doi.org/10.1002/14651858.CD012956.pub2

Tiihonen, J., Taipale, H., Mehtälä, J., Vattulainen, P., Correll, C. U., & Tanskanen, A. (2019). Association of Antipsychotic Polypharmacy vs Monotherapy With Psychiatric Rehospitalization Among Adults With Schizophrenia. JAMA psychiatry, 76(5), 499–507. https://doi.org/10.1001/jamapsychiatry.2018.4320

Zanarini, M. C., Frankenburg, F. R., Bradford Reich, D., Harned, A. L., & Fitzmaurice, G. M. (2015). Rates of psychotropic medication use reported by borderline patients and axis II comparison subjects over 16 years of prospective follow-up. Journal of clinical psychopharmacology, 35(1), 63–67. https://doi.org/10.1097/JCP.0000000000000232

Zanarini, M. C., Schulz, S. C., Detke, H. C., Tanaka, Y., Zhao, F., Lin, D., Deberdt, W., Kryzhanovskaya, L., & Corya, S. (2011). A dose comparison of olanzapine for the treatment of borderline personality disorder: a 12-week randomized, double-blind, placebo-controlled study. The Journal of clinical psychiatry, 72(10), 1353–1362. https://doi.org/10.4088/JCP.08m04138yel

Zou, M., Broadbear, J. H., & Rao, S. (2023). Exploring the Utility of Neurostimulation Therapies in the Treatment of Borderline Personality Disorder: A Systematic Literature Review. The journal of ECT, 39(3), 151–157. https://doi.org/10.1097/YCT.0000000000000916

View Details

Dr. Puder and Dr. Cummings have no conflicts of interest.

Transcript edited by Joanie Burns DNP, APRN, PMHNP-BC

In this episode, Dr. Michael Cummings, a renowned expert in psychopharmacology, joins Dr. Puder to discuss the complex relationship between psychiatric medications and weight gain. The conversation explores how medications like antipsychotics (clozapine, olanzapine, risperidone) can lead to metabolic challenges such as obesity and dyslipidemia, especially in patients with chronic mental health conditions. Dr. Cummings delves into the role of GLP-1 agonists, a new class of medications showing promise in managing weight gain and metabolic syndrome. He also covers the mechanisms behind drug-induced weight changes, including how histamine and serotonin receptors influence appetite, metabolism, and overall health. The episode provides listeners with practical strategies for managing medication-induced weight gain, offering insights on diet, exercise, and potential pharmacological interventions.

GLP-1 Agonists In Psychiatry And Weight ManagementDr. Puder (00:02:30):

You recently told me there's this push for GLP-1’s [glucagon-like peptides] to be brought into the state and I know that's a hot topic. There's a lot of expensive medications and so I imagine that's the kind of contract that you're looking at. Is that going to be helpful? What are all the details on that?

Dr. Cummings (00:07:45):

Yes, indeed, that's a hot area currently in the California Department of State Hospitals. As you might guess, with a chronically mentally ill population, most of whom are suffering from a psychotic disorder, rates of obesity and metabolic syndrome are large. We've had an obesity epidemic in the country as a whole, but it's worse among the mentally ill (Goldberg, 2023). I think our average BMI in the state hospital patient population is 29.9. Meaning, the average number in our patients is pushing just a hair short of grade one obesity. And we probably have a prevalence rate of around 60% of people who meet the criteria for obesity and a slightly lower, somewhere in the 50–55% range who meet the formal criteria for metabolic syndrome. Meaning that, in addition to obesity, they have dyslipidemia, hypertension, central adiposity, and all of the health risks that come with that (Shulman et al., 2014). The GLP-1 agonists at this point are about the only class of medications out there that are very good at actually reversing obesity (Goldberg, 2023). There are a number of medications that can slow weight gain such as metformin, but they're not very good at reversing the weight once the weight is on.

Not all of the GLP-1 agonists are great at reducing weight. However, some of the more recent ones, like liraglutide (Larsen et al., 2017), semaglutide, and, in particular, tirzepatide (trade name Mounjaro) have shown good research data suggesting that they can produce a substantial amount of weight loss in addition to correcting things like glucose tolerance and also assisting with decreasing lipid abnormalities (Flory & Lipska, 2019) . We've also discovered that the GLP-1 [glucagon-like peptide] agonists have some unexpected benefits such as reducing alcohol intake, reducing craving for illicit drugs, and at least tiny amounts of data suggesting they may decrease the number of reward-system driven behaviors. That may include things like self-mutilation, self-cutting and other things that might be of benefit in psychiatric patients. The data on those features are pretty new and still pretty small, but they're enticing in the sense that this class of drugs affects a lot of the way our hypothalamus functions in terms of modulating drives and impulses, in addition to the direct anti-obesity and metabolic benefits of the drugs.

Challenges And Caveats Of GLP-1 AgonistsDr. Puder: (00:06:58):

I was excited about these (GLP-1s) at first, and honestly, my excitement has decreased because I see people have gotten on them, and then when they get off, they gain their weight back and often the weight comes back not as the muscle that they lost, but more as fat.

Dr. Cummings:

Well, that's an important element with the GLP-1 agonist is when you make the decision to start them, this is a case of starting what is likely to be a lifelong medication, because indeed, when they are stopped, not only does the weight come back and the metabolic abnormalities come back, they will likely come back in worse form than they were to begin with. In some ways that parallels the history of weight loss diets. They've shown this all the way down to animal studies. If you put a rat on a starvation diet, make it lose weight, and when you give it access to free feeding the first time it will regain the weight it has lost and it will overshoot slightly by 5-10%. If you do the same experiment again with the same rat, it will lose the weight and then when you refeed it, will regain the weight in about half the time and overshoot by more like 15–20%. So when people either engage in repeated dieting or in use of one of these drugs, it has to be either a lifelong change in diet and exercise habits, or a lifelong commitment to take one of these drugs.

Dr. Puder:

So, just to give people an idea, if people are not exercising while they take them, they could lose 35% lean muscle mass when they lose weight. That's a lot of muscle. And you know, muscle is very helpful for so many reasons. We've talked about this a lot in the podcast before. It's like a neuroendocrine tissue for the brain. It's a very healthy tissue.

Dr. Cummings:

Indeed. The other thing we've talked about with patients is they need not only to maintain exercise, they need to maintain an adequate diet, even if they don't feel hungry. They're rare, very rare, but we've had a couple of patients that we've had to take off of these drugs because they went from being obese to being anorectic.

Dr. Puder: Right.

Dr. Cummings:

You know, an interesting case example I can think of is a woman who started with a BMI of 38—grade two obesity—and by the time she got taken off of the GLP-1 agonist by her attending physician, she was at a BMI of 19. Because, as she put it, “I have a piece of toast and a glass of water in the morning, and I'm not hungry anymore.” And of course, you can't live on a piece of toast and a glass of water.

Dr. Puder: So hunger and thirst can be eradicated at a high enough dose.

Dr. Cummings:

Yes. And, this was not so in her case. She was at a standard dose, but she was exquisitely sensitive to the effect of the drug. Honestly, she was probably out in the tail of the distribution in terms of sensitivity, but, you know, this was not a class of drugs that she could take.

Dr. Puder:

Yes. I think it's so fascinating because I've seen other patients where it reduces their drive and motivation in other domains of their life. We talked about decreasing the drive to drink alcohol, the drive to drink water, the drive to eat. It acts on the hypothalamus, the brainstem areas involving appetite regulation, reducing the appetite, slowing gastric emptying, but it also hits the reward centers of the brain–nucleus accumbens, ventral tegmental area [VTA]–influencing reward-driven behaviors. Some of which we may not want to decrease.

Dr. Cummings:

Yes. Unfortunately, we've never figured out a way to selectively alter the functioning of the reward pathway. In part, that's because neurologically it's a fairly simple pathway. The shell of the nucleus accumbens, not even the whole nucleus accumbens, just the outer layer of neurons, mediates the reward response and projects forward to both the temporal and frontal lobes. But it's a fairly simple on/off nucleus and if you alter its modulation it's not sophisticated enough that you can say, “I want this behavior to go away, but I want that one to be preserved.” The person has to make more of a choice-driven, “I'm going to do this because it's good for me and I'd like to continue this.” Not that it may feel as good as it used to.

Dr. Puder:

Right. So this could apply to things like gambling, binge eating, and shopping? Right? Those could decrease. But also you could have decreased motivation to engage in physical activities and exercise. And that's what I've seen from people. I'm pleading with them like, “Hey, try this. We need to keep exercising.” And people who have been exercising for years will say, “I just no longer… I don't know, I can't exercise while I'm on it. I don't know why I can't exercise, but I just have no desire to lift weights anymore.”

Dr. Cummings:

Yes. The motivation is gone because it no longer induces the same reward it did, which I think the only way around that, if the person really needs the medication, is to have either external ways of being motivated, such as having a trainer who goes, “Get out there and do your lifting,” or, enough internal sense of, “I need to do this because it's good for me, not because it feels good anymore.” Which is a very difficult position. I think sometimes we don't appreciate how much influence our hypothalamus has over our behavior.

Dr. Puder:

So, you're saying if someone's on this, they may need to be on this for a very long time.

Dr. Cummings:

For a very long time. Otherwise, indeed, of all of the studies that have been done now, the longest study I've seen was a two-year follow-up study, but it was the same as all of the one year follow-up studies. If people stop the medication over about a year to a year and a half, all of their weight and dyslipidemia and hypertension and diabetes would go right back to where they were, plus a little bit worse.

Dr. Puder:

To give people context, the positive studies showed that within a year on the medication, with some diet coaching, you could lose about 15–20% of your body weight. And so when people get off of it, they're gaining weight back, is what you're saying?

Dr. Cummings:

Yes. Essentially, the benefits in terms of correcting metabolic abnormalities and in producing weight loss, if you stop the medication, those benefits go away. In other words, the medication does not produce a positive permanent change in the underlying systems. The medications can modulate those systems while the medication is present.

Dr. Puder:

Do you think there's a rebound? \

Dr. Cummings: Yes.

Dr. Puder: With receptor density? Does that change? Does that rebound? Do we know about that?

Dr. Cummings:

Yes, there is a rebound and as I alluded to, it follows the same thing you see with people who lose weight via strenuous dieting. You can lose weight that way, but if you go from diet back to your usual food intake, you'll regain not only the original weight, but you'll overshoot and gain some additional weight. And, you know, anything that goes along with that, if you were glucose intolerant, odds are you'll become glucose intolerant again. If you were dyslipidemic, you're likely to do that again. In other words, if you're just talking about diet and exercise, that's why temporary diet and exercise don't work either. If people are going to change their metabolic status via diet and exercise, it has to be a permanent change in lifestyle. And I think these medications parallel that in that if you want them to produce a permanent change, then you have to take them permanently.

Dr. Puder:

So what we're talking about then is that one needs to actually change habits and on a very deep, deep level, right? So it's like the basal ganglia, the deep brain structure, is involved in habit formation, motor control and somehow we need to institute habits slowly, maybe one at a time. Or, maybe we only change one habit per month or every two months. The question is, how do you change habits?

Dr. Cummings:

With a lot of difficulty. Unfortunately, much of this is stuff that occurs well below the conscious level, and much of it is preset by our genetics. You and I have talked before about what has happened in modern cultures. Historically, obesity was not such a huge problem. If you had to do hours of manual labor, or you had to hunt for your food and chase it in order to have an adequate number of calories. Well, if all you have to do is drive through McDonald's, well that's a basic change in the environment, but our brain doesn't change very quickly.

Dr. Puder:

The problem is that a lot of the medications we give increase weight.

Dr. Cummings: Yes.

Psychiatric Medication And Weight GainDr. Puder (00:18:00):

A patient will come to me in a crisis. They could be psychotic. Their life could be completely torturous. You put them on a second generation antipsychotic, and within a couple months, they're no longer psychotic. They're no longer living in this tortured reality, but they have gained some weight. And so now, as an outpatient psychiatrist, I'm managing a new problem from the medication and I'm trying to figure out how to best help these people. So yes, this is the big sort of overarching problem.

Let's talk about different medications and why they increase weight (Mizuno et al., 2014), starting with the biggest culprits.

Clozapine and Olanzapine and Weight GainDr. Cummings (00:18:45):

Okay. The biggest culprits are clozapine and olanzapine. And they both do a number of things that increase or push the person toward gaining weight. One, they tend to produce glucose intolerance, meaning that the person does not efficiently handle glucose. When you don't efficiently handle glucose, that glucose gets shunted into lipids. And, in particular, there's a shift in balance toward LDL cholesterol as opposed to HDL cholesterol. There's a tendency toward central adiposity. That is gaining fat tissue in the abdomen around organs. That's metabolically active and produces inflammation (Goldberg, 2023). That then tends to become a self-reinforcing cycle so that the person gains weight, which worsens the problem, and they gain more weight, which further worsens the problem.

Now, in the case of these two medications, they also have additional effects that promote weight gain. They're pretty goodH1 histamine antagonists(Foster et al., 2021). They block histamine receptors. People are very familiar with that in terms of when you take an antihistamine and you may get drowsy. But, the other effect the histamines have, particularly if you're taking something that's an antihistamine on an ongoing basis, is you decrease your basal metabolic rate. You don't burn as many calories. That's another tick in the direction toward weight gain because calories you don't burn get stored. The third thing they do is, in the case of these two drugs, antagonize 5-HT2C receptors. These are serotonin receptors that function in the hypothalamus, in the satiety center, to tell you when you've had enough to eat. If you block 5-HT2C receptors, what you tend to get is carbohydrate craving. The person basically cannot pass up a donut, or a cookie, or ice cream. Which, of course, is another great way to gain further weight.

Dr. Puder:

So you have the histamine H1 receptor antagonism, which can cause some nice sedation if they're having difficulty sleeping, but also increases appetite and decreases the metabolic rate. Then you have the serotonin 5-HT2C receptor antagonism. Which they both block in the brain, which leads to…

Dr. Cummings:

… carbohydrate craving. The person wants sugar. I can't tell you how many patients I've seen put on clozapine or olanzapine and they come back and they'll tell me in so many terms, ”I am hungry all the time and what I want is every single sweet thing I see.”

Dr. Puder:

“I'm eating cereal in the middle of the night, sometimes twice.”

What about theM3 receptor antagonism? Do you think that is involved in the insulin secretion?

Dr. Cummings:

Yes. It's involved in insulin secretion, and it probably also does play a role in these people becoming glucose intolerant along with impairment of the functioning of the GLP-1 receptors, which is where the GLP-1 agonists come into the story. They directly oppose the effects of olanzapine and clozapine and similar drugs at the modulation point of that receptor. The change in insulin balance appears to be the most important of the driving forces toward obesity and metabolic syndrome with the antipsychotics. That is likely why olanzapine and clozapine are at the top of the list in terms of producing these effects because they cause the greatest disturbance in those systems.

Dr. Puder:

Okay. Let’s get a little bit deeper into leptin & ghrelin. So leptin promotes satiety. Ghrelin stimulates appetite. Olanzapine and clozapine both disrupt the normal leptin & ghrelin signaling.

Dr. Cummings:

Yes. And they essentially shift the balance of these in the direction of increased calorie intake. Whereas, the GLP-1 agonists shift the same systems in the opposite direction.

Dr. Puder:

So they increase ghrelin levels, which increases the hunger hormone. A blunted leptin response results in decreased satiety hormone. So then increased calorie intake and weight gain result.

Dr. Cummings:

Yes. And at the same time, the antihistamine effects are decreasing calorie output. So, you know, it's the classic story with weight gain. You have increased calorie intake and decreased calorie output, and that extra energy gets stored as adipose tissue.

Insulin and Weight GainDr. Puder: (00:24:52):

I think insulin is gonna be something huge to look at in coming podcasts and just how important it is to be metabolically healthy, you know, in people with increased rates of depression. If out of control, diabetes has much higher rates of depression. Insulin is impaired in these patients. You want to talk more about that?

Dr. Cummings:

Insulin is critically important in human physiology. During active exercise, skeletal muscle can take up sugar without insulin being present. But that's about the only tissue that can do that. Everything else requires the presence of insulin in order for glucose to get into cells to be used as fuel. So what you have in the case of somebody who is diabetic, type 2 diabetes in particular, is you have an elevated circulating level of insulin that can't bind to its receptor, can't get the sugar into the cells, so the sugar builds up in the bloodstream. That's why people have elevated blood sugar and diabetes. Now, in type 1 diabetes, they actually have a lack of insulin. In type 2, they typically have an excess of insulin, but it's ineffective and can't do its job. So literally, what's happening to this poor person is most of the cells in their body are starving to death because they can't get fuel because the fuel is stuck outside in the bloodstream. And that leads to a whole host of downstream adverse effects in terms of things like poor healing, blindness, neuropathies–you know, all of the long-term consequences of being diabetic.

Dr. Puder:

What I think is the most wild thing about this is the average human, without any glucose regulation issues, they probably have on average aboutone teaspoon of total sugar, total glucose in their blood at a given time. If you were to drain all of my blood, it might have a teaspoon right now.

Dr. Cummings:

That's because if you have normal physiology, the glucose is not supposed to be hanging out in your bloodstream. It's supposed to be getting into the cells where it's oxidized and used to generate ATP [adenosine triphosphate] and essentially provide the energy for the cell. This is like being somewhere in the wintertime and freezing to death, and all of the firewood is stacked outside, but you can't get it into the fireplace.

Dr. Puder:

So imagine someone who is floridly diabetic. Instead of one teaspoon in their blood, total glucose, they have three teaspoons. That's not that much if you think about it, in the big picture of how much sugar we actually drink sometimes. Three teaspoons is not that much, right?

Dr. Cummings:

No, it isn't. But it's the shift in getting it to where it needs to be. In the case of the type 1 diabetic whose beta cells in their pancreas are not producing insulin, of course they can't get the glucose to where it needs to go either, but that's just because they have a lack of insulin to get it there. In the case of type 2, it's because the person is resistant to the presence of insulin.

Dr. Puder:

And then we also think about steroid use–always increased glucose. And, someone who's in a high stress state, there's a transient fight and flight type of response in you. With hyperglycemia–high blood sugar.

So we have these medications that are great medications for treating psychosis, but do cause weight gain.

Dr. Cummings:

This fits into the discussion of the GLP-1 agonists, the antipsychotics, the antidepressants, and anything else you care to name. We have yet to discover any medication that does only the thing that we want it to. You know, the model we divide these into: effects and side effects. But, that's entirely us. The molecule doesn't make any distinction. It just does what it does. And unfortunately, you know, different drugs have different adverse effects, different risks, which is why you're always hearing physicians talk about risk benefit analysis. Are you gonna get more benefit out of this than risk? Obviously, if you don't want to take medication, if there's more risk than benefit, or engage in any other medical procedure where the risk outweighs the benefit. Part of our job, a large part, has become managing the risk profiles of many of these medications so that the patient can derive the benefits safely.

