Okay, so good afternoon, everyone, and thank you for coming today to our session, which is titled Confident Clozapine Prescribing, Motivating Clinicians to Address Racial and Ethnic Disparities in Clozapine Utilization. I'm Claire Holderness, and I'm the chair of this session. Over the next 90 minutes, you'll be hearing from me and three additional speakers, Drs. Laura Clark, Jean-Marie Bradford, and Scott Stroop. Neither I nor Drs. Clark or Bradford has any relevant financial relationships to disclose. Dr. Stroop receives grants from the National Institutes of Health and royalties from APA Publishing and UpToDate. This session will focus on clozapine underutilization and develop more confident clozapine prescribers through a combination of education, case presentations, and discussion. We'll use brief case presentations to illustrate the management of clozapine in racial ethnic minority groups with constitutional neutropenia, as well as various medical illnesses, which alone and together might be seen as barriers to the initiation or the continued use of clozapine. There will be time at the end of the session for comments and questions from the audience. We have four learning objectives for participants. Objective 1, at the conclusion of the session, the participant will understand some of the current racial and ethnic disparities in access to clozapine. Objective 2, at the conclusion of the session, the participant will understand monitoring guidelines for patients with constitutional neutropenia who are prescribed clozapine. Objective 3, at the conclusion of the session, the participant will be able to perform a risk-benefit analysis for the use of clozapine in patients with constitutional neutropenia and serious medical illnesses. And Objective 4, at the conclusion of the session, the participant will be able to find and use resources which help support confident clozapine prescribing. Clinical Indications for the Use of Clozapine. Because there are so many antipsychotic medications available and because they can be combined both with each other and also with other types of medication to treat psychosis, why are we focusing on clozapine? Simply because the potential benefits of clozapine are so impressive. Treatment-resistant schizophrenia. Treatment-resistant affects as many as one-third of patients with schizophrenia, and clozapine has been shown to be more effective in treatment-resistant schizophrenia than any other antipsychotic medication. Clozapine is also the most cost-effective treatment for treatment-resistant schizophrenia. The FDA has given clozapine approval in the treatment of treatment-resistant schizophrenia. Other Indications. Clozapine is associated with reduced hospitalizations, a reduction in self-harm, and a reduction in all-cause mortality in treatment-resistant schizophrenia. Other Indications again. Clozapine has been found to prevent suicidal behavior both in patients with schizophrenia and in patients with schizoaffective disorder. The FDA approved the use of clozapine to treat recurrent suicidal behavior in patients diagnosed with either schizophrenia or schizoaffective disorder. Clozapine has also been shown to treat aggression in treatment-resistant inpatients with schizophrenia or schizoaffective disorder. Clozapine is now considered standard of care for treatment-resistant schizophrenia. The Schizophrenia Patient Outcomes Research Team, or PORT, recommends that patients with schizophrenia and persistent positive symptoms receive an adequate trial of clozapine. The National Institutes of Health and Care Excellence Clinical Guidelines, or NICE, for schizophrenia recommends clozapine after two failed trials of other antipsychotic medications. So to what extent is clozapine utilized in the United States? Although clozapine is known to be a life-improving, even potentially life-saving treatment, clozapine remains underutilized in the U.S. It's been estimated that between 35 and 40 percent of all patients with schizophrenia should be considered for a clozapine trial. However, only 4 to 5 percent of patients with schizophrenia in the U.S. have ever received clozapine. This is in sharp contrast to other industrialized countries where approximately 20 percent or more of patients with schizophrenia are treated with clozapine. This map shows percentages of patients with schizophrenia in the United States who were prescribed clozapine in 2015. As you can see, hopefully, in only 4 states were 10 percent or more of these patients prescribed clozapine. In 15 states, between 2 and 3.9 percent of patients were prescribed clozapine. And in the remaining states, between 4 and 9.9 percent of patients were prescribed clozapine. All in all, these are relatively small percentages of patients with schizophrenia. I'm now going to stop here and turn things over to Dr. Jean-Marie Bradford, who's going to be exploring clozapine prescribing patterns in the U.S. in greater detail, focusing in particular on racial and ethnic disparities in clozapine utilization. Thank you. Thank you, Claire. Okay, so as we turn to clozapine utilization and look at racial and ethnic disparities, people in the United States of color experience disparities of access to healthcare, including quality of care and their healthcare outcomes. So we see that people from minority groups are prescribed clozapine significantly less frequently than their white counterparts in the United States. And a nationwide review of Medicaid prescribing data from 2011 to 2012 showed significant prescribing differences across the states, with non-Hispanic whites prescribed clozapine more frequently than other groups. And clozapine utilization is lower in African-American patients than among white patients, with less frequent initiation of clozapine and also more frequent discontinuation. And when we look at treatment-resistant schizophrenia and clozapine use, a retrospective cohort study from 2007 to 2017 in the U.K., with over 2,000 cases, we saw that black service users with treatment-resistant schizophrenia have half the odds of being treated with clozapine compared to