All right, everyone, hello, nice to see some of you again and meet the people that I have not met. You know, I have the wrong slide show up. This is from next week's lecture. Actually, do you guys want to hear about OCD? Sorry, we're recording. This is my mistake here. All right. Here we go. We'll fix it in post. Yeah, it's okay. Okay. I see it. You see with here now, I have to switch again. Yep. Oh, good. Okay. Here we go. All right. All right. As you guys, I mentioned in the past, this lecture is part of the opioid response network, to provide assistance to people doing substance use disorder treatment and evidence-based care. So this lecture, so anyway, this is a little bit about the ORN. If you have questions or want to make further requests, this is the info. I don't have any specific conflicts of interest related to what I'm presenting, and I do provide the support to the ORN. All right. So the goals today are to talk about, as I mentioned, history of antipsychotics, schizophrenia, to describe the classes, and then a little bit about some of the indications and some of the side effects that might come up. And we'll do as much as we can. We have two hours. Hoping we won't take a full two hours. It's a long time to sit on Zoom, but if people are interested, we'll keep going. So here's the case. A 31-year-old comes to stay with you after they were in rehab. A few weeks into treatment, they started having some paranoid delusions. He believes the government is monitoring him through cameras in his home, I guess in the home, and he reports he hears agents speaking with each other. So due to this, he has been sleeping in a park for the past few nights. So he stopped staying inside. He's sleeping somewhere else. Okay? So that's the case. Patient's sister brings him back. She says he's been smoking marijuana. He smoked marijuana a week ago, and then he stopped taking his medicine a week and a half ago. So what do we think the diagnosis is, and what do we think the best approach to treatment is? Anyone? Ideas? What's the diagnosis? Make sure I can see the chat. It's marijuana-induced psychosis. Okay. Could be. Could be. Oops. Other thoughts? Other possibilities? Stopped taking his medicine. Uh-huh. So what's the diagnosis, underlying diagnosis? He's schizophrenic. Yeah. He has schizophrenia. The patient hasn't diagnosed the disorder of schizophrenia yet. So that would be another option, which I think might fit better because he was on medication before, and then now he stopped the medicine. Often people with schizophrenia do have a worsening when they smoke marijuana. It triggers like an episode. So if it was sort of without any background, and I didn't give a lot of background, it could be it's just a one-time medication and marijuana-induced psychotic episode. But because he was on aripiprazole, and when he stopped it, he got worse, probably this is more of the schizophrenia spectrum. So here's just a quick definition of the diagnosis, which I don't know if people really need to know the details, but I guess it's good to think about. So you can see there's five things that you could have that would make a person meet the criteria. It has to be going on for more than a month, and overall it has to be more than six months, but the symptoms have to be at least a month at a time. And it has to be one of the first three of these. So the first three are delusions, which are beliefs that don't really make sense. So not that someone believes the opposite of your political views, although some people say that's delusional, but something that's really delusional would be in this case, like he believes he's being monitored. That's really irrational. He believes in something that people believe they're being followed. Sometimes they're grandiose, religious, you know, I'm a messiah, I've been chosen by God. There's all different examples. Oftentimes, delusion is actually something that you might see a lot is ideas of reference, which is the idea that something happens in the world that was a specific message for me. Like the roadside said, you know, the street name was First Street. I was on First Street. That was a message for me that I'm first or something. So that would be an example of an idea of reference. So that's one of the criteria. Hallucinations would be something changing with a person's sensory perceptions. It's almost neurologic. It's probably more neurologic than, you know, our traditional psychiatric thinking was very much a person is just sitting in a room by themselves and they hear a conversation going on as though it sounds like someone's speaking to them. That's the most common presentation of hallucinations. But you can get other hallucinations. You can get tactile hallucinations, people feeling things in their body. Also, visual hallucinations, a little less common, but they sometimes happen. So that's the second. And those are kind of some of the common ones that you think about. But there are other things. So often people with schizophrenia have disorganized speech. So maybe you'll see with people who just aren't able to have a conversation with you. Then they don't really make sense. So that is one of the criteria. So if someone's, let's say, delusional and has disorganized speech, but they don't have hallucinations, they would meet the criteria. That's how these diagnoses work. Also, you get disorganized behavior. Let's say somebody maybe speaks clearly, but they act strangely. This person is going to live in the park. So that person would meet a criteria for disorganized behavior. But often you have people who get very agitated, which can be dangerous. That's why people end up often on a psychiatric unit. So that's the fourth criteria. The last criteria is one of the most difficult to treat. But if you don't think about it so much, but it's the negative side of schizophrenia, which is one of the diagnostic criteria. So you can have this along with any of the first three. Somebody who doesn't speak very much, they might be sitting very quietly, staring off into space. You might think they're very nervous. Sometimes with kids, you get people say, oh, he's very nervous. But actually, it's because, unfortunately, it's a psychotic illness. The person's just not responding because they have these negative symptoms. Again, it sometimes feels very neurological. They're just not responding. Or they have less facial expression, less interest in doing things. So those are the five criteria. You need two of these five to meet the diagnostic criteria, just to get a sense. Any questions on these before we go? All right. We'll move on then. So with regards to the therapeutic approach, we want to establish rapport. So we don't want to just jump right into dealing with someone's delusional beliefs. So you always want to engage with the person, even if they're saying things that really make no sense. Let's say, well, there are cameras in the building that are watching me. I want to talk to you. So always start by just saying, well, thanks for coming. Thanks for engaging with the person. When a person, and I don't know, I think that someone asked about this, like how to talk to someone about this. I don't know if this has actually come up. But it's not always useful to just contradict. You want to listen attentively and take it seriously. And you can validate how scary it is. That's the next thing you would do. So you say, this sounds really scary. You feel like someone's watching. I don't understand why you wouldn't want to come here. Right? You validate, even though you know that from an outside perspective, this is irrational. It makes no sense. But you want to engage from the person's perspective and say, I understand, based on what you're saying, this sounds really scary. I get why you wouldn't want to do that. And then you could, if you want to get a little deeper, you can start, once the person's engaged with you, you can start trying to get into trying to think it through with them. So you can ask things like, tell me more about what makes you thinking that. There's a therapeutic approach, which I think I'm going to talk about in a little bit. But that's the next thing here. So you can start talking. There's something called cognitive behavioral therapy for psychosis, which is a way of trying to talk to people to help them, I wouldn't say change their beliefs, but separate from the beliefs that they're not so sure of it. You know, sometimes we think about when we think in the world, we think, oh, we either believe something or we don't, or it's right or it's wrong. But that's not really true. Right? We sometimes have a belief about something, but we're kind of like, yeah, it's probably true. But it's not like 100% true. You know, again, with political beliefs, like some people, it's 100% true, right? And there's other times it's like, well, you know, I think this is better this way, but I acknowledge that there's another side. So part of the goal of treatment here is not always to get someone to say, oh, yeah, that was totally wrong. It's to get them to at least acknowledge, you know, maybe my mind is playing tricks on me. There's a chance of that. That might be a win. And that might actually be the way people respond to medicine. We'll talk about that a little bit. But someone who's doing better sometimes still believe something that they are. And that's okay. It doesn't mean you have to change something or do something as long as it's not affecting their actions. And as long as they realize that might be my mind playing tricks on me, I'm going to ignore that. That's actually a win. So that's kind of the goal of the therapy. So you might say something like, is there any other reason why you can explain what these like the facts that you have here? Like, is there any other ways of thinking about it? That might be true. Just to get the person to be a little more flexible. You know, they can't think of anything. You can say, well, you know, does it really matter? Or, you know, tell me about what you have to do about this. Would it be okay to just ignore this? Would that be better? That kind of thing. And then you can talk about this also for safety planning. What are you thinking about to do? Sometimes patients will say, like, I started sleeping with a gun under my pillow. Like, that's good to know. Right? So, like, there are things that you want to know about just to know what are you trying to feel safer? What are other options you can do? Maybe you can just try to learn to live with this. Medication might be helpful. Those are the kind of ways we talk about it. Make sense? Yeah. Questions on this? Sort of just like the degree of validation I've always struggled with. Like, I've found with clients who suffer from psychosis or schizophrenia that there's often, like, that grain of truth at the root of the hallucination, delusion, or paranoia. Like, even for your instance, right, is, like, we live in a surveillance state. There's cameras everywhere. Like, that's, like, emphatically true. I've always struggled. I don't know if I think the government truly is monitoring us in our houses. And there's the delusion part of it, right? And I've found it really helpful sometimes to, like, identify the grain of truth with I think that's good. You're validating. I think you're right. That's right. If you validate the experience, you say, look, it's not that I think you're totally off-base here, you know. I get what you're saying. That's right. I think that's a great point. And that's a great approach