Risperidone: Influence on Weight Gain and Prolactin Dr. Puder: (00:30:40):

Risperidone is another atypical antipsychotic. This one can cause weight gain, as well. There's one mechanism which I think is unique, which is the prolactin elevation, which sometimes occurs (Shimatsu & Hattori, 2012).

Dr. Cummings:

Yes, risperidone, and its metabolite, paliperidone, are both excellent substrates for p-glycoprotein, which is an efflux pump. There are two main places of interest, the blood-brain barrier and the GI tract. The blood-brain barrier is important because it directly pumps these drugs from the brain into the hypophyseal circulation, which supplies the pituitary. So the concentration of these drugs, both of them, winds up being higher in the pituitary than it is in the brain. And in the pituitary, dopamine blockade, D2 blockade, removes tonic inhibition of both prolactin synthesis and prolactin secretion. So if you take away that tonic inhibition, the person will secrete more. They will synthesize more. And the increased synthesis will also drive division of pituicytes that make prolactin, which may eventually result in microadenoma and may eventually result in a macroadenoma (Pekić et al., 2019). All of which is to say that these drugs are especially good at elevating prolactin, which can promote weight gain. But prolactin's normal role is to promote lactation. Women who are lactating need more calories because the calories are getting delivered to the infant. If you're not breastfeeding though, and you're taking something that elevates prolactin, you're setting other things up in the body to store more calories because your body thinks, “Oh, well, we're about to try to raise another human being. So we need to store more calories to be ready.” And so people will gain weight due to prolactin.

Dr. Puder:

So in men with high prolactin, their testes may not work as well, there is decreased testosterone, they may get gynecomastia (breast tissue development). They may have erectile dysfunction, decreased libido, infertility. So, as we give risperidone, we need to watch out for this. This is not something we want them to live with chronically.

Dr. Cummings:

No. Short-term elevation of prolactin is not a medical emergency, but it's not something that you want to leave elevated, particularly if the elevation is causing overt symptoms such as galactorrhea, amenorrhea, or erectile dysfunction.

Dr. Puder:

Also, it can cause osteopenia, osteoporosis.

Dr. Cummings:

Yes. And, in both men and women, it does increase the risk of breast cancer, as well. More so in women, of course, but not unheard of in men exposed to prolactin-elevating drugs.

**Dr. Puder:**

There have been a couple questions in our Q&A that we haven't gotten to about what we do if someone has high prolactin when they're on risperidone. What's your algorithm for what you would do first?

Dr. Cummings:

If somebody's on risperidone and they have responded, one option to consider would be, might you want to switch them to an alternative dopamine antagonist? Risperidone and paliperidone are far worse than any of the other D2 antagonists at elevating prolactin. So that's one option. Another option would be if the person responds to risperidone and it's a beautiful response and they have no side effects and they really don't want to change and you don't want to change because they've had a great antipsychotic response to the drug or great behavioral response (for example, in autism), you can give them a dopamine agonist to compete with the drug in the pituitary and see if you can bring down their prolactin. The ones that people have used are things like pramipexole, bromocriptine and, you'll see it recurrent in the literature, aripiprazole. The trouble with the last one is it's very easy to switch antipsychotics in that case without meaning to. Basically, the binding of aripiprazole is so high. The binding affinity is so high that, on average, giving somebody two milligrams of aripiprazole means the aripiprazole is going to occupy 72% of their D2 receptors, which may make the antagonist ineffective because it now has nothing to target. By the time you get up to around 10 milligrams of aripiprazole, whatever antagonist you're giving the person, you have replaced it with aripiprazole. Because the other drug, at that point, has nothing to work with.

Dr. Puder:

What about dose reduction? Could you reduce the dose of risperidone?

Dr. Cummings:

You can. If the person is at a higher dose, you can reduce the dose and thereby reduce the effect of the drug on the pituitary. The caveat there is, you have to proceed carefully so that you don't decrease the dose to the point the person has a psychotic relapse.

Dr. Puder:

Let's say someone has this problem. They know that the patient probably has high prolactin. They figured that out. How fast should they solve this problem? Like, how urgent of an issue is this?

Dr. Cummings:

They should solve it within three to six months.

Dr. Puder:

Okay. That's helpful because that's a different level of a problem than like akathisia.

Dr. Cummings:

Yes, because of the effects of prolactin. Now I'm talking about somebody who's asymptomatic, which frankly most people are. You have time because the risks of prolactin are slow and long term. Now, if somebody has overt galactorrhea or amenorrhea that they don't like, or erectile dysfunction, then you may want to proceed more rapidly. But, I've seen people do crazy things with antipsychotics in response to an elevated prolactin that's asymptomatic. Like, cutting the person's antipsychotic in half. Which usually means the person's going to have a psychotic relapse fairly soon. Will it bring down the prolactin? Yes. But at a huge cost in terms of destabilizing the person. Again, in the asymptomatic prolactin elevation patient the elevation, per se, is not an emergency.

Dr. Puder:

This is good because we need to know how quickly we need to solve the issue. So you have some time. You can move slowly. You can follow them every two to three weeks. Try to make some changes. Okay. I think we're good on that one. Let's talk about the next big weight gainer on the list, probably mirtazapine (Remeron). It has some good H2 receptor antagonism.

Dr. Cummings:

It's also a great blocker of 5-HT2C. And indeed, it produces exactly the same response, i.e., the patient will be thinking, “I've never seen a donut that I don't like.”

Dr. Puder:

I've had different responses. Some patients have no issues, very little weight gain. Some people, it's like, “Whoa!” Okay, we're going 15 pounds in a couple months. And we need to think of something else here.

Assessing Side Effects And The Importance Of Early InterventionDr. Cummings (00:39:44):

And in that case, the safest thing to do is choose a different antidepressant or anti-akathisia medication–that's its other major use. Like all medications, people vary in terms of how much they respond to blockade to 5-HT2C. Some people have a dramatic response, some people don't notice much of anything. Most people will notice some increase if you watch them carefully. Some increase in calorie intake, some increase in carbohydrate intake. For some people it may not be enough to make any difference. They may just adjust their activity level to compensate. This does give a chance though, to say something. I think that should be true for all psychiatric offices. Everybody should own a scale and everyone should weigh their patients.

In my primary work is as a consultant, I can't tell you how many times I've gotten calls: “Well, I put this person on ____” (and usually it's olanzapine or clozapine where I work, but it could be mirtazapine just as easily); and I'll get a call from the psychiatrist, “Well, my patient has gained 120 pounds. Should I do something about that?” And of course, the thought that goes through my mind is, “Well, yeah, you should have done something about it about a year ago.” And you know, I think people in psychiatry should remember we are physicians first and then we are psychiatrists.

Dr. Puder:

Yes. The caveat being risk reward. I have one patient, in particular, I'm thinking of, who gained maybe 50 pounds or so. And he's lost some. He's going down slowly, with lifestyle things, but he doesn't really care. He, and his significant other, are like, “You know, we are in such a better place in terms of our marriage, in terms of the arguments we have in terms of him floridly not being psychotic, it's not our priority.” For other people, it would be…

Dr. Cummings:

…a major priority. But, our job, as the physician in this context, is to spot the problem early. You know, it should never be the case that, “Oh, my patient has gained 120 pounds.” You know, if you are actually weighing them every time they come to see you for a visit and you notice that they're gaining weight, then it becomes an issue for clinical discussion and you can lay it out for them: “These are the risks of gaining too much weight. How would you like to address this? We should talk about ways to modify this if it's something you care about, and maybe you should care about it if it's going to shorten your lifespan.” That discussion needs to occur early on, not when you finally notice when the patient can't get through your office door.

In fact, there are nice guidelines out there suggesting that somebody is going to have trouble with a given medication if you take their baseline weight and if they gain 5% above that in the first month, or 7.5% in three months, or 10% in six months. You're looking at somebody who's going to have a long-term weight/metabolic problem with the medication you're giving them.

The advantage, of course, is that if you spot the trend early, it's easier to address. You know, it's far easier to lose five pounds with a little bit of diet and exercise than it is to lose 50 pounds with diet and exercise. It's also easier to prevent weight gain with things like metformin (Chen et al., 2013; Mizuno et al., 2014). You wouldn't have to go to a GLP-1 if you're trying to keep it off, not reverse it. So, there are options out there for dealing with weight gain. But like most problems, better dealt with early than late.

Other Psychotropics Known To Cause Weight GainDr. Puder: (00:44:20):

I want to get through some of the other medications that cause weight gain. Paroxetine (probably the biggest weight gainer of the SSRIs), tricyclic antidepressants like amitriptyline, nortriptyline (have a lot of H2 and serotonin receptor antagonism that causes the weight gain and anticholinergic effects), lithium. Do you want to give any mention of lithium and how that might do it?

Dr. Cummings:

Lithium alters a whole host of things, including a lot of metabolic parameters in terms of basic energy input and output. You could think of lithium as almost turning down the thermostat on a number of things, including emotions, but also including a lot of metabolic parameters.

Dr. Puder:

Then we have valproate (Depakote).

Dr. Cummings:

Yes. Also increases weight in a number of ways. Of course, increases overall GABAergic tone in the brain, which also decreases energy expenditure.

Dr. Puder: Gabapentin, pregabalin.

Dr. Cummings: Same thing.

Multimodal Approaches To Address Medication-induced Weight GainDr. Puder (00:45:47):

Now let's try to think through what could be done. What would be some good pathways? Let's go to the most difficult case. You have treatment-resistant schizophrenia. They're finally starting to get stable on clozapine, but they've gained 50 pounds. Where do you go?

Dr. Cummings:

I can tell you that the formal recommendation from nutritionists is to introduce the person to a diet and exercise program. Unfortunately, I can tell you in schizophrenia, that's almost never successful. Even without medications, people with schizophrenia are very difficult to motivate. They often are very prone to poor dietary habits and a sedentary lifestyle. I think for many of those people who've already gained weight and who look like they're going to continue to gain weight, clozapine is their only viable option to stabilize their mental illness. Until we find things that are better, I suspect that the GLP-1 agonists or combination GLP-1 and GIP [glucose-dependent insulinotropic polypeptide] agonists, like tirzepatide, are likely to be the person's best option.

Dr. Puder:

Just with the caveat that this might be a lifelong journey.

Dr. Cummings:

With the caveat that this might be a lifelong, but, then again, they're suffering from a lifelong mental illness.

Dr. Puder:

The problem I see is, do the insurance companies even pay for these at this point for just plain obesity or just side effects?

Dr. Cummings:

My guess is, over time, the insurance companies will come to the point that they will pay for these. Frankly, a lot of the schizophrenic population are in the public domain, meaning they're being cared for by public healthcare systems. And those systems are already moving in the direction of negotiating for these drugs.

Dr. Puder:

I think at this point, I've had a lot of frustration with insurance companies, trying to get them for people unless they have diabetes.

Dr. Cummings:

Yes. Well, insurance companies don't like to pay out money. That's harder for them to argue now that some of these drugs have specific indications for obesity. And it will become harder and harder for them to argue that. My guess is availability will improve with time. One thing that happened recently that may help is Eli Lilly announced that they're going to provide their GLP-1 agonist via compounding pharmacy at a substantially reduced cost for selected patients.

Dr. Puder:

Okay. So you have this person, they're on clozapine. They're stable. So, you might consider diet and exercise. I would say the only success I've had with patients with schizophrenia is if I can get them….Well, I've had a couple that go on their own. If they were doing it before in a very systematic way, they would have more success. Yes. I would say to people that if they weren't, if I could get them to sort of be in some sort of class, you know, at the YMCA or something where there's some group. Very varying rates of success.

Dr. Cummings:

The people I've seen who most often benefit from diet and exercise are those who indeed had a fairly healthy diet and were active exercisers before the onset of their psychosis. It's very difficult to start with somebody who tended to eat a poor diet and was very sedentary prior to the onset of schizophrenia. It's very difficult to get that person up and moving. We have a few recreational therapists who try their very best to make that happen, but their rates of success are fairly low. Now granted, where I work, we're not dealing with the younger, first onset psychosis patients. Our average patient has been psychotically ill for more than a decade and has often undergone a fair amount of deterioration and is suffering not just from obesity, but usually full-blown metabolic syndrome. You can see the writing on the wall. If they don't get that under control, their life is going to be shortened by things like cardiac disease and liver disease and stroke and everything else that can happen to you if you're diabetic and overweight and have abnormal triglycerides and cholesterol (Minuzo et al., 2024).

Dr. Puder:

What about, say they're stable on olanzapine, risperidone, or another one of these bigger weight gainers like quetiapine. Would you ever consider switching to an antipsychotic that's less of a weight gainer?

Dr. Cummings:

For everything except clozapine, yes, I would consider it. Now, it takes careful consideration of the person's overall medication history. Because the big risk, of course, in switching from a successful antipsychotic to something else, is you may lose the psychiatric stability. And, I think something people underappreciate is that with every psychotic break, there's no guarantee that you're going to recapture stability, because every time the person has an episode of psychosis, to some extent, their responsiveness to antipsychotic treatment decreases. Whether it will decrease to a threshold where you just can't recapture them, it's a roll of the dice each time. Which makes you want to do everything you can to prevent relapse. Those are the elements that you have to weigh. While you're wondering, “Should I switch this person to something that's less prone to weight gain?” Unfortunately, many of the medications we have that are either weight neutral, or close to it, have so far tended not to be our most effective antipsychotics. The one that is actually weight neutral, lurasidone, is not a bad antipsychotic in relatively new onset psychosis. It has no cardiac effects. It is weight neutral. It doesn't cause metabolic issues. But I can tell you in the more chronically ill schizophrenic population, it doesn't work very well. Now, if you're treating bipolar depression, it's a wonderful drug, very potent, very effective. But for chronic schizophrenia, not so much.

Same thing is true of drugs like lumateperone. No EPS. Very little metabolic effect. Effect sizes on schizophrenia, while they achieve significance, the effect sizes were small, arguing that it wouldn't be a very effective approach in somebody with a more severe, somewhat more treatment-resistant illness. The new drug that we started out talking about, xanomeline, it's not clear how effective it will be compared to other antipsychotics. Some of the pivotal trial data suggests it may be as good as things like risperidone and haloperidol and olanzapine. But I never entirely trust pivotal trials, because they're very pristine samples and they are of limited size.

New Medications Being StudiedDr. Puder: (00:54:26):

Let's back up because that was part of a private conversation. So xanomeline, which is under investigation, targets the M1 and M4 subtypes of the muscarinic and acetylcholine receptors in the brain (Foster et al., 2021; Paul et al., 2022). So it's a unique mechanism.

Dr. Cummings:

Yes. It's unique in that, rather than trying to block dopamine postsynaptically, it regulates, or modulates, the release of dopamine and the ventral tegmental limbic circuits. So that it's more like turning the flow on or off upstream rather than trying to block it downstream. It also stimulates cortical M1 receptors, which may help with cognitive symptoms in schizophrenia. It is metabolically neutral. Also, it does not cause extrapyramidal symptoms like dystonia, Parkinsonism, akathisia. It is likely to be approved by the FDA in the late September of this year [2024], and likely will come to market in early 2025. So it will be an addition to drugs that are not likely to influence metabolic status. Its true efficacy will take time to figure out once we've got more than just the pivotal trial data to work with.

Medication Changes And The Risk of DecompensationDr. Puder: (00:56:22):

So let’s say you have a patient and they're stable on an antipsychotic. You could change the medication. That would risk them decompensating. That's a real risk. And I think you know, we had talked about it in another episode, how if someone just stops an antipsychotic, the relapse rate is 95%.

Dr. Cummings:

Yes. It's huge. It's a train wreck.

Dr. Puder:

Which I feel like the anti-psychiatry folks have no idea that's the case. They're like, “Huh, what? No, you just need to take this supplement or just pure psychotherapy.” Which, you know, I'm a fan of psychotherapy.

Dr. Cummings:

People with schizophrenia can benefit from psychotherapy once their psychosis is stabilized. But as we've talked about many times, essentially, the schizophrenia spectrum disorders are a cluster of developmental dementia. And there are things that psychotherapy can change. And there are things that psychotherapy can't change, such as your DNA. Therapy may be able to make changes in your epigenetic profile to some extent, but the neuronal loss, synaptic loss, all those things, there's no evidence that psychotherapy reverses those losses.

Dr. Puder:

Yes. So this is where I think people who follow the podcast closely know there's a good balance between modalities and there's a correct place for medications. There's a correct place for psychotherapy. There's a correct place for both, ideally. I would say psychotherapy for someone who's floridly psychotic is mainly aimed at getting them to take the anti-psychotic. And it would be mainly aimed at therapeutic alliance, connecting with them, building trust as much as possible.

Dr. Cummings:

Once they are more stable, meaning positive symptoms of psychosis have either died out or simmered down, at least, then you have the option, you know, and they may very well benefit from things like cognitive rehabilitation, CBT for schizophrenia, things that will help them deal with life as somebody who has a chronic brain disease. The medications will help decrease the overt symptoms of psychosis, but the medications don't teach people how to live.

Topiramate For Weight Loss: Cognitive Impairments, Renal Risks, And Patient MonitoringDr. Puder: (00:59:17):

We haven't really talked about topiramate and if there's any role for a little bit of topiramate for someone?

Dr. Cummings:

There is. Topiramate is another drug that can produce weight loss (Mizuno et al., 2014). Of course, its limitation is most often cognitive and memory impairment. It also, in some people, particularly if they have unstable renal disease, carries their risk of both renal calculi and metabolic acidosis. Things to keep in mind, if you intend to use topiramate, the weight loss is like many things, plus/minus, some people will lose a great deal of weight and some people it has no effect with all of these drugs. I think the underlying caveat goes back to the statement I made about everyone having a scale. That includes tracking changes for any treatment intervention you're exploring as well. Is it effective?

Dr. Puder:

Yes. I've seen an adolescent patient in a psychiatric hospital, when I was a resident, get kidney stones from topiramate.

And I think when I was taking the history, I was like, “Oh, that's interesting. They've had these kidney stones and they've been on topiramate for six months and they've had them for the last three or four months.” Put it together that they were probably related. And then, the cognitive dulling. You know, word finding issues are profound in some patients.

Dr. Cummings:

Yes. It can be very bad when people become anomic. You know you've gone too far with topiramate when you have a conversation [with someone on topiramate] and there are no nouns.

Dr. Puder:

Let me tell you a nightmarish story of this. I had a patient who was on like 200 twice a day for severe migraines and she went through a program. I'm gonna change a couple of the details here. I always protect the patient's identity. She was able to get it down to like 50 once a day, over the course of working with me for six months, and her husband came in one day and he's like, ”I have my wife back. She talks to me now. For years she didn't talk to me.” And so it's a tragic story of these medications that need to be monitored. It just blows my mind that that wasn't caught.

Dr. Cummings:

Yes. Well, you're in trouble if everything becomes a ”thingamajig” or a “whatchamacallit.”

Dr. Puder:

Tell me more about that.

Dr. Cummings:

I've had patients who were on topiramate, when they were trying to describe something, “Well, you know, it's this thingamajig. You know, the whatchamacallit. Well, it sort of, well, it kind of you know, it did that sort of thing.” And of course, I've got no idea what they're talking about because there are no nouns and no actual verbs that are helpful.