white service users. And neutropenia did not account for those ethnic differences in utilization. And when we look for, in an international study that compared, that looked from data from three countries, United States, U.K., and New Zealand, reviewing 24 high-quality studies, also found that black and Hispanic service users in the U.K. and U.S. are less likely to receive clozapine than white service users. And there was mixed evidence regarding Asian service users in those countries. And you know, the World Health Organization, and I think that we all would want everyone to have the right to health care that could be enjoyed without discrimination on the grounds of race, age, ethnicity, or any other factor, and nondiscrimination and inequality requires that states then take necessary steps to address any discrimination, any discriminatory laws or practices or policies. And we see that national disparities show that there are evidence of better quality of care that white patients are receiving than blacks, Hispanics, and indigenous and Asian patients. And some of those provider factors include that physicians actually deliver less information to blacks and Latino patients, the patients report being less satisfied with their care and rate that the provider, these are black and Hispanic patients, report being less satisfied with their care, and they rate the patient provider communication as poor, poorer than white patients. And the racial and ethnic identity of the patient can affect the provider's ability to understand the presentation of symptoms. And so we really encourage people to use things like cultural formulations, strict adherence to criteria for diagnostic instruments and medication algorithms, and using those things have shown to decrease disparities, but more research is needed on other interventions that can help. We're from New York, and so looking at one state's example in New York, the New York State Office of Mental Health was interested in improving clozapine prescribing. And I want to tell you about some initiatives that demonstrated success. So they set about to combine various forms of assistance to providers with decision support tools that are available for consumers, patients, family, and also prescribers through the Center of Practice Innovation at New York State Psychiatric Institute, and also created a telephone consultation service for initiation and clozapine use, staffed by clozapine experts, such as our own Dr. Stroop here. And the outcome was that between 2009 to 2013, the rate of clozapine prescribing of new clozapine prescriptions doubled in that time period at state-operated facilities with the additional use of these tools. So we can have some success in terms of addressing those. So now I'd like to turn it over to the barriers of utilizing clozapine, and I'd like to turn it over to my colleague, Dr. Laura Clark. »» Thank you, Dr. Bradford. So I'd like to turn your attention to clozapine and neutropenia, as this is considered one of the biggest barriers against clozapine usage. Neutrophils are the most numerous of the white blood cells. These are our first line of defense against infection. As clozapine prescribers, we are often looking at ANC to determine if it's too low for clozapine. So as a reminder, the ANC measures the percentage of neutrophils in the white blood count. What is neutropenia? Neutropenia is defined as an ANC less than 1 to 1.5. It is classified as mild, moderate, or severe. What is agranulocytosis? It's defined as an ANC of less than 500. Severe neutropenia and agranulocytosis are terms used interchangeably. In the clozapine REMS, the term severe neutropenia is used. Our normative ranges of ANC are based upon Caucasian data. African Americans have an average white blood cell count that is 700 cells less than that of white Americans. So clozapine has a black box warning for severe neutropenia leading to death, and this is why we have the REMS. The rates of clozapine-induced agranulocytosis are up to 0.8% of treated patients in the United States. The risk appears to be greatest in the first 18 to 24 weeks of treatment. The risk is higher in female gender, and the risk in Asians is 2.4-fold higher than Caucasians. Age is also a risk factor. The mechanism is unclear but is thought to involve several genes. About 1 to 3% of patients on clozapine develop mild or moderate neutropenia, which may or may not progress to agranulocytosis. Apart from potentially fatal neutropenia, other hematological abnormalities exist, which generally occur during the first weeks of treatment and are thought largely benign, such as thrombocytopenia, thrombocytosis, eosinophilia, leukocytosis, leukopenia, and lymphopenia. Eosinophilia tends to occur more often in women and between weeks 3 to 5 of treatment, resolving spontaneously. Of note, patients with eosinophilia, along with other laboratory findings, should be assessed for end-organ damage, such as myocarditis, hepatitis, colitis, nephritis, pleuritis, and pancreatitis. The differential diagnosis in neutropenia includes things as other blood disorders, such as infection, autoimmune disease, cancer, or medication-induced. Benign ethnic neutropenia, or BEN, is the occurrence of neutropenia defined by normative data in European ancestry populations and individuals of other ethnic groups who are otherwise healthy and do not have repeated or severe infections. BEN is diagnosed by repeated low measurements of ANC without identifiable cause of neutropenia. It is a diagnosis of exclusion. BEN occurs more commonly among people of African ancestry with an estimated prevalence rate of 25 to 50% in Africans. Clinicians may avoid prescribing clozapine out of the mistaken concern that it can worsen neutropenia. BEN does not increase the risk of clozapine-induced agranulocytosis nor increase the risk of severe neutropenia. BEN occurs in groups such as those of African descent and other groups that are from Middle Eastern descent. Individuals with BEN have a normal myeloid maturation within the bone marrow, but release fewer neutrophils into the peripheral circulation. These