probably to say, hey, I hear what you're saying. You know, it's true. My phone is listening to everything I say. I mean, like, sometimes it starts talking to me, like, randomly. It's like, you know, so sure, I get that. Yeah, definitely. Like, where to tread on that line, right? As to not, like, solidify delusions, but to validate experiences is something that's I think that's the trick. I mean, I think the trick is to really try to do both. And I don't think you have to worry about you certainly shouldn't try to say, like, yeah, this is real. Like, you don't want to pretend that you believe this is true because, you know, I think that just misleads the person. And, you know, but I think you can I think it's okay to be validating. I mean, I think that's always fine to say, like, I get where you're coming from. I hear your point. But you and then, you know, and then you don't necessarily have to directly contradict the person, but you also can try to help them. You know, probably like you said, all these things like problems all around it, reality tests around it. So I think that's really but you're right. It's a hard line to walk. And, you know, but I think you can always validate without saying, hey, you know, that is real. You know, you're right about that. Does that make sense? I think that, yeah, it does. And I also think that attaching the aspects of what they're going through to things that are real for us is a helpful way, as long as we do it unemotionally, of validating them and making it feel better. So I agree with what you're saying. Yeah. So what would be an example of what you're saying? Oh, well, just like it was just saying, like. So if they think that the government is spying on them, you know, I think I would naturally validate before I were to contradict, just like Abe is suggesting, you know, to say that elements of what you're feeling are true. Sometimes I feel that way myself. And it's OK. Part of living in this society is, you know. Right. Right. OK. Yeah. I think you are. I think. I think if you could show that you understand where they're coming from and experience similar things, that makes sense. I think that's a good. That's a good approach. You know, I wouldn't totally say, oh, you know, I wouldn't pretend that you agree. You have to be careful. I wouldn't be pretending that I agreed. You know, I would be speaking from a place of truth. Yeah, that's good. This is good. Good approaches to it. All right. Other thoughts? All right. I'm going to keep moving. OK. So other treatments. A little bit about the second one, cognitive behavioral therapy for psychosis. But we have also more probably more important to start with is the first bullet here. Antipsychotic medications. So people have heard of antipsychotics, I'm assuming. And we're going to go through some of the details about them a little later. The goal of treatment is always probably to start around getting a person on the medicine. As I mentioned, this feels like more of a neurological condition than many other psychiatric disorders that maybe are along the normal spectrum of human experience. Some people are more nervous than others. Maybe some people are very nervous. But when you start hearing voices of people that aren't there, and you start believing things that are really completely irrational, or the negative symptoms, they're just, you know, medication is really important in this disorder. There's not that much of a placebo response rate in schizophrenia. It's sort of another sign that I think the medicine really, the active medicine is really important. So that is always sort of the main goal, to keep people on medication. I'll talk about that. that more. That's kind of the mainstay of treatment, gold standard. But all the other things are super important because it's hard to keep people on medication. And the medications don't fully resolve all the symptoms. So like we mentioned with CBT, people may be on medicine, they may still have these voices, they may still have some beliefs, but they can sort of ignore them. So that's the role of psychotherapy. The same thing with family therapy, psychoeducation, you want to help family support, validate, approach things in the right way, not discourage the medication use or try to say this medicine, talk to people about how this can be really helpful. We can't, I don't know, get rid of this in some other way. There's specialty care treatment, which is like a wraparound approach. In New York City, it's good to know that there's this approach called On Track New York. Have people heard of that? It's a nice program. It was developed based on a research trial that showed that when you give very, like early on, if you give people wraparound services, they do better than if you don't. So they get wraparound services, meaning it's not just about medicine. It's not just about therapy. It's about medicine, therapy, vocational support, like helping people find jobs, case management, sometimes going to their house and giving them medicine. So like really, like a team based approach. And it's, so it's nice in New York, we have that system in place. So if you ever have someone who's in, I think it's the first five years after they have their beginning of their psychotic symptoms, you can refer them to that On Track New York. And it's a nice, it's a good program. Social skills training, obviously important for people in support of employment is also useful. So those are some of the approaches. So now I can give you a little bit more deep dive into antipsychotics. Unless people have questions at this point. I'll keep going. All right, so antipsychotics, it's an interesting story, actually. In the 1930s, there was a French company looking for antihistamines, right, which were like Benadryl. They weren't really looking to cure schizophrenia or treat schizophrenia. But they found this medicine called chlorpromazine, which is very anti-synergic, very sedating. And they started using it with anesthesia when they were doing surgeries. But they noticed that when they gave it to a patient with anemia, they stopped having those manic symptoms. So they realized, hey, this medicine might actually work for something besides anesthesia to make people tired. It actually turns out that it helps with schizophrenia. So it was serendipity. It wasn't necessarily that we knew and understand the disorder. And now we can figure out exactly which medicine to develop. It was kind of luck, which is often the way things develop in medicine. So the large trials started in the 1960s and the first approved medicine was, as I mentioned before, the brand name was Thorazine, which people may have heard of. People still use it. It's actually not a bad choice. And you can see the way that people used to advertise things, not exactly the way we used to do it anyway. Wait, wait, now you see the antipsychotic medicines on TV. It's like someone with like butterflies on the beach, but like here it's really targeting patients that were in, and we'll talk about the hospitals where people were in these state hospitals. So they were trying to target the psychiatrists to say, hey, try these new medicine on your patients. People will feel better. And it was a big push and it was a very successful medicine. It really helped. So in the 1950s, state hospitals were really terrible. It was terrible, obviously terrible places, but it's probably some better than others, but they were really huge. I mean, has anyone been to Creedmoor? Have you ever heard of Creedmoor? It's a state hospital in Queens that used to be like, it was called Queensville. It was like an entire like village. And there were just, I think there were 10, 20, 30,000 patients there at one point. They didn't have any real treatments for patients with psychotic illness. So they just would put them in these big state hospitals. They thought like if there was farming and it was supervised, that was a place to keep them. Unfortunately, it would get like this where there's almost inhumane conditions where people just lined up. But that was how state hospitals were. When they were rolled out of Thorazine, they were able to just completely drop out the number of people that were at state hospitals. So you see that number went up. And then in the 1950s, you get this precipitous drop. Before that, people just weren't treated and it was people living on the streets or whatever. But over the years, we developed a system to help people. And then in the 1950s, we were able to empty out the state hospitals. If you go to Creedenmore now, it's kind of like, and also the one in, I think the one in New Jersey actually became a set for a horror film. It's called Greystone. And it's still a state hospital, but they've all been shrunk by orders of magnitude. And it's like a ghost town, the rows and rows of empty buildings. Yeah, this is Greystone, the old Greystone Hospital. And now this is how it works, parts of it. So it's, thanks to antipsychotics, they really were able to treat a lot of people and they got a lot better and we don't need to keep them. And unfortunately, we still have problems with the health system, but I'm not gonna discuss that. The mental health treatment system, I'm not gonna discuss that part. But a lot of it was due to medicines that actually work to help people leave. So here's just some examples and there's a little timeline here that you can understand that there was change in the way these medicines worked. So the older ones are called typical or first generation antipsychotics. So those are the older medicines. They had a very strong effect on one particular receptor, the dopamine two receptor, the D2 receptor in the brain. And their side effect profile was very, sort of like one kind of generally kind of side effect. And the second generation has a different set of side effects. So, and I'll go through that in a minute. So the oldest one is chlorpromazine. And then we have Haldol, which people have heard of. That's an oldie but goodie, but actually, I would never use Haldol with a patient. Now, if you see someone on Haldol, I don't know. Flufenazine, theoretazine, loxapine, flufenazine. I might be reading all the names, but these are all the old antipsychotics. There was a change that happened in the early 1980s. There's this new one called Clozapine. It really deserves its own lecture, Clozapine. I'm not gonna go into it in too much detail, but it worked in a more broad way in the brain. It didn't just work on that one D2 receptor. It affected a lot of different receptors. And it didn't have the same side effect profile. So it wasn't, there was a sort of a change. And then there was newer antipsychotics that were different, related to Clozapine, but different. And that's the ones that you've probably heard about more often that people are on more. Risperidone, Olanzapine, Quetiapine, Ziprasidone. Those are Risperdal, Zyprexa, Seroquel and Geodon, if you've heard them for the generic names. Then we have even newer ones, the Belafine and the ones that aren't even listed here, like Raylar, Cariprazine, which are actually some of them, the newer ones are not even acting fully on the D2 receptor as a blocker. They're actually partially hitting the receptor and partially not. Just sort of a slightly different mechanism. So that's kind of the history of how things developed. And actually here's a, I have a little cartoon to show you how they work differently. So the typical antipsychotics work on that one D2 receptor. The newer ones, they're called the