Workshop: Methamphetamine-Associated Psychosis (MAP): Clinical Challenges and Approaches to Management-Methamphetamine-Associated Psychosis (MAP): Clinical Challenges and Approaches to Management

Methamphetamine-Associated Psychosis (MAP): Clinical Challenges and Approaches to Management
Video Transcription
Good afternoon, everyone. I know that people are still trickling in, which is great. It's been a busy day, wrapping up lunch, committee meetings, but I'm going to get us started  today. I wanted to welcome all of you to our workshop on methamphetamine psychosis and treatment implications and approaches. This is a tough topic. My name is Larissa Mooney.  I am an addiction psychiatrist on the faculty at UCLA. I'm really excited to be here with two of my close UCLA colleagues, including Dr. Mike  Zito, who is the chair of this workshop and really had the vision for this workshop as he has carved a particular clinical and research interest in this area.  In California and in our clinical settings at the VA and UCLA, we see a lot of methamphetamine use disorder and other co-occurring substance use disorders, psychiatric disorders.  So we hope that this is a lively discussion, engaging, and that you bring your approaches and your case examples to the discussion once we get through some of the intro slides and  the materials. I'm also joined by one of our fellows, Jose Flores, who I've had the pleasure of working with also at UCLA.  He has graduated Addiction Psychiatry Fellowship and is now a T32 Child and Adolescent Fellow  and will be presenting the case today on which we hope is really a springboard for discussion. So with that, I will get started.  This is our disclosure slide and these are our learning objectives. First to discuss the current methamphetamine epidemic, trends in use, production on a national  scale, describe the background of methamphetamine-associated psychosis, including some of the pathophysiology and relationship to schizophrenia.  I will also mention that Dr. Zito has expertise in serious mental illness and treatment of SMI.  Review evidence-based treatment strategies for methamphetamine use disorder with a focus on which could be favorable for individuals with methamphetamine-associated psychosis  and discuss treatment strategies that specifically target psychosis among individuals who use methamphetamine. As I mentioned earlier, this is not an easy clinical issue.  It's challenging for I'm sure all of us in this room and we really want to learn from each other.  We're going to bring and share some of our clinical experiences, what we know and what we don't know from the literature and hope we leave with some new pearls.  Another piece of history behind this workshop, a few years ago for a couple of years, I also presented with Alona Balsanova, workshops at AAAP on treatment of methamphetamine use  disorder and really want to acknowledge her and our collaborators in some of the thinking leading up to this with that specific focus and in fact one of her slides.  Okay, so with that I will move into some background slides and information about the methamphetamine epidemic and some changes in use.  We can start with a warm-up quiz question, polling question. We will ask you just to raise hands, easier than dealing with technological glitches.  But just to get us thinking, in 2007, the DEA reported that methamphetamine sampled from the community had a purity of 38.7%. In 2019, this value had changed to what?  How many would say 20%? Okay, a few. 50%, 51%. 66%. Getting there. And 97%. How many takers? All right. The answer is 97%.  So methamphetamine now that's being tested is very pure, over 95% pure, which really purity involves absence of contaminants. Why is this important?  We know that methamphetamine use is a major public health problem. About 1.5 million individuals met criteria for a methamphetamine use disorder in 2020.  Past-year methamphetamine use in adults has been increasing. Obviously it's come in some ways, but most recently since 2016 to 2019.  And we're also seeing an increase in methamphetamine-related overdose deaths, 43-fold increase over a 20-year span from 99 to 2020. That is really, really significant.  And certainly we hear about the opioid epidemic that is a major, major public health problem, but we're also seeing a rise in stimulant-associated overdose deaths.  We know that availability and accessibility of methamphetamine is on the rise. It's cheap, easy to make, and readily available.  And we'll talk a bit about the effects on some vulnerable populations, including individuals with SMI.  We have seen an increase in, as I mentioned, purity of methamphetamine when tested on the Southwest border in recent years. Purity and potency.  The purity has remained above 95% for many years, and the potency has had some fluctuation, but more recently approaching 95% as well.  And this also has to do with some of the chemical processes that have changed in how methamphetamine is made.  As I mentioned, stimulant overdose deaths are on the rise, as represented by the blue bars. Many of these are in combination with opioids, as you can see by the yellow line, rising  in recent years, but a significant proportion of stimulant overdose deaths are stimulant-only. Even in the absence of opioids or co-use, stimulant-only overdose deaths are on the  rise, and the bulk of these represented in this figure are methamphetamine. You might have seen an article in a recent book by Sam Quinones.  He's the author of Dreamland, which really focused on the opioid epidemic in this country,  and more recently has been publishing on the methamphetamine epidemic and how it intersects with the fentanyl epidemic.  And some of, again, the changes in how methamphetamine is made and the clinical impacts of those changes.  Of course, there are some journalistic interpretations on what does this mean. We know that, for example, new methods like P2P as a precursor, rather than ephedrine,  ephedrine sales were banned, but there are just new methods that are easy, cheap to make methamphetamine, and it's shifting the ratio of D to L isomers.  The isomers affect where and how methamphetamine has clinical effects in the body. So the D isomer has more CNS effects as opposed to L in the periphery.  So this shift in the ratio towards more D related to some of these changes in chemical  processes is impacting the potency of methamphetamine, potential addictive qualities, and psychiatric and medical consequences.  He takes it a step further to say this is worsening mental illness, homelessness. That could be a whole separate discussion, but I'm just pointing it out because many  of us have read, discussed, and even debated some of the points in this Atlantic article as well as the book.  This is one of our slides from the history of prior workshops related with Dr. Balasanova. The term meth 2.0 was also coined in many press articles around the new methamphetamine,  the new, more pure, more potent methamphetamine with greater addictive potential, increased cardiotoxicity and psychiatric effects, and entering the country very cheap and readily  available. In terms of mechanism of action, just as a brief review, methamphetamine increases catecholamines in the synaptic cleft.  Dopaminergic neuron enters the neuron, facilitates the release of stored dopamine and norepinephrine from vesicles.  It also blocks reuptake at the transporter and inhibits the breakdown of methamphetamine inside the neuron, which increases its neurotoxicity.  Hence we see clinical effects of methamphetamine like other stimulants ranging from elevated  heart rate, blood pressure, increased alertness and energy, decreased appetite, insomnia, anxiety, movement disorders, agitation, these are more severe consequences and symptoms,  depression, suicidality, and psychosis, which we will be focusing on today, and really the whole gamut.  Some of these symptoms and effects are the reason why people like using methamphetamine, why they're drawn to it, and their perceived benefits around reducing the need for sleep,  reducing energy, and facilitating weight loss and sexual activity. Terms of treatment, I'm going to only spend a couple of minutes on treatment approaches  for methamphetamine use disorder so that we can segue into meth psychosis in particular. We have no approved medication treatments for methamphetamine use disorder, however,  we do have behavioral treatments as the current gold standard. Emergency management is the most robust evidence-based treatment in the literature, which involves  incentivizing certain outcomes such as a meth negative urine test. Other approaches include CBT, community reinforcement approach, this has support in the literature.  CRA is an approach that involves finding other healthy reinforcing behaviors that could be available in one's life and in the community to substitute for drug using behaviors.  We of course want to apply MI across all SUDs. There's some evidence for physical exercise in the treatment of stimulant use disorder.  