We will get started. This is your clinical updates. And because the topic is obsessive-compulsive spectrum, we're going to get started right on time. And so I'm going to make this really simple. There are three of us giving talks. And, oh, by the way, the slides will be available through the APA with the clinical updates. So you don't have to worry about taking pictures of the slides, etc. There'll be three talks in a row. We're going to start with Dr. Chris Pittenger from Yale University discussing OCD. Then Dr. Katherine Phillips from Cornell Medical Center is going to discuss body dysmorphic disorder. And then I, John Grant, from the University of Chicago, will discuss trichotillomania. And we'll do all three talks and then open it up for questions at the end that you can ask about any of the talks that you've heard. Does that make sense? It's 90 minutes. We'll get through it. It should be exciting. I'm glad you're all here. All right. Hi, I'm Chris Pittenger. I direct the OCD Research Program at Yale. And it's really a pleasure to be with you today. I want to thank John for coordinating this session. And it's always a pleasure to present together with Kathy. We get to do this from time to time. And it's fun every time. So I'm going to talk for 20 or 25 minutes about obsessive compulsive disorder, give some general background, a little bit of what we know about neurobiology, and a very little bit about what we know about genetics, and then get into treatments. 20 to 25 minutes is an absurdly short amount of time to cover this material, which could easily be a couple hours. And so it is going to be quick. It is going to be 30,000-foot view. And there will be time for questions at the end. I do have some disclosures. I consult for various companies, including some developing treatments in OCD. But I will not be discussing any of that work today. I will be discussing some off-label use of medications as we go through. All right. So my guess is that everyone in the room has a pretty good concept of what obsessive compulsive disorder, or OCD, is. But I did want to take just a couple minutes, or maybe 90 seconds at the beginning, to get us all onto the same page. So obsessive compulsive disorder is defined by the DSM as consisting of obsessions and or compulsions. You can get the diagnosis if you have only one or the other. But the vast majority of patients have both. And many people who come to us saying, I have only obsessions, once you clarify things and dig into their symptoms and give them some psychoeducation, it turns out that they really do have both. They're just misidentifying some of their compulsions, usually. So obsessions, as defined here, are intrusive, inflexible, stereotyped thoughts, images, or urges. Now, that's important. We think of them as thoughts, like I'm contaminated. But they can also be more visceral. They can be intrusive images. They can be visceral feelings of incompleteness. They don't have to be thoughts that can be readily put into words, although the majority of time they are. They're intrusive. Sometimes the word egodistonic is used, which means that they don't feel imposed from outside, the way a delusion of thought insertion might feel imposed from outside. But they do feel foreign or other, as if they're generated from the brain, but they're not part of the norm. They feel different from the normal train of thoughts. And there's sort of an interesting relationship to ownership, to whether they're really mine. That's what's meant by the term egodistonic. They're necessarily excessive or irrational. And they necessarily cause anxiety or some other form of distress. If they didn't, we wouldn't call them obsessions. We would just call them thoughts. And they're necessarily difficult to control. Otherwise, they wouldn't be of clinical significance. The compulsions are actions which are taken typically in response to the obsessions. And when I say action, they can be a manifest action, like washing your hands or checking the stove to just cite some sort of classic or stereotypical and yet common examples. But they can also be internal actions. They can be reciting a prayer, counting, reviewing your actions during the day. And that is how people will often misidentify compulsions and call them obsessions, because they're internal. But they're still compulsions. They're actions that are undertaken to try to reduce the anxiety or distress associated with the obsessions. And they're repeated. They're often stereotyped. They are necessarily excessive or irrational. Usually, the sufferer understands that they're excessive or irrational. Insight is usually quite good in OCD in contrast to BDD, which you'll hear about later. And then the relationship between obsessions and compulsions is quite important. So in the classic case, and this really describes the majority of cases, I would say, is described by this flow diagram I have up at the top. And there's one or two things I want to emphasize, and then we'll move on. So everyone gets intrusive cognitions. Everyone gets thoughts that come unbidden into the mind and are a little surprising. And some of these are distressing. Some of these are thoughts that do not align with how we think of ourselves or delusions of rationality. So everyone gets those. Like in survey studies, 90% of people say they get them. The other 10% are lying. And something like one person in four gets them in survey studies enough that they feel that they're kind of annoying and they wish they'd go away. And only 1% to 3% actually have OCD, but that's a question of degree. What happens in OCD isn't the existence of these thoughts, but rather the interpretation. I don't know if you can see my arrow. You can't. So maladaptive interpretation. It's hard at the angle. So it's the interpretation of those thoughts. When those thoughts, which are actually fairly common, are interpreted as powerful and important, as something that needs to be responded to, that's setting the stage for them to be obsessions. This causes anxiety or some other form of distress, which causes people to engage in compulsions, because if you knew something you could do that would make the anxiety go away, why wouldn't you do it? Which causes some relief. So far, so good. But the problem is that that relief reinforces the idea that those thoughts were powerful and important. Phew, good thing I took that seriously. Everything's fine now. And lo and behold, you're caught in a cycle. And the way I conceptualize OCD is as being caught in this cycle, in this feedback cycle. That was a lot of time on the first slide, but hopefully it gives us all sort of a level field to move on from here. So obsessions and compulsions can be almost anything. But a majority, something like 3 quarters, fall into three broad categories that I'm sure are familiar to all of you from clinical work. One is contamination, an intrusive, inappropriate, or excessive fear that one is contaminated, one is going to get sick, or interestingly, that one is going to be responsible for sickness or harm to others. It can take either form. And the typical compulsion would be hand washing, but it can also be reassurance seeking or some kind of symbolic activity to prevent contamination. That's about 30% of people with OCD have that as their primary symptom. About 40% or 45% have a fear of harm, fear of something dreadful happening. And this would be paired most classically with checking the windows, checking the stove to make sure that dreadful thing doesn't actually happen. Importantly, this can also be a fear that they are going to do something dreadful. Intrusive thoughts of violent acts, intrusive thoughts of blasphemous or inappropriate sexual acts that become the focus of the OCD. So it's not always, I'm going to get hurt. It's often, I'm going to be dangerous to others. And finally, a minority, but a significant minority, maybe 15% of people have as their primary obsession and need for symmetry or exactness, for things to be lined up just right. I have to say this picture bothers me quite a bit, but it's meant to cap, a need that I can't go on. I feel uncomfortable if things aren't lined up or quite right, okay? Couple points about why do we care? So OCD is surprisingly common. It remained, it was wildly underdiagnosed prior to DSM-3 in 1980. It remains significantly underdiagnosed. Part of this is because of the insight. People often know that their thoughts and behaviors are irrational, and yet they, and they have enough control to hide them from others because they don't want to be judged. And this can contribute to people hiding their symptoms. And the delay between first systems and diagnosis can be up to 10 or 15 years in some published data. I hope that that number has come down. It does affect about one person in 40 over the course of a lifetime, one person in 80 in any given year. Of the DSM-3 anxiety disorders back when OCD was lumped with the anxiety disorders, it was the one that was most likely to be severe. So if someone was diagnosed with OCD, they were most likely to have a severe impact on their function or, and suffering. So we don't, what do we know about the causes? This could be a very short slide. I could say we don't know, and that would be true. But we do know it's about 40% genetic. It's actually less genetic than many psychiatric disorders. It's less genetic than schizophrenia, autism, bipolar. A little more than major depressive disorder. So, but there is, it does run in families, and we see this all the time, where someone will have, will tell us about parents who have OCD. There's an interesting relationship to stress and trauma. Stress and trauma can certainly worsen OCD. It can trigger OCD. It can sculpt the nature of the symptoms. Whether there's a more specific causal relationship is an interesting question of active research. It's certainly not as tight and obvious a causal relationship as most obviously PTSD. But there is often an interaction between stressful or frankly traumatic experiences and OCD. And there's an interesting literature suggesting a relationship to neuroinflammatory conditions. This is most evident in PANDAS, which is a pediatric condition, which would be a whole different lecture. But there's some evidence that there may be a contribution of neuroinflammatory factors more broadly than just in that narrowly defined pediatric condition. And it remains unclear whether that's a nonspecific destabilizing effect. You get sick, things get worse. Or whether there's a more specific tie-in, and