Dr. Puder:

It's a tragic funny. It's an awful funny. I see it mostly beyond the dose of around 50. In some people, going from 50 to a hundred, some people going from a hundred to 150, all of a sudden they have less ability to recall names of things. And then if you push it up even higher than that and it gets even worse.

Dr. Cummings:

Whenever we start a medication with a patient, we need to educate the patient about what the medication's risks and benefits are, including with topiramate. If you start noticing you can't remember things or you can't find words, I need to know about that sooner rather than later.

Integrating Strength Training And Psychiatry: Building Habits For Providers And PatientsDr. Cummings: (01:03:31):

In conclusion, I would say this is an area that psychiatry has neglected to pay attention to. And, in fact, we're actually doing a study in the state hospital system to look at that issue. It's one we need to pay more attention to, because, again, we're the patient's physician, not just their psychiatrist.

Dr. Puder:

I think my closing remarks would be that, as providers, we need to also develop the habits that we ourselves espouse or desire. I've had a number of listeners reach out and say things like, ”Oh, you know, from listening to your episodes on strength training exercises, I've started a routine and I've been doing it for three years, and it's helped me so much.”

Dr. Cummings: Excellent.

Dr. Puder:

I hope that we can inspire. It takes a while to build a habit. It really does. For me, my habit of strength training is Tuesday and Thursday. I have a group I go to, with eight people, and I've been doing that for years. And then I try to do something every day.

Dr. Cummings:

Very good. I've got a gymnasium in my garage, which helps because it's convenient. I don't have to go anywhere. And my schedule is Monday, Wednesday, Friday for a full workout and Tuesday and Thursday for a more minor workout. And then Saturday and Sunday are just more recreational things. Is it tough some days to get up and go, “Yeah, I'm gonna go out there and do a full workout. I don't feel like it.” But, you know, that's the point where you have to tell yourself, “Well, I'm gonna do it anyway.”

Dr. Puder:

In the ideal setting, we find something we can enjoy. And I would say ideally also we find something that we can do with other people. Ideally some of that is in nature. What is the best sport for you as you get older, the one that you enjoy? For some, it's pickleball. And all they can think about is pickleball. I've kind of moved away from thinking that everyone needs to squat and deadlift. Although, I do think everyone needs to squat and deadlift. I think it's great.

Dr. Cummings:

I think a little bit of weight training is a very good thing for everyone. There's no better form of exercise that will help maintain muscle mass and bone strength. Now, it doesn't have to be a major amount. If you add just a little bit of weight training to the more aerobic things it doesn't take all that much to derive the core benefits. In other words, you don't have to become a bodybuilder to get there. But, a little bit of weight training goes a long way.

Building Lifelong Healthy Eating Habits: Small Dietary Changes For Sustainable HealthDr. Puder: (01:06:34):

And then diet. I think diet is another habit that takes time. And how do you eat healthy in a community with other people? And enjoyable food. For me and my wife, we've improved our habits of eating healthy and now we do sushi. Which I consider a very healthy food. And less steak and fries, more sushi. So, small changes over time. Right. And trying to do it in a way that's going to be doable; and not just doable for like one week and then you switch back.

Dr. Cummings:

Yes. What I would counsel people is, “Don't do things where you're going to do something drastic for a short period of time, because typically that produces more loss than gain. You may see gains in the short term, but in the long term, it'll cost you. Small changes that are going to last for the rest of your life are far better for you.”

Dr. Puder:

Awesome. Okay. We will leave it there for today. Thank you, Dr. Cummings. As always, it’s a pleasure to talk to you. Thank you for your continued mentorship and I've gotten so much from this… from you, over the years, and I appreciate you. So, thank you.

Dr. Cummings: Oh, thanks.

Dr. Puder: Okay. All right. We'll leave it there for today.

   References:Chen, C. H., Huang, M. C., Kao, C. F., Lin, S. K., Kuo, P. H., Chiu, C. C., & Lu, M. L. (2013). Effects of adjunctive metformin on metabolic traits in nondiabetic clozapine-treated patients with schizophrenia and the effect of metformin discontinuation on body weight: a 24-week, randomized, double-blind, placebo-controlled study. *The Journal of clinical psychiatry*, *74*(5), e424–e430. https://doi.org/10.4088/JCP.12m08186

Flory, J., & Lipska, K. (2019). Metformin in 2019. JAMA, 321(19), 1926–1927. https://doi.org/10.1001/jama.2019.3805

Foster, D. J., Bryant, Z. K., & Conn, P. J. (2021). Targeting muscarinic receptors to treat schizophrenia. Behavioural brain research, 405, 113201. https://doi.org/10.1016/j.bbr.2021.113201

Goldberg, J. F. (2023). GLP-1 agonists for weight loss: What you need to know. Current Psychiatry, 22(1), 20–27. https://doi.org/10.12788/cp.0318

Larsen, J. R., Vedtofte, L., Jakobsen, M. S. L., Jespersen, H. R., Jakobsen, M. I., Svensson, C. K., Koyuncu, K., Schjerning, O., Oturai, P. S., Kjaer, A., Nielsen, J., Holst, J. J., Ekstrøm, C. T., Correll, C. U., Vilsbøll, T., & Fink-Jensen, A. (2017). Effect of Liraglutide Treatment on Prediabetes and Overweight or Obesity in Clozapine- or Olanzapine-Treated Patients With Schizophrenia Spectrum Disorder: A Randomized Clinical Trial. JAMA psychiatry, 74(7), 719–728. https://doi.org/10.1001/jamapsychiatry.2017.1220

Mizuno, Y., Suzuki, T., Nakagawa, A., Yoshida, K., Mimura, M., Fleischhacker, W. W., & Uchida, H. (2014). Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis. Schizophrenia bulletin, 40(6), 1385–1403. https://doi.org/10.1093/schbul/sbu030

Paul, S. M., Yohn, S. E., Popiolek, M., Miller, A. C., & Felder, C. C. (2022). Muscarinic Acetylcholine Receptor Agonists as Novel Treatments for Schizophrenia. The American journal of psychiatry, 179(9), 611–627. https://doi.org/10.1176/appi.ajp.21101083

Pekić, S., Medic Stojanoska, M., & Popovic, V. (2019). Hyperprolactinemia/Prolactinomas in the Postmenopausal Period: Challenges in Diagnosis and Management. Neuroendocrinology, 109(1), 28–33. https://doi.org/10.1159/000494725

Shimatsu, A., & Hattori, N. (2012). Macroprolactinemia: diagnostic, clinical, and pathogenic significance. Clinical & developmental immunology, 167132. https://doi.org/10.1155/2012/167132

Shulman, M., Miller, A., Misher, J., & Tentler, A. (2014). Managing cardiovascular disease risk in patients treated with antipsychotics: a multidisciplinary approach. Journal of multidisciplinary healthcare, 7, 489–501. https://doi.org/10.2147/JMDH.S49817

Further reading not covered in episode:Reich, N., & Hölscher, C. (2022). The neuroprotective effects of glucagon-like peptide 1 in Alzheimer’s and Parkinson’s disease: An in-depth review. Frontiers in Neuroscience, 16. https://doi.org/10.3389/fnins.2022.970925

Shetty, R., Basheer, F. T., Poojari, P. G., Thunga, G., Chandran, V. P., & Acharya, L. D. (2022). Adverse drug reactions of GLP-1 agonists: A systematic review of case reports. Diabetes & metabolic syndrome, 16(3), 102427. https://doi.org/10.1016/j.dsx.2022.102427

View Details

James Swanson, Liam Browning, David Puder, M.D.

None of the presenters have any conflicts of interest to report.

Peer reviewers: Dr. Erica Vega, Dr. Jeremiah Stokes

Integrative Psychotherapy: Dr. Paul L. Wachtel’s Pioneering Approach to Blending Therapeutic ModelsDr. Paul L. Wachtel is a distinguished psychologist, psychoanalyst, and professor known for his integrative approach to psychotherapy. His work blends concepts from cognitive-behavioral, psychodynamic, humanistic-experiential, psychoanalytic, behavioral, and systemic therapies. A central theme in Dr. Wachtel’s work is his rejection of rigid adherence to any single therapeutic model. Instead, he advocates for a comprehensive framework that incorporates insights from various approaches to best serve patients’ needs. In this episode, we explore his idea of “making room for the disavowed” and other significant topics in psychotherapy.

Dr. Wachtel’s psychotherapy practice is shaped by his extensive study across multiple therapeutic domains. Initially trained in psychoanalytic ego psychology at Yale’s clinical psychology doctoral program, his approach later expanded to include relational psychoanalysis, behavioral therapy, family therapy, and more. This broad exploration led to his integrative view of psychotherapy. As a pioneer in integration, Dr. Wachtel has significantly contributed to the field by founding the Society for the Exploration of Psychotherapy Integration and authoring numerous influential articles and books. One of his notable works, Making Room for the Disavowed: Reclaiming the Self in Psychotherapy, will be the focus here, highlighting key topics from the podcast discussion.

Reintegrating The Disavowed Self In Therapy: A Path To Holistic HealingDr. Wachtel introduces the term “disavowed self” to describe aspects of an individual’s identity, emotions, or experiences that they have unconsciously rejected or denied. Grasping this concept is crucial for a comprehensive understanding of the therapeutic process. Wachtel highlights a “dialectical tension” that characterizes all well-practiced therapy, regardless of nominal orientation. The therapist must simultaneously manifest a genuinely empathic and validating stance with the patient while being clear-eyed about the ways of thinking and behaving that contribute to the patient’s problems. Ultimately, the therapist’s focus must be more on making room for the thoughts, feelings, desires, and potentials that have been squeezed out or cast aside in the course of development than on interpreting or correcting errors or distortions. Many patients come to therapy already demoralized, and it is essential to maintain an environment that allows them to reclaim their capacity to experience the full spectrum of emotions, even the ability to simultaneously feel seemingly contradictory emotions (such as sorrow and joy), and to develop a full range of adaptive and problem-solving capacities.

Wachtel’s book is filled with practical clinical examples and recommendations that complement his theoretical clarifications. Below, we offer a hypothetical scenario of a client and therapist that illustrates what it means to make room for the disavowed, not just to interpret it.

Case Study: Addressing Anxiety and Assertiveness in Therapy Using Disavowed Self ConceptIn therapy, a client sought help for anxiety and difficulties in his professional relationships. The therapist observed that the client had trouble asserting himself at work, generally going out of his way to avoid conflict and, in the process, frequently suppressed his own needs. Growing up in an environment where his opinions were often dismissed, the client had learned to disavow assertiveness or desire for recognition and to view them as unacceptable. This led him, with little conscious awareness, to consistently downplay his contributions and avoid taking credit for his successes. As a result, he often felt unappreciated and overlooked and, in ways he was not very aware of, to overcompensate for this frustration and deprivation by subtly undermining colleagues’ ideas, creating tension in his workplace relationships that left him puzzled about why his interactions at work were so fraught with difficulty.

Some therapists would focus on pointing out and correcting these problematic behaviors and beliefs in the patient. However, the client’s self-esteem was already fragile, and many ways of pointing out the pattern – even if accurate – could simply add to his experience of incompetence or of being misunderstood or not appreciated. To address this, the therapist needs to help the client accept the legitimacy of the feelings and desires he has long deemed unacceptable. By helping him to reclaim his assertiveness and wish for recognition, and to reintegrate those elements of behavior and experience into his adaptive repertoire, the patient can begin to modify the more abrasive elements of his interactions that had unwittingly arisen as a reaction to his blocked access to more adaptive self-enhancing behavior.

Benefits Of An Integrative Approach In Psychotherapy: A Comprehensive PerspectiveThe integrationist perspective is crucial in psychotherapy because no single orientation in the field has an exclusive hold on truth. As Dr. Wachtel notes, psychotherapy consists of “evolving and open-ended systems of thought and practice whose boundaries with the other major approaches are often, on close inspection, rather porous.” Despite these porous boundaries, each approach maintains a distinct identity, style, and contribution to the therapeutic process.

This perspective challenges the “silo problem,” where practitioners believe that one domain has nothing to offer another, thus limiting the potential for richer, more effective therapeutic outcomes. Embracing an integrationist approach allows for the blending of different perspectives and therapeutic modalities, such as attachment theory and third-wave cognitive behavioral therapy, critical elements in the further evolution of Dr. Wachtel’s integrative approach in his latest book. By combining these diverse approaches, therapists can create a more nuanced and flexible framework that better meets the complex needs of their patients.

How Integrative Psychotherapy Treats Anxiety: Combining Cognitive-Behavioral and Psychodynamic TechniquesDr. Wachtel’s emphasis on making room for what has been repressed, cast aside, or disavowed (rather than on interpreting what the patient has been hiding from himself), is rooted in a key revision of psychoanalytic thought that should have created more fundamental change in therapeutic practice than it did. As Dr. Wachtel points out, Freud essentially “shifted the cornerstone” of psychoanalysis in 1926, when he clarified that it was anxiety that was the fundamental cause of repression rather than vice versa. (Dr. Wachtel also discusses the important ways in which the causal arrows go in both directions.) Attention to this fundamental role of anxiety highlights that, most of all, helping the patient overcome the anxiety that underlies his self-disavowals is what enables both insight and behavior change. This, in the current era, when exposure has become such a prominent element in the treatment of anxiety, opens a crucial path toward combining the strengths of the psychodynamic and cognitive-behavioral approaches.

Dr. Wachtel argues that some of the key anxieties that underlie psychological difficulties are anxieties associated with the person’s own thoughts, feelings, and behaviors. Psychodynamic interpretations, from this view, are not simply clarifications or generators of insight but, when effective, are to a great extent promoters of exposure. When the therapist’s comments bring the patient into closer contact with experiences he has previously avoided, the effect is very similar to what happens when a cognitive-behavioral therapist promotes exposure to the experiences that that approach tends to place in its theoretical foreground. His work illuminates a range of ways in which the perspectives and the strengths of each approach can be brought together when this critical role of anxiety and of exposure is understood. The two approaches still differ in many ways, but that is a strength rather than a problem. When cognitive-behavioral therapists understand the ways in which psychodynamic approaches are grounded in foundations that significantly overlap with theirs, and psychodynamic therapists understand the powerful ways in which methods central to cognitive-behavior therapy overlap and can contribute to their own work, the possibilities of synergies that benefit patients are greatly enhanced.

Treating Phobias in Therapy: Uncovering Disavowed Emotions for Better OutcomesAn example of how this combined approach can work is seen in the treatment of a patient with a debilitating fear of pigeons that severely limited both her social life and her work life. The patient lived in New York City, where avoiding pigeons to the extent she did meant curtailing much of normal living. The patient viewed the origins of her phobia as lying in a childhood incident where she was bitten by a parakeet, but in the course of the therapy it became clear that a powerful contributor was an extended experience, around the time the phobia began, during which her father was frequently hospitalized due to both cancer and heart disease. Her family, attempting to shield her from this disturbing reality, provided misleading explanations for his prolonged absences and very obvious poor health when he was home (business trips, a bad cold, etc.), but these reassurances failed to reassure. The patient had sensed something was terribly wrong, but she was left with only a vague, persistent feeling of unease and, in essence, the message that there was no room for her to express her worry (because “nothing was wrong”).

The pigeon phobia offered a focus and an explanation for her anxiety, and also some sense of control, since she could diminish her anxiety by avoiding pigeons. Had her parents shared with her, in a developmentally appropriate way, something of the reality the family was facing, it would have been difficult and painful, but she also would have learned ways to cope with (if not totally erase) anxiety through communication and connection. Instead, she learned only avoidant strategies, and because those avoidances ended up also leading to avoidance of the sometimes uncomfortable, but also essential experiences of learning to cope with social and work challenges, her skills in those areas remained undeveloped, adding further fuel to the maintenance of an avoidant and restrictive way of life.

At the time the therapy began, there were many indications that she felt quite angry at her mother and other family members for not having been honest with her or giving her any opportunity to talk about her anxieties and worries, but it was difficult for her to let herself experience that anger. She was also impeded by a clear and understandable mistrust of the honesty or sincerity of others in her life. This mistrust, like the anger, was largely obscured to her by a manifest indifference. She did not let anyone get close enough to her for these uncomfortable feelings to surface, but, of course, that also meant healing experiences and countervailing gratifying experiences were also limited. She viewed herself as interested only in overcoming the pigeon phobia.

Both an exclusively interpretive or insight-oriented approach and an exclusively exposure-focused approach are limited in their ability to address the needs of a patient like this. One element of the treatment did include both imaginal and in vivo exposure to pigeons, but as she began to move through the exposure experiences and made some progress, she began to “forget” to practice between sessions and increasingly disparaged the value of such a “limited” approach. In this, she called upon her increasing interest in the larger dynamics that contributed to the phobia, which made addressing her original presenting complaint seem trivial to her. But in working more directly on the complex of feelings and inhibitions that contributed to her difficulties, she would checkmate those explorations when we got too close to uncomfortable feelings by stating things like “I’d like to see my friends more and pursue more interesting and rewarding work options, but I can’t because of my pigeon phobia.” In her effort to maintain what felt like a fragile equilibrium, psychodynamic exploration could become a source of resistance to exposure therapy and vice versa. Any therapeutic approach that risked disturbing the delicate balance between her sense of safety and underlying dissatisfaction was met with resistance, causing her to retreat from whichever aspect of the therapy—whether psychodynamic exploration or exposure work—felt most threatening at the time.

Ultimately, what she needed was a complex mix of multiple therapeutic methods, deriving from different theoretical rationales, in order to address the complex lattice of anxieties and inhibitions that maintained her unsatisfying stasis. She could not commit herself to wholeheartedly participating in a regimen of exposure until she had worked through the many layers of mistrust that were the heritage of her childhood experience and that, hardly surprisingly, extended (often without much acknowledgement) to the therapist and the therapy. She could not carry through on her increasing insight about the complex feelings generated by those childhood experiences without attention to the ways in which her avoidances had affected her social and occupational skills in the present, an insight that, to be a genuine source of change, required behavioral skill training exercises, as well as other interventions. Each element of the work was supported by and required for the fully effective implementation of other elements from other perspectives, that, in turn, required the support of the first.

Breaking Vicious Cycles in Therapy: The Role of Cyclical Psychodynamics and Disavowed EmotionsThis patient’s pigeon phobia and the limitations it placed on the rest of her life represents an example of “cyclical psychodynamics,” where negative early experiences disrupt the development of crucial skills necessary to connect with others in age-appropriate ways and to express and regulate emotions. This then leads to patterns of avoidance and problematic interactions that further impede the development of those skills, and so further maintain the pattern of internal states and external behavior in a way that locks it in through its own consequences.