And all of these approaches can be readily integrated with harm reduction approaches. Really we want to think about a comprehensive treatment approach for our patients, meeting  them where they're at, and always thinking about reducing harm and risk no matter where they're at in their readiness for a full treatment program, such as safe injection practices,  needle exchange, naloxone, we know that methamphetamine can be contaminated with fentanyl, or co-use is now very common, offering naloxone and providing that education.  And fentanyl test strips, HIV prevention approaches. Won't spend much time on this, this slide is not comprehensive, but it highlights some  of the medications for which there are signals in the literature demonstrating benefit in the treatment of methamphetamine use disorder.  Reduction in methamphetamine use or prolonging abstinence, again these are all off-label, and even among these medications there are some negative studies.  But when I'm approaching methamphetamine use disorder treatment in my patients, I think about these medications, bupropion, mirtazapine, the more recent study combining naltrexone  and bupropion. Methylphenidate is a stimulant approach that has shown some evidence in the literature, topiramate and even modafinil.  I think about these medications and what are the other co-occurring psychiatric symptoms that may be prominent for that patient, or a clear disorder, depression, ADHD, are they  really anxious and have a lot of insomnia, such as mirtazapine. So if I can use one of these medications for an indicated disorder or just a prominent  symptom that they're struggling with, that may help me select among these medications to treat patients with methamphetamine use disorder.  So with that, I'm now going to turn this over to Dr. Zito to really focus on how we pull some of this together when thinking about the treatment of methamphetamine-associated  psychosis. Thank you. Thank you, Lursa, for that introduction. So I'm going to be talking about meth psychosis.  This is something that I do a lot of teaching on locally, and it's really a privilege to sort of speak in front of a wider audience. Just a little bit about me.  So I'm a psychiatrist. I graduated from residency in 2018, and after that, did a research fellowship at the Los  Angeles VA with Lursa as one of my mentors, and in that time, really took an interest in methamphetamine psychosis.  I did a lot of literature review, and I also designed and implemented a pilot clinical study on an intervention for people with meth psychosis.  And I also have an interest in schizophrenia. I work in the VA, it's called the Thoughts and Perceptions Clinic.  It's our specialized schizophrenia clinic, and I also work in a research program for first episode schizophrenia at UCLA called the After Care Program.  And really, in this talk, I wanted to focus on kind of three questions that might come to the mind of a clinician treating this population.  Number one, what do we know about methamphetamine and psychosis? So this is really kind of going into more of the basic observations and basic science  behind meth psychosis and what we know about that. I won't go into super detail about that, because this is more of a clinical talk, but we'll talk about that some.  Also, how can we distinguish meth psychosis from schizophrenia? This I feel is one of the more puzzling questions, and it's certainly one of the things that  really got me interested in this topic, kind of coming into residency and expecting things to be kind of simple and diagnoses to be clear.  That was really not the case, especially early on in training when you're spending more time in inpatient units and emergency rooms.  And then finally, what does good clinical care look like? This is obviously about treatment, and I'm going to try to touch on not only what the  literature says, and it's a fairly limited literature, but also what recent guidelines from the AAAP and ASAM have to say about psychosis and also just integrating our clinical  experience in treating this population. So what do we know about methamphetamine and psychosis? We know that meth exerts its pharmacologic effects primarily through dopamine.  Larissa touched on this, and I'd like to show this picture of the brain, specifically it's  the dopamine reward circuit, to really emphasize that dopamine projects to and has influence on a variety of brain regions, from cortical regions involved in executive functioning  and decision making, to subcortical regions involved in motivation and affect states, learning and memory, and motor movements.  I also show it to acknowledge the relationship between dopamine and psychosis. So dopamine, obviously for decades, the dopamine hypothesis was sort of the central explanatory  model for schizophrenia, and even though now we know that schizophrenia is much more  complicated and involves other neurotransmitter systems and other factors, and it's a developmental  disorder, the association with dopamine and psychosis is obviously still important. And it of course is for meth as well.  Obviously a dopaminergic neuron, sorry, a dopaminergic substance we know causes dopaminergic alterations which can lead to psychosis.  But the picture for meth psychosis is also more complicated, and some of the limited research has looked into other factors and things like neuroinflammation and free radicals  and neuronal damage as probably being important. We know that psychosis has been induced in a laboratory environment.  This is now a historic study from the early 70s in which individuals, healthy individuals  were recruited and had infusions of dextroamphetamine, and in this particular study all but maybe one or two of these healthy volunteers could be induced into a psychotic state.  We know that psychosis is common in people who use methamphetamine. This should come as no surprise if you treat this population.  But a fairly recent meta-analysis calculated a rate of 36.5% for prevalence, and this was using a DSM definition of substance-induced psychotic disorder, so a fairly high threshold.  We know that there's something of a dose effect, so more methamphetamine used, more severe patterns of use, and also earlier onset, age of onset of methamphetamine use have all been  associated with more psychosis. The route of administration is a little bit less clear. The studies that have been done don't point to something like injection, for example,  being necessarily more likely associated with psychosis. We know that family history is important, so this also is probably fairly intuitive  as a clinician, but one study from 2005 found that first-degree relatives of people with  methamphetamine were more likely to have schizophrenia than their relatives who never had psychosis.  Not only that, people who had persistent psychotic symptoms with methamphetamine, that association was greater for those individuals in terms of psychosis.  Sorry, the risk of schizophrenia was greater in first-degree relatives of those with prolonged psychosis compared to acute.  One of the things that's fairly consistent from just the literature on stimulant use disorder is that chronic methamphetamine use is associated with an overall dampened  dopamine signaling. This is from a high-impact meta-analysis that came out in 2017, and this is just a summary figure from that meta-analysis.  Some of the important findings here are that in stimulant use disorder, so this is also they looked at cocaine, people who use cocaine and also methamphetamine, there's a reduction  in dopamine transporter, dopamine release, and D2D3 receptor density. So those were the findings that were statistically significant from the meta-analysis.  We know that animal models have been used to simulate meth psychosis, so dating back to early research in Japan in which macaque monkeys were infused with methamphetamine  and then had sort of differential responses to the methamphetamine, depending on their rank in the social hierarchy, to more kind of modern animal models, usually involving rodents.  So you can infuse a rodent with amphetamine and it will develop a sort of psychotic-like state with stereotyped motor movements, and also there's a sensitization effect, so the  longer that it enters that state, the easier it can get into that state in the future from amphetamine infusions.  And also the phenomenon of pre-pulse inhibition, which is also observed in people with schizophrenia,  which involves a reduced startle response from an auditory signaling, and that can be induced with amphetamine as well.  And so these animal models are used to sort of get at what are the important factors for the development of psychosis, like cellular factors and neurochemical factors.  We also have observed, Larissa and I in some of our research, that individuals with meth psychosis have high acute care needs.  This is from a publication in which we looked at secondary data from our health care system  and found that people who had received diagnoses of meth use disorder and undifferentiated psychosis  really had an increased risk of basically coming back to the hospital for an admission or an emergency room visit compared to various similar groups.  