that's also an interesting area of ongoing research. Comorbidity, as all clinicians in the audience know, is the norm. Something like 10% of people with OCD have only OCD. This is from a study some years back, survey study measuring the comorbidity. The differences, the details don't particularly matter. But intuitively comorbidity with other neurotic conditions, so anxiety and depressive conditions is common. Addictive comorbidity is fairly common. Usually conceptualized, I conceptualize it as self-medication, and so it's usually with downers, with opiates or alcohol. But comorbidity is very common and always influences the approach to treatment. So what do we know about the brain in OCD? So OCD was, as far as I know, the first psychiatric disorder in which specific regional brain abnormalities were found in the very early days of functional brain imaging. This is the first study that I know of that did this. This is from Lou Baxter and colleagues at UCLA, published in 1987. And they did, this is a very early pet imaging study. My pet imaging colleagues today would be embarrassed to put this image up, but it's 20, it's 40 years old. Yeah, give him a break. So this is a brain perfusion imaging study. So this is measuring brain activity in an individual, horizontal slices through the brain, warm colors mean more activity, in a healthy controlled individual on the top row at three different levels, and someone with obsessive compulsive disorder on the bottom row. And you can see some things like the occipital cortex at the bottom of the brain images are brightly lit. People have their eyes open, their occipital, their visual cortex is active. But if you look at the top of the brain in the frontal cortex, as well as in some of the deep structures, you see significantly greater activity in OCD. And this is, I picked the, for historical reasons, the first study, but this has been shown multiple times that you have hyperactivity in the orbitofrontal cortex, the caudate and putamen, and the thalamus. The same thing is seen, so this is the first study. This is from Scott Rauch and colleagues at MGH a few years later. This is the first study that did the same kind of thing, but instead of comparing OCD to healthy controls, they took individuals with OCD, scanned them, and then made their symptoms worse to see within the same subject what happens. The way they made the symptoms work is they handed them a sweaty gym towel and set it with someone else's gym towel, which I think was rather effective. But anyway, when they do a within subject subtraction image to see what parts of the brain are more active, they see basically exactly the same circuit. They see the orbitofrontal cortex, the caudate, the putamen, and the thalamus. And these circuits, as most of you probably know, comprise the corticobasal ganglia circuitry. So this circuitry, this network of projections from the frontal cortex, basically the entire frontal cortex, to the caudate and putamen, which are shown in blue on this slide, through a network of deeper structures, the globus pallidus and the thalamus, and then back again to the cortex. So for heuristic purposes, it's just worth noting that this is a feedback loop, that we have the cortex projecting through the basal ganglia and deep structures, thalamus, and back to the cortex. There's more complexity here. There are positive and negative feedback loops that exist in balance. And there's nuance, which I'm not gonna get into, but it's heuristically interesting that this uncontrolled activity in this feedback loop between discrete structures in the brain and this uncontrolled feedback loop between psychological constructs that I illustrated at the beginning is, I find that interesting. I'm certainly not suggesting that intrusive thoughts correspond to the orbitofrontal cortex or anything, any one-to-one, simplistic one-to-one correspondence like that, but both at the biological level and at the psychological level, I conceptualize this as feedback gone bad. Now, in more recent work, this is work from my own group with my colleague Alan Antisevich using functional neuroimaging to look not just at the activity of the brain, but at how different brain structures are connected together. And I'm not gonna digress into the details, but I'll just say we've discovered some of the same things, but also some additional nuance, which is shown here. So these are now images through the brain, a coronal view this way, an axial view, the same as the images that you saw before, and then a sagittal view, showing the basal ganglia. And what you can see is that in the dorsal components of the basal ganglia, the caudate and putamen, we see increased connectivity with the rest of the brain. But in the ventral components, the nucleus accumbens, it's actually decreased. And I could go on at some length about why I think that is or what it means. The point that I want to make here is just that it's a little more complicated than just hyperactivity in the corticobasal ganglia circuitry. There appears to be differentiation between these different parts of the circuitry, and that's something we and others are working hard to understand better. So with that overview, I'm now going to jump to treatments, standard treatments, both psychotherapeutic and pharmacological. I'm not going to be able to go into great detail about the psychotherapeutic treatments, but I do want to emphasize that both are critically important. In fact, in studies, the effect sizes for cognitive behavioral therapy done intensively and with appropriate technique are larger than for pharmacotherapy. It's certainly easier to write someone a prescription for Prozac than to do CBT for OCD well, but the CBT absolutely has to be part of any treatment plan. At least it needs to be considered, and there needs to be a good reason not to do it if you're not doing it. So that's really important. The CBT, and also really important, is there are many wonderful CBT therapists who don't really know how to do exposure therapy for OCD. It is a specialized skill, and that's really important to recognize. And the goal of the CBT I conceptualize as trying to interrupt or break this feedback loop. What you do is you expose people to their intrusive thoughts, and you don't let them engage in their compulsions or avoidance or reassurance seeking or anything else that might mitigate the anxiety and distress. You just sit there with it. This is hard. It's really hard for the patient. It's also pretty hard for the therapist because we didn't get into this business to make people miserable, but that's exactly what you have to do. You let them sit there with it, and the anxiety peaks, and then there's the meta-anxiety that I'm worried that my anxiety is going to keep going up until my head explodes, but it doesn't. And then it gets better on its own. This is an unusual experience because when you're experiencing something unpleasant and you know how to make it go away, you make it go away. Sitting there with it until it gets better on its own is not, it's like putting your hand on a hot stove and leaving it there. It's not a normal thing to do. And yet, if you do it, the first thing is you get better at tolerating anxiety. That's no fun, but it can be useful. The second thing is the anxiety goes down through a process of habituation. But then the third thing through a process of associative learning is you take the fuel away from this feedback loop. And over time, that makes not only the people better able to deal with their obsessions and compulsions, but it actually makes both the frequency and the intensity of the obsessions and compulsions get better over time. So very effective, needs to be part of any training plan. There have been dozens of studies of this technique, which is called Exposure and Response Prevention or ERP. In OCD, this is from meta-analysis by Naomi Feinberg and her student, Tara Reed, a little bit ago. And many of you may be used to seeing these plots. Each line here is an individual study. The box is the effect found of that study. The line, the horizontal line, is the variance of the confidence interval. And the zero here would be the line of no effect. So studies that land on zero found no effect. Studies whose effect, whose confidence interval overlapped zero didn't find a statistically significant effect. Ones that separate from zero did. You put them all together meta-analytically and you get this red diamond at the bottom. And basically, it's not on zero. So you put it all together, the meta-analysis robustly shows that this works quite well. How about pharmacotherapy? So the first and second and really even third line pharmacotherapy for OCD is really very straightforward. We don't have that many tools. And that's tragic, but it makes our algorithm pretty easy. The first line pharmacotherapy for OCD is the SSRIs. There's robust evidence for all the SSRIs. The first four on the list here are FDA approved for OCD. Citalopram and S-citalopram are not. But good quality studies suggest they're exactly as effective. Meta-analysis suggests there's no global difference in efficacy across the different SSRIs. Luvox or fluvoxamine is often thought of as the go-to medicine for OCD, but that's for historical and marketing reasons. It isn't actually better for OCD. And I personally don't use it very much because it tends to have more side effects and more drug-drug interactions than most of the other SSRIs. My personal favorites are fluoxetine or Prozac and S-citalopram or Lexapro, simply because they tend to be better tolerated in the higher dose range, not because they're more effective. And I don't have stock in either company. But the SSRIs are the first-line treatment. And about 40% of people will respond to SSRI treatment. Not to remission, not as if their OCD had never been, but we'll get a clinically significant improvement. 