In this and many other examples, the inhibitions, avoidances, and truncated expressions of emotion create consequences that perpetuate those very inhibitions, avoidances, and emotional restrictions. The result is a vicious cycle, and effective treatment must address multiple facets of the pattern in order to break that vicious cycle. An understanding of what is being impeded or left out (on the part of both the therapist and the patient) is essential, but understanding alone is insufficient. Multiple interventions contribute by making room for the feelings and behaviors that have been restricted. These interventions address anxiety through verbal clarifications and examinations, promote exposure to the avoided experience, and create opportunities for skill development, practice, and greater comfort and familiarity. The mix of interventions can include explicit formal exercises, as in some therapeutic approaches, and more informal interactional and relational experiences in the therapy room. Often best is a mix of these, with the therapist learning a wide range of skills to help the patient in both the therapy room and in his daily life.

Role Play Case Study: Applying Integrative Therapy Techniques For Complex PhobiasDr. Puder presented the case of a patient who presented with a phobia of elevators at work that caused him intense anxiety, panic attacks, and insomnia (days before riding the elevator). This patient had developed the phobia when he found out he was promoted.

In role playing how he would work with this patient, and in discussing what he did in the role play, Dr. Wachtel explored the possible meaning of the elevator phobia in relation to a fear of “moving up in the world,” symbolized by the movement of the elevator from the lobby to the office high above. He explored the ways in which receiving the promotion and raise was related to engaging in competition or defeating rivals and also to having more and more to lose.

In doing so, he did not “interpret” the meaning to the patient, but invited him to feel certain feelings, to “sit in” the feelings, and, in other ways, combined a more insight-focused approach with an approach in which exposure and actually experiencing the feelings that have been hard to experience was central.

Interpreting Dreams in Psychotherapy: Understanding Unconscious Patterns and MeaningsThe patient had a dream in which he was unable to use the elevator and was fired. Then, because he was fired and lost his income, he defaulted on his house payments and was thrown in jail, losing his family and everything important to him.

In discussing how he would approach this dream, Dr. Wachtel pointed out that in traditional psychoanalytic theory, dreams are understood to have both manifest content (the literal storyline of the dream) and latent content (the hidden, symbolic meaning).

• The manifest content of a dream is what the dreamer remembers and describes, like the patient’s dream of being unable to use an elevator, getting fired, and subsequently losing everything.
• The latent content, according to this theory, represents the unconscious wishes, fears, and conflicts that the manifest content disguises.

Traditionally, the focus was on the latent content, on figuring out what the dream “really” means. Dr. Wachtel argues that instead of identifying a single latent content of a patient’s dream, a single “correct” interpretation, it is useful to view the dream as a sample of mental activity in a state of mind in which the defenses were half asleep, providing a window onto many features of the patient’s psychological makeup that are disavowed in the waking state.

Within the role play, Dr. Wachtel picked up on a further elaboration on the dream that the patient reported the following week – he was now in the jail cell, playing chess with a lion, and although he has now lost everything, he is calm and peaceful playing chess with the lion. Dr. Wachtel initially responded to chess as a game that is competitive, that has a winner and a loser. However, the patient stated that when his father taught him to play chess it was not about winning and losing—his father would not let him lose. Instead, the father would turn the board around to himself if his son was losing, giving the son the stronger position. Dr. Wachtel picked up on how the father protected his son from the experience of losing, and wondered about an implicit message that losing was very bad and to be avoided at all costs.

The patient objected to this framing, saying his parents did not care about winning or losing, and even went to his high school athletic events only to hear the band. Dr. Wachel utilizes this information to further highlight the family’s disavowal of competition, commenting that going to sporting events only to hear the band conveys, “I’m not going to look at what’s aggressive and competitive, only what is harmonious.”

Dr. Wachtel acknowledges there is an element of that attitude that could be supportive or reassuring, but states, “That’s only part of life, and you’re trying to figure out, how do I include in myself that part of me that wants to knock heads and clash and engage in rough and tumble competition?” Again aiming for a more experiential and exposure-centered alternative to a purely interpretive approach, he asks the patient, “What does it feel like when you picture yourself really engaging competitively?”

He also explores other issues suggested by the dream, such as feeling safer taking on a lion—a strong, worthy adversary—than a competitor who is vulnerable and afraid of aggression, as perhaps his father was.

How Attachment Theory Shapes Modern Psychotherapy: Key Insights And ApplicationsCategorical Views on AttachmentOur earliest interpersonal relationships play a pivotal role in shaping how we experience ourselves and others and behave throughout life. In one sense, a child is entirely vulnerable, relying on their caregiver to meet their most basic needs. To manage feelings of safety and cope with anxiety, children often adjust their thoughts, emotions, and behaviors to preserve their bond with the caregiver. These adaptations help reduce anxiety and strengthen the relationship, but they can also be a source of maladaptation in the person’s life going forward.

Attachment theory was largely developed by John Bowlby and Mary Ainsworth. Initially, while researching precursors of delinquency, Bowlby (1944) found that emotional regulation and behavior could be explained by experiences of attachment between a caregiver and child. Mary Ainsworth later published additional research backing this idea and clearly categorized the different styles of attachment (Ainsworth et al., 1978). In the literature, attachment styles are broadly categorized as seen below:

• Secure/Autonomous Attachment - Child expects that their emotional needs will be met by their caregiver.
• Insecure Attachment - This form of attachment is driven by the expectation that the caregiver will not attend to the child’s needs.
• Avoidant/Dismissive - Child will try to avoid the feeling of neglect and vulnerability by withdrawing from caregiver.
• Ambivalent/Anxious-Preoccupied - Attempts are made to get the attention of the caregiver, but the child will likely not be consoled when attention and care is given.
• Disorganized/Unresolved - Child does not have a clear idea of what they need to accomplish/their emotional needs and they will oscillate from clinginess and distancing themselves.

There is substantial evidence supporting the enduring nature of attachment styles throughout life. Several factors contribute to the strength and persistence of these attachment styles. Wachtel approaches these continuities by examining the feedback loops that develop that maintain patterns.

For example, someone with an anxious attachment style may be looking for constant reassurance from a loved one, which can lead to anxiety, frustration, or withdrawal on the part of the caretaker, thereby further perpetuating the child’s anxiety. On the other hand, a child who is avoidantly attached may show signs of emotional detachment from their caregiver, which in turn may cause the caregiver to feel incompetent, unloved, or unneeded, ultimately leading them to feel less emotionally engaged with their infant, contributing to a vicious cycle that further perpetuates the child’s defensive withdrawal.

Attachment dynamics play a crucial role in psychotherapy, as they shape how we express or suppress our thoughts, feelings, and behaviors. For better or for worse, the patterns we develop in our earliest relationships often influence how we navigate interpersonal interactions throughout life, including therapeutic settings. From these foundational relationships, we gain a sense of which of our thoughts, feelings, and inclinations are accepted and enable us to engage safely and effectively with others and which aspects of our psychological makeup disrupt the sense of mutuality and

resonance that is critical to healthy psychological development (Wachtel, 2023, p. 191). Understanding these dynamics allows therapists to work with clients to explore how early attachment experiences may affect their current emotional responses and relationships.

Reevaluating Attachment Theory in Therapy: Dynamic Interpersonal Processes ExplainedWhile Dr. Wachtel recognizes that the categorical view of attachment can be clinically useful, citing David Wallin’s book, Attachment in Psychotherapy, as an example, he focuses more on the idea of attachment as an evolving interpersonal process. He encourages clinicians to focus on attachment dynamics—specifically, how “attachment experiences contribute to shaping which of their thoughts, feelings, or ways of interacting with the world the developing child accepts and integrates into their sense-of-self… and which get shunted aside… and impeded in their capacity for elaboration, refinement, and further development” (Wachtel, 2023, p. 182).

Parents are the source of safety, but they also provide safety, comfort and security in an inevitably selective manner. They do not accept all experiences, and do not respond in a genuinely comforting way to all feelings, behaviors or desires. So even as the child learns that the parents are a source of safety, it also learns that the parents are a source of contingent safety, that they are safe and secure if they act and feel within certain parameters. What doesn’t fit in those parameters is at least somewhat banished from the evolving personality’s behavioral and experiential repertoire.

Practical Applications of Attachment Theory in Therapy: Techniques and Tips for CliniciansSo the question remains: how exactly do clinicians, armed with the knowledge of attachment theory, help their patients grow and meet their goals? Below are helpful tips that Dr. Wachtel highlights in his book.

• The work of the therapist can be thought of from the vantage point of the metaphor of search and rescue. The searching aspect refers to finding “the thoughts, feelings, and behavioral inclinations that have been obscured or impeded or rendered difficult to acknowledge” (Wachtel, 2023, p. 225). Rescuing, on the other hand, involves helping the patient become able to incorporate their disavowed thoughts, feelings, and behaviors.
• Help the client understand how their attachment style directly impacts their current experiences. It is not enough to focus solely on analyzing their past upbringing to understand attachment style. The client should also recognize how their attachment patterns perpetuate adaptive or maladaptive ways of being in the present day.
• Attachment styles, particularly insecure ones, can reinforce the anxieties and inhibitions developed in early life. The therapist’s job is to help break the cycle that maintains these feelings and inclinations being disavowed by fostering a safe environment for the client to express them. This process can be facilitated through role plays, modeling, rehearsals, or planning graduated goals for the patient to achieve, enabling them to incorporate their disavowed thoughts and feelings into everyday life.
• A patient's experience of whether a therapist is helpful or unhelpful may be influenced by the impact of earlier significant relationships. For example, if a patient has come, in the course of development, to readily feel invaded or that their boundaries are violated, the therapist must be cautious in making suggestions or interventions. Conversely, a patient who has experienced abandonment or insufficiently active and structured parenting may find a more active approach more helpful.

Understanding Attunement and Emotional Disavowal in Therapy: Effective ApproachesBeing unseen, unheard, or unrelated to by the attachment figure is one of the most difficult experiences. For example, the Still Face Experiment, conducted by Dr. Edward Tronick, involves a mother interacting with her infant, initially engaging in normal, responsive play. Then, the mother is instructed to suddenly adopt a neutral, unresponsive expression—referred to as the “still face.” The infant, who had been happily interacting, quickly becomes distressed, trying various behaviors to re-engage the mother, such as smiling, cooing, or reaching out. When these efforts fail, the infant often becomes increasingly upset, showing signs of confusion and distress. The experiment demonstrated the critical importance of attunement.

The behaviors and expressions that are not met with responsiveness tend to be the ones that are disavowed. This need not imply overt disapproval or harshness. The mere absence of responsiveness can be powerfully motivating.

For example, Dr. Wachtel describes a patient who (clearly categorized as securely attached) entered therapy because, despite a warm and loving, and even physically affectionate, relationship with her husband, she was unable to experience pleasure or arousal when they had intercourse.

At one point, in a conversation with her older brother, he mentioned something he had noticed when she was about a year old and just learning to speak. Her mother was teaching her the names for the parts of the body, as so many mothers do, naming each and pointing to it. Her brother, who was a teenager then, noticed that their mother went from head to toe rather thoroughly, but when she arrived at the belly, she paused for a long time and then skipped down to the knees, anxiously omitting the genitals. As they spoke further, they both recalled many instances of their mother leaving the room during sexual scenes in movies “to fix everyone a snack,” and in many other ways manifesting discomfort with the sexual and sensual side of life, even while being a generally very affectionate and engaged mother.

This discussion with her brother stirred a host of recollections that surprised the patient because they had been both obvious and, nonetheless, largely overlooked by her. She suspected that her mother was not even aware of this avoidance, that it happened automatically and in a way such that both the elements of sexuality, and the avoidance of discussing or acknowledging them, were rendered invisible. “‘Boy, she’s good at that,’ the patient said. ‘It happens so quickly and so smoothly that no one notices. Or at least, I never noticed.’”

Her mother never expressed overt prohibitions regarding sexuality. It was the absence of her response to this side of life, her rendering it invisible, that had the more powerful impact. This kind of parental discomfort can, even in the absence of overt criticism or prohibition, impact the full spectrum of human emotions and experiences. In understanding our patients’ histories, we must of course be alert to instances of trauma, harshness, rage, and so forth. But we must also be attuned to invisibility, both to what the patient has rendered invisible in him/herself and how their key attachment figures were unable to be attuned to or to subjectively tolerate one or another dimension of human experience.

Expert Tips From Dr. Wachtel On Becoming A More Effective Therapist* Ask yourself, “What am I not picking up on?” Just as a parent cannot be equally attentive to or love equally every facet of a child, we cannot respond to every aspect of a patient’s experience that needs attention. * Consult other professionals, as they are likely to notice what we do not. * Consider what personalities or types of patients with whom you connect best. Do not feel bad about referring a patient to another provider if you feel a sense of stagnation or if you feel they would be a better fit. * Avoid theoretical silos and make use of an approach that draws on multiple viewpoints. * Continue learning about yourself and be honest with yourself about the fact that you are human and will continue to make mistakes.

“My analysis expanded my empathetic capacities in other ways. I became slowly, painfully familiar with my blind spots, and with my vanity, greed, envy, sadism…which were only possible to admit and explore because of my analyst’s matter-of-fact acceptance.” -Nancy McWilliams

Resources:Ainsworth, M. D. S., Blehar, M. C., Waters, E., & Wall, S. (1978). Patterns of attachment: A psychological study of the strange situation. Erlbaum.

Bowlby J. (1944). Forty-four juvenile thieves: Their character and home-life. International Journal of Psychoanalysis. 25:19–52. DOI:10.4324/9780203779958-9

Freud, S. (1926). Inhibitions, symptoms, and anxiety. Standard Edition, Vol. 20 (pp. 87-172). London: Hogarth Press, 1959.

Wachtel, P. L. (1977). Psychoanalysis and behavior therapy: Toward an integration. Basic Books.

Wachtel, P. L. (1987). Action and insight: Psychoanalysis and the active patient. Guilford Press

Wachtel, P. L. (1997). Psychoanalysis, behavior therapy, and the relational world. American Psychological Association.

Wachtel, P. L. (2007). Relational theory and the practice of psychotherapy. The Guilford Press.

Wachtel, P. L. (2013). Therapeutic communication: Knowing what to say when (2nd ed.). The Guilford Press.

Wachtel, P. L. (2014). Cyclical psychodynamics and the contextual self. Routledge.

Wachtel, P. L. (2023). Making room for the disavowed: Making room for the self in therapy. The Guilford Press.

Wallin, D. J. (2007). Attachment in psychotherapy. The Guilford Press.

View Details

Liam Browning, David Puder, MD

A Global History Of Heat Therapy: From Ancient Finnish Saunas to Modern Medicinal UsesTimeline of Heat Therapy: A Global HistoryCirca 4000-2000 B.C.E.:

• Ancient Finnish Saunas: Early saunas originated in Finland as large pits lined with animal skins, where fires were built to heat stones. These saunas were used for both medicinal and social purposes.

Circa 2000-1000 B.C.E.:

• Ancient Egyptian Sand Baths: Egyptians used hot sand baths for treating inflammation and pain, representing early passive hyperthermia therapy.

Circa 1000 B.C.E.:

• Traditional Chinese Medicine and Ayurveda: In China and India, heat therapy techniques like moxibustion and steam treatments are employed for improving circulation, reducing pain, and promoting detoxification.

Circa 500 B.C.E.-500 C.E:

• Greek and Roman Bathhouses: The Greeks began using heated baths and steam baths, referred to as laconica. Communal bathhouses became central in Roman society, with figures like Galen writing about hot baths to treat melancholia and other ailments.
• Ottoman Hammams: Public baths in the Middle East and North Africa, known as hammams, were common throughout the region, offering both hygienic and therapeutic benefits. It later rose to greater prominence as an integral part of Islamic culture beginning in the 7th-8th century. The buildings contained a hot room (Hararet) with underfloor heating by a furnace and also a cold room (Soğukluk) for cold water immersion.
• Native American Sweat Lodges: Indigenous tribes across North America developed sweat lodges, used for purification, spiritual rituals, and healing. These lodges were a staple in Native American culture and closely mirror sauna practices.

Middle Ages (Circa 500-1500 C.E.):

• European Bathhouses: Communal bathhouses were widespread across medieval Europe, combining hygiene with socializing and therapeutic practices.
• Mayan Temazcal: In Mesoamerica, the temazcal, a type of sweat lodge, was used for ritualistic cleansing and healing, particularly in the context of childbirth and illness.

19th Century C.E.:

• Victorian-Era Turkish Baths (Hammams): Western Europe, particularly the U.K., experienced a revival in communal heat therapy with the introduction of hammams, or Turkish baths.

1900s C.E.:

• “Malaria Fever Cure”: Austrian physicians Julius Wagner-Jauregg and Rudolf Rosenblum introduced heat therapy via induced fever to treat psychiatric symptoms related to syphilis, particularly neurosyphilis, and later experimented with it for other mental health disorders. Before the discovery of penicillin, this method led to significant improvement in about 30-50% of cases; however, some patients experienced worsening symptoms, and approximately 15% died from complications.

1960s C.E.:

• Development of Infrared Saunas: Infrared saunas, which heat the body directly using radiant heat, were introduced as a modern alternative to traditional saunas, allowing for lower ambient temperatures.

21st Century C.E.:

• Modern Medical Hyperthermia: Hyperthermia treatments in oncology emerged, where heat is used to target and destroy cancer cells as part of therapeutic protocols.

Present Day:

• Sauna Culture in Finland: With an estimated 3.2 million saunas for a population of 5.5 million, sauna use remains deeply embedded in Finnish culture and is recognized for its cardiovascular and wellness benefits globally.

How Physical Health Conditions Elevate Depression Risk: Unveiling The Mind-Body ConnectionThere is a strong link between physical health and mental health.

Increased risk of depression with these diseases:

**Key Findings From The Kuopio Ischemic Heart Disease Study: The Long-Term Benefits Of Sauna Use**The strongest literature on sauna is from a longitudinal observational study in Finland, called the Kuopio Ischemic Heart Disease (KIHD) Risk Factor Study.

• 2,327 middle-aged men (mean age 53 y/o)
• Grouped participants by sauna frequency:
• Group 1: Once per week
• Group 2: 2-3 times per week

• Group 3: 4-7 times per week

• Most participants used a dry sauna at an average temperature of 80°C (170°F) for an average of 14 minutes (range 2-90 minutes)

• One of the first publications of this study looked at cardiovascular outcomes, stroke, and all-cause mortality after 21 years (Laukkanen et al., 2015).
• Compared to once weekly sauna users, the 3-7x/week users had a 40% reduced risk of all-cause mortality, 50% reduced risk of fatal cardiovascular disease, 48% risk of fatal coronary artery disease, and a 63% decreased risk of sudden cardiac death.
• This is after adjusting for age, BMI, SBP, LDL, smoking, previous MI, T2DM, activity, and SES.
• In the unadjusted analyses, the 2-3x/group had a significantly reduced risk of these outcomes, suggesting a dose-response relationship.
• The dose-response effect was also seen with sauna session duration.

• Compared to sauna users with sessions less than 11 minutes, the HR for sudden cardiac death was 0.93 (95% CI, 0.67-1.28) and 0.48 (95% CI, 0.31-0.75) for sauna users with average sessions of 11-19 minutes and >19 minutes respectively, supporting this dose-response relationship.