This suggests not only that this is a high-risk population for sort of additional episodes  of psychopathology, but also that this population might be particularly high-risk for using acute resources heavily.  So shifting gears a little bit, how can we distinguish meth psychosis from schizophrenia? And going to a polling question here, which clinical characteristic is most likely to  distinguish meth psychosis from a primary psychotic disorder like schizophrenia? And I should add, according to the DSM.  Time course of symptoms, presence of bizarre delusions, positive urine drug screen for amphetamine, or response to an antipsychotic? How many people for A?  Okay, B, C, D.  So if you're looking at the DSM, the answer is A, just sort of written into the definition of the DSM, which I'll get into right now. So this is sort of the guidance that we have.  And so this is what the DSM tells us, particularly if you have someone who's experiencing psychotic symptoms, and also using a substance at the same time.  In our case, we're talking about meth. So diagnosing a primary psychotic disorder, the individual, their psychotic symptoms  are likely to precede the onset of substance use. This is sort of a piece of historical information that can be very useful.  It can sort of shortcut the process of making a diagnosis.  That information isn't always present, or it's not always clear if the individual had the symptoms before the onset of meth use.  Number two, psychosis persists for a substantial amount of time into abstinence, or about one month. So the person has achieved abstinence, and then their psychotic symptoms  persist after that abstinence. This one-month guideline is a bit problematic, and I'll get into that in the next slide.  Or number three, there's other evidence suggesting an independent and non-substance-induced psychotic disorder, fairly vague.  To diagnose a substance-induced psychotic disorder, the symptoms usually develop during or soon after substance use or withdrawal. So there's a temporal relationship  to the onset of symptoms.  And the involved substance is capable of causing psychosis. We know that meth is, and there's no previous primary psychotic disorder. So where do we like to focus history-taking?  So obviously the time course. If you can get the information of whether the psychosis preceded the methamphetamine use, that's obviously important.  And then how long were the periods of abstinence? As I mentioned before, this can be kind of hard to ascertain. So I really like to link this particular information  with, you know, in their timeline.  If there's a period in their life that they can say during that time they were definitely abstinent, usually that's residential treatment.  Or it could be incarceration. Because it can be hard to know when you were abstinent, when you were not, when you were experiencing  psychotic symptoms or not, trying to remember that,  you know, at some point in the future.  And then did the psychosis resolve during periods of abstinence, and was antipsychotic medication given? These are all important questions.  And then that one-month guideline is problematic, particularly because persistent psychosis has been repeatedly observed in literature.  And most of this actually comes out of literature from Japan. So in the mid-20th century, Japan had sort of a monosubstance epidemic with amphetamine.  And there are numerous publications out of Japan that were summarized nicely in this review from 2010.  And there are some questions about sort of the diagnoses from this, from some of these studies,  whether they truly met criteria for substantive psychosis or more likely schizophrenia. But there really is enough consistent observation  that at the very least, this one-month criteria is not really sufficient, that people really do are capable of, or vulnerable to psychosis for longer, like multiple months,  even six months or longer.  So it's also important to pay attention to psychosis-related factors, such as the pattern of psychosis onset. This is something that, for example,  if somebody has more like a classic schizophrenia presentation, like insidious onset of negative symptoms with ultimate development of positive symptoms, loss of functioning  around that time, that is sort of our classic,  one of our classic presentations of schizophrenia compared to like an acute onset of psychosis, which we know can also happen in schizophrenia.  But those are some of the sort of factors that may help you lean one way or another in this sort of clinical determination.  The severity of psychosis is important. I mean, I think that this is important generally to understand the severity of psychopathology,  but so determining whether during periods of psychosis the person had hospitalizations, whether they had kind of severe behavioral issues.  And I put this also because you may be seeing somebody with meth psychosis in a residential treatment program, for example, who looks really good, and maybe they have  full insight into their psychosis, they're abstinent from meth, they hate their psychosis, they don't want to use meth again, they're sort of a model patient.  So it may be tempting to kind of forget about the fact that maybe when they were psychotic they had very severe symptoms. I'm thinking in particular of one patient  who was high functioning but on meth, had very severe delusions and actually attempted homicide.  You know, and that sort of differential, I've seen that with a few patients, sort of the differential between the severity of their psychosis and then how good they look  when they come back to their baseline.  And then the characteristics of psychosis, so this is a question that often comes up, of like, if you have somebody and they have these sort of like, you know,  classic schizophrenia-like symptoms, like grandiose delusions, like Schneiderian first rank symptoms like running commentary, is this enough to tip you in one way or one direction  or the other in terms of diagnosing a primary psychotic disorder? This has actually been studied in the literature and there are studies in which comparisons are made  between meth psychosis and primary psychosis.  In fact, there's a meta-analysis from 2018. In reading it through, there's not terribly a lot of useful, like clinically useful sort of conclusions to draw from it.  One of the things that the meta-analysis tells us is that people with schizophrenia may be more likely to have disorganization and negative symptoms,  which is fairly intuitive, I think, for most clinicians.  So ultimately, I would say that there's not enough from that particular literature for clear guidance  on how to use the characteristics of psychosis. One of the things that I would say is that if someone does have bizarre delusions or these kind of schizophrenia-like delusions,  it's not enough to say that that person definitely has schizophrenia, that you can see those in meth psychosis and that has been documented.  Of course, history of treatment response is really important to know. If they were on an antipsychotic in the past that they did well on, that's important to know,  obviously, for your treatment planning.  I include these slides just because I like to share kind of how I like to envision history taking internally with this sort of sense of a timeline of a patient's life,  and then I fill in things like hospitalizations, which are important events to know. And then this person has two episodes of methamphetamine use  with psychosis that began after the onset of methamphetamine use, and then one of these episodes, both of them resolved, one resolved with medication,  the other didn't, and this is a, we can feel fairly confident that this is likely methamphetamine-induced psychotic disorder.  This is a different patient, and this person has chronic methamphetamine use interposed by a period of abstinence in the context of residential treatment, and then this person  also has chronic psychosis. And then what do you do with a case like this? I think these are some of our more challenging histories to take. And so the answer lies in how long  this period of abstinence was. Was it two weeks? Well, two weeks isn't actually a terribly long amount of time, and really, we would need more information.  Two weeks kind of fits squarely into that very conservative one-month guidance from the DSM. So if it's only been two weeks, I would say  that we still need to observe this individual before making a definitive diagnosis. Six months, six months is actually a fairly significant amount of time.  The brain has had a lot of time to sort of recover from the effects of methamphetamine, and if somebody has psychosis for six months into abstinence, I would start to get  pretty darn concerned about schizophrenia at that point.  