40% is not a great number, but that's what we got. Typically if the first SSRI doesn't work, it's often rational to try a second SSRI. Even though they work, I've told you that they work about the same, but that's on average across studies. In individuals, someone may respond better to a second than a first. Now the odds of responding to the second are substantially lower if you have already failed the first. But it happens all the time and is probably worth doing because of the generally well-tolerated nature of the SSRIs relative to the other options. And then the next option is this drug, clomipramine. This is a tricyclic antidepressant. Of the tricyclics, it is the one by far that is most serotonergic. And it was the first drug to be shown to be helpful with OCD, actually by Tom Insull originally in the early 80s and others. And there's some evidence that it's more effective than the SSRIs. It's a little unclear in the meta-analyses if it is actually more effective or it's just because the patients were more treatment-naive because it was the first drug that was out. So it's not clear if it really has a larger effect size. But I have absolutely seen patients who didn't respond to the SSRIs and did respond to clomipramine. So it's an important thing to consider. It has more side effects than the SSRIs. It's dangerous in overdose. You have to monitor blood levels when you start to get to higher doses. So it's more complicated to use, which is why we typically don't use it as first line. But as a second or third line, it's an important option to keep in mind. Do these work? Yes, they do. So this is a meta-analysis from some years ago. There have been a couple more studies since then. And I realize this is very small and impossible to read. But if you just look at the effect at the bottom, the black diamond, in this case to the left, just because the way the table's laid out to the left means superior to placebo, you average all of these studies together, you get a very clear signal that SSRI treatment is superior to placebo. How long does it take? It's slow. So this is from a meta-analysis we did, led by my colleague Michael Block, looking at thousands, 3,500 or so patients with OCD who were treated with SSRIs versus placebo and looking for the effect over time. So the first thing you see is it's slow. And this is in all the textbooks. That OCD is slower to respond to depression, and a good trial is 12 weeks, and you shouldn't give up until at least six or eight if you've seen absolutely nothing, okay? I do want to point out the other thing, and this is the surprising thing that came out of the meta-analysis. It's not nothing for six weeks and then a response. It does look like the response begins immediately, averaging across patients, but accrues very gradually. And so it's important to do a trial of adequate length. The other thing that's important is do a trial of adequate dose. So for reasons that we don't understand well, higher doses work much better in OCD, to an extent that isn't true when the same drugs are used for depression. This is from another meta-analysis with Michael Block, where he took all available multi-dose SSRI trials, categorized SSRIs into low, medium, or high dose. So a low dose would be 10 or 20 of Prozac, a medium would be 30 or 40 of Prozac. High dose would be 60 to 80 of Prozac, and I go to 120 occasionally. So these are high doses. And then looked at the effect size, and what you can see is that the low and medium had a significant effect size, but the high doses clearly had more benefit. So two things to take from this. Higher doses above the PDR dose range, above the traditional dose range that we all learned in school, are appropriate and often effective. That's the first thing to recognize. However, we do get responses at the lower doses. So it's not the case that nothing happens until you get to 60 of Prozac, and of course everyone is different. I've had patients who've done well on 10 or 20, and I've had patients where nothing happened until 80. But on average, higher is better. I tend to go high pretty quickly if there aren't side effects or some other specific reason not to, because I want people to get better. I don't want to wait around. But it's not needed for every patient. Do side effects go up with higher doses? Of course they do. This is from the same study looking at side effects. So the side effects do go up with higher doses, but not as much. And if you look at the cost-benefit ratio, there is clearly a net benefit on average from going to higher doses. Interestingly, if we go back and look at the brain scanning, there's a robust literature suggesting that the treatment—this is actually for CBT and SSRIs and clomipramine—treatment mitigates the hyperactivity in this circuit. So the circuit's hyperactive in people who are sick. You treat them, the symptoms get better, the circuit calms down. And this is one of several pieces of evidence that makes us think that there really is a causal connection between this circuit-level hyperactivity that's been seen in neuroimaging studies and the clinical outcome. This is another meta-analysis done by Damian Denise and Wander Stratton and colleagues. These are all of the studies, and this diamond shows that specifically—they looked at the whole circuit—but specifically in the orbitofrontal cortex in this slide, you see a reduction in the orbitofrontal cortex hyperactivity with treatment, which is kind of cool. And there are studies looking at a correlation between the improvement, clinical improvement, and the OFC improvement that suggests that there's a direct relationship. What do we do when these standard treatments, both CBT and first-and-second-line pharmacotherapy fail? Unfortunately, this is a very common question. With CBT—I mean, some studies say that they get 90% response rate, but that's in ideal circumstances with selected patients who are fully engaged in treatment. In the real world, it's probably 50% or 60% good response to CBT, 50% or 60% good response to a couple rounds of thoughtfully titrated pharmacotherapy. So what do I do now is a really common question. So one thing you can do is you can do more intensive CBT. Clinical CBT is once or maybe twice a week for ideally 90 minutes, if you can get insurance to pay for it. But you can do IOP-level CBT, which is 12 hours a week. You can do residential-level CBT, which is like 40 to 60 hours a week. And there's a very clear dose-response relationship between the hours spent in exposures and clinical response. So that's one thing. Do more CBT. Another thing you can do is you can switch the SSRI. You can increase the dose of the SSRI, okay? If you tried—started with an SSRI, you can add CBT. If you started with CBT, you can add an SSRI. So these are all fairly obvious things that you can do. Then we have no other drugs that work as monotherapy for OCD, other than the SSRIs and clomipramine. So there isn't another class of drugs. The other antidepressants, insofar as they've been tested, don't work very well. With venlafaxine and duloxetine, the literature is small and mixed, so I won't say they are proven not to work, but there isn't good evidence to suggest that they work as well as the SSRIs, which is a little weird, but that's what the data show. And other things that have been tried, you know, remeron, buspar—buspar is mixed—bupropion, they don't work as well. The SSRIs are our go-to, man. But you can augment. You can add on a second drug to make the SSRIs work better. The very best evidence for that is with the neuroleptics. These are not FDA-approved, but both first- and second-generation neuroleptics typically used at rather low doses, which helps mitigate their otherwise problematic side effects, can give you improved response. This was first shown with haldol and risperidol by Chris McDougall and his colleagues who were then at Yale, but more recently has been shown with all of the second generations. The best evidence, just because it has the most studies, I think, is with aripiprazole. So I use risperidol and aripiprazole are the two that I tend to use. And again, the doses don't seem to need to be very high. I tend to use risperidol if someone has a tic disorder and aripiprazole if someone has mood instability. But there isn't good data behind that. That's just my practice. There is recent evidence for transcranial magnetic stimulation being helpful for OCD, but it's not the typical transcranial magnetic stimulation with the superficial stimulation of the dorsolateral prefrontal cortex that works for depression. It requires targeting of deeper structures, which requires a special hardware. So it's got to be the right coil done in the right way. And then in the most refractory cases, there are deep brain stimulation or surgical treatments are sometimes used at specialty centers, but that's in a small minority of patients when everything else has been tried. I'm going to skim over the meta-analysis of neuroleptic augmentation. There is interest in glutamate modulators as treatment for OCD. None of this is proven in good controlled studies. There are some studies out there for riluzole. There's some studies out there for memantine. There's some studies out there for N-acetylcysteine. We do use these things clinically after we've exhausted the well-proven standard of care because unfortunately a lot of patients don't benefit. And there have been some studies of other agents. But I am at the end of my time, so I'm going to wrap up. I want to acknowledge lots of colleagues who I've learned from over the years, as well as, of course, my patients who I've learned from even more, funding of my work and research. And I want to thank you all. I'm going to leave you with the really disturbing Fig Newton slide, and I look forward to questions and discussion at the end. Thank you. Great, so it's a wonderful pleasure to be here today and to have the opportunity to talk about body dysmorphic disorder, BDD, which is common, usually very impairing, associated with very high rates of suicidality. And as you'll hear, it has many similarities to OCD and some to trichotillomania, which you'll be hearing about next, but also some important differences. So my disclosures. So BDD is defined in DSM-5 as preoccupation with one or more perceived defects or flaws in physical appearance that are not observable or appear slight to others. So when your patient with BDD walks into your office, you cannot tell by looking at them what they are going to be so obsessed about, what they think is so ugly about how they look because they look normal to others. Criterion B, repetitive behaviors, much like OCD rituals, such as excessive mirror checking, compulsive grooming, compulsive skin picking, reassurance seeking, and sometimes compulsive repetitive mental acts, such as comparing their appearance with that of others. And the preoccupations drive these repetitive behaviors. For the diagnosis to be made, these preoccupations must cause clinically significant distress or impairment in functioning. And then if someone is concerned only that they are overweight or that parts of their body are too fat, when this is not the case, and