  Follow-up studies from this same cohort showed that compared to once weekly users and controlling for similar confounds, the 4-7x/week users had:

• 47% lower risk of hypertension (Zaccardi et al., 2017)

• 62% lower risk of stroke (Kunutsor et al., 2018)
• 66% decreased risk of dementia and a 65% lower risk of Alzheimer's disease (Laukkanen et al., 2017)
• 37% reduced risk of pneumonia (Kunutsor et al., 2017)
• 78% reduced risk of having a psychotic disorder diagnosis on Finnish Hospital Registry (Laukkanen et al., 2019)
• This did not change when considering sauna session duration
• Reported rate of psychosis per 1,000 person years
• Included delirium psychosis potentially

• At the beginning of the study they excluded study participants who were on antipsychotic medications.

  Sauna vs. Other Interventions: Comparing Long-Term Health Impacts Of Exercise, Diet, and More* Compared to other interventions + Aerobic exercise - 35% reduction in all-cause mortality in participants of the KIHD cohort who were above the sample median VO2 max value compared to the participant below the median (Kunutsor et al., 2017) - A meta-analysis of 11 prospective cohort studies by (Garcia et al., 2023) showed that exercising an equivalence of 8.75 metabolic equivalents (METs) (walking 2.5 hr/week) and 17.5 METS (walking 5hr/week) compared to 0 physical activity led to: * 31% and 34% decrease of all-cause mortality respectively * 29% and 35% CVD mortality * 15% and 18% cancer mortality

• Given the median in the study sample was 10.5 MET, this is relatively mild-moderate physical activity. The dose response seems to continue with vigorous physical activity according to other studies.

• All-cause mortality by VO2 max percentile compared to the bottom 25th percentile (“Low”) (Mandsager et al., 2018):
• 25-50th percentile (“Below Average): 20% reduced risk
• 50-75th percentile (“Above Average”): 63% reduced risk
• 75-97.5th percentile (“High”): 74% reduced risk
• 97.5-100th percentile (“Elite”): 80% reduced risk

• Even going from “Below Average” to “Above Average” conferred 29% reduced risk

• Diet

• Greater adherence to mediterranean diet compared to lowest adherence to mediterranean diet according to a meta-analysis of 43 studies (Becerra-Tomás et al., 2020)
• 21% reduced risk of CVD mortality

• 20% reduced risk of stroke

• Meta-analysis of 17 prospective studies showed that being in the top quintile of EPA/DHA omega 3s (marine sources) was associated with a 15-18% reduced all-cause mortality risk compared to bottom quintile (Harris et al., 2021).

• Limitations/cautions of the KIHD study

• Differences in baseline characteristics between once weekly users and 4-7x/week users (although this was controlled)
• 4-7x/week group was 2 years younger than once weekly group
• Less smokers (20% vs. 36%)
• More prevalent alcohol consumption (95% vs. 83.%)
• Less diabetes (2% vs. 6.6%)

• Less hypertension (28.1% vs. 35%)

• Healthy user bias

• Somewhat mitigated SES differences given how prevalent sauna usage is in Finland

• Takeaways

• Regardless of subtle baseline differences between the groups, the results are striking.
• 20-minute dry sauna sessions at least 4x/week and 80°C (172°F) show the greatest benefit.
• However, hot baths may be comparable if a sauna is unavailable, as one prospective cohort study in Japan showed reduced risk of stroke and cardiovascular events with daily hot tub baths:
• Ukai et al. (2020) https://pubmed.ncbi.nlm.nih.gov/32209614/
• Reduce the risk of adverse cardiovascular outcomes by about 23–46%.
• Hot tub baths almost daily or every day versus zero to two times/week were associated with risk reductions in cardiovascular outcomes ranging from 23–46%.
• However, this is in a younger cohort (40-59 y/o) and in Japan, where cardiovascular deaths are not as common at this age.

Cardiovascular Health Insights: Findings from the KIHD Study and Other Key Research on Physical Wellness* Blood pressure: + The KIHD study from Zaccardi et al., 2017 showed that sauna sessions 4–7 times weekly was associated with a 47% relative decrease in the likelihood of developing hypertension in the 25-year follow up, controlling for age, smoking, body mass index, glucose, creatinine, alcohol consumption, heart rate, family history of hypertension, socioeconomic status, and cardiorespiratory fitness. This effect was insignificant in 2-3 times/week when controlling for these confounds. + Sauna acutely decreases SBP/DBP by about 5-10mmHg for minutes to hours post-sauna (Laukkanen et al., 2018). + Pizzey et al., 2021 reviewed 4 RCTs of repeated (3-5d/week) immersion in hot water (38.5-40.5°C) showed an average reduction in SBP by 5.9 mmHg and DBP by 3.9 vs. sham control. This decrease was observed in healthy, obese, and heart-failure participants with hypertension. + Compare to SBP decreases observed with other lifestyle modifications: - 1mmHg per kg of body weight loss in overweight individuals (Neter et al., 2003) - 6-11mmHg with Dash Diet (emphasizes fruits, vegetables, whole grains, and low-fat dairy products while reducing sodium intake) (Sacks et al., 2001) - 4-9mmHg with aerobic exercise (Cornelissen et al., 2005) - 2-8 mmHg with sodium restriction (He & MacGregor, 2002) - 2-4 mmHg with alcohol moderation (Xin et al., 2001)

• And 10-15mg decreases in SBP with antihypertensive monotherapy (Paz et al., 2016)
• The antihypertensive effects of sauna are thought to be due to endothelium-dependent dilatation, reduced arterial stiffness, modulation of the autonomic nervous system (Laukkanen et al., 2018).

Sauna may mimic exercise: The acute changes and after-effects of sauna on cardiac load, blood pressure, and vascular hemodynamics is extremely similar to that of moderate intensity exercise (Ketelhut & Ketelhut, 2019).

Sauna will frequently bring the heart rate to over 100 BPM and even to 150 BPM in more intense settings (Laukkanen & Kunutsor, 2024).

Does sauna provide a different benefit than exercise?

• Lee et al., 2022 conducted a study comparing 8 weeks of exercise alone, exercise + sauna, and control participants. Both the exercise and sauna routines were progressive in nature. They found that, compared to exercise alone, exercise + sauna improved V02 max (2.7mL/kg/min), total cholesterol (-19mg/dL), and systolic bp (-8mmHg).

  Limitations:

• Sauna + exercise group experienced more time in which they had elevated HR. If sauna acts as an exercise mimic, time should be controlled.

• Exercise group did not improve as expected.
• Aerobic exercise in combination with frequent sauna use has a synergistic effect on lowering cardiovascular-related mortality and all-cause mortality, according to one article from the KIHD study. The strongest reductions in mortality were found in people with high cardiorespiratory fitness (>50th percentile VO2 max) and high frequent sauna bathing (>3 sessions/week) HR ​​0.60 (95% CI: 0.48–0.76), followed by high cardiorespiratory fitness and low frequent sauna bathing 0.63 (95% CI: 0.54–0.74), and then low cardiorespiratory fitness and high frequent sauna bathing 0.78 (95% CI: 0.64–0.96) (Kunutsor et al., 2017).
• Median follow up 26.1 years

• 520 CVD deaths and 1124 all-cause death

  DJP: different sports and how long people live, tennis seemed to win- 1) high SES or 2) interaction with people. How much of the sauna is interaction with people?

Exploring Additional Health Benefits of Heat Therapy: Insights into Heart Failure, Diabetes, Joint Disease, and More* A meta-analysis of low-quality studies involving heart failure patients suggests that heat therapy, such as sauna use, can help improve symptoms and reduce levels of B-type natriuretic peptide (BNP), a marker of heart failure severity (Ye et al., 2020). * Qualitative studies of Waon therapy, a far-infrared dry sauna treatment, show improvement in peripheral artery disease (PAD) through enhanced ankle-brachial index (ABI), increased blood flow, and the development of collateral vessels (Tei et al., 2007). * Type 2 diabetes + A review of five studies (Sebők et al., 2021) on Type 2 diabetes found that while there was no significant change in glucose or HbA1c levels with interventions like heat therapy, including sauna use, there was a consistent reduction in systolic blood pressure, averaging 5-10 mmHg. This improvement is important because sustained reductions in blood pressure are associated with a lower risk of cardiovascular events and complications in diabetic patients, making it a valuable adjunct in managing long-term cardiovascular health.

• Inflammatory joint disease
• Cozzi and colleagues (2018) reviewed several randomized-controlled trials (RCTs) that demonstrated the benefits of balneotherapy in improving the subjective clinical course of conditions like ankylosing spondylitis, enteropathic spondylitis, and psoriatic arthritis. The studies showed that patients experienced significant relief from symptoms such as pain, stiffness, and fatigue. These improvements were primarily attributed to the anti-inflammatory and pain-relieving effects of balneotherapy, which involves bathing in mineral-rich waters. The findings suggest that balneotherapy can be a valuable complementary treatment option for managing these chronic inflammatory conditions.

Sauna Use for Depression: An Evidence-Based Review Of Infrared And Whole-Body Hyperthermia StudiesThe First RCT on Sauna Use for Depression: Masuda et al. (2005)* The only study on sauna use for depression was a randomized-controlled trial by Masuda et al. (2005). + 28 individuals with mild depression and somatic symptoms were randomized to 4 weeks of infrared sauna sessions or bed rest. + Saunas were 5x/week at 60°C (140°F) for 15 minutes. + Somatic complaints were significantly decreased (t = 4.84, p < .001) and mental complaints were decreased to trend-level significance (t = 2.02, p = .054) in the sauna group according to the Cornell Medical Index. + There were no differences on the Self-rating Depression Scale. + Of note: this was not the most effective dose, as noted above, being of lower temperature and also lower duration of time.

Whole-Body Hyperthermia and Depression: A Review of Key Studies (2019)**Review of depression studies up until 2019:** The impact of whole-body hyperthermia interventions on mood and depression – are we ready for recommendations for clinical application? (**Hanusch & Jansenn**, 2019)

• Three studies provided whole-body heating in a hot bath and four in infrared chambers.

  Infrared chambers

• Most protocols included a 45-minute heating time to reach a rectal temperature of 38.5-39 °C followed 30-60 minutes of rest inside the chamber.

• Bath
• Water temperature of 37 °C (98.6 °F) and was increased by 1 °C every 10 min for 47 min on average (Hanusch & Jansenn, 2019)
• Water temperature of 40.2 °C (104.3°F) for an average of 22.6 min (Naumann et al., 2017)
• There were three open label studies and four RCTs
• 3/3 open label studies showed significant improvements in depressive symptoms. Two of the open label studies reported effect sizes: 1.71 and 1.85.
• 3/4 RCTs showed superiority for the hyperthermia group, with inconsistent effects.

Randomized-Controlled Trials on Whole-Body Hyperthermia for DepressionThe most impressive of these RCTs was from Janssen et al. (2016): Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder A Randomized Clinical Trial

• Methods
• 34 moderate to severely depressed patients randomized to whole-body hyperthermia (WBH) via infrared chamber (n=16) vs sham-controls who received very mild heat (n=14).
• Participants underwent a single infrared session in which they sat in the heated chamber until their rectal temperature reached 38.6°C (101.5°F) (avg 47 min), followed by resting in the machine for 60 min.

• Depressive symptoms were assessed 1, 2, 4, and 6 weeks after WBH using the Hamilton Rating Scale for Depression (HAMD).

• Results

• Active WBH group showed significantly reduced HAMD scores across the 6-week post intervention study period (WBH vs sham; week 1: −6.53, 95% CI, −9.90 to −3.16, P < .001, d = 2.23; week 2: −6.35, 95% CI, −9.95 to −2.74, P = .001, d = 2.11; week 4: −4.50, 95% CI, −8.17 to −0.84, P = .02, d = 1.66; and week 6: −4.27, 95% CI, −7.94 to −0.61, P = .02, d = 1.66).

• Limitations/Takeaways

• The treatment group did have a higher baseline expectancy of the treatment’s efficacy.

  The authors did perform a moderation analysis controlling for expectancy effects, but did not include this variable in their original analysis. The effect size following the moderation analysis was also not reported.

• However, it is worth noting 70% of the sham group did believe they received the active treatment.

• Given this is a single session and is unlikely to provide much of a physiological stimulus lasting 6 weeks, more attention should have been given to the belief in treatment efficacy.

The other RCTs used multiple sessions:

• Hüppe et al. (2009) randomized 36 patients to hyperthermia, sham-control, or waitlist control.

• There were no significant differences in depressive symptoms, as baseline scores were low and different between groups.

• Romeyke & Stummer (2014) allocated 104 patients with severe fibromyalgia and MDD to an average of 5 hyperthermia sessions or waitlist control.

• Pain improved more in the hyperthermia group, but both groups improved in depressive symptoms, with no trend-level differences favoring the hyperthermia group (p = .055).

• All patients received physical therapy, physiotherapy, acupuncture, psychotherapy.

• Naumann et al. (2017) randomized 17 moderately depressed patients to 2 weekly hyperthermia baths at  40°C (104°F) for 22 minutes for 4 weeks vs. sham-control that received green light exposure.

• Significantly more improvement in the hyperthermia group compared to sham-control at week 2 (p=.0370; d = .62 95% CI [-.05 to 1/29) but not at week 6.

General Takeaways and Limitations in Heat Therapy for Depression* Initial findings are promising, but there is a need for more, larger studies using repeated sauna sessions.

How Heat Exposure Enhances Antidepressant Effects: Unveiling The Science Behind Sauna Use and Mental HealthHeat stress and exercise increase the expression of brain-derived neurotrophic factor (BDNF) (Kojima et al., 2018)Whole-body hyperthermia to a core body temperature of 39.5 °C (103.1 °F) via hot water bath (20-min at 42 °C [107.6 °F]) increased BDNF levels 66% for 15 minutes (Kojima et al., 2018).

Inflammation and Heat ExposureSimilar to exercise, whole body hyperthermia increases plasma levels of pro-inflammatory IL-6 and anti-inflammatory IL-10 (Katchinski et al., 1999; Windsor et al., 2018). However, the impact of these changes on depression and their potential to cause long-term alterations in inflammatory markers remains uncertain (Mac Giollabhui et al., 2024).

The Role of Heat Shock Proteins (HSPs) in Sauna Therapy: Mechanisms Linked to Physical and Therefore Antidepressant EffectsHSPs are a family of proteins observed in all forms of life from bacteria to humans and are crucial for a cell’s protein quality control systems. Cells are largely made of proteins, and over time, proteins will inevitably lose their function and shape. HSPs can physically change the shape of dysfunctional or misfolded proteins. They also help new proteins fold correctly, disaggregate proteins that are clumped together, and target proteins for degradation. When cells are faced with hypoxia, heat stress, nutritional stress, or other stressors, HSP are upregulated to help make new proteins and to repair damaged ones (Rosenzweig et al., 2019).

HSPs may be vital for preventing some of the effects of aging. The cell’s ability to counteract stress declines with age due to a variety of reasons that stem from metabolic dysfunction as a result of mitochondrial decline or accumulations of DNA mutations. Protein quality control systems also decline with age as well, as the number and efficiency of HSPs decreases. As a result, more defunct proteins are formed and our cells become less capable of handling them. Declines in particular HSPs are related to neurodegenerative disorders associated with protein aggregates such as Alzheimers, Parkinson’s, and Huntington disease, and may be related to normal cognitive decline. They also are important for recycling the proteins involved in neurotransmission and can be neuroprotective in cases of seizures and strokes (Stetler et al., 2010).

Sauna and exercise both increase the expression of HSPs, likely through the effects of hyperthermia at temperatures >38.5°C (101.3°F) (Hunt et al., 2019). To what extent elevated HSPs confer a benefit is unclear, but some passive heat exposure studies in rats and humans (serum) have observed that a 30-40% increase in HSP was associated with conserved muscle mass and greater mitochondrial function (Yoshihara et al., 2013; McGorm et al., 2018).

Hormonal Changes with Sauna Use: Short-Term Boosts in Growth Hormone, Testosterone, and CortisolSimilar to aerobic or strength training, sauna increases growth hormone concentration in the short term, often by about 2- to 5-fold (Kukkonen-Harjula et al., 1989). Some studies have also reported small increases in testosterone while others have shown mixed effects on cortisol (Laukkanen & Kunutsor, 2024).

These effects seem similar to that of exercise, as they last only a few hours and do not seem additive when combined with exercise. For instance, one study did not observe an additional increase in GH, testosterone, or cortisol with the addition of sauna following endurance, strength, or a combined workout (Rissanen et al., 2020).

The Detoxifying Power of Sweating: How Sauna and Exercise Aid Heavy Metal ExcretionSweating is often touted as a method to aid heavy metal detoxification. Research suggests that sweat can enhance the excretion of certain metals like aluminum (3.75-fold), cadmium (25-fold), cobalt (7-fold), and lead (17-fold) compared to urine (Genuis et al., 2011). However, the effectiveness and composition of sweat can differ based on whether it’s induced by passive hyperthermia (sauna) or active hyperthermia (exercise).

A small study (Kuan et al., 2022) found that sweat from exercise had higher concentrations of metals like nickel, lead, copper, and arsenic compared to sauna sweat, while mercury levels were similar. This difference likely stems from the greater metabolic activity during exercise, which mobilizes more toxins. In contrast, sauna-induced sweating primarily serves thermoregulation, potentially leading to lower concentrations of some metals.

There is evidence suggesting that dementia may be associated with elevated levels of certain heavy metals in the brain. For example, studies have identified higher concentrations of aluminum, mercury, and lead in individuals with Alzheimer’s disease, pointing to a potential link between metal accumulation and neurodegeneration. While cohort studies from Finland have shown a correlation between frequent sauna use and lower rates of dementia, it remains unclear whether this benefit is directly related to heavy metal excretion or other factors, such as improved cardiovascular health and reduced inflammation. It is important to note that the majority of heavy metals are excreted through stool, with smaller amounts eliminated via urine and sweat. In cases of significantly elevated heavy metal levels, chelation therapy remains the gold standard for treatment.

Safety And Precautions Of Heat Exposure: Risks, Contraindications, And Special ConsiderationsRisks in Extreme Competition:

Death and serious health issues can occur during high-intensity competitions in hot environments, especially when participants push their physical limits.

Pregnancy:

• Exposure to extreme heat during pregnancy has been linked to central nervous system birth defects, such as anencephaly and spina bifida, and the suggested teratogenic threshold for core body temperature is 39.0 °C (102.2 °F) (Graham et al., 1998).

Contraindications:

• Heat exposure should be avoided in individuals with certain conditions (Patrick & Johnson, 2021), including:
• Alcohol use (due to impaired thermoregulation)
• Hypotension (especially in older adults), which increases the risk of fainting
• Recent myocardial infarction, unstable angina pectoris, and severe aortic stenosis
• Altered or reduced sweat function, which impairs the body’s ability to regulate temperature

Hydration and Electrolyte Balance:

• Dehydration is a common risk during heat exposure, which can lead to complications like heat stroke and fainting. Adequate water and electrolyte intake is essential, especially during prolonged sauna sessions or intense exercise.