atypical ones, which are the second generation. That's how we call it now. They don't just work on that one D2 receptor in the brain, they work on the serotonin. The 5-HT ones, these are all serotonin receptors. These are muscarinic and histaminergic. So there's all different receptors in the brain, different cholinergic. So there's different receptors that these are acting on. So it's a much broader effect. And then there may be even new receptors that are gonna be worked on. There's actually a new drug, which I'm not gonna talk about. Just to prove that it worked on the muscarinic, the catenic muscarinic receptor, which is a different receptor, works totally different. But I don't wanna go into that. It's very, it's really brand new. So, I mentioned there's differences between side effects. So just to say as an overview, I'm gonna go through some of the side effects in a minute, but as an overview, the first box, the top box, which are the typical medicines, those are the ones you have to worry more about the movement disorders. So you get people with acute dystonia, which we'll talk about, which is someone gets stuck, but they can't move. There's a more higher likelihood of people getting like Parkinsonism, which is stiff and shuffling, tardive dyskinesia, which is a movement disorder. Those are more common with the typical antipsychotics. They still happen with the atypicals, but much less. Then the second box, the lower ones, instead of having those problems, you have other problems. Most significantly is weight gain and changes in cholesterol and blood pressure. So these medicines often have a problem with weight gain, although some of them are less, some of them are more. The biggest ones for weight gain are clozapine and olanzapine. Those are like the biggest, and they cause the most weight gain. Okay, so that's sort of an overview of the side effects in terms of which antipsychotics cause which. May I ask a question? Sure. With that weight gain side effect, is that like super severe, or is it like if a person's exercising and eating healthy, it's not so much an issue? It's pretty severe. I would say it's very, very difficult to overcome for someone who's like at risk. Not to say that you can't work on it, and not to say that for people like this it isn't good to exercise, but the body metabolism does change. The appetite increases. It's just hard. It's very hard for people sometimes to lose weight when they have, let's say if they're on olanzapine. Not everyone gets the side effect, but if you do get it, it can be pretty severe and hard to treat and hard to deal with just with diet and exercise. So it's always good to encourage people to be healthy. But they may need medicine to help them. It's honestly a difficult balance. And sometimes someone really needs that medicine, and then you kind of have to deal with the weight gain, but it's hard. No one wants to gain weight, especially certain people who really don't want to. The newest medicines cause a little bit less weight gain, but they cause other problems. So it really depends. I had a question as well. Yeah, what's that? Is there ever any use case for using a typical, so yeah, I was looking at the receptors, is for using a typical and an atypical antipsychotic on a client patient? Like a how long and- As far as I know, I'm not like a researcher at schizophrenia. As far as I know, there is no real good trials that show that adding a second antipsychotic to a first is helpful. What you're really supposed to do, and unfortunately, and this gets into some of the details of psychiatry and how it works and doesn't work. Like for example, in New York State, one of the things that they say is a quality metric for outpatient clinics is how many people get on two antipsychotics. So they actually really discourage people being on two antipsychotics because they think it's not a good idea. There are reasons to in certain exception cases, but if it's just because the person hasn't gotten better on an antipsychotic, let's say they're on a piperazole, but they still have a lot of psychosis and they're really not functioning well. The right thing to do isn't to add a second, the right thing to do is to switch to another one. Like now let's try a lansipine, let's try. And then if that one doesn't work, really the right thing to do is to switch to that one I mentioned before, the special one, clozapine. Because clozapine, and I wasn't planning on talking about this, but clozapine, they did trials where people that failed everything else, when they switch them to clozapine, there's like a miraculous recovery. There was a second emptying out of state hospitals when they discovered clozapine and they brought it into the United States because there was a portion of people that nothing else works, but clozapine does work. So that's really what they should be doing. You shouldn't really be using two. That's the evidence base in the field. What happens in reality is something else. And clozapine has its challenges, which I mean, we can talk about that. But if you guys really want to dig into the psychiatry and the pharmacology of antipsychotics, we can. So let me know, but. Personally, I think it would be helpful. I would like to feel the room out and see what people think, but I think it would be helpful for us to have a rudimentary understanding of these things if possible. I mean, because the first question I had was just, why doesn't everyone just always start on clozapine? That's a good question. So it gets into the reason that things, clozapine causes the most weight gain and has a lot of unusual side effects. And there actually, when it was first, I'll give you clozapine. Do I have, let me see if I have it in my clozapine. Do I, no, I didn't put the clozapine slides in for you guys. I didn't take those. I thought it was too detailed, but. So I'll tell you, the reason that we don't use clozapine first line is that if you take the general population, it doesn't necessarily work better than any other antipsychotic. It's only for those people that don't respond to anything else. That's the group that we know that the clozapine works better for. And when they first developed clozapine, they actually pulled it from the market in the United States because it has a serious side effect of causing people's bone marrow to stop producing white blood cells. It's pretty scary. So one of the things that you have to do as a doctor when you're prescribing clozapine is you need to do blood tests in the beginning every week. So I actually just started some of the clozapine this week. So you go to an online site and you write the patient's name and you write the blood test, the last blood test they got, and you write how many neutrophils they had. It's called, it's one of the kinds of white blood cells. And you have to list that and you have to keep putting that in. It's a very important safety thing because the FDA doesn't want people just writing it and forgetting about it. It's sort of required that you do this monitoring. It doesn't happen to a lot of people, but when it happens, it's deadly. So we have to have this in place. So it's extremely annoying for patients to go every week to get a blood test. It's a real headache. There's a lot of reasons why you wouldn't want to use clozapine unless you really need to, but you would use it if you have someone, if you have a loved one who is not functioning because they have treatment resistant psychotic symptoms, you really want to use clozapine and it's worth it because then maybe they can get their life back. I mean, some people on clozapine really can get back to living in the community, having a job, having a family, maybe having a family. So there's really a huge benefit for those people that need it, but you want to use other things first. So that's the clozapine story. That's the reason. And actually it's a New York story that the person who brought clozapine to the United States is John Kane, who was the chairman at Long Island Jewish Hospital for a long time in psychiatry. So that's the clozapine story. Other, and New York's done a lot of cool stuff. Actually, we were the first ones to do methadone too. Great city, New York. And I guess I can, it's okay that we're recording this for it's a New York program, so I can say that. All right, all right. Other questions? You guys have other things you want to hear about with regards to any like things that come up? The next thing I want to do is I'm going to go through the side effects that you could like look out for and talk to patients about like, hey, you should talk to your doctor about this one. Or just like, you know, that's the next thing. But any other things you want to discuss before we go on to that? Well, yeah. I'd like to discuss about the blood tests for clozapine. Sure. Besides it being a requirement, what is the danger if one doesn't keep blood monitored? So that's the thing. You can have a situation where a person won't necessarily know this, right? Because you don't know if your white blood cell count is dropping. So they can have a situation where they get immune deficient without knowing it. And then they can get like a severe infection, like they have cancer or AIDS. Like you get in situations where it's deadly and where they can get an infection that really. So that's the thing that could happen. You really have to, I mean, if you know anyone on clozapine, there's a lot of safeguards in place that they will follow this. No, I don't think any doctor would prescribe without getting the blood test. It's pretty much like part of the system. The pharmacy won't write the prescription unless they have like, you know, a record that it's in the REMS, which is the online system. But yeah, that's the fear if you don't do the blood test. So I'm sorry to run too deep into this, but the blood test is specifically for the white blood cell count. It's not for clozapine levels in the system? Clozapine levels is something else, but no, no, it's not. You check clozapine levels just because you want to know how it is therapeutically if you have enough, but that's just, you do that for lots of medicines. They're for lithium. You do that for valproic acid, Depakote. So, you know, but yeah, but that's something else. The safety and the doing it every week is just, you do, it's called a, this is what you order. You order a CBC with DIF, which means you get a differential of all different kinds of white blood cells. And one of them is the neutrophils. That's the one that you need to know. The absolute neutrophil count, if you, I'll never ask you, it's the ANC. And so you write that every time you write the order, you say, hey, last ANC was on this date, and this is the number, it's above the right amount, or it's a high enough amount, it's above, you know, a thousand basically. And then you can keep writing the clozapine. So that's how clozapine works. And yeah, I mean, if you have people that you know are on clozapine, it's an important thing to help support that process, to help make sure they get their labs, to make sure that the doctor gets the results, because that can actually sort of mess everything up. If there's some problem in that process, then the pharmacy says, well, I can't write the prescription, and the patient doesn't have their medicine, and then they might go back to having fluorid and psychotic symptoms. If you stop clozapine for too long, you actually have to start at a low dose, because if, this is another thing that's hard about clozapine, if