they have a diagnosis of anorexia nervosa or bulimia nervosa, we would consider the weight or concerns with body fat to be a symptom of the eating disorder rather than BDD. And then once you've made the diagnosis, you ask if these specifiers apply. So muscle dysmorphia afflicts primarily boys and men who are preoccupied with having the inaccurate belief that they have small or insufficiently muscular body build. So they think they look like the arm on the right, but they really look normal or in some cases hugely muscular because about 20 to 40% of guys, usually with the muscle dysmorphia form of BDD, abuse anabolic steroids, potentially dangerous both medically and psychiatrically. And they are very good at building muscle. So this is a way, I think, an important way in which BDD is different from OCD. We also specify level of insight. And just to emphasize, if someone has absent insight, i.e. delusional beliefs, they're completely certain that they look ugly or abnormal, that is diagnosed as BDD, not as a psychotic disorder. So BDD is common, currently affecting close to 2 to close to 3% of the population. And you will see that it's pretty common in cosmetic treatment settings. That's a problem because cosmetic treatment is virtually never helpful for BDD and can make it worse. Another difference from OCD is the seeking of these kinds of treatments. About 60% of adults with BDD are female, about 80% of youth are female, and like OCD, the preoccupations and the rituals, which we also call compulsions or repetitive behaviors, are difficult to resist or control, and they're time-consuming. But then we see some important differences between BDD and OCD. BDD is much more likely to cause social anxiety and social avoidance, which makes sense because they think they look ugly, even though they don't, and they think other people agree with them, and that everyone can see how horrible their nose looks, for example. And so they get very anxious around others. Unlike OCD, insight is usually absent or poor. So prior to treatment, about 70% of people with BDD have poor or absent insight. They're mostly or completely certain that they look abnormal or ugly. In OCD, insight is usually good. And then ideas or delusions of reference are common. Thinking that other people take special notice of them in a negative way because of how they look. So mistakenly thinking other people are laughing at them or staring at them. The skin is the most common area of concern. It can be anything about the skin. It's too red, it's too white, wrinkles, perceived acne, perceived scarring. Hair is number two. It can be anything about the hair. It's too curly, too straight, uneven. Men are more likely to be preoccupied with going bald. And women are more likely to be obsessed with perceived excessive body or facial hair. Nose concerns usually involve size or shape. But BDD can affect any part of the body. On average, over the course of the illness, people are preoccupied with maybe five, six, seven different body areas. But sometimes it's just one thing. My chin looks horrible. You know, receding looks horrible. Or it can be any part of, every part of the body. And then we see the repetitive behaviors, criterion B of the definition. And about 90% of people with BDD try and hide what they think looks so awful. They may, you know, if they think their eyebrows look too bushy, they may have bangs down over their eyebrows. But the camouflaging behaviors can be repetitive. So for example, wearing a baseball cap pulled down to hide your supposedly ugly eyes, but you may be adjusting it to make sure your eyes are hidden. Reapplying makeup throughout the day. Comparing with others. Mirror checking. Checking other kinds of reflecting surfaces, rear view mirrors, windows, backs of spoons. Excessive grooming, like hairstyling or makeup application. Asking others, can you see this on my face? Do I look okay? Only 40% compulsively pick their skin. And this, like these other behaviors, can be, you know, it's hard to resist or control. And many patients use sharp implements to do this. Like staple removers, pins, needles, knives. And they actually can create actual noticeable skin lesions from doing this. They're not trying to. This is not intentional self mutilation. They're just trying to make their skin look better, but they can't stop. So these patients are an exception to the rule that people with BDD look normal and the flaws aren't visible to others. This behavior can be dangerous. I know of a patient who picked and picked at a pimple on her neck with tweezers and she dug so deeply that she exposed her carotid artery and needed emergency surgery. If she'd gone through the artery, she probably would not have survived. I also want to mention that skin picking in BDD is different from excoriation, parenthesis, skin picking disorder, and other obsessive compulsive and related disorder in DSM. Skin picking as a symptom of BDD is triggered by thoughts that there's something wrong with my skin and I have to fix it. Compulsive tanning, another potentially risky behavior because of the cancer risk. And this is done usually to darken skin that is thought to be too pale. But repetitive behaviors are not limited to these. Compulsive selfies, comparing one photo with another, et cetera. And these can be a clue to the presence of BDD. So functional impairment and quality of life span a range, but on average, these patients are quite impaired and their quality of life is usually very poor. So we found in one study, for example, that 39% of individuals with BDD had not worked for at least a week in the past month because of mental illness, and for most of them, BDD was the primary diagnosis. We see high rates of school dropout. They just think they're too ugly to be seen by anyone and the people are making fun of them or they're too obsessed or wrapped up in the BDD rituals. We see high rates of being housebound due to BDD, psychiatric hospitalization, and lifetime substance use disorders. In about half to two-thirds of those who abuse substances, the reason that the patients give is the BDD. That it's so distressing, they feel so socially anxious. So lots of self-medication. And then on standardized measures of quality of life and social functioning, we see very poor average scores and effect sizes that are very large compared to normative data. And the poorer, the more severe the BDD symptoms are, the more impaired the functioning and quality of life tend to be. What I really worry about as a clinician is the suicidality. We have high rates of suicidality in BDD and we have very little data on completed suicide. Just from one study. So the numbers that you see on the slide have a large confidence interval around them. But what we found is that suicide rates in those with BDD, deaths that were confirmed by death certificate to be suicides, compared to the suicide rate in the general population, but adjusted for age, geographic location, and gender, which gives us the SMR, the standardized mortality ratio, the rate of suicide was 22 times higher in individuals with BDD. We added in the probable suicides for whom we could not obtain a death certificate, 36 times higher rate of suicide in BDD than in the general population. To put these numbers in context, a meta-analysis found 20 for major depressive disorder, 15 for bipolar disorder. And a meta-analysis found significantly higher levels of suicidality than other psychiatric disorders, including OCD, eating disorders, anxiety disorders, with high risk for suicidal thoughts and behaviors. And then a more recent study from a partial hospital setting found higher odds of suicidal ideation and suicide attempts than for any other psychiatric disorder examined, including OCD, PTSD, unipolar depression, bipolar depression. And greater BDD severity is associated with higher risk for suicidality. So BDD is almost certainly a complex multifactorial disorder in terms of its etiology, but we know from twin studies that genes explain somewhere between 37 and 49% of the variants. And that there is shared genetic vulnerability with both OCD and trichotillomania, plus BDD-specific genes. And abnormalities in corticosteroidal circuitry have been found, just like OCD, as well as other brain connectivity abnormalities, as well as widespread compromised white matter integrity. And multiple deficits and biases in cognitive and emotional processing have been found, and an example is people with BDD tend to misinterpret neutral facial expressions as contemptuous or threatening, which I think really fits with the ideas and delusions of reference that are so common in this disorder. And then multiple studies show that people with BDD have perceptual visual processing abnormalities. They have increased visual processing of detail. So when they are in an fMRI scanner looking at images of faces or houses, we see hyperactivity in parts of the brain that are specialized to see detail. So their brains are trying to pull detail out of what they are seeing. And at the same time, we see abnormally reduced neural activity and connectivity in visual areas that are specialized for what's called global holistic visual processing. Seeing the big picture. So the details of what they are looking at become prominent and overtake what they see, and it's difficult for them to contextualize the details. And really, they're just tiny. So I think this explains probably the poor insight, poor and absent insight, that's typical of BDD, because they're actually seeing themselves differently than other people see them. My colleagues and I recently found that we could enhance global holistic visual processing on a computerized, by training on a computerized task. And Jamie Fusner's group found that they could enhance global holistic visual processing by using ITVS, which is a form of TMS. So these are very preliminary data, recent data, but may pave the way for new treatments. Environmental factors. Twin studies have shown different environmental risk factors for BDD versus OCD and versus TRIC. Studies have shown increased teasing and bullying compared to people without BDD. Higher rates of perceived childhood neglect and abuse compared to healthy controls and compared to OCD. Low perceived parental warmth. Sociocultural pressures almost certainly play a role as a risk factor for BDD. Social media, I wish we had an answer. We don't. We don't have good studies. But I think as a clinician, it makes sense that using certain forms of image-centric social media could be a risk factor