Age-Related Risks:

• Older adults are more susceptible to heat-related complications due to decreased cardiovascular resilience and sweat function. Additional caution is advised for this population.
• Children are more vulnerable to heat exposure due to their underdeveloped thermoregulation, higher risk of dehydration, and reduced sweating efficiency. They are also less aware of their physical limits, increasing the risk of heat-related illnesses like heat exhaustion or heat stroke. For young children, especially under 6, sauna sessions should be brief (5-10 minutes) at lower temperatures, with close supervision and regular hydration. Gradual acclimatization and education on hydration and rest are key to minimizing risks.

Chronic Health Conditions:

• Individuals with conditions such as diabetes, multiple sclerosis, or autonomic dysfunction may have reduced heat tolerance. Consultation with a healthcare provider is recommended before engaging in sauna use or intense heat exposure.

Acclimatization:

• Gradually increasing exposure to heat, starting with shorter sessions at lower temperatures, can improve tolerance and reduce risks, particularly for those new to saunas or hot environments.

Medication Interactions:

It is important to consider that there are life-threatening medication-related hyperthermia syndromes in psychiatry, but that these are not caused by heat exposure (Ahuja & Cole, 2018). These include:

• Neuroleptic Malignant Syndrome (NMS)
• Serotonin Syndrome
• Malignant (or Lethal) Catatonia (often linked to antipsychotics and mood stabilizers)
• Anticholinergic Toxicity Syndrome
• Stimulant (cocaine, amphetamine) toxicity
• Malignant Hyperpyrexia (typically due to anesthetic agents like succinylcholine and inhalational anesthetics)
• Parkinsonism–Hyperpyrexia Syndrome (can occur with withdrawal from dopamine agonists or abrupt changes in Parkinson’s medication)
• Thyrotoxicosis (Thyroid Storm) (exacerbated by certain medications like amiodarone)

However, other medications can impact heat tolerance and have been associated with higher risk of adverse heat events (heat exhaustion, heat stroke, dehydration) and greater morbidity in the elderly and in people with predisposing cardiovascular conditions according to a limited number of case studies and case-control studies (Bongers et al., 2020; Kalisch Ellett et al., 2016):

• Cardiovascular drugs
• Diuretics, which increase dehydration risk.
• ACE inhibitors, which can impair thirst.
• Propranolol, a beta-blocker, increases sweating and therefore fluid replacement is essential.

• Vasodilators like nitroglycerin, hydralazine, isosorbide dinitrate lower blood pressure by relaxing blood vessels, which can dissipate body temperature, but can lead to hypotension and syncope.

• GLP-1 inhibitors impair thirst.

• NSAIDs, potentially through altering prostaglandin signaling, which is known to be important for generating a fever.
• Anticholinergics (amitriptyline, oxybutynin, diphenhydramine, benztropine) and drugs with anticholinergic activity (tricyclic antidepressants, clozapine, olanzapine, quetiapine, chlorpromazine, and thioridazine) can impair sweating.

• See episode 102 for a deep dive into anticholinergic medications.

• Antipsychotics, especially first generation through their high-affinity for D2 receptors, can cause hyperthermia through neuroleptic malignant syndrome (NMS) and potentially through non-NMS mechanisms by affecting the hypothalamus, the body’s principal heat regulator.

• Also consider that antipsychotics bind to other sites:
• Blockage of alpha-1 adrenergic receptors (especially those with strong sedative properties like chlorpromazine and olanzapine) reduce peripheral vasodilation.

• Blocking histamine H1 receptors can also reduce vasodilation.

• Clozapine

• Fever is a notable side-effect within the first few weeks of initiating the drug, and its prevalence has been suggested to be between 6-60% of patients. It is hypothesized to result from immunomodulatory effects on the hypothalamus (Verdoux et al., 2019). If a patient on clozapine presents with a fever, other adverse clozapine reactions (agranulocytosis, myocarditis) need to be ruled out.

• Clozapine is highly anticholinergic, and it is thought that it can reduce sweating in some patients. This anticholinergic effect also leads to constipation and urinary retention. However, clozapine also has a paradoxical agonism at some muscarinic receptors in the body, leading to excessive drooling and, in up to 6% of cases, excessive sweating (Clozaril package insert; Kenton et al., 2023).

• SSRIs can impair thermoregulation of the hypothalamus and increase risk of hyponatremia related to SIADH, particularly in the elderly taking fluoxetine or citalopram (Chiu et al., 2020; Kirpekar & Joshi, 2005).

AcknowledgementsWe extend our gratitude to Dr. Rhonda Patrick, Dr. Jari Laukkanen, and Dr. Setor Kunutsor for their insightful reviews on sauna and heat therapy (Patrick & Johnson, 2021;Laukkanen & Kunutsor, 2024), which played a crucial role in shaping this episode.

References:Ahuja, N., & Cole, A. J. (2009). Hyperthermia syndromes in psychiatry. Advances in Psychiatric Treatment, 15(3), 181–191. doi:10.1192/apt.bp.107.005090

Anderson, R. J., Freedland, K. E., Clouse, R. E., & Lustman, P. J. (2001). The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes care, 24(6), 1069–1078. https://doi.org/10.2337/diacare.24.6.1069

Becerra-Tomás, N., Blanco Mejía, S., Viguiliouk, E., Khan, T., Kendall, C. W. C., Kahleova, H., Rahelić, D., Sievenpiper, J. L., & Salas-Salvadó, J. (2020). Mediterranean diet, cardiovascular disease and mortality in diabetes: A systematic review and meta-analysis of prospective cohort studies and randomized clinical trials. Critical reviews in food science and nutrition, 60(7), 1207–1227. https://doi.org/10.1080/10408398.2019.1565281

Bongers, K. S., Salahudeen, M. S., & Peterson, G. M. (2020). Drug-associated non-pyrogenic hyperthermia: a narrative review. European journal of clinical pharmacology, 76(1), 9–16. https://doi.org/10.1007/s00228-019-02763-5

Chiu, C. Y., Sarwal, A., Azhar Munir, R., Widjaja, M., Khalid, A., & Khanna, R. (2020). Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Induced by Long-Term Use of Citalopram and Short-Term Use of Naproxen. The American journal of case reports, 21, e926561. https://doi.org/10.12659/AJCR.926561

Cornelissen, V. A., & Fagard, R. H. (2005). Effects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factors. Hypertension (Dallas, Tex. : 1979), 46(4), 667–675. https://doi.org/10.1161/01.HYP.0000184225.05629.51

Cozzi, F., Ciprian, L., Carrara, M., Galozzi, P., Zanatta, E., Scanu, A., Sfriso, P., & Punzi, L. (2018). Balneotherapy in chronic inflammatory rheumatic diseases—a narrative review. Int J Biometeorol 62, 2065–2071. https://doi.org/10.1007/s00484-018-1618-z

Enache, D., Winblad, B., & Aarsland, D. (2011). Depression in dementia: epidemiology, mechanisms, and treatment. Current Opinion in Psychiatry 24(6):p 461-472. DOI: 10.1097/YCO.0b013e32834bb9d4

Garcia, L., Pearce, M., Abbas, A., Mok, A., Strain, T., Ali, S., Crippa, A., Dempsey, P. C., Golubic, R., Kelly, P., Laird, Y., McNamara, E., Moore, S., de Sa, T. H., Smith, A. D., Wijndaele, K., Woodcock, J., & Brage, S. (2023). Non-occupational physical activity and risk of cardiovascular disease, cancer and mortality outcomes: a dose-response meta-analysis of large prospective studies. British journal of sports medicine, 57(15), 979–989. https://doi.org/10.1136/bjsports-2022-105669

Genuis, S. J., Birkholz, D., Rodushkin, I., & Beesoon, S. (2011). Blood, urine, and sweat (BUS) study: monitoring and elimination of bioaccumulated toxic elements. Archives of environmental contamination and toxicology, 61(2), 344–357. https://doi.org/10.1007/s00244-010-9611-5

Graham Jr., J. M., Edwards, M. J., & Edwards, M. J. (1998). Teratogen update: gestational effects of maternal hyperthermia due to febrile illnesses and resultant patterns of defects in humans. Teratology, 58(5), 209-221. https://doi.org/10.1002/(SICI)1096-9926(199811)58:5<209::AID-TERA8>3.0.CO;2-Q

Hackett, M. L., & Pickles, K. (2014). Part I: frequency of depression after stroke: an updated systematic review and meta-analysis of observational studies. International journal of stroke : official journal of the International Stroke Society, 9(8), 1017–1025. https://doi.org/10.1111/ijs.12357

Hanusch, K. U., & Janssen, C. W. (2019). The impact of whole-body hyperthermia interventions on mood and depression – are we ready for recommendations for clinical application? International Journal of Hyperthermia, 36(1), 572–580. https://doi.org/10.1080/02656736.2019.1612103

Harris, W. S., Tintle, N. L., Imamura, F., Qian, F., Ardisson Korat, A. V., Marklund, M., Djoussé, L., Bassett, J. K., Carmichael, P., Chen, Y., Hirakawa, H., Küpers, L. K., Laguzzi, F., Lankinen, M., Murphy, R. A., Samieri, C., Senn, M. K., Shi, P., Virtanen, J. K., Brouwer, I. A., ... in collaboration with the Fatty Acids and Outcomes Research Consortium (FORCE). (2021). Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies. Nat Commun 12, 2329. https://doi.org/10.1038/s41467-021-22370-2

He, F. J., & MacGregor, G. A. (2002). Effect of modest salt reduction on blood pressure: a meta-analysis of randomized trials. Implications for public health. Journal of human hypertension, 16(11), 761–770. https://doi.org/10.1038/sj.jhh.1001459

Hunt, A. P., Minett, G. M., Gibson, O. R., Kerr, G. K., & Stewart, I. B. (2020). Could Heat Therapy Be an Effective Treatment for Alzheimer's and Parkinson's Diseases? A Narrative Review. Frontiers in physiology, 10, 1556. https://doi.org/10.3389/fphys.2019.01556

Hüppe, M., Müller, J., Schulze, J., Wernze, H., & Ohnsorge, P. (2009). Treatment of patients burdened with lipophilic toxicants: A randomized controlled trial. Activitas Nervosa Superior Rediviva, 51(3-4). http://rediviva.sav.sk/51i34/133.pdf

Janssen, C. W., Lowry, C. A., Mehl, M. R., Allen, J. J. B., Kelly, K. L., Gartner, D. E., Medrano, A., Begay,T. K., Rentscher, K., White, J. J., Fridman, A., Roberts, L. J., Robbins, M. L., Hanusch, K., Cole, S. P., & Raison, C. L. (2016). Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 73(8):789–795. doi:10.1001/jamapsychiatry.2016.1031

Kalisch Ellett, L. M., Pratt, N. L., Le Blanc, V. T., Westaway, K., & Roughead, E. E. (2016). Increased risk of hospital admission for dehydration or heat-related illness after initiation of medicines: a sequence symmetry analysis. Journal of clinical pharmacy and therapeutics, 41(5), 503–507. https://doi.org/10.1111/jcpt.12418

Katschinski, D. M., Wiedemann, G. J., Longo, W., d'Oleire, F. R., Spriggs, D., & Robins, H. I. (1999). Whole body hyperthermia cytokine induction: a review, and unifying hypothesis for myeloprotection in the setting of cytotoxic therapy. Cytokine & growth factor reviews, 10(2), 93–97. https://doi.org/10.1016/s1359-6101(99)00006-4

Kenton, E. M., Zoellner, S. M., & Nelson, L. A. (2023). Diltiazem for clozapine-induced generalized hyperhidrosis. The mental health clinician, 13(4), 193–195. https://doi.org/10.9740/mhc.2023.08.193

Ketelhut, S., & Ketelhut, R. G. (2019). The blood pressure and heart rate during sauna bath correspond to cardiac responses during submaximal dynamic exercise. Complementary Therapies in Medicine, 44, 218-222. https://doi.org/10.1016/j.ctim.2019.05.002

Kirpekar, V. C., & Joshi, P. P. (2005). Syndrome of inappropriate ADH secretion (SIADH) associated with citalopram use. Indian journal of psychiatry, 47(2), 119–120. https://doi.org/10.4103/0019-5545.55960

Kojima, D., Nakamura, T., Banno, M., Umemoto, Y., Kinoshita, T., Ishida, Y., & Tajima, F. (2017). Head-out immersion in hot water increases serum BDNF in healthy males. International Journal of Hyperthermia, 34(6), 834–839. https://doi.org/10.1080/02656736.2017.1394502

Kuan, W. H., Chen, Y. L., & Liu, C. L. (2022). Excretion of Ni, Pb, Cu, As, and Hg in Sweat under Two Sweating Conditions. International journal of environmental research and public health, 19(7), 4323. https://doi.org/10.3390/ijerph19074323

Kukkonen-Harjula, K., Oja, P., Laustiola, K., Vuroi, I., Jolkkonen, J., Siitonen, S., & Vapaatalo, H. (1989). Haemodynamic and hormonal responses to heat exposure in a Finnish sauna bath. Europ. J. Appl. Physiol. 58, 543–550 (1989). https://doi.org/10.1007/BF02330710

Kunutsor, S. K., Khan, H., Laukkanen, T., & Laukkanen, J. A. (2017). Joint associations of sauna bathing and cardiorespiratory fitness on cardiovascular and all-cause mortality risk: a long-term prospective cohort study. Annals of Medicine, 50(2), 139–146. https://doi.org/10.1080/07853890.2017.1387927

Kunutsor, S. K., Khan, H., Zaccardi, F., Laukkanen, T., Willeit, P., & Laukkanen, J. A. (2018). Sauna bathing reduces the risk of stroke in Finnish men and women: A prospective cohort study. Neurology, 90(22), e1937–e1944. https://doi.org/10.1212/WNL.0000000000005606

Kunutsor, S. K., Laukkanen, T., & Laukkanen, J. A. (2017). Frequent sauna bathing may reduce the risk of pneumonia in middle-aged Caucasian men: The KIHD prospective cohort study. Respiratory medicine, 132, 161–163. https://doi.org/10.1016/j.rmed.2017.10.018

Laukkanen, T., Khan, H., Zaccardi, F., & Laukkanen, J. A. (2015). Association Between Sauna Bathing and Fatal Cardiovascular and All-Cause Mortality Events. JAMA Intern Med. 175(4):542–548. doi:10.1001/jamainternmed.2014.8187

Laukkanen, J. A., & Kunutsor, S. K. (2024). The multifaceted benefits of passive heat therapies for extending the healthspan: A comprehensive review with a focus on Finnish sauna. Temperature (Austin, Tex.), 11(1), 27–51. https://doi.org/10.1080/23328940.2023.2300623

Laukkanen, T., Kunutsor, S., Kauhanen, J.,& Laukkanen, J. A. (2017). Sauna bathing is inversely associated with dementia and Alzheimer's disease in middle-aged Finnish men, Age and Ageing, 46(2). 245–249. https://doi.org/10.1093/ageing/afw212

Laukkanen, T., Kunutsor, S. K., Zaccardi, F., Lee, E., Willeit, P., Khan, H., & Laukkanen, J. A. (2018). Acute effects of sauna bathing on cardiovascular function. J Hum Hypertens, 32, 129–138. https://doi.org/10.1038/s41371-017-0008-z

Laukkanen, J. A., Laukkanen, T., & Kunutsor, S. K. (2018). Cardiovascular and Other Health Benefits of Sauna Bathing: A Review of the Evidence. Mayo Clinic proceedings, 93(8), 1111–1121. https://doi.org/10.1016/j.mayocp.2018.04.008

Laukkanen, T., Laukkanen, J. A., & Kunutsor, S. K. (2019). Sauna bathing and risk of psychotic disorders: A prospective cohort study. Medical Principles and Practice, 27(6), 562–569. https://doi.org/10.1159/000493392

Lee, E., Kolunsarka, I., Kostensalo, J., Ahtiainen, J. P., Haapala, E. A., Willeit, P., Kunutsor, S. K., & Laukkanen, J. A. (2022). Effects of regular sauna bathing in conjunction with exercise on cardiovascular function: a multi-arm, randomized controlled trial. American journal of physiology. Regulatory, integrative and comparative physiology, 323(3), R289–R299. https://doi.org/10.1152/ajpregu.00076.2022

Li, Z., Li, Y., Chen, L., Chen, P., & Hu, Y. (2015). Prevalence of Depression in Patients With Hypertension: A Systematic Review and Meta-Analysis. Medicine, 94(31), e1317. https://doi.org/10.1097/MD.0000000000001317

Lichtman, J. H., Bigger Jr., J. T. , Blumenthal, J. A., Frasure-Smith, N., Kaufmann, P. G., Lespéance, F., Mark, D. B., Sheps, D. S., Taylor, C. B., & Froelicher, E. S. (2008). Care and outcomes research: Endorsed by the American Psychiatric Association. Circulation, 118(17). https://doi.org/10.1161/CIRCULATIONAHA.108.190769

Mac Giollabhui, N., Lowry, C. A., Nyer, M., Foster, S. L., Liu, R. T., Smith, D. G., Cole, S. P., Mason, A. E., Mischoulon, D., & Raison, C. L. (2024). The antidepressant effect of whole-body hyperthermia is associated with the classical interleukin-6 signaling pathway. Brain, behavior, and immunity, 119, 801–806. https://doi.org/10.1016/j.bbi.2024.04.040

McGorm, H., Roberts, L. A., Coombes, J. S., & Peake, J. M. (2018). Turning Up the Heat: An Evaluation of the Evidence for Heating to Promote Exercise Recovery, Muscle Rehabilitation and Adaptation. Sports medicine (Auckland, N.Z.), 48(6), 1311–1328. https://doi.org/10.1007/s40279-018-0876-6

Mandsager, K., Harb, S., Cremer, P., Phelan, D., Nissen, S. E., & Jaber, W. (2018). Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing. JAMA Netw Open. 1(6):e183605. doi:10.1001/jamanetworkopen.2018.3605

Masuda, A., Nakazato, M., Kihara, T., Minagoe, S., & Tei, C. (2005). Repeated Thermal Therapy Diminishes Appetite Loss and Subjective Complaints in Mildly Depressed Patients. Psychosomatic Medicine 67(4). 643-647. DOI: 10.1097/01.psy.0000171812.67767.8f

Naumann, J., Grebe, J., Kaifel, S. Weinert,T., Sadaghiani, C., & Huber, R. (2017) Effects of hyperthermic baths on depression, sleep and heart rate variability in patients with depressive disorder: a randomized clinical pilot trial. BMC Complement Altern Med 17, 172. https://doi.org/10.1186/s12906-017-1676-5

Neter, J. E., Stam, B. E., Kok, F. J., Grobbee, D. E., & Geleijnse, J. M. (2003). Influence of weight reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension, 42(5), 878–884. https://doi.org/10.1161/01.HYP.0000094221.86888.AE

Patrick, R. P., & Johnson, T. L. (2021). Sauna use as a lifestyle practice to extend healthspan. Experimental Gerontology, 154, 111509. https://doi.org/10.1016/j.exger.2021.111509