You still have justification in calling it a substance-induced psychotic disorder based on the Japanese literature,  but I would say that this is where I'm really starting to feel more  confident about the schizophrenia diagnosis, particularly if the symptoms are waxing and waning, or maybe getting worse at times, maybe you're adding more medications,  and they don't seem to be responding.  So this is off or on medication? So this is, so I didn't put that on the slide, but I think whether they're on medications or off is an important factor to consider.  Obviously, if they're on medications, that makes your case even better that they might have schizophrenia.  Three months is more of a gray area, and three months I might start to pay more attention to those sort of other factors, such as the onset of, the characteristics  of the onset of their psychosis, whether that was particularly compellingly schizophrenia-like,  and also things like the progress of their symptoms through time, whether they received medications and so on.  Okay, so finally, treatment. What does good clinical care look like?  So this is some information about the clinical approach.  So care should be delivered simultaneously. This comes from recent guidelines from ASAM and AAAP that were released recently on stimulant use disorder,  and I think this is a pretty well-known  just treatment guideline for all of addiction psychiatry that we really shouldn't wait until one of, until the psychosis is better  before treating the substance use disorder or vice versa.  This is also a very kind of basic thing to say, but therapeutic relationship is the core of treatment, and the hardest part of treating individuals like this  is could be getting them to accept the treatment,  and people with meth psychosis really have two reasons to be hard to ally with. They have psychotic symptoms, which may interfere with their ability,  which may sort of make them more suspicious  or guarded or paranoid, and also just the ambivalence of addiction  may interfere with their ability to really consider your treatment recommendations.  So I like to show this figure, which I borrow from the CPD for psychosis literature, and some of you may be familiar with it, but it's really guidance on how to respond  when someone talks about a delusion, so really there are kind of like two extremes on how to respond. One is confrontation, which is basically telling a person,  no, your belief is false, and here is the evidence for which it's false, and I'm gonna try to change your mind on that, whereas collusion is the opposite,  which is like either tacitly or actively allowing them to kind of believe that you believe their belief along with them, and that one is kind of less common  and less kind of like of a temptation, but really what CBT for psychosis, what that kind of literature tells us is that it's best to kind of be in the middle,  and so really enhancing things like validating their distress, really speaking to their distress,  so saying things like, I see that this really bothers you,  your neighbor is spying on you, or the stalking, and I'd like to reduce some of that discomfort so we can really get to the bottom of what's going on,  and so that sort of empathetic treatment approach I think is especially important in this population of people with co-occurring disorders,  and then provide the patient additional care and resources if needed. This is a figure that I borrowed from the first episode literature of CSC or Coordinated Specialty Care,  and really it's an acknowledgment that people early on in psychosis really benefit from a lot of different services,  particularly if they have a co-occurring substance use disorder, have numerous reasons for needing that extra support,  such as in addition to their mental health treatment, supported employment and education, peer support, and things of that nature.  And then of course delivering stigma-free care using person-first language and psychoeducation.  Okay, another polling question. So a 29-year-old man is brought to the ED for acute psychosis and agitation in the setting of unremitting methamphetamine use.  Identify what could be part of a appropriate medication treatment plan for this patient. Droparadol, which is a first-generation antipsychotic,  lorazepam, olanzapine A and C, or all of the above?  How many for A?  B?  Okay, C?  A and C?  So the answer I have is all of the above. Um.  Yeah.  And this really comes from literature that has looked into a few of these different treatment options.  So another guideline is when able, treat the psychosis with appropriate pharmacology. So, and this is really a response to I think what a common idea in terms of the,  focusing on some of the risks of antipsychotic treatment in methamphetamine intoxication, such as NMS or seizures. And really what the literature has shown  is that those risks are a little bit overstated. So do treat with an antipsychotic if the person has significant psychotic symptoms.  Yeah, so as I mentioned, the use of antipsychotics in acute agitation and psychosis is generally supported. This is from the emergency medicine literature.  Um. And one of the points that the guidelines also make is to always include a wide differential if somebody is coming in an acute and agitated state  to not forget about sort of life-threatening medical issues that could be causing that person's presentation as well.  What about methamphetamine-induced psychosis? So what does the literature say about, say if you're treating a person with this entity, either in an inpatient unit  or maybe in your office as an outpatient.  And so again, one of the main take-homes is that this literature is fairly limited. We can say that antipsychotics are generally effective.  This is from low-quality evidence with a high risk of bias. There has been one Cochrane review, which is old now, but which included one study.  Since that time, several more clinical studies were completed, and actually a network meta-analysis was done in 2021.  This is just a table from that meta-analysis showing the six studies that were included in it.  And so all of these studies were  from different countries, from the United States. Most of them were inpatient. And all of them included a comparison of two antipsychotics to each other.  So you see like olanzapine compared to haloperidol, Abilify compared to risperidone. And then the durations were fairly short, up to 42 days.  And what really, what was seen in these, from the meta-analysis of these studies is that they all kind of reported no significant difference between antipsychotics on main symptoms.  So basically, if you were somebody with metipsychosis in one of these clinical trials, you generally got better from your symptoms if you were receiving those antipsychotics.  The network meta-analysis also came up with sort of a rank order of antipsychotics. And I wouldn't read too much into this because of the kind of low number of studies  and comparisons, but what they did report was that olanzapine and quetiapine were found to be superior to risperidone,  and that Abilify was found to be inferior to olanzapine, quetiapine, haloperidol, and paliperidone.  And so how do we make a choice for an antipsychotic? Especially given the sort of limitations of the literature, what we do is basically, we consider the same factors  as you would in schizophrenia.  So I put patient preference first because I think it's a very important factor. Obviously the best, heard earlier today, the best medication is the one your patient will take.  I think there's truth to that, and particularly in this population.  And then we look at side effect profile. So some common comorbidities among people who use methamphetamine would be insomnia, psychomotor symptoms, anxiety.  And so something like quetiapine is a pretty good choice if you're considering those comorbidities. Quetiapine unfortunately has the disadvantage  of not only having a lot of metabolic side effects, but also needing to get to a high dose for the antipsychotic effect. So olanzapine and risperidone are sort of two  of my personal favorites. Risperidone is what I used in the clinical trial that I designed. And also kind of looking into their treatment history.  And this is, again, more basic stuff. But knowing what their trials were like in the past, it's basic, but doing the basic things really well really goes a long way.  So looking at how long they were on the medication, were they compliant with it, what doses were achieved, and so on.  Long-acting injectables are probably helpful in this population. And this is something that gets talked about in the literature. And I think it kind of relates to,  you know, this population has multiple reasons for being kind of like poor functioning with poor follow-up. So if you can get them on a long-acting injectable,  it's probably a good idea to consider that.  One thing we can say is that it's also probably a good idea to use Abilify with caution. And this relates to a few observations that have been made in the literature.  