individuals do not show an increased risk of infections, and their response to infection is similar to those without BEN. Patients with BEN are not at increased risk for developing clozapine-induced neutropenia. The possible etiology of BEN is attributed to the Duffy null polymorphism. The Duffy glycoprotein is a receptor for chemicals that are secreted by blood cells during inflammation. Homozygotes for this polymorphism do not express the Duffy antigen and express an average ANC that is roughly 1.5 less than groups of heterozygotes or non-carriers without evidence of immunocompromise. The Duffy null phenotype, the non-expression of the Duffy antigen on red blood cells, is commonly found in those of African descent. This has led to a conversation about changing the name BEN. In a recent hematology meeting, hematologists discussed changing the term BEN to Duffy null associated neutrophil count. This change supports the need for a Duffy null-specific ANC reference range. Having a Duffy null-specific reference range would depathologize a common and healthy variant as well as correlate the variant with a biological marker rather than ethnicity. The authors also concluded that these changes would improve health and ameliorate a significant inequity in medicine. For example, if someone has DANK, Duffy null associated neutrophil count, as an explanation for their white count, that person would be less likely to have unnecessary interruptions in their chemo treatment or be exposed to unnecessary workups for neutropenia. Some drawbacks to consider is DANK does not account for all benign neutropenias. DANK would require testing for Duffy receptors on cell surfaces, which is costly. Psychiatrists have also discussed updating terminology. Dotson and other authors propose renaming BEN to either benign familial neutropenia or constitutional neutropenia. The authors conclude that changing the name would be better than changing the ANC reference value range. The problem with using a race-specific normal values is that this uses a race-based medicine approach, which could lead to undue biological credence to social categories. And the problem with just expanding the normal ANC range is that this uses a colorblind approach that could overlook meaningful genetic diversity in the population. And the clinical vignettes in this talk will be using the term constitutional neutropenia. And now I'd like to turn your attention to the REMS Treatment Guidelines for BEN. In 2015, the Clozapine Risk Evaluation and Mitigation Strategy established separate monitoring for patients with benign ethnic neutropenia. The updated monitoring guidelines, along with clinician support, may help impact the barrier associated with Clozapine prescribing to patients with BEN. In this slide, it shows what neutropenia is for the BEN population. And I have to point out that the emphasis is to continue treatment with Clozapine unless the ANC is less than 500. It also allows for continuation of Clozapine if clinically appropriate. And this is from the REMS website. So researchers have looked and are continuing to look at what the impact the updated REMS Guidelines has. And the likelihood is that it will allow for more Clozapine access and less treatment interruptions. And now for our clinical vignettes. These cases are from our state-run clinic system in New York City. We have the benefits of location to a large medical center and a close collaboration with hematology. This collaboration has been key to supporting our psychiatrists. If we have concerns about trended abnormalities, we contact hematology for review. The consulting hematologist usually requires additional information for such things such as how long the abnormality has been present, the absolute count versus percentage blood count, medical comorbidities, cigarette use, and a medication list. Our first clinical vignette was chosen as it illustrates a positive outcome in reducing polypharmacy. Like many other healthy patients with constitutional neutropenia, this patient was prescribed lithium as a way to augment her white count, the hope that she can remain on clozapine and need less frequent lab draws. Ms. D is a 26-year-old female with schizophrenia and constitutional neutropenia. Her psychotic symptoms involved derogatory auditory hallucinations of angels that comment on her actions and delusions that angels control her movements and broadcast her thoughts. She had two full trials of two other antipsychotics. She identifies as Dominican American. And after she struggled with ongoing symptoms, a family session was held and Ms. D agreed to a clozapine trial. Lithium was added to augment her white count. Her ANC was hovering around 1.5. She did well on clozapine. And in the first several years of clozapine treatment, attempts to stop using lithium were made. Each attempt was met with a drop in ANC that prompted frequent blood draws and at times her clozapine was held and reviewed. Her lithium was discontinued after REMS update. And this allowed for discontinuation of a medication that exposed her to risk without clear benefit. Interestingly, the patient's family raised concern that if her lithium was to be discontinued, she may be at risk for having her clozapine held. We addressed this concern in family sessions and the patient continues to do well on clozapine and has only needed monthly lab drops. This clinical vignette shows the importance of consulting with hematology as this patient had a pretty low baseline ANC. Mr. Al is a 25-year-old male with constitutional neutropenia and treatment-resistant schizophrenia. He had his first break during college and his mental illness really impacted his educational goals. He identifies as Haitian American. Why clozapine? Well, he had failed trials of at least three antipsychotics and due to ongoing prominent positive negative symptoms, he agreed to a clozapine trial. Baseline ANC was one. He hadn't experienced any fevers, chills, night sweats, weight loss, chest pain, shortness of breath or any other signs and symptoms of infection. His blood spear was normal. Hematology was