Paz, M. A., de-La-Sierra, A., Sáez, M., Barceló, M. A., Rodríguez, J. J., Castro, S., Lagarón, C., Garrido, J. M. M., Vera, P., & Coll-de-Tuero, G. (2016). Treatment efficacy of anti-hypertensive drugs in monotherapy or combination: ATOM systematic review and meta-analysis of randomized clinical trials according to PRISMA statement. Medicine, 95(30), e4071. https://doi.org/10.1097/MD.0000000000004071

Pizzey, F. K., Smith, E. C., Ruediger, S. L., Keating, S. E., Askew, C. D., Coombes, J. S., & Bailey, T. G. (2021). The effect of heat therapy on blood pressure and peripheral vascular function: A systematic review and meta-analysis. Experimental physiology, 106(6), 1317–1334. https://doi.org/10.1113/EP089424

Puder, D. (Host). (n.d). Anticholinergic Burden (No. 102) [Audio Podcast Episode]. In Psychiatry & Psychotherapy Podcast, Emotion Connection, LLC. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/anticholinergic

Rissanen, J. A., Häkkinen, A., Laukkanen, J., Kraemer, W. J., & Häkkinen, K. (2020). Acute Neuromuscular and Hormonal Responses to Different Exercise Loadings Followed by a Sauna. Journal of strength and conditioning research, 34(2), 313–322. https://doi.org/10.1519/JSC.0000000000003371

Romeyke, T., & Stummer, H. (2014). Multi-Modal Pain Therapy of Fibromyalgia Syndrome with Integration of Systemic Whole-Body Hyperthermia – Effects on Pain Intensity and Mental State: A Non-Randomised Controlled Study. Journal of Musculoskeletal Pain, 22(4), 341–355. https://doi.org/10.3109/10582452.2014.949336

Rosenzweig, R., Nillegoda, N. B., Mayer, M. P., & Bukau, B. (2019). The Hsp70 chaperone network. Nature reviews. Molecular cell biology, 20(11), 665–680. https://doi.org/10.1038/s41580-019-0133-3

Sacks, F. M., Svetkey, L. P., Vollmer, W. M., Appel, L. J., Bray, G. A., Harsha, D., Obarzanek, E., Conlin, P. R., Miller, E. R., 3rd, Simons-Morton, D. G., Karanja, N., Lin, P. H., & DASH-Sodium Collaborative Research Group (2001). Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. The New England journal of medicine, 344(1), 3–10. https://doi.org/10.1056/NEJM200101043440101

Sebők, J., Édel, Z., Váncsa, S., Farkas, N., Kiss, S., Erőss, B., Török, Z., Balogh, G., Balogi, Z., Nagy, R., Hooper, P. L., Geiger, P. C., Wittmann, I., Vigh, L., Dembrovszky, F., & Hegyi, P. (2021). Heat therapy shows benefit in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, 38(1), 1650–1659. https://doi.org/10.1080/02656736.2021.2003445

Stetler, R. A., Gan, Y., Zhang, W., Liou, A. K., Gao, Y., Cao, G., & Chen, J. (2010). Heat shock proteins: cellular and molecular mechanisms in the central nervous system. Progress in neurobiology, 92(2), 184–211. https://doi.org/10.1016/j.pneurobio.2010.05.002

Tei, C., Shinsato, T., Miyata, M., Kihara, T., & Hamasaki, S. (2007). Waon therapy improves peripheral arterial disease. Journal of the American College of Cardiology, 50(22), 2169-2171. https://doi.org/10.1016/j.jacc.2007.08.025

Ukai, T., Iso, H., Yamagishi, K., Saito, I., Kokubo, Y., Yatsuya, H., Muraki, I., Eshak, E. S., Sawada, N., & Tsugane, S. (2020). Habitual tub bathing and risks of incident coronary heart disease and stroke. Heart (British Cardiac Society), 106(10), 732–737. https://doi.org/10.1136/heartjnl-2019-315752

U. S. Centers for Disease Control and Prevention (CDC). (2023, June 20). Depression and Aging. https://www.cdc.gov/aging/olderadultsandhealthyaging/depression-and-aging.html

Verdoux, H., Quiles, C., & de Leon, J. (2019). Clinical determinants of fever in clozapine users and implications for treatment management: A narrative review. Schizophrenia Research, 211, 1-9. https://doi.org/10.1016/j.schres.2019.07.040

Windsor, M. T., Bailey, T. G., Perissiou, M., Meital, L., Golledge, J., Russell, F. D., & Askew, C. D. (2018). Cytokine responses to acute exercise in healthy older adults: The effect of cardiorespiratory fitness. Frontiers in Physiology, 9, Article 203. https://doi.org/10.3389/fphys.2018.00203

Xin, X., He, J., Frontini, M. G., Ogden, L. G., Motsamai, O. I., & Whelton, P. K. (2001). Effects of alcohol reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension (Dallas, Tex. : 1979), 38(5), 1112–1117. https://doi.org/10.1161/hy1101.093424

Ye, W. N., Thipse, M., Mahdi, M. B., Azad, S., Davies, R., Ruel, M., Silver, M. A., Hakami, L., Mesana, T., Leenen, F., & Mussivand, T. (2020). Can heat therapy help patients with heart failure?. Artificial organs, 44(7), 680–692. https://doi.org/10.1111/aor.13659

Yoshihara, T., Naito, H., Kakigi, R., Ichinoseki-Sekine, N., Ogura, Y., Sugiura, T., & Katamoto, S. (2013). Heat stress activates the Akt/mTOR signalling pathway in rat skeletal muscle. Acta physiologica (Oxford, England), 207(2), 416–426. https://doi.org/10.1111/apha.12040

Zaccardi, F., Laukkanen, T., Willeit, P., Kunutsor, S. K., Kauhanen, J., & Laukkanen, J. A. (2017). Sauna Bathing and Incident Hypertension: A Prospective Cohort Study. American Journal of Hypertension, 30(11). 1120–1125. https://doi.org/10.1093/ajh/hpx102

View Details

Emerald Norman, Liam Browning, David Puder, MD

None of the authors have any conflicts of interest to report.

The Expressive Writing ParadigmLibba Bray, New York Times bestselling author of the young adult novel, The Diviners, once wrote, “There is no greater power on this earth than story.” And right she is. Throughout history, the use of stories, narratives, and prose has played an integral role in the way humans relate to both the natural environment and intangible ideas. Today, storytelling continues to be a vehicle used to understand and utilize scientific paradigms and complex emotions. There are many examples of how pervasive storytelling is within our society, from the stories we print, publish, and film, to the stories we tell ourselves. Hollywood media narratives shape the popular cultural standards for art, beauty, and luxury. Arguments transform what should be objective news reports into rousing political attacks. Perhaps the simplest but most compelling case is one’s own private journaling, which allows for the processing of complex emotions experienced throughout the day and condenses hours of living, breathing, talking, and interacting into a single written perspective on a sheet of paper.

One of the ways we can use storytelling to understand the world, each other, and ourselves is through writing. Research is beginning to emerge that suggests writing, composing a story, may prove to be a therapeutic avenue by which we overcome trauma.

“The goal here is to put upsetting experiences into language.” - James Pennebaker, PhD

James Pennebaker, PhD, Professor Emeritus of Psychology at the University of Texas at Austin, is one of the pioneering voices on the topic of utilizing writing as a therapeutic tool for exploring and treating trauma. In an interview with Kim Mills, host of the podcast “Speaking of Psychology,” Pennebaker explains how his research began with looking at the connection between psychological stress and physical symptoms for his book, The Psychology of Physical Symptoms (1982). Through simple questionnaires he developed, his team found that participants with secret past traumatic experiences were more likely to be hospitalized for various physical illnesses. He then shifted his research to exploring the health benefits of disclosing traumatic events, specifically through expressive writing, as a form of trauma therapy.

A Study on Disclosure vs. Non Disclosure of Traumatic EventsPennebaker began his work with establishing the relationship between undisclosed traumas and long-term physical and mental health. His 1988 study included 384 employees of a large Texas-based corporation. Participants completed the SMU Illness Questionnaire, a 49-item checklist that assessed major (e.g., cancer, heart disease) and minor (e.g., colds, headaches) health problems that occurred within the past year. The participants were also asked about childhood (traumatic sexual experiences, divorce or separation of parents, death of a family member or very close friend, victim of violence, or other trauma) and recent (within the last three years) traumas. They found that childhood traumas were much less likely to be confided than recent traumas, and that participants with childhood trauma were more likely to experience health problems within the past year compared to those without trauma, regardless of whether they disclosed the trauma. Additionally, those with undisclosed childhood trauma had significantly more physician visits within the past year compared to participants without trauma. In summary, while the study found that the illness scores for the trauma-non-confided group (mean = 8.60) were slightly larger than those for the trauma-confided group (mean = 7.57), the difference between these groups did not reach statistical significance. The significant impact on health symptoms was primarily due to the experience of childhood trauma itself, regardless of whether the trauma was confided (Pennebaker et al., 1988).

Trauma disclosure is the foundation for expressive writing as therapy. Expressive writing provides a way for one to disclose their trauma, which is associated with decreased total illness.

A Study on Expressive Writing for the Treatment of PTSDPennebaker’s work, throughout the course of his career, found that expressive writing was useful for decreasing a number of physical and psychological pathologies (Pennebaker and Beall, 1986; Pennebaker et al., 1988). A common strategy he used involved having the participants write for 15-20 minutes over three to four days on their deepest thoughts and feelings on emotionally disturbing events and traumatic experiences(Pennebaker and Beall, 1986; Pennebaker et al., 1988).

A 2010 study by Joshua Smyth focused on whether expressive writing could be used as an intervention for treating symptoms of PTSD. It was a randomized trial where subjects were assigned to an experimental expressive writing group or a control group in which they wrote about time management. The subject pool consisted of individuals with a diagnosis of PTSD either from war/combat or sexual assault.

Participants did baseline measurements (completing PSS-I [PTSD Symptoms Scale Interview], POMS [Profile of Mood States], and salivary cortisol testing) then completed three writing sessions (with three prompts) in one day. Writing sessions lasted for 20 minutes and were separated by 15-minute rest intervals. The experimental group was told to write about thoughts and feelings associated with their past trauma.

• The first prompt had participants identify and label the event along with thoughts and feelings associated.
• The second prompt instructed participants to tell a story about the event and how it affected them.
• The third prompt had participants reflect on what they had written in previous sessions and retell their story with any new insights. It also instructed them to examine the rationality of their negative beliefs.

The control group was instructed to write about time management and their daily plans for all three sessions. Writing was unstructured. Follow-up assessments were conducted at three months post-writing.

The study found that expressive writing did not worsen PTSD symptoms, and participants did not indicate being harmed by expressive writing interventions. Mood states such as anger, tension, and depression were decreased in the experimental group with (p-values <.05), (p-values <.05), and (p-values <.10) respectively (Figure 1). In addition, the experimental group showed lower cortisol levels when exposed to imagery of traumatic memories compared to controls (p <.01) (Figure 2).

Overall, they found that expressive writing about a trauma showed a decrease in anger and tension, but not PTSD symptoms.

Limitations of this study include the lack of specific analysis of clinical significance. The researchers reported no decrease in the number of PTSD diagnoses or PTSD-related symptom severity as a result of the intervention. Therefore, we cannot say if this change in mood or neuroendocrine response is large enough to make a difference in the treatment of PTSD. However, we can conclude from this study that expressive writing mildly decreases dysphoric moods and stressful physiological responses in traumatized people, which could potentially facilitate positive adaptation and coping with distress.

It is also unclear if the POMS scores showed a clinically significant change (how many points would be noticeable). The total score for mood disturbance on the scale ranges between -32 to 200 because each item on the 65-item questionnaire can be scaled from 0 (not at all) to 5 (extremely). A lower score indicates a more stable mood profile because most of the items are negative emotion items.

The individual mood components are scored differently based on how many questions pertain to them within the scale. The highest possible score for anger is 48, confusion is 28, depression is 60, fatigue is 28, tension is 36, and vigor (a positive component therefore scored in the opposite direction) is -32. The graph shows that the anger domain had a mean change of approximately -6 (p<0.05) and the tension domain had a mean change of approximately -5 (p<0.05). In the context of the highest scores in each domain category, those small shifts cause a substantial change in the individual mood profile components of anger and tension. Although, again, the clinical significance needs to be judged by clinicians.

Regardless, it is important to note that positive changes in a self-reporting mood scale show that participants were at least perceiving their emotions as being more positive after the intervention. While it is hard to prove from this study that expressive writing makes a real positive difference clinically, we can at least draw the conclusion that a PTSD patient narrativizing their traumatic experience is not harmed by doing so. In fact, it can create more positive feelings and mood states, which we know is a step towards healing. Any low-stakes intervention that can decrease the perceived distress of a sufferer is worth pursuing or adding to other known things that decrease symptoms.

A Study on CPT with Expressive Writing for the Treatment of PTSDA 2012 study on PTSD treatment by Patricia Resick et al. also demonstrated that writing out an account of one’s trauma along with cognitive processing therapy can increase the rate and overall amount of PTSD symptom change when compared to CPT therapy alone in patients with high levels of dissociation.

The researchers used the 30-item Multiscale Dissociation Inventory to determine levels of dissociation. This self-report test measures six types of dissociative response:

1. Disengagement
2. Depersonalization
3. Derealization
4. Emotional Constriction/Numbing
5. Memory Disturbance
6. Identity Dissociation

Respondents indicate how frequently they experienced each item on a 5-point scale where 0 = never and 5 = very often. A higher score represents a higher degree of dissociation.

PTSD symptom severity was assessed using the Post-traumatic Stress Diagnostic Scale (PDS). The Post-traumatic Stress Diagnostic Scale is a 24-item self-reporting scale that evaluates the severity of PTSD symptoms within the last month according to DSM-5 criteria. Symptoms are computed on a 5-point scale of severity and frequency ranging from 0 (not at all) to 4 (6 or more times a week/severe) (Foa, 1997). There are items for each of the 20 DSM-5 diagnostic criteria and 4 items addressing duration, symptom onset, and effect on life. Again, a higher score represents more severe symptomatology, with 96 being the highest possible score.

The study used two interventions and one control (about 50 people in each group). The first two included CPT therapy with (CPT) and without (CPT-C) a written account of trauma. Patients were directed to write a detailed account of their trauma, which they were directed to read to themselves and to the therapist who assisted in processing emotions and challenging maladaptive thought patterns. After several sessions, patients were instructed to write about other topics related to safety, esteem, intimacy, etc. and to correct overgeneralized beliefs related to these themes. The control group wrote about the trauma and also read their account aloud to therapists, who provided supportive comments but without challenging cognitive distortions (WA). These interventions lasted six weeks. Measures (PDS, MDI, and others) were taken pre-intervention, during each week of the intervention, posttreatment, and at a six-month follow-up.

Here is an excerpt of the writing prompt from the CPT therapist and patient manual (veteran/military version):

“Please begin this assignment as soon as possible. Write a full account of the traumatic event and include as many sensory details (sights, sounds, smells, etc.) as possible. Also, include as many of your thoughts and feelings that you recall having during the event. Pick a time and place to write so you have privacy and enough time. Do not stop yourself from feeling your emotions. If you need to stop writing at some point, please draw a line on the paper where you stop. Begin writing again when you can, and continue to write the account even if it takes several occasions. Read the whole account to yourself every day until the next session. Allow yourself to feel your feelings. Bring your account to the next session” (Resick, 2014).

It is worth mentioning that both CPT and CPT-C protocol start off with having the patient write an impact statement, or an account on why they believe the traumatic account occurred, without going into details about the trauma.

Here is excerpt of this prompt from the CPT therapist and patient manual (veteran/military version):

“Please write at least one page on why you think this traumatic event occurred. You are not being asked to write specifics about the traumatic event. Write about what you have been thinking about the cause of the worst event.

Also, consider the effects this traumatic event has had on your beliefs about yourself, others, and the world in the following areas: safety, trust, power/control, esteem, and intimacy. Bring this with you to the next session” (Resick, 2014)

Following that first session assignment, within the CPT format, patients discuss the event with the therapist. In session 2, they complete worksheets to identify connections between events, thoughts, and emotions. During session 3, the patients write a detailed account of their trauma and their emotions around it. This is the element that is not found in CPT-C (the intervention without writing). Sessions 4 and 5 consist of therapists challenging the patient’s thoughts and emotions around the meaning of the event. After session 5, the sessions become more focused on teaching tools that allow them to mitigate the effect of trauma on their lives and challenge negative beliefs. In Sessions 6-12, patients learn how to identify problematic life patterns and use worksheets that focus on different themes each week. The themes are esteem, intimacy, power-control, safety, and trust. During session 11, patients rewrite their impact statements from the first session and reflect with the therapist on how their beliefs change.

The study found that all groups significantly improved on the Post-traumatic Stress Diagnostic Scale and on measures of dissociation (TIS, MDI), with no significant differences between groups at posttreatment and six-month follow-up.

**Writing Increases Speed Of Symptom Reduction For High Dissociation**Figure 1: When looking at 2 SD above the mean for the whole dissociation score (TSI DIS 87.63), CPT (with writing) decreased faster than CPT-C (without writing) (note: difference was in rate of change, not overall change).

Interestingly, at two standard deviations above the mean on the MDI (score of 18.45), the study’s regression equation predicted post treatment Post-traumatic Stress Diagnostic Scale values of 7.75 for those doing CPT with writing and 27.93 for those doing CPT without writing (a 1.12 SD difference!).

Figure 2: Comparing low depersonalization (1 SD below the mean= 6.81) vs. high (1 SD above the mean = 13.79).

**Those Who Depersonalize Are Good Candidates For Writing**When considering the results of those who scored high on the depersonalization subgroup of “high dissociators,” we can see that story writing has a profound effect on symptomatology. The results of this study suggest that the narrativization of trauma is beneficial for those who tend to dissociate, but even more so those who tend to depersonalize, to separate themselves from their own story. This introduces a population of patients who may find value in supplementing their therapy with expressive writing as a method of reintegrating their identity into their story.

However, it is important for more studies to support these specific findings, given these regression analyses extrapolated based on participants at two standard deviations above the mean.

Also, it’s interesting that these graphs demonstrate that WA (the writing alone condition), also improved PTSD symptoms without any of the extra therapy attached. Patients in every intervention got better, showing that writing does have an effect (though less pronounced) even as a stand-alone treatment.

Change in dissociation was the same for all treatment conditions (Table 3).

The primary outcome of resilience was assessed with the Connor-Davidson Resilience Scale (CD-RISC), a validated 25-item scale. The scale carries a five-point range of responses: “not true at all (0), rarely true (1), sometimes true (2), often true (3), and true nearly all of the time (4).” The scale is rated based on how the subject has felt over the past month. The total score ranges from 0 to 100, with higher scores reflecting greater resilience (Connor & Davidson, 2003). The scale was developed by studying the characteristics of resilient people and then formulating them into statements that the user can rate from 0 to 5, corresponding to the above statements.

The current study found a mean increase in resilience scores of about 10.0 with a 95% CI of 5.6-14.4 and a large effect size substantiated by Cohen’s d = 0.75.