you raise the dose too fast, there's a risk of seizures. So it's a complicated medicine, really, honestly, most psychiatrists don't like to use it, it's too hard for them, but I'm teaching you about it in case it comes up, but there's a lot of kind of, it's really important that when people is, when someone is on clozapine, that you want to keep them getting their blood tests when they're supposed to. I also, I could just tell you, in the beginning, it's every week, but then as time passes, the chances of the problem happening are lower, so then it goes to every other week, and then it goes to every month after a little while. So eventually, people are just getting a once a month blood test, and they're getting their script for a month, but, you know, all right? I have a question. In what percentage of patient usage cases does the severe white blood cell count diminishment happen? Is this something that occurs in like 5% of cases, 2% of cases, 10% of cases? I am not remembering that, so look it up. Okay, sorry to put you on the spot. I think it's like- Of course, it's very concerning, but is it common? And how long do patients stay on this, on clozapine? Can you stay on it for years? Usually stay on it indefinitely, because it's- I mean, and it's true in general. I mean, if someone truly has a diagnosis of schizophrenia, it's a chronic illness. It's not something that goes away, unfortunately. So you might lower the dose if someone's stable, but if someone gets to the point where they end up on clozapine, chances are we really want to encourage them to stay on it until they die, honestly. I mean, it's like having a seizure disorder, you know, or type 1 diabetes, honestly. You need the medicine to maintain yourself. And, you know, with schizophrenia, with bipolar, that is sort of not treatment-resistant, there may be cases where maybe it was the wrong diagnosis. You could try stopping the medicine. You know, if someone has like one episode, maybe in the context of marijuana use or cocaine use, you know, maybe that was a one-off. But if something's happened, let's say, more than once or twice, and it happens maybe outside the context of drugs, then probably they would need to be on medicine indefinitely, you know? It's not, it's different than depression and anxiety. Like I said, like depression and anxiety could probably deal with the therapy, but with schizophrenia, you know, general rule is you have to stay on the medicine. So, yeah. I think the number for how often you get the ANC drop is like maybe one in a thousand. You know, maybe it's a little more, but I don't remember. You have to check. But it wasn't like it happens every time, but it happens enough that in medicine, like a deadly outcome, one in a thousand is kind of unacceptable because it's too, you know, we don't want one in a thousand people that we give this medicine to to die. So we would, I think it's something around that. It's not like one in ten. Yeah, that's good to know, because our assumptions could run all over the place to like 10%, 20%. One in a thousand is pretty minuscule, but worth knowing. It's something like that, but we would catch it. I mean, the thing is that we would know if it happens because that's the whole point of all this monitoring. We would catch it and you wouldn't get the serious problem. We would just have to stop the clozapine. That's what all the monitoring is for, to say like, okay, we're going to do all this monitoring and we're not going to have this happen. So nothing, like we won't have this problem. That's fascinating and fascinating learning the history of these sort of, you know, milestone drugs that literally changed society when they were introduced. They really do. Fascinating. Yeah, it's pretty interesting. Yeah, I would tell you a book story. I don't know what's a good popular literature book to read the whole story. The one that I like about schizophrenia, the diagnosis and the healthcare system is called The Great Pretender, which is by Callahan, I believe, Susanna Callahan. She's a great writer. It's a really interesting read and it's about diagnosis and the system. But I don't know, I don't know a good book about the story of antipsychotics, but I'm sure they're out there. Um, all right, so I'm going to move on to some of the side effects and then we can, if people have questions, we can talk definitely just, you know, at the end, but I want to make sure we get through the side effects. There's a bunch of them. Um, so, um, first one I think is important to know is called akathisia. So people have heard of it before. This is a pretty typical case. A person has diagnosed schizophrenia. They started on one of the antipsychotics, risperidone, which is a new, one of the newer ones, um, two weeks ago. So what happened? She says she's visibly distressed, shifting her weight from foot to foot, can't sit still. She says, I feel like I need to keep moving. It's just this, there's this restlessness inside me. They won't go away. I can't sleep. I pace around for hours. It's worse than the voices were. Very typical case, but unfortunately easily misdiagnosed, right? Someone might see this woman and say, Hey, she's having some psychiatric problems. She's getting more psychotic. She's acting weird. We have to raise the dose and then you make it worse. And then, then you get really bad. She can be in so much distress, can lead to suicidal ideation. It can lead to suicide. You got to recognize this one, akathisia. And that is this feeling of internal restlessness. So this is the slides. I'm going to read these slides, but it's basically for people that are reviewing the slides at some point. Um, it's a feeling of restlessness, pacing, rocking, shifting. Um, it happens usually within days to weeks of starting a new medicine. Sometimes when you, um, raise the dose quickly, you get that. Um, and I've seen it many times. This is not an, I don't know that again, I think I should have like what percentage it happens. I don't know the exact numbers and it depends from medicine to medicine, but, um, the newer ones, which don't cause weight gain, like, uh, Raylard, Rupersine doesn't cause as much weight gain. It does sometimes cause akathisia. So you probably would see this. You could easily see this with someone who started a new medicine or even they started a few months ago. Like I'm always pacing. I never had ADHD, but now I feel like I can't sit still. You know, you got to think about maybe this is akathisia. Maybe they need to switch antipsychotic. So what do you do in a case like that? When this comes up, the first thing to do is to just switch because it's always better to not treat the side effects with another medicine. So try just this. There's many different choices. Just try a different one. Um, quetiapine and lenazepine have lower risk than some of the other ones. Um, those cause more weight gain and less of this problem. Um, if you feel like this is the medicine the person really needs, then you can try to treat the side effects with another medicine. So some people use these, I'm not going to go through all the details of the medicines, but sometimes people use benzos, like clonopin. Sometimes they use propranolol, which is actually like a medicine for, um, high blood pressure, but it slows things down. I think that might help, but it's a very important thing to look out for akathisia. Has anyone seen it? Has anyone heard about this before? But it's a good thing to know about. Um, yeah. So that's, um, that's akathisia and it's considered one of like the movement disorder issues. Uh, here's another one, another example, a different problem. This one is a little, you probably see this a little bit less because it's more of the early antipsychotics like Haldol, but if you see someone on Haldol and they just got out of the hospital or they're relatively early on, this could, uh, this could definitely happen. Um, so you have this person just got an, uh, Haldol shot six hours later, they have severe neck stiffness, involuntary upward gaze. They can't, the person's in a lot of distress. He's kind of stuck. He feels like his jaw's like very scary, obviously horrifying. Um, this is kind of what a person might look like when they're having it. Um, so, um, you can have it in different places. You can have it in almost any muscle. So you have to look out, you have to keep a lookout for wherever it appears. I think the most common is in the neck. Um, and it usually happens pretty early on. Um, so this is a, this is a, this is a different disorder. So this is acute dystonia. I would say if you see it, I'd send the person to the emergency room. They should be treated right away. Um, I, I, it would be unlikely that you'd see it as an outpatient. It's more happens in the hospital, but you know, somebody just was prescribed Haldol from the clinic. They just started it. Now they're in, you know, like this, so they can't move. Their eyes are stuck up. I would send them to the emergency room to get, you know, right up, treated right away because it's very unpleasant. Um, you can, you know, all right, next, uh, sign. And these are very, they're pretty scary. And I, you know, that's, this is why you try not to use antipsychotics unless you have to, but for psychotic disorder, you, you would use them because there's the, the, the disorder is worse than these pop, the possibility of these side effects. All right. The next one is tardive dyskinesia. People heard of this one? So this is a movement disorder. Um, it's different than the others that I've mentioned because it actually happens more slowly over time. Someone's on the medicine for years. The risk of this happening kind of builds up. This picture is trying to show that this person is kind of going back and forth with this movement. I don't know if you've seen people who are chronically on Haldol, sometimes they have like a twitch in their mouth like that, or their eyes might be blinking like that. It looks a little bit like a tick. Um, sometimes in the hands, it's like, it's not like a tremor. It's like a involuntary movement. Um, yeah, I don't like that. Um, so you get, so, um, so it's just something to talk to patients about, look out for if it's, if it's severe, it's pretty, um, debilitating. But for most people on the newer antipsychotics, I have patients that are, maybe have very, very mild tardive dyskinesia. Um, and I usually just live with it, but if it gets bad, this issue with tardives, it doesn't usually go necessarily go away when you stop the medicine. So it's good to catch it, um, to catch it early. Um, so doctors should be checking for it, but they may not. So if you hear about it or you hear about someone, and it could happen relatively early on. So if someone says to me like, oh, my hand keeps doing this, or I keep having that, like that may be from the antipsychotics. There are treatments for it now. There are new medicines. When I was training as a resident 10 years ago, um, they were just coming out, uh, but, um, there are now a couple of approved medicines that could treat tardive. So there are ways to do it. Usually you try to switch the medicine or stop the medicine they're on or lower the dose or they try to avoid it. But if, if you need to keep someone on a medicine, then there are ways to treat this. So that's tardive. Um, all right. Questions. Um, I have a question, just difference between risperidone and clozapine. Um, I've just as a layman, I've seen both drugs work miracles. And, um, uh, risperidone more so for people that