consulted. And over the first 18 months of treatment with clozapine, his ANC ranged from 900 to 2,700. The hematologist recommended maintaining the patient on clozapine as long as his ANC is greater than 500, assuming no infectious cause. This helped establish a normative range for this patient. From 2015 to present, his ANC did drop at times being .7, at other times being .9, again with no signs of systemic illness. When it dropped this low, the pharmacist declined to dispense clozapine. Mr. L is aware that he has a baseline low ANC. He is also aware that he is healthy and he is motivated to be on clozapine. So each time he contacted his psychiatrist and we were able to get him his clozapine. I think the key here is that since we had the hematology consult, it really helped promote the ongoing use of clozapine for this patient. Also during the pandemic, we were concerned that if he were to need unnecessary repeat blood draws, that this wouldn't be so feasible for him. So having the hematology consult was very, very key for him. Our last clinical vignette was chosen as it shows an example of continued use of clozapine in the setting of treatment with another agent known to cause neutropenia. Ms. S is a 68-year-old with a diagnosis of schizophrenia. Why clozapine? She has a past psychiatric history significant for tardive dyskinesia and at least two failed full trials of antipsychotics. Her medical history is significant for breast cancer, status post-lympectomy, radiation treatment followed by adjunct tamoxifen treatment for five years. After consultation with oncology and also a family session, she was continued on clozapine and she was doing well. Approximately five years after breast cancer treatment, her psychiatrist noticed abnormal levels in her CBC with differential. Her Y count was greater than 17,000 and her platelet count was elevated. An expedited hematology consult was obtained and Ms. S was diagnosed with an accelerated phase of chronic myeloid leukemia and treated with imantanib. The decision to continue clozapine during the accelerated phase treatment was made with Ms. S, her family, her medical team and her psychiatric team. The benefits of clozapine were too important to be discontinued and outweighed the potential risk of using dual agents that can cause neutropenia. According to the REMS website, if clozapine is used concurrently with a medication known to cause neutropenia, consider monitoring the patients more closely. Ms. S had a favorable response to therapy. She continues to be psychiatrically healthy and is active in her treatment decisions. So these clinical vignettes were chosen as they show cases with treatment-resistant schizophrenia, unconstitutional neutropenia, collaborative care, shared decision-making, and the impact of the updated REMS monitoring guidelines. And now I'd like to turn our conversation over to Dr. Stroup who has written extensively on the topic of clozapine. Thank you. I want to thank my colleagues for their presentations and for giving me the opportunity to speak here. I realize in preparing for this that I've been beating around the clozapine bush for a long time and also realize I probably should have prepared some slides, but we'll see how I do. So the first thing that I ever did with clozapine was a study. I was peripherally involved with a study in the 90s that was conducted in China and led by Jeff Lieberman and Michael Phillips. And they were taking advantage of the notion that clozapine was used for everyone in clozapine. It wasn't reserved for people with treatment-resistant schizophrenia. So doing a first episode psychosis trial was ethical. And they compared clozapine to chlorpromazine in people with first episode psychosis. And my estimate of that study was that it really didn't show advantages for people with first episode psychosis. Outcomes were very similar after one year. And they subsequently did a seven or nine-year follow-up where there were some small advantages for clozapine. But I would say that that supported the idea that clozapine's real advantages are not for people who would be expected to respond to any antipsychotic, but perhaps reserved for people who need something special. The next thing that I was involved with in clozapine was with the Cady Schizophrenia Trial. And you may remember that that study, if you heard of it, was a randomized controlled trial of five antipsychotics in people with multi-episode schizophrenia. And it was olanzapine, quetiapine, risperidone, perfenazine, and zaprazidone. And if people who started on one of those medicines discontinued, they went into a second phase of the study. If they discontinued the first medication for tolerability reasons, they went into an arm that did not include clozapine. But if they discontinued because of efficacy issues, they could be randomized to clozapine. And in that study, if you discontinued for efficacy reasons and were randomized to clozapine, clozapine was more effective than olanzapine, quetiapine, or risperidone. Those are the other medicines in that study. So again, supporting that clozapine is highly efficacious and, you know, is good when other things aren't working efficacy-wise. And then subsequently, we did a study using Medicaid, using a large, you know, claims-based study or registry-type trial. And there we identified from claims people who we thought had treatment-resistant schizophrenia. And here we were trying to show, did clozapine work better in the real world, you know, not just in a randomized controlled trial? And so there we took people who had evidence of, you know, treatment resistance by having changed the antipsychotics a couple times and having a hospitalization over the past year. And there again, we found that switching to clozapine was more effective than switching to any other antipsychotic. So, you know, clozapine continued, consistently does very well. And this led me and others in New York State to develop this clozapine intervention, the clozapine campaign, I guess we called it. And it has multiple components. And, you know, we've found modest success in