So Abilify has been found to be associated with an increase in some of the rewarding and stimulatory effects of methamphetamine. This is from a laboratory study in which Abilify  and methamphetamine were co-administered. And also Abilify in one clinical trial  was found to be associated with higher amphetamine-positive urines that actually led to the study termination, early termination.  These two observations are not, you know, robust and compelling to say never prescribed Abilify, but they are, you know, they're there.  And I would say that they warrant careful consideration, you know, particularly if you have other options  to try those other options first. If you have somebody who, say they did well on Abilify in the past, or they really like Abilify for some reason, I wouldn't withhold it.  And sort of a similar vein is to use first-generation agents with caution. So this is basically something I follow and I think a lot of us follow  for the treatment of schizophrenia in general.  But I think, you know, it gets talked about in the literature that first-generation agents might be associated with sort of a rougher course  of treatment in people with co-occurring disorders. And there's this sort of discussion of neuroleptic dysphoria that occurs with Haldol in people using substances  that might contribute to cravings. So this is something that I would say might be a prudent thing as well.  And then another point from the recent guidelines is to avoid oral stimulants and modafinil due to psychotic risk, risk of psychosis.  What about tapering the antipsychotic? So if you have an individual who has gotten better, maybe their abstinent and their psychotic symptoms have improved, how long do they have  to be on an antipsychotic?  I think also for schizophrenia, this is an area of debate, and there are a lot of different notions about it and things to say about it.  I would say that in terms of methamphetamine psychosis, we really know very little about the appropriate duration of antipsychotic treatment.  So a lot of this comes down to your clinical judgment. But the recent guidelines do encourage us to consider an antipsychotic taper after a period of remission,  and this is related to the known adverse effects of antipsychotics and being on them long-term. And somebody with a substance-induced psychotic disorder  is sort of at risk to be on these medications for longer than necessary. So careful consideration of whether a taper is warranted, I would say, is really important.  Before you do the taper, I think it's also important to assess the accuracy in your diagnosis. So how much do you really believe  that they have a substance-induced psychotic disorder versus primary psychosis? So looking back at their history,  looking back at doing a chart review, doing further interviewing with them, I think would be important here. The taper is also something of a diagnostic test in itself.  Obviously, if you have somebody on antipsychotics that you're tapering and their psychosis comes back and they're still abstinent, that would give you useful information  and make primary psychotic disorder more likely.  And then, of course, consider the typical clinical factors that you would when planning a taper. So the timing of the taper is obviously important.  So you don't wanna taper somebody off a medication when they have stressful things going on in their life, like starting a new job, new housing, or any kind of stressful issue.  Also, the speed of the taper is kind of important  to consider.  Somebody who's been on antipsychotics, like 30 of olanzapine for years, may be someone you'd wanna taper more slowly than if they were on risperidone,  one milligram or something for two months.  And again, these are sort of basic tenets of kind of good psychiatric practice.  Regular monitoring and observation is important. It can be kind of a luxury, particularly for this population  who may have poor follow-up, and you may really struggle to keep them in your office.  But if you can monitor them through the taper process, it's really important.  And then, of course, care setting is relevant. If you're treating someone in a residential setting or an inpatient setting, you may have the ability to observe them more closely,  and therefore, you may be able to do the taper more quickly  given that closer contact.  So, with that, sort of wraps up my part of the discussion.  I'm gonna pass the baton over to Jose Flores, who's gonna talk about a case.  Thank you.  All right. Thanks.  Okay.  Hello, everyone. So, this part, we would like it to be more interactive, and to me, it's really important  to participate in this discussion. When I trained, I trained at Yale University. We didn't have as much of a prevalence of methamphetamine use.  I saw many other types of substance use disorders, but then I moved to UCLA, and I have been working for the Office of Reentry,  Diversion and Reentry, and the prevalence is enormous in this state. And as the prevalence increased, I saw that the complexity of the patients that I was seeing also increased.  So, in terms of involvement in the criminal justice system,  being unhoused, all of it was increasing, and even the comorbidities, mental health comorbidities, and also the different types of use disorders.  So, today,  can you hear me there?  Sorry. Okay, there? Okay. So, in this interactive part of the talk, I would like to focus on four issues. I will be presenting a case,  and I don't know if you can feel free to jump in and also ask of Dr. Ciro and Dr. Mooney.  So, we will be focusing on diagnostic issues, antipsychotic maintenance and tapering, social factors, and medical comorbidities.  So, this is the case.  You have a new patient who walks into your office for medication management and follow-up of auditory hallucinations and drug cravings. He's a 32-year-old man with a history  of methamphetamine use disorder, and also has a history of opioid use disorder, and has a documented history. This is an important part of the presentation.  He has this documented history of schizoaffective disorder, and a medical history of HIV. He reports that now he's overall doing well. He has some cravings for methamphetamine,  and he denies psychotic symptoms at this moment. So, this is a real-world scenario, and you might see some inconsistencies, but they're part of the medical record.  So, this is the time course for psychosis. Psychosis started after the onset of methamphetamine, in this case, in 2019.  Psychosis lasted for three years, but it resolved. He has not had any symptoms for nine months. He has also not had any substance use for one year. He's in a housing program,  and this has been confirmed multiple times with urine toxicology. And there's a three-month period of psychosis during a time that he was abstinent.  The characteristics of his psychosis included auditory hallucinations. He heard voices telling him to steal cars, to fight with others. He had delusions.  He thought that he was constantly being monitored by the police. He had thoughts that police was monitoring and reading his own thoughts.  And this resulted in him starting carrying concealed weapons because he thought he should defend himself.  And eventually, this resulted in, ultimately, over 11 arrests.  He experienced delusions, so he misidentified pedestrians. He was paranoid, and he thought that they were police officers. With a very high severity,  every time that he presented, he was arrested. And this was likely the principal cause of his arrest.  And his functioning started to decline. This is the past psychiatric diagnosis. He has a diagnosis in the record of schizoaffective disorder.  And that was received in jail when psychosis was observed. But the timeline is unclear. He has a diagnosis of opioid use disorder that started with using heroin in 2015,  and then progressed to IV use in 2019.  This led to multiple emergency room visits that required naloxone. But interestingly, he was never psychotic during opioid use.  However, he also had mood symptoms. He had depressive symptoms. He never experienced psychosis during the mood symptoms. And it's unclear whether there was psychosis  without any mood symptoms.  There were episodic suicidal ideas, but never attempted to kill or hurt himself. So this is more, it's a basic question, but also I wanted the audience to consider  what are the diagnosis that you see frequently, or that you consider when somebody comes to you with a likelihood that this could be methamphetamine-induced psychosis.  So what is the differential diagnosis?  It's any psychoactive disorder, like pulmonary anemia with psychosis, other stimulants, other drugs, such as drug drugs with reason and psychosis.  And not only with meth, but with things they're using. Right, exactly. And thank you so much. And we actually forgot to include here  comorbid substances, right? And in real practice, that's what I've seen a lot, the combination of this with cannabis,  with other stimulants as well, and also with withdrawal from other substances as well.  