for developing BDD. And then you see various findings for temperament, personality, although causality is unclear. So just like OCD, SRIs are a first-line medication for both non-delusional and delusional BDD. SRI monotherapy. We have fewer studies than in OCD, by the way, but fluoxetine has been shown to be more efficacious than placebo. SRI clomipramine more efficacious than the non-SRI antidepressant dizipramine, again, just like OCD. And in a placebo-controlled relapse prevention trial, we found that responders to 14 weeks of open-label escitalopram who continued the escitalopram for six more months were less likely to relapse than those who were switched over to placebo. And then some prior open-label trials showed high response rates with these various SSRIs. Now we don't know what the next best step is, actually, I first want to mention this. So my own approach is to try to reach these SSRI doses within about five to ten weeks if tolerated and if a lower dose isn't starting to help. Certainly if a lower dose is starting to help, you can keep it there longer and see if symptoms improve with more time. But a lot of patients will need the doses you see here. The tricyclic clomipramine is guided by blood levels. And with younger youth and elderly, I usually start with a lower dose and raise it more slowly and may not reach as high a dose. And then like OCD, we want a total trial duration of at least 12 weeks before determining whether the medication is helpful. I usually keep people on one of the above doses for at least, you know, four weeks, four of those 12 weeks. And often this approach works. If it doesn't, it's unclear what the next best step is. What I usually do is to increase the SSRI further. I find this is usually well tolerated. And you see in the brackets, in the middle column in the brackets, the FDA maximum doses for these medications. And then you also see the maximum doses used for BDD and OCD. The 120 of Prozac, 400 of Sertraline, et cetera, are in the APA practice guideline for OCD. And in a recently published international paper on pharmacotherapy of BDD. As you look down that column, we don't exceed 250 for clomipramine. It has a low therapeutic index. And I don't exceed 40 for citalopram. That's a revised FDA maximum. And in my mind, it's firmer than the other SSRI maximums because of the potential pro-arrhythmic effect. I don't use it anymore for that reason. And you see my more or less order of preference for the SSRIs. But they probably all work equally well for BDD. We don't have the kind of nice dose finding studies that we have in OCD where people are randomized to different doses of a particular SSRI. The only data I know of comes from my clinical practice. So you will see that over on the right-hand side. I suggest not exceeding the FDA maximum dose with preteens and get EKGs with Lexapro more than 30 a day, always with clomipramine, and consider with high doses of other SSRIs. We have a little augmentation data, SRI augmentation, not as much as OCD. I did a pimicide versus placebo augmentation of a good trial of fluoxetine. Very negative trial, different from OCD, actually. Pimicide is now contraindicated in combination with SSRIs. Not at the time I did the study, but because of the potential pro-arrhythmic effect. Chart review studies show equivocal results, but expert consensus suggests efficacy for adding an atypical, maybe perhaps aripiprazole to the SSRI if needed. And sometimes I will add an atypical before I've done an adequate SRI trial. If the patient is very severely depressed, if they have very worrisome levels of suicidality, for example. We have a little bit of data for BuSpar with reasonable response rates, large effect size. It's usually very well tolerated. We sometimes will add clomipramine plus an SSRI. This is a little trickier because the SSRIs can kind of unpredictably increase the clomipramine levels, which has a low therapeutic index, so you have to check clomipramine levels along the way. We have no data on glutamate modulators, but in my clinical experience, they can be helpful when added to an SRI for, not only for BDD, but sometimes for mood, and they're usually very well tolerated. You can always switch, you know, like OCD, we're kind of limited to SSRIs as our first line treatment, so if one SSRI doesn't work, a good trial, switch to another, and if several haven't helped, we try the SRI clomipramine. There are small positive open-label trials for venlafaxine and levotiracetam, and then you see some unstudied serotonergic options that may work, but we don't know for sure. CBT, our psychosocial treatment of choice, it does need to be tailored to BDD's unique symptoms, and efficacy of CBT has been shown in a whole variety of studies, and we recently published a paper showing that at least six months of weekly CBT is usually needed, and sometimes more. So we set the foundation for treatment. People with BDD need a lot of psychoeducation, because a lot of them want to go and get a rhinoplasty instead of seeing you, right? So it takes a lot of psycho-ed, we set valued goals, you may need MI early in treatment, and then we always do cognitive restructuring in BDD. Very standard. We help them identify cognitive errors in their BDD thoughts, and develop more rational and helpful thoughts. So an example might be, oh, I can't go to the party tonight, everyone's going to think I look like a freak because my skin is so red. Well, a lot of cognitive errors in that, right? Fortune-telling, catastrophizing, mind-reading, labeling, all-or-nothing thinking. So we help them develop more rational ways of thinking. We do exposures, more slowly than in OCD, and we always include behavioral experiments. So they collect evidence while they're out doing their exposures, and the exposures are usually to social situations. Ritual prevention is critically important. The rituals like the mirror checking are toxic behaviors that keep the BDD going. So we help them try to cut back. We do perceptual retraining. We try and enhance their ability to see the big picture, their global holistic visual processing which seems to be reduced and underutilized in people with BDD. And eye tracking studies show that when people with BDD look at themselves in the mirror, they zero in on what they don't like and don't really even see the rest of them, including areas they might like. So we do a very short, about five minute exercise each day with a full length mirror where they just briefly describe themselves from head to toe without paying any more attention to disliked areas than other areas. Neutral, not negative language. And we also, and again, it's not staring in the mirror. Staring in the mirror is a ritual we want to stop. This is just helping them briefly see all of them. We also use advanced cognitive strategies for self esteem and negative core beliefs like I'm unlovable, I'll always be alone. Writing, filling out forms is so important when learning CBT and homework is critically important to learn the skills. And then sometimes we use habit reversal training for those who pick their skin or pull their hair as a symptom of BDD. Some pull out their hair because they think this one's ugly or my eyebrows are uneven or I have too much facial hair. And behavioral activation for more severe depression. So there are two published evidence-based CBT manuals for therapists to use when treating BDD. There are many studies that have directly compared BDD and OCD and over you can see a list of similarities, most of which I've discussed today, as well as some important differences. The poorer insight in BDD, more comorbid major depressive disorder and substance use disorders, more suicidality. And the CBT is different. We always do cognitive work. The perceptual retraining, you may need to focus on a desire for cosmetic treatment, which we don't want them to get. We do have a reversal training if they're picking their skin or pulling their hair. I think there's a greater need for MI and the treatment is longer. BDD versus trichotillomania, you see some similarities as well as some differences. In BDD, the hair pulling is triggered by thoughts that the hair looks ugly. And we use the habit reversal training, which is trichotillomania treatment, only if the patient is pulling their hair or picking their skin, but you also need the other CBT components that I described. And then we have different first line medications. So in summary, BDD is common, but often under-recognized. Suicidality rates are very high and psychosocial function and quality of life are typically very poor. BDD is similar to, but also different from, other obsessive compulsive spectrum disorders and you wanna treat it as a distinct disorder. SRIs, often high doses, are the first line medication for both non-delusional and delusional BDD. So like OCD, but different from trichotillomania. And CBT tailored to BDD is the first line psychosocial treatment, but there are important differences in the CBT for BDD versus the CBT for OCD or trichotillomania. So thank you very much. Thank you. Thank you for sticking around. I'm now going to talk about perhaps the sort of lesser known or unwanted stepchild of the O.C. spectrum world, trichotillomania, which, as I'll mention, I think deserves a lot more attention both in terms of research and treatment that it deserves, as I'll make a case for too, and discuss how it's quite unique from the other O.C. disorders within the category of the spectrum. This is my disclosure information. I should highlight I would love to have a conflict of interest. That is about trichotillomania, so anybody out there who's in pharma, listen, because we don't have an FDA-approved drug for trichotillomania. We don't have any pharmaceutical interest in trichotillomania, and so this is my sort of wake-up call to people that I would love to say I'm conflicted up the yin-yang, ultimately. François Halepot, the father of trichotillomania, who described it in the 19th century to describe hair-pulling frenzy, and he described this, interestingly enough, in an adult male, and I think that's really important because, as I'll mention, this is one of the few disorders in psychiatry that arguably is really heavily female, and in animal models of hair-pulling, it's also heavily female, which is really, I think, really important, and it screams for understanding even hormonal genesis of this, as I'll mention in a bit, but it actually goes back further than Halepot. Hippocrates was trying to educate young doctors, and he said