improving clozapine prescribing. I'll tell you more about it. And I am on this clozapine consultation service. I'll tell you more about that in just a minute. So some other stuff we've done that was already mentioned was look at who gets clozapine. First of all, not very many people. And second of all, it's more likely to be men. Younger people are more likely to get it. And people who are white are more likely to get it. And so that is, you know, poor access for people of color to the best available treatment for treatment-resistant schizophrenia. There's another thing in those studies that we found is we didn't just look at access to clozapine. We looked at access to other medications. And people for long-acting injectable medications, well, people who are black are more likely to get long-acting injectable medications. So it's kind of a flip side. And I don't have the explanation for that. But it is something that deserves some attention for sure. Another question is, you know, when should we use clozapine? Treatment-resistant schizophrenia, for sure. You know, I've argued for a long time that we should use clozapine sooner rather than later, you know, so we don't go through three, four, five antipsychotics. So, you know, after two, I've encouraged people to get on to clozapine. Not everyone believes that. Many of my colleagues think that before you try clozapine, you should have a trial of long-acting injectable medications to rule out pseudo-treatment resistance. So I don't totally agree with that, but I've more or less lost that battle. So many, many people think a trial of long-acting injectables is indicated before going to clozapine. I think it's equivocal, personally. It was mentioned that Jan Balavka did a study showing in inpatients that clozapine was more effective than other antipsychotics in reducing agitation, agitation or hostility. And so that has led a group of us to see, you know, that has this notion that clozapine can help prevent violence in people with schizophrenia. And so we are now conducting a multi-site clinical trial sponsored by NIMH that's enrolling people with history of violence in the last six months and randomizing them to clozapine or treatment as usual. It's called the REVISIT-C study. It's being conducted in Los Angeles by Alex Kopelowitz, Augusta by Joe McEvoy, University of North Carolina by Brad Yarskog, Don Goff at NYU, and J.P. Lindenmeier at the Manhattan Psychiatric Center, and my close colleague, Raghi Gergis, at the New York State Psychiatric Institute. And Raghi has really taken the lead on that. But we'll see. We'll see if we can have a rigorous study of clozapine for people at high risk of violence is if there's a new indication, we can get a new indication for it. As you might imagine, it's not that easy to enroll people at high risk of violence into a randomized clinical trial. But we're working hard at it. And one thing that we've come to recognize is that most of the violence among people with schizophrenia is not with guns and knives. It's more pushing, slapping, hitting. And so anyway, we'll learn a lot from that study. It's still just in its early phases, but we're excited to be able to test that for an indication that many people think clozapine is likely to be better. So the other thing is for clozapine for suicide. You know, a randomized controlled trial showed that clozapine was more effective than olantapine for reducing suicidal behaviors in people with schizophrenia or schizoaffective disorder who didn't necessarily have treatment-resistant schizophrenia. They just had persistent suicidality. And because of that study, there's an indication for clozapine for suicidality. So we've been recently looking, as part of our trying to improve clozapine prescribing in New York, we recently looked at where people with schizophrenia who made a suicide attempt and survived, starting on clozapine. And so here, there's a young colleague at New York State Psychiatric Institute, Natalie Berese, who's been doing this analysis. But she looked at Medicaid across the state. I think there were about 1,000 suicide attempts in the state. Anyway, the people who started clozapine, it was very low. It was basically the same as the base rate, 5% or lower. So it's not being deployed, you know, for that indication yet. And those rates during the pandemic dipped even further, but did seem to rebound since the pandemic has let up a little bit. So part of the stuff we did in this clozapine campaign in New York State was do a lot of education, trying to, you know, set benchmarks for what kind of prescribing we thought would be indicated in the state hospitals in New York. We developed a handbook, which is very handy for consulting when questions come up. And then we have this consultation service, which I, and now it's down to, we've had a little attrition, but now it's me and three other people. We take calls during weekdays from the state services to answer questions about clozapine that come up. And so now it's every fourth week, it's not keeping me or anyone very busy. We get about one call a week, but it's, it's interesting. And you know, a lot of the questions are about what do you do with abnormal clozapine levels or, but a lot of it is about managing side effects or what do you do? And so the things that people worry about and that the state worries about the clozapine are intestinal obstruction. That's what people get in trouble with. And so we really try to get people to stay ahead of that. And then, you know, there have been people who have died in New York state in the last decade from intestinal obstruction. And so it's really important to pay attention to that. You know, people don't, especially outpatients, you know, they don't like sedation, they don't like cialuria, but those aren't quite as dangerous as intestinal obstruction. And then myocarditis comes up a little bit, comes up a good little bit. But you know, you stop clozapine, people usually recover pretty quickly from that. But you know, that's, those are sort of the comments I had. It's a very useful drug. It's not necessary for