are, maybe you have a bipolar diagnosis and not a schizophrenia diagnosis. Does that, does that track? No, no, no, no. Risperidone can be used for both schizophrenia and bipolar. It's, it's approved for both. It's not, I wouldn't say that it's one or the other. Um, and I would say that you have to kind of think about the indications for antipsychotics, like for example, um, bipolar or, or schizophrenia. Um, you, you would use them kind of interchangeably. There's no reason to think one works better for one of them. Now with bipolar depression, there are some medicines that are approved and other medicines that are not approved. So that's the only exception to the rule, but risperidone happens to be one that's not approved for bipolar depression. So, so you would use like, for example, for bipolar depression, the ones that are approved are quetiapine, seroquil, lorazidone, olanzapine, along with something else. Uh, some of the new, new ones chiroprosine, but, um, but I don't, I think it gets, treating bipolar is complicated and, uh, it's probably, if you want, it's all another lecture, but I, I, but, um, you know, and I, I can't, you know, so that, but, but I wouldn't say that you would use risperidone more for bipolar versus schizophrenia. And the same with clozapine, if you have like a really bad, severe case of bipolar, people would use clozapine in that case also, but only if everything else fails. Uh, and it actually, I think a little less likely to use clozapine because we already have lithium, which works very well. Um, you don't usually need clozapine also, but it is used sometimes. So, um, that's how I would, but I wouldn't think about them. I would think of them as just a class. Like we use antipsychotics for both disorders and, you know, they're all kind of equally useful for both bipolar mania and schizophrenia, similar in terms of like, which, which drugs are used to treat them. Um, makes sense. Um, all right. So last side effect, these are the ones that more common, this is the one that's more common, as I mentioned with the second generation antipsychotics. I already talked about it, but this is a pretty typical case where somebody starts a medicine, they start olanzapine, they start gaining weight. Um, and so what do you do, right? So people develop this over a long period of time because you gain weight slowly, but sometimes people will gain it relatively over the first couple of months, but it could happen even over like a year. Um, and it's, it's tricky because people gain weight even when they're not on antipsychotics, right? So, but it just makes things a little bit harder. Um, and you have to try to really address it. So the first thing you do is try to focus on, um, well, I'll say a few, a few things. One is make sure the person goes to a regular doctor to just get checked out because a primary care doctor can treat high blood pressure. They can treat, you know, high, high cholesterol. Um, and that will, that will help this person not have a heart attack, right? So just getting regular routine, um, primary care is really important. Always encourage eating a healthy diet and exercise that can always help. Um, but then you have these other options of, should you switch the medicine? Because maybe you want something that won't cause as much weight gain. Should you treat the side effects, um, with another medicine? Um, like there's different medicines that you can use to treat, um, this, the weight gain in this case, I'm not going to even go into all them. Do we know if the new, the new, uh, medicines to, to, to treat weight gain, you know, obesity are effective. I'm not sure if we've done, if anyone's done studies on them yet, but the GLP-1 agonists like Ozempic and, uh, Terzapatide, uh, you know, Menjara, all the, all those new ones that everyone's talking about, right? They probably work for this problem also. So in theory, you could try to help the person get those, but it's relatively new. Um, so that's the weight, that's the weight gain side effect. Yeah. Yeah. Any questions on that? Yeah. So I was just curious if you know what the mechanism is that actually leads to the weight gain, like, is it, um, does it, the medications cause overeating or is it actual, uh, metabolic changes? Both, probably both. It causes increased appetite and it also causes slowing of the metabolism. So, um, it's tough. I mean, it's not, you know, yeah. And the exact mechanism, I'm, I think it, I'm trying to remember the exact mechanism. I think you're not asking about the neurobiology, but I, um, I think it has to do with something with the serotonin receptors. Um, but I don't remember. Yeah. I'm not sure if we really know. I mean, people may say they know, but I'm not sure if we totally know why it causes weight. Um, all right. Other questions on this side effect? No. All right. So we talked a little about indications, but, um, just to go over it again, some of the things you might see antipsychotics used for, and which would be reasonable. So bipolar, we said you use most antipsychotics for that. Bipolar depression, there are these lists of medicines you could use. Um, now there are some antipsychotics that are approved for using in depression. Um, the two that are approved are Abilify or Piperzol and Cariprazine Freilar. So they were used, they were approved by the FDA to be used as an add on. If someone takes like an SSRI, which we're talking about next week SSRIs, but you take like a medicine like Zoloft or Prozac and they're not getting better. So we have an approval that you can use these other medicines as an add on. And there's also an indication if someone has autism, they get aggression. We have an indication to use certain antipsychotics for that. So antipsychotics aren't only used for schizophrenia, used for other things, but it's a little bit more spotty, which one is approved for what. And you have to be careful not to overuse them because in psychiatry, there is a little bit of a, sometimes, sometimes people end up on too much medicine because you're treating anger issues, or maybe they get like someone's getting very upset or, and then they end up on an antipsychotic just because. So you have to keep an eye out for that kind of thing also. But, but I guess that's more about for the psychiatrists to decide, but that's the indications. Here's some things. Yeah. So here's some things that. I have a question. Yeah. I know very little about bipolar, what's it called disorder, but is it, is it true that sometimes they're manic and sometimes they're depressive and would you take, would they, could they be taking different medications at those different times? So it's a great question. And it's one of the reasons why treating bipolar is complicated. So the definition of bipolar disorder is having a manic episode, but most people who have bipolar have also depressive episodes, which are part of the disorder. So a lot of times people get, have a manic episode, which is extra energy, not needing to sleep. And then they often will have after the manic episode of crash, but they end up having a depressive episode. As you can see, some of the medicines are approved for depression. Some aren't. It makes it a little tricky when you're treating someone and they treated the mania with something that's not approved for depression. And now they're becoming depressed. What do you do? So it's a good question, but the answer is we, we don't have FDA approval for all the antipsychotics for bipolar depression. And some might work, even though they're not approved, some we're not sure, but, you know, you could use, for example, olanzapine for both, right? Mania and, and depression. You could use cariprazine for both. So, you know, that's a, that's a good point, but yes, I mean, in theory, if someone's on, let's say, risperidone or aripiprazole, and now they're depressed, one of the things you would do is try putting them onto a medicine that's approved for bipolar depression. Does that make sense to answer your question? Yeah. And, and I guess maybe they would, they would maybe just switch to one that's on that approved list. Yeah, that would be, that would be a thought. Yeah, that would be a thought. Thank you. Yeah, no problem. But again, bipolar is, it is tricky because there's all these phases of the disorder. It's not like, most disorders, you're just, you know, you have it, you don't, but there's, there's mania, and then there's depression. And there's also maintenance, which is one of the risks in bipolar disorder is people that are doing fine, they're pretty high risk to have another episode, you don't want that to happen. So you have to do something to maintain them to decrease the risk of having another episode. So that's, there's like at least three phases, there's really more, but it's at least three phases of the disorder. So it's tricky to, and there's also two classes of medicines, you use antipsychotics, and you also use mood stabilizer. So that's why it gets, it gets complicated. So some of the reasons people use antipsychotics that are not indicated, someone who has dementia and gets aggressive, people use it frequently. It's dangerous to do that. But a lot of times someone with dementia, you're willing to take the risk because you're getting violent, you don't know what else to do. Personality disorders, a lot of people who have borderline personality disorder end up on an antipsychotic. At some dose, people that are very aggressive might end up in antipsychotic to decrease their violence, and it seems to help with those things, although it's not a proof. And then OCD, there's evidence that some antipsychotics work, like Risperidone has some evidence, some medicines have some evidence that they help with OCD. So there's different, and PTSD, I didn't put on this list, but people use it for PTSD as well. So antipsychotics are used for all different things. And so you have to keep an eye out for if someone's on them for all those side effects. All right, that's it. That's all my slides. It's only one o'clock, so we have plenty of time for questions. And if anyone has any questions, we can do that. Let me stop sharing. I was wondering if you could talk for a bit about autism and its presence, its spectrum, and its current diagnosis in cases where antipsychotics or psychosis has been identified or treated. I feel like it's something that we encounter a lot, but it's also something that isn't always officially diagnosed or spoken about openly in the process of mental health care. By the time someone's ended up in the ER, they're usually not looking at, they're looking at the more immediate risk factors. And so we're not seeing those conversations happen, I think, as much. And I'm just curious in your experience. Yeah, sorry. It's sort of open-ended. Yeah, it's a good question. I'm not an expert on autism. Autism, and it's getting a lot of press now, the Congress is talking about autism. The rates are increasing. I think we're recognizing it more. I think historically, the thing about autism is it's a developmental disorder and it manifests very young. It doesn't develop. Schizophrenia, I don't know if I've mentioned this, but usually people manifest the full-blown symptoms starting around 17, 18, 19, 20, early. It's very devastating for a family that a kid is relatively normal and then all of a sudden they develop this horrible disorder. Autism is different in that it usually manifests much younger and there's a wide range of how the diagnosis presents. So you have people with severe autism