you should always ask your patients if they pick at their skin or pull their hair. There you go, DSM-BC, whatever, right? And yet, how long did it take? I mean, it took until DSM-5 to put skin-picking in, and trichotillomania is still somewhat ignored. These are the diagnostic criteria for trichotillomania. It's actually a fairly easy diagnosis to make if people ask the patient. I was chatting with a young girl about 15, and she said, my parents have taken me all over to dermatologists. They wondered why I had alopecia spots, and she said nobody asked me. She said I would have said I pull my hair. I mean, so I think even for parents, they're often baffled by why they may see their young daughters, particularly with alopecia or no eyebrows or thinning eyebrows, and they'll think to go to general doctors or dermatologists, but, you know, just asking the person what they're doing, and most of the time, but not always, people are at least aware enough about their pulling. So the lifetime prevalence, about 1.7%, which puts it on par with OCD, BDD, et cetera, right? So it's not this sort of unknown disorder, but as you'll see, most people, untreated duration is 20 years. So these people start pulling in adolescence at around puberty or shortly after puberty, right? So again, kind of screaming for a better understanding of what's going on at that developmental period, but it takes 20 years before they come in, and they'll often describe it as I felt that I just had a bad behavior, that I should be able to stop this, so why would I ask a mental health professional or even go to my primary doctor for help? It sort of just reflects my problem of sort of doing a bad thing. So, and as you see here, heavily female, probably four to one in terms of female ratio, although some other studies maybe suggest that boys and men with it may hide it better, because if they're pulling their beard hair and they start shaving, they do it, or even male pattern baldness may be an excuse, and so we may not be picking up a lot of men who have this problem. It can, however, be seen in children. It's been documented as young as 12 months, and you will see these little kids who are pulling quite a bit. Some of them tend to sort of age out of it. It tends to get better with time, although when it's significant, it can lead to a large amount of bullying and social isolation, even in grade school, and so I wouldn't wait to sort of see if the person ages out. It should be treated when even a child is doing it, but that may happen. Some of the correlates, so it can be focused or automatic or both, and that can fluctuate with people, and this sort of gets to the idea of its connection to OCD. Many people don't describe their pulling as being driven by a lot of thoughts. Oh, I was studying and I just keep pulling while I study. I do it sort of automatically. Now, whether when they started pulling, it may have been driven by a thought, but quickly in many cases becomes quite habitual, so it might be a kinky hair, an odd hair. I was playing with it. That feels kind of wrong, and therefore it has some parallel to OCD in that respect, but often then when it takes off, people will describe it as, I'm not even aware of it, unless my parents hit my hand when I'm sitting watching TV. I'm just pulling, and then there's a pile of hair on the floor or something, so it seems as if it's much more almost compulsive without obsessions in some way, kind of the sort of flip side of OCD for people, and some people find it quite rewarding, and this is a quality that many folks are kind of embarrassed to talk about, in all honesty, because it makes them feel like I'm really harming myself, and it doesn't have a correlation to self-injury, but that they're doing something that's causing problems, but they're enjoying it, and that may be the reward that people get when they get a good hair, and it feels a certain way, they get a good sort of follicle on it, it's kind of squishy, they might have some rituals around it, they bite it, it feels nice, it's sort of like, and if you kind of don't get that, which a lot of your faces would suggest you don't, you know, it's sort of the same way that when people, I mean, we all do some of this stuff, right? I mean, everybody pulls a weird hair, you all pick at something, I've been watching half of you, and we bite our nails and things, and there is something like, even if I'm bleeding, I'm going to get that weird little thing off my fingernail, because, and you know, that might have an OCD quality to it, I want smoothness, I want a certain feel when I pull my hair, so I'll keep pulling until I get that feeling, but it can also be quite rewarding, and many people will describe their hair pulling as an addiction. They'll say, I feel addicted to this, meaning it's rewarding, but it's causing me problems, I mean, it kind of parallels what many people who come in with drug or alcohol problems often say, why can't I stop, but I kind of don't want to stop, but I kind of, right? A fair amount of ambivalence about it, too. And this has led, you know, many of us to think maybe, you know, even though we tend to think in disorders, maybe within the group of people who have trichotillomania, it could be better conceptualized differently for different people, meaning some people, it might be very obsessive-compulsive, I get rid of kinky hairs, I need to get a certain feel, et cetera. For other people, it could be kind of an addictive disorder, you know, that it feels rewarding, even though it's negative. Maybe for some people, it's almost like a tick, you know, sort of just a motor, I'm not even aware, I just do it, and it happens. Or maybe it's its own unique category. And so I just suggest that maybe ten people with trichotillomania, there might be three or four different driving forces, which is some of what the therapy gets at, but it might also sort of necessitate different, uniquely different treatment approaches pharmacologically, given how people clinically present their behavior. Does that make sense? And so this may be also why for big pharma out there, if any of you are there, that it may defy an easy medication for trichotillomania. It might be that there might need to be a couple that we have always sort of in our back pocket to help folks. The comorbidity also, you would think, well, maybe this is all about sort of OCD, and people have a lot of OCD in their family. Well, they do, but they also have a lot of impulsive problems. As their comorbidity, they might come in with compulsive internet use, compulsive sexual behavior, compulsive buying, all these kind of rewarding behaviors. Actually, OCD, according to some of our recent research, is maybe not the most common comorbid problem. And then they will often have, with hair pulling, other sort of body-focused repetitive behaviors, such as skin picking and nail biting, lip biting, something like that. The relationship to OCD is still kind of complicated, and so why do we even talk about this? Most people who have trich, if they're going to see a psychiatrist, often will end up seeing somebody who specializes in OCD. And OCD has sort of been a home for folks with trich, because many other people in psychiatry don't see much of it and haven't known what to do with it. But again, it might be quite different. In fact, they're much more impulsive than people with OCD. When we've looked at, this is sort of hard to see from a distance, but this is a cognitive task that we do on folks with trichotillomania, and compare them to all other mental health disorders. And you just see here, the highest red bar are people with trichotillomania, much higher than other mental health disorders, including substance use, at least on one task of checking to see how well they stop themselves once they start doing something. It's kind of the potato chip test. Can you stop and say no? And this is what we see in folks who struggle with addictions, that they often, they can't stop the behavior. But we see that same cognitive predisposition to impulsivity. In terms of family history, what we see is a range of things. And OCD, again, not the most common in these families, when everything is said and done. Depression, and as I'll highlight here, substance use and alcohol use are actually much higher than OCD in the families, although OCD is higher than in the population at large. So what do we do with all this information? And I think, you know, it's very interesting. We can know so much about some disorders, and yet then after we, you know, when people come and want to be helped, then we sort of, it's a little lackluster, unfortunately. You know, we sometimes have a couple options, and if those don't work, we start scrambling for things. And as I'll show, the evidence base for treatment for trichotillomania is woefully small. And, but here's the thing, the people that you will see if they come in for trichotillomania will know it all. These are some of the most amazingly well-educated patients you will ever run into. Just as an aside, I gave a lecture one time to a group of young kids who had trichotillomania, and I was talking about the brain in trichotillomania, and halfway through it, this 12-year-old said to me, she said, why didn't you bring up the O'Sullivan study from 1994? You know, I quickly said, oh, that was not very good. You know, but I thought, I thought, damn it, I don't know the O'Sullivan, whatever. You know, so it was really quite, so people, and what people tell me is that they've had to educate themselves because their primary doctors don't know, their psychologists and psychiatrists, unfortunately, they don't feel often that they run into people who are really well-educated about trichotillomania. So what do we have? On the therapy side, we have habit reversal therapy, as Dr. Phillips mentioned. This has sort of been tried and true to some degree for about 40-plus years or so, 50 years. It's using certain elements of competing responses, keeping people's hands busy when they want to pull so that they can't, changing the environment if they pull in their bedroom, when they do their homework to move them into the living room, etc. It's sort of basic behavioral interventions that make sense and that people, unfortunately, have often tried by the time they walk in the door. But it does have evidence. The one drawback, as Dr. Pittensher mentioned, it's often hard to find people well-trained in ERP for OCD. It's very hard to find people well-trained in habit reversal for trichotillomania, particularly