everybody. Many people with schizophrenia can do well on medications other than clozapine. But when it's, when it's needed, treatment-resistant schizophrenia, it really should be used. Suicidality, it's just not being used very much, but it's the only thing that's been shown to really reduce suicidality, or not technically, it's the only thing that's been shown more effective than other things to reduce suicidality in people with schizophrenia. We'll, hopefully we'll have an answer from a randomized controlled trial about clozapine violence. It'll be a couple years before we have that. Yeah, so I hope that you all use clozapine when it's indicated, and I think we would all entertain questions. Hi everyone, thank you for a very enlightening session. My name is Dr. Rotem Gidron-Bodovsky, I'm a physician from Israel, actually from the Teva Pharmaceutical Company, and we are doing a phase three with olanzapine LAI for schizophrenia patients. This is something that I really, I'm the clinical study physician, and I encountered this phenomena in the, you know, clinical trial a lot, especially in the African American population, and we are like, we have this exclusion criteria for a northropenic patient. Because it's an LAI, we're taking a larger margin of safety, it's like we have exclusion criteria for a neutrophil, neutrophils not below 1,200. So my question is, in your experience and what you've, that you have shown now, it's like we have this patient who probably after taking like the, for tolerability, we gave her olanzapine, she lowered her counts. In your experience, was it related or not? Because you demonstrated what you said that it's not necessarily related. She just did her usual kind of a she had like the benign the Ben and so we see that a lot in our our Population in some population in the In the african-american in our clinical trial, so it should we be like Feel safer to give that and not to exclude these patients because it's a it's but it's part of the Population and we want to give that treatment to everyone and I know that Clozapine and olazepine has similar kind of safety Aspect in the index, sorry in the counts of the nitrophils, so This was a long question, sorry I'm not trying to whoops. Is it hot? Is it on? Yeah so the issue is in an olanzapine trial you're conducting you're seeing lots of Neutropenia or slight neutropenia. We're seeing a lot of Ben Actually and at baseline and we are constantly Trying to Decide whether on a case-by-case basis either to recruit these patients or not because we saw like it started because we had a one a patient who who had like a one 1,400 and then we gave her all runs up in for tolerability before we gave there the all The LAI and then she lowered it to a zero point like for 850 so we'll um, I will Be interested to hear what dr. Clark has to say about this. Um, but First of all, you better listen to the FDA But You know if I understand correctly people at Ben are not with yeah are not at increased risk of clozapine induced agranulocytosis, I Would be tempted to Extrapolate that to a lanzapeine, but I just don't have that evidence Thank you for bringing this up because I think it speaks to one clinical trials and To what to do if you're a clinician, which might be two different things So for neutropenia, you know, a lot of medications cause neutropenia it's not just clozapine and It does Bring about provider anxiety when you see an A&C dropping. Yeah, so I can speak to the clinician side that We really are helped by hematology They kind of help us determine like is this Is this related or is this just normal Drop in the A&C that you would expect I think if we go by the REMS guidelines It seems like it's more frequent lab draws to try to determine what's a normal baseline per the patient and then so as you're saying it's an individual basis and I Can't speak to the research side, but it seems like it may be something like designing more blood draws to then establish a normative range for each patient Thank you, this is exactly what we're doing and actually a lot of these patients we are putting there after they Have the diagnosis of schizophrenia for more than one year So usually the sites the hospitals know them and they know they have the ban So they are saying to us it's okay. We know them. We know this is they're bringing that from home and they don't have a like a more risk for Infections or anything like that and so we are recruiting them because we don't want to exclude them So this is like what you speak speak about. This is exactly what we're encountering every day. And thank you for that it's really kind of Reassured me that we're on the right track because in the label of olazepine and clozapine. There is no contraindication for For this patient, so we just have to closely monitor their counts Yeah, so thank you so much. Thank you Hi there, I'm Arthur Aliva from University of Louisville and Louisville, Kentucky, I really appreciate this talk and I've actually learned a lot just listening to that my question goes to the prescribing differences between Europe and America My understanding is a lot of European countries have up to 20% of their patients on clozapine compared to America Where it's you showed about 5% of max some states with 10% What I know, you know Europe and America a lot differences a lot of racial differences a lot of Healthcare system differences, but what lessons have we learned from Europe and how they prescribe clozapine that makes it such more readily available and prescribed I Don't think I know why it's been more successful in in Europe But I have some ideas about why it hasn't been so successful in the u.s Soon after clozapine was introduced here, you know, it had a reputation of being hard to be hard to use It was bundled where monitoring was very expensive for a while So there was slow it was slow at the beginning but then the second-generation antipsychotics were marketed very successful as clozapine without the risk and and You know, they're they're quite efficacious to and in general variably efficacious But I think a lot of trainees in the u.s. People