For the first of their secondary outcomes, perceived stress was measured by the 10-item Perceived Stress Scale (PSS-10). Scoring is from 0-4 on a 5-point scale, with 0=never and 4=very often. The current study found a difference in perceived stress with an approximate mean decrease of -6.1 and a large effect size shown by Cohen’s d = 0.76.

Depression symptoms were assessed using the 20-item Center for Epidemiological Studies Depression Scale - Revised (CESD-R), which has response values ranging from 0-4 (0=Not at all and 4=Nearly every day for 2 weeks) and assesses DSM-5 criteria symptoms. A CESD-R score of 16 or higher represents possible major depression. Glass’s team found that depression scale scores decreased by a mean of approximately -6.0 ± 11.98 points, with a medium effect size shown by Cohen’s d = 0.52.

Lastly, rumination, defined as “compulsively focused attention on the symptoms of one’s distress,” was measured using the 22-item Rumination Response Scale (RRS). The RRS indicates the frequency of each item on a 4-point scale ranging from 1=Almost never to 4=Almost always. Examples of items include: [how often do I…] “think about how alone you feel” and “think about a recent situation, wishing it had gone better.” The study found that RRS scores decreased from baseline, with a mean decrease of −8.6 ± 10.58 points and the largest effect size of Cohen’s d = 0.82.

Participants also used a scale of 0-10 to answer the question: “To what degree was the writing meaningful and valuable for you?” The table below includes the average ratings. Affirmative writing was found to be the most meaningful by the writers, with an average rating of 8.78, while poetic writing had the lowest meaningfulness rating at 6.92. All types of writing were rated on average above 5, thus concluding that all writing styles were meaningful to the average participant.

This study demonstrates that expressive writing is psychologically beneficial and improves various mental domains. There was a significant improvement in resiliency. Those who write expressively are better equipped to bounce back from traumatic events. Furthermore, breaking resiliency down to some components covered in the CD-RISC reveals that expressive writing helps encourage patience, tolerance of change, adaptability, a sense of humor, and more. These aspects are crucial for maintaining joy and balance in our constantly shifting and evolving lives, even during adverse times.

The secondary outcomes also had significant and large effects, which is useful for identifying which patients will benefit most from a writing intervention. Patients with depressive symptoms can expect modest improvement from this simple and low-cost intervention. Those experiencing persistently high stress, such as business owners, parents, and workers within a competitive field, may significantly lower their stress levels through expressive writing.

A Study Suggesting Writing Decreases RuminationThe study findings suggest that expressive writing significantly lowers rumination with a large effect size. In a 2006 paper, Pennebaker theorized that increased rumination heightens depressive symptoms and that expressive writing mitigates these symptoms by decreasing rumination (Gortner, Rude, and Pennebaker, 2006).

Additionally, participants seemed to enjoy the activity and found it meaningful, as evidenced by the high ratings of acceptability. The paper included favorable participant comments such as, “This process was very new to me and it felt great to express thoughts that come out differently written than in my own head. I find it difficult to express myself verbally and am hopeful this strategy will allow an outlet to my deeper feelings.” This suggests that many people not only comply with but also enjoy this intervention.

However, it is important to note that the study participants signed up voluntarily and were not compensated, which could mean that these effects are most prominent in people who are already interested in writing. The study also lacked a control group, so confounding variables such as the passage of time and the establishment of routine cannot be ruled out as contributing factors to the psychological benefits observed.

A Study on the Effects of Writing on AnxietyAs an undergraduate student, I collaborated with the psychology department chair to craft a randomized controlled trial (RCT) using Pennebaker’s framework to test if an expressive writing condition could decrease anxiety in study participants. Our sample consisted of undergraduate students at Andrews University. We utilized the State-Trait Anxiety Inventory-S Anxiety (STAI-S), created by Spielberger in 1983 and reviewed in 2010 (Spielberger, 2010), to measure state anxiety. The STAI-S contains 20 items using a 4-point Likert Scale (1 = almost never, 2 = sometimes, 3 = often, 4 = almost always). Participants responded to statements indicating how they felt at that moment, such as, “I feel that difficulties are piling up so that I cannot overcome them” and “I feel nervous and restless.”

Experimental participants wrote about a stressful life event, while the control group wrote about the activities of their day. Anxiety scales were collected pre-intervention, 30 minutes post-intervention, and 15 days post-intervention. We found a decrease in state anxiety over time for those assigned to the experimental group compared to the control group. Both groups’ anxiety levels dropped below baseline measurements over time, but the decline in anxiety was steeper for the expressive writing condition than the control condition.

The effect size appeared to be very small for both groups, substantiated by η² values of 0.11 between the experimental and control groups, and η² values of 0.04 and 0.002 between the 30-minute and 15-day time intervals within the experimental group, respectively. The max score on the State-Trait Anxiety Inventory-S Anxiety inventory is 80. We found that participants in both groups had an average score that declined from 46 pre intervention to approx 40 by 30 mins post then increased to 41 by Day 15.

We can conclude from this study that expressive writing has a modest but statistically significant effect on anxiety over time. However, we did not measure clinical significance.

Expressive Writing Decreased Clinical Symptoms For Patients With Asthma And Rheumatoid Arthritis After Four MonthsA study completed by Joshua Smyth in 1999 examined the relationship between expressive writing and physical symptom improvement in patients with mild to moderately severe asthma (n=61) or rheumatoid arthritis (n=51).

Prior to the intervention and then 2 weeks, 2 months, and 4 months after the intervention, the asthma patients were evaluated with spirometry, and the rheumatoid arthritis patients were evaluated by a licensed rheumatologist. For both groups, a strong difference in outcomes was found at the 4-month follow-up (P = .016).

For the asthma group, the average percentage of expected forced expiratory volume in 1 second (FEV1) improved from 63.9% at pre-intervention to 76.3% at the 2-week follow-up (P < .001).

The rheumatoid group showed a global decrease in rheumatoid disease activity at the 4-month assessment (F1,46 = 11.48, P = .001).

The study also measured the clinical significance of the results. They found that for both the asthma and rheumatoid arthritis groups, “participants showed greater rates of improvement and lesser rates of worsening than the control group across both diseases (χ² = 10.42, P = .005; Fisher exact P = .0060)” (Smyth, 1999). This demonstrates that there is a clinically significant difference, as well.

The mechanism for why this occurred is still unknown. The study hypothesized that it might be due to psychophysiological improvements in immune function. Another theory suggested that creative writing improved health behaviors by providing an outlet for decreased stress, which might have mitigated the use of other unhealthy coping mechanisms such as smoking or alcohol use. The asthma group also showed statistically significant improvement earlier than the rheumatoid group, which may suggest that there are two completely different patterns of response to expressive writing. Further studies will hopefully dive into the internal processes stimulated by expressive writing that allow for clinical symptomatology improvement.

**Decreased Perceived Emotional Stress Improves Wound Healing In Post Surgical Patients.**Mitigation of stress may play an important role in how expressive writing positively affects mental and physical health. It is well known how stress and anxiety interact hormonally with several body systems. Dr. Edward Tagge discusses these psychobiological interactions in his 2013 paper, *Psychoneuroimmunology and the Pediatric Surgeon*. The paper discusses the bidirectional communication network between the brain and the immunological and endocrinological body axis. His paper found that stress mitigated by cognitive behavioral therapy (CBT), mindfulness meditation, and touch therapy improved wound healing and other post-surgical outcomes, likely through immunologic and inflammatory regulation by an “unstressed” brain.

This randomized control trial measured this by analyzing ePTFE tube for hydroxyproline deposition in surgical patients post-cholecystectomy. They used the above-mentioned therapy modalities as their intervention and measured participants’ perceived stress. The study found that intervention group patients showed a reduction in perceived stress compared to the control group and had higher hydroxyproline deposition (p=0.03). This means that less-stressed post-surgical patients had significantly improved wound healing as a result of increased immunological and endocrinological function.

Although I was unable to find studies that directly compare the aforementioned treatment modalities with expressive writing, we know that expressive writing is effective for lowering perceived stress (Glass, Dreusicke et al. 2019) and improving mood (Smyth et. al. 2010). Therefore, we can expect that having patients engage in expressive writing therapy modulates the immune and inflammatory systems in a similar way to the therapies studied in the above RCT.

Clinical Application“In your writing, whatever you write about, just let go and explore your very deepest thoughts and feelings.” - James Pennebaker

Expressive writing has shown small but significant effects in mitigating mood states and physical symptoms. It is a low-cost and easy-to-implement therapy intervention. Of course, the next question is, how can clinicians incorporate expressive writing into clinical practice?

For several of Pennebaker's studies (Gortner, Rude, and Pennebaker, 2006; Baike, Wilhelm 2018), instructions for the experimental condition were as follows:

“For the next 3 days [for ~20 minutes], I would like you to write about your very deepest thoughts and feelings about any difficult or emotionally disturbing events you are experiencing in your life right now. You may also tie your topic in with any past stressful or traumatic experiences you’ve had. In your writing, I’d like you to really let go and explore your very deepest emotions and thoughts. You might link your topic to your relationships with others, including parents, lovers, friends, or relatives. You may also want to consider linking your experience to your past, your present, or your future, or to who you have been, who you would like to be, or who you are now. You may write about the same general issues or experiences on all days of writing, or on different experiences each day. Don’t worry about grammar or spelling—that is not important. All of your writing will be completely confidential.”

This is a template for how a therapeutically successful expressive writing intervention may be introduced to a patient. It is important that the focus is on one’s emotions and connections to memories and relationships rather than on timeliness or grammar.

Pennebaker encourages that the patient should assess themselves after each writing exercise: How am I feeling about what I wrote? Was that really what I should be writing about? How can I explore this topic from a different perspective?

Writing can be done using a computer or on physical paper. Pennebaker says in an interview with Nelda Sue Yaw that physical writing style can be experimental and change to whatever makes the writer most comfortable. That could mean writing with their dominant or non-dominant hand, forgoing paper and writing with just their finger in the air. However one chooses to write, just get it out.

We also can surmise by integrating the studies reviewed earlier that using prompts that encourage variety in style and perspective of writing is also useful for enriching the total experience. Therapists can use the exact prompt above but may also be encouraged to have several writing sessions where affirmations, aspirations, other people’s perspectives, or new insights are proposed as prospective writing topics. In addition, the 2018 Glass study had participants write in metaphor. Having your client try writing a poem, song, sonnet, or story to represent their trauma may be a creative way to have them explore the narrative of their experiences in a fresh, artistic manner.

Based on all that we have discussed, I believe patients who would receive maximum benefit include those who struggle to talk out loud with clinicians or friends and family about their feelings, emotions, and traumas and those with high levels of dissociation. In addition, patients who have a tendency to ruminate or compulsively revisit previous traumas may find expressive writing therapeutic. Other patients who would benefit from expressive writing as an ancillary therapy along with other certified treatment modalities would be patients who struggle with anxiety, chronic stress, chronic disease (e.g., asthma, rheumatoid arthritis), PTSD, or who are post-surgical.

The most important takeaway is that writing should be free and uncurated, as that allows for peak self-expression. Patients should be allowed to focus on current or past traumas and relate them to their past or future, contemplate how they or others are affected, etc. They can write about different traumas or repeat the same traumas. No set agenda, just 20 minutes of free-flowing ideas, allowing them to create a story out of their experiences, ordering the chaos of trauma into a narrative they can accept.

Personal AnecdoteTo end the episode, Dr. Puder challenged himself and me to try expressive writing for a couple of days using the same prompt and a 20-minute timer so that we could experience the intervention firsthand.

Here are my (Emerald Norman) thoughts after completing a couple of sessions:

I initially found it hard to begin and sit down to do the intervention. Every time I attempted to do so, something else grabbed my attention. (More research may be needed to see if this treatment is effective for people with untreated ADHD!) Once I was able to sit myself down for my first writing prompt, I found myself awash with boredom and unsure of what I even wanted to write about.

I have experienced a couple of scenarios in my life that could be interpreted as traumatic. However, none currently affect me (or so I thought). Because I couldn’t think of any current stresses, I began writing about a situation that happened to me many years ago in high school. I was surprised to find that as I began engaging in the story, the time melted away. While I had begun the intervention wrestling with boredom and inattention, within seconds, I was immersed in my writing and emotionally back in high school.

I recounted the story as much as I remembered it but then found myself focusing on how it still affects me today. I admitted to myself feelings that I had taken much conscious effort to suppress over the past years and months. In doing that, I saw how so many of those feelings stemmed from and found root in that past trauma. So much of my self-talk, even today as a medical student, was so obviously shaped by that experience and similar ones. I realized that my past stress was very much my current stress.

The timer went off as I was mid-sentence. I was so engrossed in typing that 20 minutes passed by in what felt like 20 seconds. Physiologically, I was much more aroused than at the start of the task. I was sweating lightly, my heart was pounding a bit, and my thoughts were racing. I took a few minutes to walk around the room before packing my things to head home that first day.

From what I have learned from the articles I read, it is normal to be immediately excited after writing expressively, and the calming, stress-reducing benefits tend to show up weeks and months later. Immediately, I can say that I appreciated being able to make those connections between my past and present feelings as a short-term benefit. Although, it definitely came at the cost of awakening emotions within me that were not positive. I guess the next thing to do is wait.

Audience ActivityWe encourage you to follow the prompt above for 3 days. Try writing in a different style every day, or continue in one style if that is most comfortable to you. See where your writing takes you!

References:American Psychological Association (APA). (March 2024). Expressive Writing. (No. 277) [Audio Podcast episode]. In Speaking of Psychology. https://www.apa.org/news/podcasts/speaking-of-psychology/expressive-writing

Baikie, K. A., & Wilhelm, K. (2005). Emotional and physical health benefits of expressive writing. Advances in Psychiatric Treatment, 11(5), 338–346. doi:10.1192/apt.11.5.338

Cohen, S., Kamarck, T., & Mermelstein, R. (1983). Perceived Stress Scale [Database record]. APA PsycTests. https://doi.org/10.1037/t02889-000

Connor, K. M., & Davidson, J. R. (2003). Development of a new resilience scale: The Connor‐Davidson resilience scale (CD‐RISC). Depression and Anxiety, 18(2), 76-82. https://doi.org/10.1002/da.10113

Foa, E. B., Cashman, L., Jaycox, L., & Perry, K. (1997). The validation of a self-report measure of posttraumatic stress disorder: The Posttraumatic Diagnostic Scale. Psychological Assessment, 9(4), 445–451. https://doi.org/10.1037/1040-3590.9.4.445

Foa, E. B., McLean, C. P., Zang, Y., Zong, J., Rauch, S., Porter, K., ...& Kauffman, B. (2016). Psychometric properties of the Posttraumatic Stress Disorder Symptoms Scale Interview for DSM-5 (PSSI-5). Psychological Assessment, 28, 1159-1165. doi:10.1037/pas0000259

Glass, O., Dreusicke, M., Evans, J., Bechard, E., & Wolever, R. Q. (2019). Expressive writing to improve resilience to trauma: A clinical feasibility trial. Complementary Therapies in Clinical Practice, 34, 240-246. https://doi.org/10.1016/j.ctcp.2018.12.005

Gortner, E. M., Rude, S. S., & Pennebaker, J. W. (2006). Benefits of expressive writing in lowering rumination and depressive symptoms. Behavior Therapy, 37(3), 292-303. https://doi.org/10.1016/j.beth.2006.01.004

Heuchert, J.P. and McNair, D.M. (2012) Profile of Mood States 2nd Edition. Multi-Health Systems (MHS), Toronto. https://doi.org/10.1037/t05057-000

Kessler, R. C., Andrews, G., Colpe, L. J., Hiripi, E., Mroczek, D. K., Normand, S. L. T., Walters, E. E., & Zaslavsky, A. M. (2002). Short screening scales to monitor population prevalences and trends in non-specific psychological distress. Psychological Medicine, 32(6), 959-976. https://doi.org/10.1001/archpsyc.60.2.184

Norman, Emerald Danielle, "Express Yourself : A Study of Expressive Writing and State Anxiety" (2020). Honors Theses. 242. https://dx.doi.org/10.32597/honors/242/

Pennebaker, J. (2017, October 12). How to write expressively and heal yourself [Video]. YouTube. https://www.youtube.com/watch?v=zP2O_-dE9E8

Pennebaker, J. W., & Beall, S. K. (1986). Confronting a traumatic event: toward an understanding of inhibition and disease. Journal of abnormal psychology, 95(3), 274–281. https://doi.org/10.1037//0021-843x.95.3.274

Pennebaker, J. W., Kiecolt-Glaser, J. K., & Glaser, R. (1988). Disclosure of traumas and immune function: health implications for psychotherapy. Journal of consulting and clinical psychology, 56(2), 239–245. https://doi.org/10.1037//0022-006x.56.2.239

Pennebaker, J. W., & Susman, J. R. (1988). Disclosure of traumas and psychosomatic processes. Social Science & Medicine, 26(3), 327-332. https://doi.org/10.1016/0277-9536(88)90397-8

Resick, P. A., Suvak, M. K., Johnides, B. D., Mitchell, K. S., & Iverson, K. M. (2012). The impact of dissociation on PTSD treatment with cognitive processing therapy. Depression and Anxiety, 29(8), 718-730. https://doi.org/10.1002/da.21938

Sloan, D. M., & Marx, B. P. (2019). Expressive writing for military-related trauma: A promising therapeutic intervention. Depression and Anxiety, 36(10), 931-939. https://doi.org/10.1002/da.21938

Smyth, J. M., Hockemeyer, J. R., & Tulloch, H. (2008). Expressive writing and post‐traumatic stress disorder: Effects on trauma symptoms, mood states, and cortisol reactivity. British Journal of Health Psychology, 13(1), 85-93. https://doi.org/10.1348/135910707X250866

Smyth, J. M., Stone, A. A., Hurewitz, A., & Kaell, A. (1999). Effects of writing about stressful experiences on symptom reduction in patients with asthma or rheumatoid arthritis: A randomized trial. JAMA, 281(14), 1304-1309. https://doi.org/10.1001/jama.281.14.1304

Spielberger, C. D. (1989). State-Trait Anxiety Inventory: Bibliography (2nd ed.). Palo Alto, CA: Consulting Psychologists Press. https://doi.org/10.1016/S0005-7967(98)00023-0

Tagge, E. P., Natali, E. L., Lima, E., Leek, D., Neece, C. L., & Randall, K. F. (2013). Psychoneuroimmunology and the pediatric surgeon. Seminars in pediatric surgery, 22(3), 144–148. https://doi.org/10.1053/j.sempedsurg.2013.05.002

Treynor, W., Gonzalez, R., & Nolen-Hoeksema, S. (2003). Rumination reconsidered: A psychometric analysis. Cognitive Therapy and Research, 27, 247-259. https://doi.org/10.1023/A:1023910315561

View Details

Tom Wooldridge, PsyD, ABPP, FIPA, CEDS-S

Part BThis article is Part B of the episode with Tom Wooldridge, PsyD. Find Part A here.