outside of big urban areas. And so, you know, that's one of the drawbacks about the therapy. Also the evidence base for the therapy is very small. It's often compared to wait lists in a few small studies. So we don't have a lot. So I would argue that if people have creative means of helping people from a behavior therapy standpoint, and it's working, write it up and put it out there someplace because we need to know about some other options. And these have been modified. I mean, there are lots of versions of HRT and other therapies that have less data from a behavioral acceptance supportive therapy. And these have also shown some benefit, although there's a fairly high placebo response, placebo even in therapy with people with trich, often because at first, because they may be getting a lot of support for the first time, it may be the first time their illness is being taken seriously. And people can kind of ride that wave for a period of time. And then we sort of see some of the benefit reduced after about three or four months. These are all of the treatment studies for pharmacotherapy in the last 60 years or so, right? So, and you see here, woefully small numbers, no funding. All of us who do this research do it really trying to find pennies in the seat cushions, you know, to sort of weave it together. But you'll see a few things. One, clomipramine showed in a very early study by NIMH, you know, that it was more helpful than the zipramine in the treatment of hair pulling. And that was encouraging because it also sort of almost made everybody think, oh, it's OCD then, right? This is going to be another OCD problem. The SSRI trials have not been successful for trichotillomania. Everyone that I've treated with trichotillomania, if they've gone to see a doctor before me, has been put on an SSRI. They all come in on them, and they all say, why am I on this SSRI? Or that the SSRI helped for maybe four to eight weeks, and then it wore off. And my take on it for many people is that it's helping with the anxiety piece, which may worsen hair pulling, but not directly with the hair pulling itself. But we do have some other options. The good folks in Canada did a lovely study. Thank you, Michael. Many years ago, looking at olanzapine in the treatment of trichotillomania and found some benefit. You'll see here, not remission of pulling, but significant reduction on a scale, a self-report scale of hair pulling. And it was not used as an augmentation like you would if you were using it for OCD. And acetylcysteine, we've published studies looking at it both for hair pulling and skin picking as a related disorder. It's an amino acid. It's very well tolerated with a little bit of GI, you know, queasiness for a couple days. It's over-the-counter antioxidant. The problem is there's no quality control when it comes to all natural options. And so there are a gazillion brands out there, and I don't know how good any of them are or if, right? I mean, there's a lot of just uncontrolled quality. Some, there was a small study in children that showed it wasn't really more helpful than placebo. And we could talk forever about maybe some of the differences between kids with polling and by the time they become adults. And this is the study showing it was able to reduce the polling symptoms. If not, again, it didn't lead to remission, but it led to significant reduction. And then a recent study that we published last year is looking at memantine, a glutamate agent, which has a lot of, as Dr. Pittenger mentioned, a lot of theories about glutamate's role in OCD. We thought, could we use memantine as a standalone agent? Again, not as an augmentation as one might do for OCD. 10 to 20 milligrams. And it was able to reduce picking and polling in a substantial number of people compared to the placebo. I will say that we went to 20 milligrams. In my clinical practice, I use 30 milligrams if I'm getting any response. And it's quite an effective medication, I think, without really much side effects, except for a little dizziness that may happen when people start it. And I just wanna mention, you know, because I know the time is running out here. I wanna mention something about, a little bit about how that kind of heterogeneity might be useful. So there was a study by Gary Christensen back in the early 90s looking at naltrexone for hair pulling, an FDA medication for alcoholism, right? I mean, you think, what the heck is going on there? And he actually found some slight benefit. Never published it. We later did a bigger study against placebo, and it didn't separate out from placebo. But in those people who had, and that's just showing you it didn't work, but in those people who had a strong family history in first degree relatives of alcohol dependence, alcohol use disorder, they responded really quite robustly to naltrexone for their pulling. So Susan Johnson comes in and she's like, no, nobody in my family has TRIC, but everybody in my family has a problem with alcohol. Okay, naltrexone may be a useful option. Somewhat like the hair pulling is their version of whatever familial, heritable kind of reward thing might be running in the family. So this is where I think sort of being able to sort of be a sort of beyond, almost without an FDA drug for hair pulling, it allows us to really understand the complexity of this and not necessarily buy into just one approach only. And it's really based on all of that clinical information that we get from people. So that's kind of it. And now there's a monitor up here to field questions. Thank you. Thank you. So one of us needs to get to the right. Do you wanna take the, which? Go ahead. Okay. Thank you very much. And we are going to be taking alternating questions from the microphone. And also we have a remote audience who are sending questions in. And please, and if your question's gonna start with, I have a patient who, please don't, but generalize the question. Go ahead. Michael Hanow, lately of Walden Behavioral Care. This has been such a treat, such a tour de force, and to see three of my heroes give these talks and pass on this wisdom. I very much appreciate the transdiagnostic approach and thinking about phenomenology. So I have so many questions. I'll narrow it down to one. So lately I'm treating folks with eating disorder, with anorexia. And I've been thinking about in folks with comorbidity between eating disorder and OCD. Is the OCD informing the eating disorder? Is it the other way around? Are they comorbidities? So my question is, do you have experience thinking about anorexia as a facet of or a manifestation of an occult primary OCD? And how does that inform your conception and treatment of the patient? Thank you for that. Thank you for that question. These cases can become very complicated. Oh, is that microphone not on? Why don't you speak from here? Thank you for the question. You've highlighted a really challenging clinical presentation that unfortunately is not rare. There's increasing evidence that anorexia is very similar to OCD in many ways. Obviously we see that phenomenologically, but also the genetics are starting to look similar and there's some more biological evidence. So I think that there's a deep relationship there. Some of the rigidity of thought and the need for control that you see in anorexia, you often see in OCD. So I do think there's a relationship. In terms of treatment, it's very hard to generalize. It's an individualized decision. Obviously, if the anorexia is very severe, if it's medically dangerous, then that has to be addressed first, not only for medical safety, but also because malnutrition can lead to cognitive rigidity and make it more difficult to improve or to respond to therapy. So in the extreme cases, the anorexia needs to be addressed first. But in cases where there isn't that degree of medical instability, it's a very individualized thing. And I think it's an error to do first just one and then the other, because they're likely to be reinforcing one another in a dynamic way. So it is important to conceptualize the case. So you really are thinking about both and the interaction between them. I don't have a clean algorithmic answer. It's challenging. And question now from our remote audience. Sorry. There's a question of any specific thoughts in the treatment recommendations for excoriation disorder, or can we apply what we know from trichotillomania to excoriation disorder as well? So I think in general, most of the information from trichotillomania can be applied to excoriation disorder, with the exception that if people are picking to improve their skin, as Dr. Phillips mentioned, that it's more likely to be a phenomenon of the BDD, which then you would try high-dose SSRIs and CBT slash exposure therapy. So to kind of understand that in detail when somebody comes in excoriated, to know why they're doing it. Again, in furtherance of appearance, or sort of more out of a more habitual sort of drive that isn't really driven by those obsessive thoughts of feeling ugly or disfigured, so. If I can add a comment about trichotillomania, people should know about trichotillomania by proxy. I have had a few cases. Yes, it's not all that common, but it does happen. And I think the important thing about trichotillomania by proxy is mothers who have trichotillomania will start pulling their children's hair sometimes. The important thing about that is that the mother almost always feels so terrible. I mean, I can't even describe the amount of distress that the mother has. She feels that she is abusing her child. And so it just needs to be, one, education around all of this, and then to work with the family on a behavioral plan to keep the child from the mother's grasp. But because it's not talked about a lot in the literature, the mother will feel like she's so abusive. And in some ways, it does sound that way. I'm not diminishing the effects on the child, but it clearly is much more complicated, so. And I've had patients who do that with their dogs, and little girls with their dolls, and some adults with their boyfriends and girlfriends. Okay, next. Thank you. I treat mainly patients with schizophrenia, and it's not uncommon for some to develop OCD symptoms, it seems, spontaneously. So I'm just wondering, would I treat them for OCD as though they didn't have schizophrenia, or differently? And for those patients that fit that profile, what success do you have in treating their OCD symptoms? Thank you. Thank you. Yeah, this is complicated, and the literature is very sparse, because