that aren't able to speak sometimes. And so that's, I think traditionally, historically, that's how field was focusing on that population, which is more severe. And then now the diagnosis has sort of come to encompass more things. They got rid of the diagnosis of Asperger's from the DSM. So there's just a spectrum of autism spectrum disorder. So there are people that are high functioning that maybe have some of these, I think it's a very broad question, but I would say that there are people that probably have both or may have something that looks like schizophrenia, like some of the negative symptoms that, and maybe, you know, maybe odd behaviors that might look like schizophrenia, but it's actually autism. I don't know the number off the top of my head of like how often they overlap. But if someone does, but the reason I came up in this lecture is that I think for autism, for people to get agitated, we do know that antipsychotics seem to help. So like I'll put people who have the diagnosis on aripiprazole and it sometimes really does help them. So, but it's, you know, I think schizophrenia is different. I mean, I think if someone has schizophrenia, you kind of, it involves, you can have both, but if someone has delusions and hearing voices, it's not just autism, it's autism plus schizophrenia. They may have both, but that's certainly, you would treat them like they have, if they meet the criteria of schizophrenia, then you would treat them as though they have schizophrenia. Well, it's just, is this a new phenomenon? I mean, I have friends who's teenage children, or like every other one of my friends that have teenage children, they say my kid's on the spectrum. Yeah. Is it, what is the phenomena that this is happening more? Is it just being, I don't, I don't really know. I mean, it's a good question. I'd say being identified more. I don't, I'm not, I don't know. I haven't read much up on it. It is a book that I haven't read called Neurotribes. I mean, it could be that historically people just said, oh, that guy is just that personality. And now we're calling it a spectrum. You know, I don't, like people were a little, you know, maybe a little nerdier, a little more into science. And we just thought that was just their personality. And now we're saying that's autism. But I really don't, I'm not an expert on it. I haven't read the literature on it. So I'm not sure. Yeah. And one more question. You said that the OneTrack program, is that what it's called? OnTrack. OnTrack. OnTrack. Why is there a five-year cutoff? Well, it's, it's meant to be, there's a lot of funding for it, but it's not meant to treat everyone with schizophrenia. It's meant to be an early intervention to help people from ending up with a severe illness, living on the street in a shelter. The idea is to support people early on so that they maintain their functioning. So that's why, that's the reason. I mean, it would be great if we could do that for everyone. And there are treatments that are good for everyone that, you know, there's lots of good treatments. New York City has lots of good psychiatric treatment for people with severe mental illness, but the OnTrack program was specifically designed to help people early on to prevent them from developing, from sort of, get, catch the, catch the illness early. That's the hope. It doesn't, that they should maintain some of their functioning. So we have more than a few clients on some of these medications you listed. And I was wondering if you could just describe to us like a sort of baseline best practice in the event that a client misses a dose, like with these different generations, these medications, are there best practices for waiting till the next day, taking as soon as possible? I think it's, you really have to talk to the psychiatrist about it. Each medicine is different. Like, you know, aripiprazole, so this is a good, something I didn't talk about, but it's good for you to know. Like there's a difference between the different medicines in terms of their half-lives. Like, so two of them that have the longest half-lives, Abilify and, or Aripiprazole, which is the same, and Cariprazine, Verilar, those two are the, they're relatively new. They both have very long half-lives. So if you miss a dose, it's probably not the end of the world. If somebody's on Olanzapine or someone's on Risperidone and miss a dose, it's probably more of an effect because they have less than a, you know, one, probably about a one day halfway. So would the psychiatrist say to take the dose the next morning and then take another dose at night? Yeah, you really, it's case by case. If someone's on like the highest dose there is of Olanzapine and they miss, you know, and you give, now you're doubling the dose from like, let's say they're on 20 or 30 and then you're going to 60. Like that's a lot of Olanzapine in one day. Psychiatrists may say not to do that, you know, but if they're on a low dose and they're thinking of raising the dose anyway, they might be like, yeah, just give it in the morning. So it really depends. I think it depends on the person. It depends on the perspective of the psychiatrist. It's probably good to ask if you can. I mean, I know probably psychiatrists aren't available that morning to answer, but I can't give you a rule. I can tell you, you know, I can tell you that it probably depends on the person and how sensitive they are. You want to try to not miss too many doses, but I like to use the drugs that you take that have a long half-life because I know that people don't always take their medicine. So I generally, I like to use. I like Verilar a lot because of that reason it could be given. It's very forgiving if someone misses doses. So I don't really like that about it because people with schizophrenia, they often will skip a week worth and they'll just say, I don't feel like being on my medicine. So that medicine is good because it actually, you can actually get away with that sometimes and they won't end up having a problem. So, but it's a good question. I really can't tell you, I can't give you a best practice. I think it depends. Thank you. I have a question. If you can take us in a generalized sense into the therapy room, what is the long view, long horizon goal in a general sense of a psychiatrist with a patient suffering with psychosis? And dovetailing that with what you discussed at the beginning, we are managing and caring for the clients suffering with schizophrenia. So what best practices can we employ immediately and long view to help foster the best outcomes for them long term? So I think, I think I understand your question. So let me say, there's two, there's different personalities of psychiatrists. There are people, and there's also a personality of this system in general. One is you have to take your medicine if you don't want to send you to the hospital and that's the way it is, right? That's probably not the best practice. The best practice is to try to be as patient centered as you can, and really engaging as you can. We talked about acknowledging this, Gary acknowledging that there are side effects, being honest, really trying to work with the person, like some of the substance use disorders, like where they're at, like trying to engage with them as much as possible. And if you do that well, hopefully the person will say, I trust you, I'm willing to take this medicine or take something, and I'll tell you when I'm not taking it, as opposed to just laying down the law, they're going to cheat their medicine, they're going to hide it. There's a lot written about this. It's not, this is not my area, but there's a lot, but I think every psychiatrist is their area because it's just so common. And there, I'm trying to remember, there are resources in the community about ways of talking to people, but I think the role of the support teams is to really like, stay engaged with people and just really talk to them how it's good to talk to your doctor and your medicine really does help you, like can help you, like even if you don't say, okay, fine, you know, maybe that, I don't want to say your delusion is wrong, but you'll just feel better. You're not going to be as upset. It's like, you won't, this won't bother you as much. The cameras won't bother you as much if you take the medicine. It's not that I, I think the cameras are going to go away, but you know, I think you'll just be, you'll be able to live a better life if you take this and, or, you know, it's like, you know, and I really want to try to help you like really trying to take that patient centered approach. I think that's the role of everyone around someone suffering from these illnesses to try to keep them engaged and not, not to be too punitive and not to be too paternalistic and say, you know, this is, you gotta do, you gotta do what you gotta, the doctor tells you, cause that's, you know, you know, you want, you know, if not, you'll bend it back in the hospital. Like that's probably true. And like, but if you're going to say that, you want to try to be as like empathetic as possible and say, I really want you to do whatever, however you can gauge. But does that answer your question? I mean, I think. Yes. And you know, of course we all want to be kind, patient, supportive, but you gave us some excellent suggestions about asking questions along the way. Like is there a different way perhaps you could be looking at this or that, or can you go further with explainings? Yeah. I like suggestions you're giving us of ways to communicate that open up possibilities that perhaps dissipate the immediate anxiety. Right. Well, right. We're looking, we're looking for as many strategies as we can employ to help make the client's experience calm, pleasant, and of course, address and quell the moments when they are agitated and activated. And, you know, we just want to make the most informed, you know, decisions and strategies. Yeah. Agitated and activated. Sometimes it's a good time to take a little more antipsychotic, but right. Use a lot of these medicines as needed. Like you can take another half a dose of a lens of pain. It's usually okay. But, but obviously you have to make sure the doctor's okay with it, but, but yeah, great points. And yeah. Yeah. Can I ask one more question too? I'm curious about, I've heard about, of course, how marijuana can induce psychosis. Can you talk about other drugs and alcohol and how gross abuse can onset psychosis and the process of the mind unwinding and healing from that over months and years, the absence of that? Sure. So, so the, the, the drugs that are most associated with psychotic symptoms are, like you said, marijuana and also stimulants. So cocaine, obviously in the moment when people are intoxication can cause psychotic symptoms, but also high doses of Adderall for people that have schizophrenia or that are, have a pre like sort of a predisposition to develop the problem. So then stimulants can really be a problem as well. I'm not to say that you can't give stimulants if you're on an antipsychotic, but you, so, so if someone's abusing Adderall and abusing cocaine, those are the ones that are the most concerning. I'd say if it happens once and someone, then people do often. So this isn't really another case. It's really another lecture, but in a case where someone has like a substance induced psychotic episode, which happens sometimes you sit down with other people that they get psychotic only when they're using drugs and they, that often will last for a while afterwards. And