So this is useful tools. So we saw different cases when Dr. Zito was presenting. This is on bringing the patient's life, and you can see the start of opioid use disorder first,  and then the progression to another use disorder, to meth use, and then the start, very close to the meth use, the start of psychosis.  But in the middle of this, there was a diagnosis of schizoaffective disorder. Then medication was started, and you can see here, or you can not see the cursor,  you can see a period there of one year of abstinence  with some lingering psychosis for the first three months. So in red, that period is of three months.  And it's three months after using meth, after he stopped using meth as well. So right now, he has no psychotic symptoms, but he continues to use,  he continues to be on antipsychotics. So in this case, from that chart, what do you think is the evidence for methamphetamine-induced psychotic disorder?  Psychosis starts after methamphetamine use. Right, so that's why, yes? Psychosis starts after methamphetamine use? And stops after he stops using methamphetamine.  Stops after use, right? So longitudinally related. I think he said the patient was 35, and then the patient started in the 2090s, and he was already in his 30s  after the methamphetamine use started. Right, exactly, yeah.  And also, psychosis was not reported when he was only using opioids.  And the patient denies that he ever experienced psychosis during mood episodes, yes? Is the patient in treatment for HIV now? He was in treatment for HIV, yes.  Would it be a medical problem causing psychosis, HIV?  Not diagnosed at the time? Right, right, yeah.  What was that, sorry?  That's a good point. Yeah, that's a good, that's an excellent point, absolutely, yes. And those should be workers raised back here, age one and seven. Right, mm-hmm.  All right, and then what are some factors that would make this diagnosis challenging, and made this diagnosis very challenging in the real world? Yeah.  Use of medication.  Is the symptom made because of the medication or because of the drug that you're using? Right, so there was treatment, and it was correlated with symptom resolution, yeah.  He had a whole year of not using and still psychotic for three months. Right, so the- That was mostly due to his schizophrenia, schizophrenia. Right, so some of the timeline  goes with schizophrenia disorder, right.  Some other things, does, this, yes? I think the point that has been made, but maybe not spoken of, is,  if we think of opiate use disorder, opiate use disorder in the age of fentanyl is different than opiate use disorder in the age of heroin. Right. And you can kind of consider  not, you know, in your talks, the issue of how much, how often you dose methamphetamine related to how much psychosis you get. I think the point that, and I tell my patients,  and I think this is probably a good way to think about it, methamphetamine is 10 times as available as it was 10 years ago.  It's 10 times as strong, because it's more available and it's 10 times cheaper. Right.  People I talk to in our psychiatric units, I've worked often on our psychiatric units for 40 years,  a third of our patients that have been at the hospital now are related to the methamphetamine. 10 years ago, it was five or 10%, maybe. Right.  So, I think the amount of methamphetamine and the duration, how often, we have people just using, we have several times a day, day in, day out, forever.  And I think you got more likely, you more likely have drug related and maybe even brain damage related symptoms due to just the doses 10 times higher than it used to be.  And all those meta-analytic studies are studying data that was 10 or 20 or 30 years old. So, it's like studying, pretending like what we knew about opiates  10 or 20 years ago was the same as what we know about fentanyl world right now. It's a different world. Absolutely, yes.  So, was your point that  the meth nowadays in the community is more potent and different? It's similarly to how, or analogously to how fentanyl is different from heroin,  the meth now is like chemically different. The amount of chemical is 10 times more than it used to be.  Whether it's because of potency or just sheer amount and frequency. 20 years ago in Seattle area, we used to read about that, the methamphetamine operations growing up.  And so, there'd be methadone for a while and then there wouldn't be methadone for a while. Now there's methadone all the time. So, I think you're highlighting the importance  of the really high prevalence of meth in the community. Prevalence, potency, and dose. Yeah, all three. So, but I... I'm not likely to get extended psychosis, that's my thing.  Yeah, I bring up, because I think it is an important distinction. I think it's an open question about whether...  First of all, I don't think that it's... I mean, the clinicians that you talk to, especially those in the room, we all have observed a lot of meth psychosis  and there's just something in...  And there is data from, at least locally in LA County, I think in San Francisco, that is also observing that.  But the open question is, is this phenomenon of meth psychosis related to prevalence?  Is it related to the chemical composition? And I think that's not clear right now. One of the things that I think,  Larissa and I have talked about it, is that prevalence is probably a really important factor,  but the chemical composition, it's less clear to whether that purity and potency is responsible for more meth psychosis. I don't know if you have any additional comment.  No, we know from your dexeter slide it's dose related. Right, psychosis being dose related. I'm just reiterating the comments for those who can't hear.  One of the challenges is that diagnosis can be steeped up.  The setting in which this person had a diagnosis made was a custodial setting. Sometimes the barrier for diagnosis is lower in a custodial setting because the desire to have someone  completely controlled is high.  Where did it fit on those timelines, the diagnosis? And presumably when he was in custody, he received treatment and was not able to access medicine.  So I was wondering where that fitted on the timeline. Is he able to access what? Wasn't able to access, he could be medicated, but not able to access drugs.  Right. Possibly. Yes, exactly. So in this case, the diagnosis happened in jail.  Yes.  And when I received the patient, I received after 11 arrests, and it was very difficult to know exactly when the diagnosis was given. So this is part of the conundrum here, yeah.  Was the time he was short in custody? Some of them were short, and some of them that were significant, like more than three months, yep.  But I think the point about the sticky diagnosis is a really good one. And I think it speaks to just kind of like this sort of clinical inertia where someone gets a diagnosis  and it's really hard to go back against that diagnosis.  And there may be sort of like barriers on both sides.  It may be hard for you to go back and change a diagnosis like that the person has had for years. And it may actually be hard for the person too. I mean, we can talk.  So there may be benefits associated with having that diagnosis.  And so that person may not wanna give up that diagnosis, or conversely, they may really want to give up the diagnosis. So there are sort of challenges on both sides.  There were some benefits in this case. There was an immigration case pending.  And the patient really wanted schizoaffective disorder  to be in the chart as well. He thought that having a severe mental illness  would help him stay in the country as well. So a lot of factors. Yes, Julio.  You kind of answered the question that I was cooking. But I was thinking for some of these patients, unfortunately, there's no doubt that he's struggling.  So whether it's an addiction diagnosis or it's a schizoaffective diagnosis, he needs help. Social work help comes to mind. So I almost feel tempted to think  I'd rather keep this schizoaffective diagnosis because that would make my patient more eligible for social support, rather than think too much, is this schizoaffective,  is this substance, and potentially lower the amount of resources that they can access. But I think some people might not agree with that. So I was hoping to hear thoughts.  Well, I think the balance, too, is like, in the real world, when I'm seeing this patient,  he was also, as you'll see, he was experiencing some side effects of the treatment. And so there's this question of whether you're gonna keep someone who has a diagnosis  of a psychotic disorder versus a diagnosis of a drug-related disorder when they are no longer using. So what benefits are they getting from chronic antipsychotic use?  So that's one of the risk-benefit analysis that you have to do. But we'll get into some of those points.  So this is what happened. So he was treated with a Lansopine, 20 milligrams at night. Symptoms did improve in jail, but he had adverse effects. He experienced weight gain, sedation,  dry mouth, constipation. He was also on valproic acid,  1,000 milligram twice daily.  