didn't get experience learning how to prescribe clozapine and so we've had Generations of psychiatrists who are not as comfortable prescribing Because they just didn't get the experience And we found it at a very hard time getting old dogs to learn a new trick I also just wanted to add that just the monitoring there aren't that many medications that require monitoring systems that are and so that frightens providers and in other countries They not all countries require that type of monitoring at all, you know, and so and it's not registers not national So that's that is like just having a monitoring system makes one anxious about this is a more dangerous medication that I need to be you know, kind of worried about And so that like decreases the you know Desire to use that medication for prescribers in the United States versus in other countries where the monitoring is not as You know, it's like in that not not all have a national monitoring system. And then the other thing is that You know The system differences are important also and so in Terms of if you're practicing in a health care system that does have sort of these are available medications They also seem more Equal equal options to choose from as opposed to the United States where If that's not what's being used in your facility or with your providers or your docs and it's also seems like a more Extreme medication that's only used in certain circumstances. And so it also comes to your mind less frequently to use that So that should be treated that can many people sort of feel like oh in the United States like docs feel like oh that should Be treated in a clinical system where they have lots of resources to support that individual as opposed to in other countries Got you. And if I may ask a follow-up to that briefly the so is Do some countries Europe don't have a much different monitoring system is a REMS protocol less intensive than America Yeah, I'm not familiar with all that, you know, like all of Europe But I do know in certain cut we work with a lot with people who are coming actually from the Dominican Republic So not Europe, but you don't need my you don't you don't need monitoring there So we're talking to doctors in Dominican Republic. It's not monitored there in that way So they don't have to do that at all And so there it's very easily to receive it's very easy to receive clozapine abroad in the most of our patient population In is that's abroad is coming from the Dominican Republic. I see it's one example. Thank you Hi I'm Rob. I am a Psychiatrist that lives and works in New York City I'm the deputy director of psych at Project Renewal, which maybe you're familiar if you're not large homeless health care organization and You know, I think Obviously, I think primarily the patients that we work with there are Black and Latin X and I think a lot of that is because they're kind of correlates with the rates of homeless and unhoused individuals and I think that Many of the providers at our organization working in shelters and housing programs have a lot of difficulty with prescribing clozapine Don't automatically think of it, you know bias I think does play a role but I also think the social determinants of mental health play a huge role in that and that the need for kind of comprehensive help with prescribing clozapine and You know, I have trouble getting my clients to continuously show up Let alone to show up for You know lab appointments to show up to a pharmacy to pick up their medications they have a million other things They're trying to figure out and navigate So I'm curious if you can comment number one on maybe some of the differences in inpatient versus outpatient medicine and and and you know How we could potentially increase clozapine prescribing? Particularly in outpatient levels of care and different levels of care We don't have great access and number two if you have any comments on like I hesitate to prescribe it because of these reasons Does it make sense to just go ahead and try it anyway and and and see if we can get the person Started and maybe better or do you have other suggestions for how to maybe build different kinds of infrastructure for these special kinds of populations? Sorry, that was a lot It's a tough question because I think that the unhoused population is a special case And so then, you know that it is, you know The ability to monitor the patients to get them to come to lab, you know to get their blood monitored Is difficult and so that is a special case where it's even, you know, kind of more challenging for that reason and also Obviously, you know, the other thing is again, it's it's not when people are not taking their medicate their clozapine Consistently oftentimes you need to restart and so then that's just more challenging if you're having a You know patient population that's more that's less able to make their appointments and even then be found sometimes When they're missing those appointments, so I don't know if either of you guys or Claire have additional comments about what actually could be helpful No, I think that's right. This is this isn't directly related this but it reminds me of another thing We were doing a few years back was trying to We were looking at the assertive community treatment teams in New York about were they able to prescribe close feeling not and we found out That many of them were not prescribed had no one taking clozapine and we thought that was kind of alarming that you know a group of Severely old people who were you know in need of great services were not getting clozapine And so they were developing a treatment standard, you know to say, you know You have to have the capacity to prescribe clozapine but the thing that came up a lot there was things about the blood draws getting people to go get blood draws and so they Were I I just remember some of the agencies somewhat like yours ICL. I think in Brooklyn they were arranging for the Quest or whoever to anyway trying to meet people where they are a little bit I can't remember how but they were there were some things and people are always hoping for