they, you usually, we use an antipsychotic in those moments that we think it helps decrease the length of that recovery. It makes the recovery faster. So you would want them to be prescribed something and to take something. And it depends on the person. I mean, some people have resolved very quickly, but sometimes someone will use marijuana, you know, and Adderall, and then they'll have psychosis that will last for a month or two, you know, or three, and then they'll still have residual symptoms even like, you know, at the end. But one thing you should just be aware, like be cognizant of is that whenever you have psychotic symptoms, there's difference between someone who's floridly psychotic and that they're gonna, they're like wandering the streets looking, you know, you know, maybe acting bizarrely versus someone who's having like paranoid thoughts where they're able to still live their lives. And it comes, you know, the thoughts come in, maybe they're able to recognize this as irrational. People around them were able to slow them down. That's what you'll see. I mean, I don't know if you've seen this, but you'll see that with someone who's on the tail end, they might still be getting episodes of that, but as it goes away, it will usually taper off. You gave us a very good list at the beginning of questions we can ask, like, if you could give us like, you know, five or six, like questions like, can you elaborate on that? Or can you tell me, you know, more about why you're thinking this or that? Or is there any way I can help these questions that we can ask our clients in these moments that maybe we haven't thought of that can help them? Well, one thing I'd say is it's not always best to ask a question. First thing you want to do is just empathize and say, like, I can see you're really upset. We're trying to do all of that. I'm just thinking about going beyond that. Yeah, I mean, it's specialized. I think it really depends on suggestions, but I'll tell you some of the things they say in CBT for psychosis. Some of the things they say are, you know, just if you wanted to do it, you might ask, like, how sure are you that this is really you're being monitored by the cameras? And you hope that they don't say 100%. If they say 100%, you probably just, you know, probably just have to say, yeah, you know, maybe I'll give you some medicine that will make you less bothered by it because the cameras are there, right? But if they say to you 80%, so then you can say, yeah, so there's 20% chance it's not real. What else could it be? You always want them to do the talking. You want to be giving them the answers. So, and people don't, this is hard. I mean, I have to tell you, CBT for psychosis is not like a big branch of psychiatry or therapy. Very few people do it. It's not a big thing. Probably just supporting people and just being patient-centered and case management is probably much more important. But if you're going to do the CBT for psychosis, that would be the kind of thing you might say, like, you know, the 20%, you know, what's that, you know, what was the reason for that? Like, you know, where's that, what would be the alternative explanation? And you have to sort of live with the fact that you're not necessarily going to convince the person. You always have to be thinking that you're trying to just create some space between this belief and how strongly the person believes it emotionally. So the belief will probably still be there, but you want them to be able to say somewhere along the lines, like, yeah, the thought came, but I realized that was just my brain playing tricks on me. So that language, it's very mindful. And if people who know about mindfulness therapies, you can bring those into this treatment very much. You can say, if the person's, as the person gets more engaged, you can say, you know, let's just try to like notice that, like, and name it. We'll probably talk about that more actually next week because I want to talk about that. Absolutely fascinating. Brilliant. Thank you. Yeah, no problem. Thank you. All right. Other, other questions? If you have any opinions about diet and exercise in relation to psychosis. I like diet and exercise for everyone. There's a book, if you want to read a book about like metabolism and psychosis, which I was, I don't think it's developed. The field's not developed far enough to say whether this is how much this is true or not. It's, it's called brain energy. It's by a guy from Harvard. It's a real researcher. And he wrote about, he wrote a whole book about how he thinks that, you know, the psychiatric disorders are metabolic brain disorders. And if you did a, like a, what's it called? A ketogenic diet with no carbs, maybe that would help. I've had patients on ketogenic diets that I don't know if it really helped them, but no one's really done real trials on it. So I can't say, but I'm always in favor of diet. And diet and exercise definitely are really important for all these things. And when people start recovering, they often start exercising. I mean, they take care of themselves. So, but I, yeah. So, and obviously these anti-psychotic side effects, you really wanna be much, people should be very attentive to their health. So. I have a question and Simon, you had one too, right? Do you wanna go first? Mine is tangential. Please go ahead, Alex. Okay. Yeah, mine is separate from some of the things that we've been talking about. I'm curious if you can clarify why most patients who suffer from schizophrenia are also med non-compliant. It seems like a specific, No, it's a great point. It's a great point. It's actually, yeah, I should have mentioned it in my discussion of disorders. It's not in the diagnostic criteria, but one of the, and now I'm forgetting what term it's, anosognosia or something. One of the elements of the disorder is that people don't realize they have it, right? There's different kinds of disorders in psychiatry in general, actually. In neurology, you can have the same thing, right? You can have a situation where a person where someone is unable to maybe move part of their body, but they don't realize that, they don't even know that that part of their body exists. Or someone else says, I wish I could move it, but I can't. Same thing here with psychiatry. You can have a situation where somebody says, I feel horrible and this is terrible. I have this disorder. Whereas someone else might say, well, no, I don't have a disorder at all. I, they're just, the cops are, the government, the US government is monitoring. I don't have it. The government, the US government is monitoring me. And the voices I'm hearing their brain interprets as the government is beaming the conversation into my mind. And so there's no insight. And that's actually part of the disorder. It's a known problem in schizophrenia. And it is a big part of the illness. That's why you often, people often start treatment in the hospital and they don't have, you know, but so that is a very big part of it, but there is an element of how we talk to people and how we engage with people that helps people get past that. Not taking the approach of like, you take your medicine, I'm right, you're wrong. Instead of trying to be very validating in the patient center, that does help decrease that. There was a great video on this, which I, you know, if I try, if I can find it, I'll send it to Simon and he can send it up. It was a psychiatrist, his brother has schizophrenia. And he talks about how in the beginning, his brother kept being hospitalized again and again. He was so frustrated with him. But then when he changed his approach and he said, I'm gonna start being centered on like his, my brother's perspective and realizing like for him, this is like horribly scary. Like he believes that, I don't know what he believed. He believed that his mother was something, trying to kill him or something. And he, by acknowledging that, he was able to engage with him enough that he was able to keep him on medicine and keep him out of the hospital. So even that part of the disorder, it does respond, we think, to the right psychosocial intervention. So, but it's a great point. It is part of the problem. It's part, it's a neurologic condition. And part of the horrible thing about it is that people don't even realize that they have something wrong with them. And that's part of the cost of medicine. Yeah. And to follow up on that, is it also because their medication is like reducing the amount of dopamine in the brain and therefore it's like, they want to feel that excitement and then they don't feel that anymore? Or is that not always the case? I don't know. It's possible. I don't know if we know the answer to that, but patients often say they don't like their medicine. They don't like the way it makes them feel. But that's sometimes because it's, usually it's not, you know, you could say it's dopamine. I think it's, medicines are very sedating and they make people feel blunted on them. They just don't like the way that they feel. Maybe that is a dopamine blockade. But definitely the medicine is, there's a lot of different sides to that. I mean, often people are put on higher doses than they really need, maybe too fast. And so it's tricky balance, like hitting the dose that will have antipsychotic effect versus helping people, letting people get used to the dose and like maybe tolerating more psychosis for longer until the person gets used to it. So, but medicine is an important piece to it. You're right. And these medicines are not benign. Who wants to take a medicine that's gonna make them tired and gain a ton of weight, you know? Tell us. Oh, exactly. And just one final follow-up. And also because we come from a world where like, you know, mostly dealing with drug addicts who like can't get enough of their medicines or deal with so many, it's interesting to kind of be in this opposite world. And so the final question that I have is a lot of the, a lot of times when we have symptomatic clients, they are aggressive with staff. What is the best way to deal with a client who is showing aggression toward staff as part of a symptomatic episode when they're also feeling relatively non-med compliant? Good question. I don't, I'm not an expert on deescalation and you should obviously do it. We've done some of it. We've done some of that already. I always say safety first. I mean, if someone's dangerous, you should call the police and call EMS to bring them to the hospital. But when you do, when you don't and ways to deescalate, I mean, I think non-verbal communication is very important. Like not trying to be non-threatening in the way you talk and the way your hands are. And this is what I learned when I was a resident. I'm just telling you what I learned. And I think it does work to some degree. I think if you try not to escalate and you try, then it often will help someone settle down. You want to have more than one person sometimes that sometimes having a few people around helps deescalate someone, not making it a one-on-one where it's like multiple people are sort of there. And, but yeah, I think those are the biggest. The biggest situation we've run into is, or at least personally I do, is whether to engage or whether to let, if they're like kind of secluded, whether it's best to leave all enough alone. Because I think we run into like, they're not taking their meds, but they're also not hurting anybody right now. Like, should we bother them to take their meds, which might cause them to outbreak