We were not sure if this was actually effective.  But overall, during periods when he left jail,  there was very poor adherence and he would come back.  So the current medications right now, he's on Invega Sustana, 234 milligrams.  There are minimal side effects. He is also taking a Lansopine, but at a reduced dose. And he is also taking Bupropion every morning and Naltrexone, oral Naltrexone, in this case.  So my question for you is, your patient now asks you if he needs to continue taking antipsychotics now.  What are your thoughts?  When's the last time he's been incarcerated or like what's his social situation? Right now he's in a in a housing program. Is it long term?  It is long term and it's an interim housing program. Is he a case manager? He does have a case manager right now. Yeah.  Obviously personally I feel like if someone's been doing well on medication and have been sober, I mean medications have definitely played a big role.  Of course you need social support, that's important as well, but I would be skeptical to get the patient off the medication completely.  I mean we can taper like Dr. Zito had mentioned before, but I would go, I would be very cautious, like we are slow, we can kind of break down the medication.  Yes. That was a vote for a slow taper, be cautious because person's doing well, not wanting to rock the boat. Understand, good point. Yeah. Yes, go ahead.  I would prescribe it to somebody with an intracranial injury just because of the metabolic side of it. Right, so that's also one of the considerations as well, tapering of  olanzapine first. Are you on olanzapine now? They are on both. Both? Yes. So 15 now? 15, yeah.  I feel like keeping him on some medication is also a good way of keeping him off of the system and having him  on medication, so you're not going to be psychotic versus removing him off the medication by making him not going to be psychotic anymore, but doing it that way.  Right, so medication is helping him be in the program. Yes, absolutely. Would anybody decrease the dose of Invega first or would try something like that?  No? Right, there's a lot of poor adherence. Say that again? Which one would, which medication would, if we remove which medication, which one would be  more effective? Withdrawal. Withdrawal effects, uh-huh. I can say that. If you taper the sustainer down very gradually by going from 156 to 120 or  102 doses below, you can do that, and they probably wouldn't notice anything unless he's  really going to get a reinstitution of psychotic symptoms. With olanzapine, he's getting mostly,  not so much dopamine blocking, but he's mostly getting a sedation, and so you could decrease his  overall antipsychotic metabolic load hugely by tapering or cross-tapering the olanzapine over  to mirtazapine. You get some weight enhancement there, but you don't get the TD and some of the  other stuff. That's interesting. Now, the other question about do you want him to stay on  benefits and have a schizoaffective diagnosis, this is another way to look at it. You know, I've done big contingency management studies. What's his motivation to get better if he's  got a schizoaffective diagnosis and he's getting disability business benefits, and he knows that by  continuing to have some kind of symptoms or telling, it doesn't take a brain surgeon for  patients to figure out, I need some symptoms, so they keep calling me schizoaffective disorder,  and so you don't know whether they're manufactured or not. If you look at him and he seems like he's got a pretty normal mental status and he looks like his symptoms have gone away,  what you want him to be able to do is more likely participate in addiction recovery kinds of stuff and job kind of stuff, not being a disabled person, not working and getting paid  for having symptoms. Right, right, and he did work before. You've got to balance that stuff off too. Absolutely, thank you for that.  Right, so I think that when we started in Vega, there was a significant effect and he felt a lot  of relief, but also the point that he still wants a diagnosis, he still is benefiting from having a  diagnosis, so I think he's in some parts complying with the treatment. So these are some additional  questions, some of them you have already alluded to. Would you consider a trial of antipsychotics  completely? He has at some point expressed that eventually he wants to be off antipsychotics,  but he's also expressed that there might be some benefit from being on Vega,  and in fact people were reluctant to peel off olanzapine, even though there were some attendings that wanted to consider that, and he was okay on staying on olanzapine in Vega.  So if tapering off, what might be the length and speed of the taper?  Does anybody have any opinions about that? Right, so there's also the worry that he's going to be remanded, right? So he's already  being arrested 11 times. I don't know if I've said that, yeah. And so we said that maybe considering  the olanzapine first, right, would be one idea. So what are the advantages and disadvantages of using an LAI here? And I think, Julio, you were thinking about...  That he's taking it, he's taking it. It's psychotic. We know why.  Right, you have multiple medications, yes.  And in this case, what is the role of naltrexone and bupropion?  Meth cravings, right? Off-label, yeah.  Right, but once abstinent, how long would you continue it?  The naltrexone, bupropion.  He does have a history of opioid use disorder as well.  Yeah, right.  Right, so various comments about naltrexone could also help with any recurrence of OUD.  Bupropion, either one, ask him about cravings. How long are the cravings persistent? When is he really feeling secure in his abstinence or recovery from methamphetamine and opioids?  Yeah, you could come down to 300.  Necessarily. Right, right. Stagger the tapers of both. Hold that one. We had one hand up for a while. Yes.  If I heard you correctly, think about counteracting the weight gain from the olanzapine, that they may be helpful in that.  Right, Combo is Contre, brand name, yes, for obesity treatment. Yeah. One moment. You had your hand up.  Well, we've kind of gone down the psycho farm rabbit hole, but when we start talking about getting him off all his other medications, the real question that hasn't come up is,  what's he doing about his recovery? What are his behaviors? What are his habits?  Has he changed his playmates, his playgrounds? That, I think, is going to be the most important  thing before we start tapering any of his other medications for substance use disorder. All right.  Yeah, really excellent point. How secure is his overall recovery plan, his community, his network, his activities, productivity? If the medication is a tool, are we going to pull  that tool away when we don't know what else is in place? Yeah, very, very, very good point. Your hand was up in the back.  Yeah, tobacco cessation for the bupropion. He was smoking more, and he has reduced smoking, and there's a family history of tobacco use disorder as well. Another great point.  Right. Okay, so this is the social history. He's a Cuban immigrant. He does not have family in Los Angeles. Before OUD, he was able to sustain employment. He was actually a  pretty productive mechanic. He eventually, with OUD, became unable to pay rent. He was evicted. He became houseless, and then he turned to MA, and when he told me why, he said that  when he was evicted and he didn't have a house anymore, he used methamphetamine to stay awake,  to have energy, and to endure living on the streets.  So this is another important point that I often see people trying to deal with a social situation  that is very difficult and then turning to methamphetamine. The family history. There is a family history of tobacco use disorder in his father. However, there are no other  family history or other psychiatric problems that I thought was important to think about when thinking about schizoaffective disorder or schizophrenia. So this is the legal history.  Eleven arrests. Multiple criminal activities. Attempting to steal a car. Shoplifting. Fights.  During arrests, he was very disorganized and psychotic. The latest arrest was in 2022. He attempted to break into his own previous apartment that he was evicted from. There was  physical altercation with the landlord. He was charged with assault, battery, trespassing,  vandalism, and then he was released to our jail diversion housing program and mandated to do  SUD treatment. The past medical history includes HIV that was acquired during opioid use, IV opioid use, and also multiple opioid overdoses and hospitalizations.  So what are some social factors? I think some of them we were discussing. Social factors that are important to consider with methamphetamine-induced psychotic disorder.  Absolutely. Housing. Sorry to talk again, but  even with the best of treatments, about 10% of people with schizophrenia work regularly for any  long period of time, and about 5% can work full-time even for relatively short periods of time. That's if they're case-managed and everything else. So the chances of this guy  having schizophrenia, having worked as a mechanic for some years, is virtually zero.  