people with psychosis tend to be excluded from OCD studies, and most studies in psychosis aren't paying much attention to the OCD if it's there. There is an interesting thing. It's very clear that Clauseril can induce or worsen OCD symptoms. It's a very robust case literature on this. I've seen multiple cases, I'm sure others here have as well. It's a little less clear if the other atypicals can. It's thought to be because of their effects on serotonin 2A receptors, so maybe the other atypicals do. It's a little less clear, but Clauseril absolutely can. It's also the case that OCD can be a prodrome, or what is diagnosed as OCD can be a prodrome for schizophrenia, so some fraction of individuals with OCD in adolescence will end up developing schizophrenia. But coming back to your question, how do we address this clinically? There isn't a literature. What I do is treat it the same way that we would otherwise. Obviously, whether an individual patient can engage in the CBT is gonna depend on their particular strengths and weaknesses and their level of motivation, and so that's an individualized decision. In terms of the pharmacotherapy, I treat with the SSRIs, and I'll even push to high-ish doses in the presence of a neuroleptic. So typically, neuroleptic first, get them stabilized, and the same is true of bipolar. You wanna get the mood stabilized first before playing around with an SSRI. So in the absence of more robust literature, that's what I do with mixed success. They're difficult cases. So there's an ask for dosing instructions for NAC. So when we use NAC for trichotillomania and skin picking, 600 milligrams twice a day, I start people on to get them used to it, because again, of the possible GI issues, and the studies, although the studies went up to 1,200 twice a day, I now push that even a bit further, up to 1,800 twice a day. There doesn't seem to be any extra benefit in my experience going further than that, and it's generally well-tolerated, and even has, in some people, a bit of an anxiolytic effect, too, so. Yes. Hi, thank you for these great talks and questions. Since COVID, I have seen some very disturbing things that I'm gonna characterize broadly and see what you have to say about it, if you would. Okay, so I get a lot of very sick patients in my practice, and since COVID, either a parent, a spouse, a parent, you know, or a child will call up about a patient who doesn't think they're ill, who has like three or four things going on at once, like a BMI of less than 19 with an anorexia, OCD that's really very bad, and then like a picking situation. And so, you know, in my case, the first thing that I have thought of is like, oh, you've gotta get that, you've gotta address that eating disorder first. And then after like two years, I mean, they kind of plateau and they start to plummet again on big doses of SSRI and some of these other things that you guys have like totally gone through. And I'm trying to codify things differently where, you know, you're looking at all these things at once, and even if somebody's got a low BMI, like, is that the first thing that you would go after? Or what is your thinking about like panning back and trying to figure out which one to do first? Oh, and by the way, the patient doesn't think they have a problem. Yeah, no, the challenging case. And then when it's in the context of COVID, you know, is this an infectious thing? Is it a stress thing? Is it a psychological response to isolation? I mean, we're all struggling with these diagnostic challenges. With your specific question about the BMI, I would address the eating disorder first at a BMI of like 14 or 15. Then you've gotta, you know, when you're getting to the point of both medical concern and concerns about its effect on cognition and rigidity of thought, that's when I would almost always address first. At a BMI of 19. That was the highest one. Yeah, it'd be at 18 or 19. No, I don't think it's necessarily the case that that has to be prioritized. That's gonna be individualized. One thought that comes to my mind, but this is entirely speculative, there is an uptake in PANDAS or PANS, because it's not streptococcal, so PANS in the context of OCD, and we don't know how to identify the possible neuroinflammatory contributors to these complex presentations in adults, right? PANS and PANDAS are defined in kids, and we have some idea of how to characterize them. We really don't know how to characterize that in adults. I bet it's happening. So I think, and whether that's a worsening of something that was there before, or truly a triggering of a new process, I don't think we know. But that's one thing that occurs to me in hearing the story. Do you see any, like, with that question, are there any bumps, or are there any clues with, like, vaccines? Do things get worse after post-vaccine? I don't know of any data suggesting that, no. Thank you. Yeah. Thank you. So one of the questions is about aripiprazole, because one of the side effects of it is compulsive behavior. So how is it, then, a medication that you can use for OCD? Yeah, so this is, as I said, particularly clear with Clozarel, that it can cause obsessive behavior and frank OCD. This may be true of other neuroleptics as well. And yes, I have some cases with aripiprazole. I would never use aripiprazole monotherapy in someone with OCD, but only in augmentation of an SSRI. And that tends to mitigate that difficulty, although I can't say it eliminates it in cases. Could arise where it makes things worse. But broadly, on average in studies, it's a benefit at low doses in augmentation. As far as I know, aripiprazole's never been studied as monotherapy for OCD, but other first and second generation neuroleptics, including Clozarel, have, and they are not effective. So these do not appear to be effective as monotherapy. It's only as augmentation. So that's the difference. If I can ask a follow-up question about that. I was under the impression that there's an assumption that the compulsive behavior with Abilify comes from the mixed effect on dopaminergic receptors, similar to what happens when you give a dopamine agonist to somebody with Parkinson's, particularly since the compulsions seem to be similar, gambling, sexual. Yeah, that may be. I can't speak to whether they're the same. I mean, certainly that can happen, that you get something that's a little bit more like a primopexal effect, absolutely. I believe that I have seen cases where you can also get something that really looks more like OCD. So I think that, and maybe that's because the serotonergic effects rather than the protoplaminergic effects. But that's speculative, I don't know. Yes. Hello, thank you very much for your presentations. I come from abroad. I come from Greece. I'm a second year psychiatry resident there. And I had the opportunity to work in two different places. In the first place, I was working in an adult unit, outpatient adult unit, and we would subscribe to Horizon Medicine to patients suffering from OCD and related disorders. And I had the opportunity of working in a sub-internship in a behavioral therapy unit, where we would do behavioral interventions. And I was trained under supervision of treating people with behavioral interventions, suffering from OCD, trichotillomania, and related disorders. So this is not a formal research work, of course. It's just an observation, and I'm stating it here. So what I observed was that patients without ERP and without behavioral interventions, but by taking SSRIs, it would take them longer for the symptoms to relieve. And I noticed something else, that they would keep on doing their habits and rituals, but without the regret and without the dysphoric feeling that people with no medication would get. So this is just an observation, I'm stating. And my question is that, is there a treatment without the self-efficacy that people gain for ERP of confronting their fear, part of their treatment of their therapy? Can we treat OCD and related disorders without ERP and without these tools that we give to patients? That's it. Thank you for the comment. I mentioned that in studies, the effect sizes for ERP are larger than the effect sizes for medication for OCD, although there are many caveats about who's being treated and so forth. There was a really interesting analysis where it looked like that when psychiatrists who have a pharmacological bent are running the studies, then the SSRIs will work better. And when psychologists who have a dedication to a psychological framework, but then therapy tends to work better. So there's complexity there. I 100%, if it is the case that in an ideal universe, therapy works better or longer than two possible reasons are one, as you said, the sense of self-efficacy and two people get tools to help them manage symptoms when they do arise, and that which then can feed back into self-efficacy. I think that's absolutely true. I don't think any of us should be prescribing SSRIs and not doing anything else, not providing psychotherapy, not providing reinforcement, not enhancing motivation. And so hopefully when we're prescribing SSRIs, thoughtfully, we are still giving some tools, some insights, some self-efficacy. And I think to not do so would be poor practice. Absolutely, ERP is gonna do that in a more structured and rigorous way. So anyway, these are my thoughts. So yes, I think what you're doing is what your observation is likely true, but it's gonna be more true if all you're doing is giving the meds and not all of the rest of the apparatus that a thoughtful prescriber is gonna be giving, especially over time as you get to know a patient in an outpatient setting. Both are important. It was very interesting for me that the fact that the dysphoric feeling was a motivator to get therapy. I don't know if this makes sense, but that's what I observed. And this is what I want to state. Thank you. So we're at time at three o'clock. So if, just for some of the people online, who had some questions about one, Dr. Pettinger's, your slides, those will end up posted on the clinical updates toolkit webpage sometime and probably in the next week. And also someone asked about hoarding disorder and actually there is a clinical update talk about that. That was happening tomorrow, Sunday. Otherwise, thank you. Thank you.

OCD

body dysmorphic disorder

trichotillomania

neurobiology

psychotherapeutic treatments

pharmacological treatments

CBT

SSRIs

cognitive distortions

habit reversal therapy

genetic influences

personalized treatment