and become more disruptive or not? Yeah, I don't know. Okay. Neither do I. You gotta ask. I mean, you really should have to talk to the psychiatrist and try to like, I mean, I would think, I would think, you know, it's hard. You should, you know, yeah. I don't know. I don't know if there's a right answer to that. I mean, I'm in the hospital. You have this situation a lot where people are very agitated and then you try to get them to take a by-mouth peer. And I think if you do it the right way, they often will be willing to just take something and settle down. I think the right way is what we're trying to nail down. Yeah. Yeah. That's like I said, non-threatening, you know, with enough people, have the medicine ready, say, oh, do you want me to take this? Yeah. But you don't have as much control if you're out in the community. I mean, if they want to get violent with you, you don't have security teams that come running and help you. So, and you don't, you know, so it's, you know, maybe it's better to just let them settle down. It's always a judgment call. I think it's case by case and you have to decide when someone needs to be hospitalized. I mean, it's tricky. It's a hard decision. This seems like it also returns to one of your first slides where you talked about empathizing, validating, and then kind of trying, like establishing rapport, right? Things before we get to the like med issue. Yeah. Does that seem like it is pertinent here? You can try. I mean, sometimes when people are agitated, you can't, they could, no matter what you do. I mean, that's the thing. When let's say someone's in early, yeah, that's definitely good. But sometimes it's not even what you say. It's just the tone of voice. It's the way you're standing. It's a lot of more subtle subconscious things that are probably maybe even more important when someone's getting agitated, but it's not really about like validating. I can see you're upset. It's just speaking like in a calm voice and just keeping your hands in front of you in a non-threatening way, you know, that kind of thing. Not taking like a defensive stance or like angry stance, you know, like, yeah, exactly. So, but yeah, again, really not my area. I don't, this is not the kind of thing that I usually deal with on a day-to-day, so it'd be good if you- Well, your lack of clarity gives me clarity that like the idea of every situation being its own situation and we just have to do the best we can is the best we can do. Well, that's, yeah, that's definitely true. There's no rule. You can only do your best. In some situations, there are like clear, actionable steps and in some there are not, and it sounds like this is one of them in which there are not. I don't think there's enough of this, but I don't know. Again, there may be someone who's an expert who will say, you do this, that'll work. So. Okay. Thank you. Yeah, I, my question, as I mentioned, is quite, it's not exactly tangential, it's just sort of change of topic. You talked a little bit about bipolar. If people are open to it, do we have some time to review that now? Because next week is OCD alone, correct? Yeah, OCD and SSRIs, I was gonna talk about that. Yeah. If we have some time, can we go a little bit deeper into bipolar now? Well, what do you want to know about bipolar? I mean, I didn't prepare this lecture. I mean, I can tell you a little bit about it. But, you know. I think that. I don't know, why don't we, maybe we should save it for a whole nother discussion. I mean, I think, I think I could give you another, if you want, we could just schedule something in a month or two, you know, with a bipolar lecture, if you want. I mean, bipolar is, I mean, I could go over the diagnostic criteria of mania and depression and some of the treatments and things to look out for in that. Lithium, we probably, if I were giving a lecture on bipolar, I would probably talk to you about lithium, lamotrigine, and depico, which are the three commonly used mood stabilizers. And, and it's, you know, and they all have their own, they all have things that are probably worth discussing. So, I mean, yeah. If you have questions about it, I can answer, but I don't think I want to try to like squeeze it in off the cuff, you know. Sure. I guess just, you know, we can talk maybe separately about setting up a separate standalone training for that. But then, until then, what would be the kind of red button things where we see this, and then it's like, okay, this, we have to speak with a psychiatrist or their care team immediately. Like, what are the kind of warning signs? Well, with mania, the big risk is if people are, if you notice someone isn't sleeping, that's probably one of the big red flags. Talking very fast, being aggressive and irritable with everyone. Those are some of the symptoms of mania. If, you know, with depression is, you have to worry about suicidality, but with mania, it's not needing to sleep, increased gallbladder activity, irritability. Those are the things that you worry about that they're starting to ramp up. If someone's up all night cleaning their room, planning things, it could be that they are using cocaine or opioids, but it also could be they're having a manic episode. So, you know, I think that would be like the thing that you, that's when you would like call the psychiatrist and say, hey, this person might need more of an antipsychotic to break the mania. That's what I would say. Can you speak at all to paranoia when it's directed towards the care team and just any maybe tools or perspectives you've gained that are helpful in that? Yeah. That's a tough one. It's hard. I think you can just do your best to try to just stay. Well, this is my, this is personal experience. This isn't evidence, no longer evidence-based, but I think it's obvious, but I think it's not like, just keeping in mind this is probably the person's disease and just trying to stay as empathetic and engaged and not fall into like the trap of like defending yourself or getting angry at the patient because they're getting angry at you, just trying to like acknowledge they're upset, say that you really want to try to help them. But at a certain point, you won't. If someone's directly, if someone's poorly psychotic directing their paranoia at you might not work. You might just have to send them to hospital or like not treat them. It's, I think there's a balance. But, you know, as an outpatient doctor, if someone's too paranoid about me, I mean, I try to remain empathetic, but at a certain point, they'll just go and seek treatment somewhere else. So, because they really think that I'm doing something wrong. I think part of Abe's question maybe is also like, cause we're only one part of most people's care team here. Yeah. And so they're telling us like, hey, my psychiatrist is doing X, Y, Z thing. And they're paranoid about that? Yeah. But they have a greater degree of trust with us. Is there a way? Yeah, I mean, I think you can do all the stuff we talked about. I mean, you can try to say like, yeah, I think your psychiatrist probably is, you know, I mean, you could say, you know, it depends. I mean, sometimes psychiatrists are, don't really care and they're busy and they're like, right, sometimes. And so you don't want to be like, invalidating of that feeling, right? But sometimes they're like paranoid about the psychiatrist. So they're like, they're poisoning me with this medicine and they believe that they're trying to kill them. So that you can do the same stuff we talked about before. I'm like, oh, you know, really? That's interesting. Tell me more about that. Like, I never would have thought that. Like, what's making you think that? You know, you can just be, again, be curious, and then just try to like, help them see that there's another side to this story. Help them see that there may not be, this may not be 100% obvious, so. What are the most helpful type of notes that you receive, say like from clients, loved ones or care teams in regards to psychosis, paranoia, or schizophrenia? Like what kind of information for you as the doctor is? I mean, well, I would want to know if things are getting worse or better of the medicines that I'm using, right? Like if you notice that the person's getting more agitated or violent. Side effects, akathisia is very important. If you see akathisia, tell the doctor, and they can tell them to stop it. You really don't want to be the psychiatrist causing a person to be miserable, you know? Akathisia is the pacing? Akathisia is the pacing, like the feeling, like the feeling like I need to move. Yeah, okay. Like I, but I just generally, I think, are they taking their medicine? Are they able to function? Are they getting less agitated? You want to know how your treatment response is. It's very hard to know as a psychiatrist. You see a patient who comes every month who doesn't really speak a lot and just says, I'm fine. Or, you know, they don't even talk. Or they just, you know, people with schizophrenia, it's one of the negative symptoms. They don't really give you a lot. So hearing from the care team is very valuable to say, yeah, since you raised the dose, that person seems to actually be able to engage a little bit better or not, or they're really not engaging. They're still in their room. They're really not doing well. That's a useful information for a psychiatrist to know. Because it's, just getting facts for a psychiatrist is very valuable in someone with schizophrenia. Thank you. I was wondering about the third generation medication, like what those receptors were, the T-A-A-R. I've just never seen that. I don't know if you can answer that right now. No, I'm not sure. There's, it's a downstream, I mean, I kind of know what it is, but I'm not an expert in neuroscience. But it's, the brain, the nerve cells are amazingly, the brain is an amazingly complex organ. It's a really amazing thing. So the receptors are the way that the cells talk to each other. But after the receptor gets activated, there are things that happen down, like in the cell that change. And that's one of those things. So you can actually modulate things that are more subtle by affecting some of the downstream effects of the drug. I think that's what TOR is. And so, and I think that's more theoretical, I don't know. The new, like the new one I mentioned to you, it acts on the nicotinic, just a different receptor, so. Yeah. All right, well, I think, I feel like I've spoken enough. So I'm gonna, well, we have next week to talk more. And if people have more questions they think of, I think the OCD lecture is a little shorter, although OCD, if you really want to know how to treat OCD, that could take a course. So, but we've talked, let's talk more next time. And we can also, if you guys want to do a bipolar talk, we can do a bipolar talk and I'll just give you, it's the same idea, but the diagnostic criteria and some of the other medicines that we didn't talk about today that are relevant and we can go over it. Lithium is, lithium is an important one to understand because it has a lot of different side effects that you have to look out for and monitoring and different things, so. All right. Thank you so much. Dr. Shulman, thank you so much for your time. Great to see you.

schizophrenia

Opioid Response Network

antipsychotics

paranoid delusions

marijuana use

medication non-compliance

diagnostic criteria

second-generation antipsychotics

cognitive behavioral therapy

family support

patient engagement

dual diagnoses

medication adherence