People with schizophrenia have pre-schizophrenia for some time. It's very unlikely.  Number two, people with schizophrenia don't tend to assault other people. They tend to get assaulted. So all of these kinds of things fit right into having a methamphetamine-induced  disorder. People with methamphetamine-induced disorder have a jail rate much higher than the  average population, and they have an assault of others rate much higher than the population. So  you've got three more factors that say this guy's got a really bad methamphetamine-induced disorder  plus a heroin or other opiate-induced disorder, and his meds may have been needed for a short  time but probably are not going to be needed for a long time. So you're leaning more towards  tapering? Yeah, tapering. See what you get? I mean, I have several patients who are absolutely 100%  certain do not have schizophrenia, but they have long-standing, usually very narrow-angle kind of  hallucinations, auditory hallucinations, or paranoid kinds of things. But they're functional in life.  They can work. They can do things like that. They interact with you. If you met them in the grocery  line, you'd say they were a normal person. They don't show thought disorder or social mix-up,  that kind of thing. And that's how he presents. And they've gone on for years. I was just talking to  one of my ladies yesterday who's had this job and functioning for 10 years, and she still has some  problems. She's on one milligram of Haldol because nothing else worked. So you can have long-term meth stuff, but not in the term. She doesn't do all this other stuff.  My response to that, just playing kind of devil's advocate to keep the differential open.  I agree with what you said, but I will add that schizophrenia can present at different times in life. So he could have had pre-morbid good functioning in his 20s and had had  a onset of schizophrenia in his 30s.  Also that people who use methamphetamine are going to be more likely to have aggressive  behaviors and impulsive aggression. So that could also explain maybe a person with schizophrenia is going to be less likely to be violent, but in the setting of methamphetamine,  that might change things.  He was. He completed about two months, and then he stopped.  We have a question coming.  Yes. Just one thing I would want to kind of usually think about and hear more about. We did a little in this case. It's just a really deeper understanding of what function the  methamphetamine is serving in this patient's life, and we talked a little bit about the homelessness and trying to stay safe, but in my experience, people use this for so many  different reasons, whether it's they need to work three jobs to survive in California, or it's totally fused with their sexuality, and they can't function without it sexually,  or they can't access certain sexual things they want without it, or maybe it's dystonic, and they don't like what they do on it, but that plays a lot into the meaning, and usually  that type of deeper understanding guides what treatment plan is actually going to be helpful  for them, regardless of the diagnosis or the meds or those type of things. So I just think keeping that in mind. Such a good point.  There was a cycle of dysphoria here, too, that he became very dysphoric upon withdrawing,  and then continued to use, to treat that, and so absolutely, that was one of the reasons, yeah. I just want to also respond to the comments about- Untreated ADHD, too.  To the comments about meaning, I think are really, really important and valuable. One of the things  that I kind of uncovered in the qualitative part of the study that I conducted was just a wide spectrum of attitudes towards methamphetamine among people who use psychosis, from  individuals who understand that the psychosis is bad, they don't like it, it's dysphoric, they never want to use meth because of the psychosis. The person I had mentioned in my  talk who was close to committing homicide, he never wanted- was saying that he never wanted  to touch it again for that reason. Other people, interestingly, had more nuanced attitudes towards  methamphetamine in terms of their psychosis, and kind of nuanced attitudes actually towards the  psychosis, kind of in a surprising way. Some people actually felt that there was something important to these experiences that they were having, like it was cluing them in on some  interesting reality that no one else could see. There was also people- this is kind of more of a  classic description of the paranoia for them feeling like it was necessary for survival,  so meth being this gateway or allowing them to be vigilant in a way and to see  the dangers of the world so they could defend themselves. So that's all to say that the meaning behind meth use is incredibly important, also idiosyncratic and nuanced  and different for each individual, but can be used obviously in your treatment with them. And that goes back to the point that I was making about treatment alliance and therapeutic  relationship. It should never be lost, in my opinion, and it can be obscured and I think we can get lost in discussions about medications, but I do believe that that is  one of the most important, if not the most important, factors here.  Thank you. I think we have time for one more question though. We will be available for anyone  who wants to come up after and continue any discussion. Yes. Hi. So one thing that I don't  know has been directly addressed, and I was hoping anyone on the panel might be able to speak to, is the idea of, you know, methamphetamine use as a risk factor for the development  of a primary psychotic disorder like a schizophrenia. And, you know, what is the latest understanding in terms of how we understand that risk, how we discuss it with our patients?  Because I think that also affects the treatment planning. Are you using antipsychotics long term  because you're worried about a psychosis that will emerge if you stop or taper versus what happens  if you stop, then they use, get psychotic again, and now they're maybe more at risk for that primary psychotic disorder? Sure. I'll start. So my reading of the literature is that  people, there are studies that look at sort of substance induced psychotic disorder as being  a risk factor for later development of a primary psychotic disorder. There's a few studies from  Scandinavia, like registry studies. I think the question of is this a direct cause of schizophrenia  is, most of what I read is that it's probably not the case, that it's a component cause,  so that individuals carry these sort of inherent risks, genetics, early life experiences,  and substance use, and even a substance induced psychosis is sort of one piece of the pie in terms of their risk of ultimately developing schizophrenia. But I really like your point  particularly because I think it's super intuitive to be thinking that way and also adds a clinical  urgency. Like if you're a young person with psychotic episodes who potentially is at risk for those psychoses to become chronic and like part of a lifelong psychotic disorder,  that adds urgency to the treatment. Or if it's your family member. And that changes how you think about their treatment, that changes some of the actions that you might make.  I have one particular patient from my study who I'm thinking of that kind of breaks my heart  because he was like in his early 20s, actually no, late 20s, but still very, very psychotic.  And I approached this idea with him of like, we don't know. And this, the more you use this  substance, you may be putting yourself at risk for these experiences to never stop and for you  to have a lifelong disorder. He was kind of indifferent to that. And I tried to involve family. Unfortunately, mom was also using meth. They often use together. But she, there was a  part of her also that I think really wanted to help him. And she was very ambivalent towards  her meth use. So just to say that, yes, I believe that that's a very important thing to consider  and add to the discussion. And there's a lot of questions just scientifically we don't know right  now about that. Yeah. And I'll just add, for example, the literature on cannabis as an  independent risk factor for the later development of a psychotic disorder, particularly added if  it's initiated at earlier age, early adolescence, and a dose-dependent effect. Research is just more  clear on that. Still a lot of confounds and debate around it. But I don't think it's as clear for  methamphetamine other than, of course, it can be the stressor, substance use, or another stressor  can kind of precipitate the onset of a psychotic disorder. This was, I think we're out of time.  This was a really interesting, engaging, lively group. Thank you for participating. And again, we're here if anyone has remaining questions. Thanks again.
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