this point-of-service blood draw to make it More convenient, which I guess is becoming a bit of a reality. I Yeah, I mean even in our FQHC's in the shelters we draw blood ourselves So like even that could potentially help but even just getting people to show up for that in the first place is hard enough So some systems can ameliorate that I think it's it's more about building the system where you're at to help support Individuals, but even then, you know, there's all these other outside factors. So sorry I don't know if you're gonna say something else. So I run an inpatient unit We're starting people on clozapine. I think it's relatively straightforward Sorry, so I run an inpatient unit and it's relatively straightforward to start people on Clozapine and to handle Challenges if they do come up but one thing that we use if people if patients are Not so sure whether they want to go on clozapine is show them a video that Some medical students made a couple years ago where they basically interview patients about their experiences on clozapine and they talk about what they worried about before they started it what it's been like what's been easier or more difficult than they imagined and That that has actually been a really useful Tool for us and Also, just having a peer who works on the unit to talk with Our patients who are thinking about going on clozapine so that somebody could talk to them in real time about what it's like And then also as we're preparing to discharge people Home or to a residence or wherever to see if we can get them a case worker to facilitate getting to blood draws or to the pharmacy or wherever If their family's not able to help them as much as we would hope and just to get a little extra support And I would imagine for your folks, you know as much more support as possible Could be could be really useful Yeah, we even thought about using visiting nursing services and getting people enrolled I think you made a great point with like a potential point person or case workers Somebody that they can develop a relationship with to keep that going Also, just you know, Claire really nicely articulated a lot of the interventions for the patients But those some of the same things that she was mentioning could be used for the providers as well So if you have providers that are resistant to using it or just you know This is a real special case that that has you know unique complexities about using it in terms of locating the patients or arranging the blood draws and and so that if you're having a Group of patients that are having some success you can then you know create Informational and educational materials for the providers like here's what works, you know this is like we're gonna have this relationship with VNS or you know with Quest and all they need to do is, you know show up there and then say this one thing and they'll look up their account You know through us and you know things like that can be arranged and we arrange that for our own patients Um, you know, especially during the pandemic where they could access, you know and then you could just provide a kind of list of kind of things that worked an instructional video perhaps and then also, you know The real-time access to kind of question and answers that she mentioned this is for patients obviously But for providers as well, and so that's like the benefit of that consultation service But you guys could range your own just for your providers within your agency. So some of those things could be really helpful Thank you so much I'm Randall white. I'm the medical director for mental health and substance use services in Vancouver, Canada, and we've been undertaking a quality improvement initiative to Increase clozapine prescribing in our mental health services including a Serve community treatment as well as the adult outpatient mental health teams So Well, first of all, I I want to ask dr. Strupe a specific question just related to the clinical trial of clozapine for aggression And are they excluding people with TRS from that trial? Because that would be a confounding factor, of course um people with People they are not excluded. They're not Just it broadens it. So Pete, you know, the the criteria is have you committed an act of violence in the last six months? The one thing actually though is it you know There's sort of a clinical trial equipoise thing if it's very clear you need clozapine because of treatment resistance You wouldn't be adequate boy. So there it is sort of and we don't think we're getting a lot of people treatment resistant schizophrenia Okay In our experience. We were just talking about the barriers including being unhoused Other barriers, we've noticed that people with concurrent substance use disorders People with a high burden of both negative and positive symptoms, but the so-called Quiet psychosis, they just don't get they don't cause as much turmoil So people just don't bother, you know to offer them something like clozapine But I think the main thing is that And we're trying to increase clozapine prescribing mostly in community settings. So First of all, you have to have teams that are trained and comfortable to deliver the treatment So it's not just you know telling a doctor, you know, you should prescribe Clozapine you have to have the support there to make sure that patients get the blood test all the things We just talked about also get their vital signs monitored, etc I mean ideally having a clinical pharmacy specialist as part of the team is very helpful in Canada we have three brands of clozapine Unlike in the US where you have one monitoring system as I understand it the REMS We have three each company has its own so you have to kind of keep on top of which company You're dealing with furthermore Now each company is coming up with its own proprietary system to Improve or make more accessible the blood monitoring for instance So one has this point of care device that just requires a finger prick to do a white count It's very convenient another company has something it's not a Capillary blood test is actually a venipuncture, but again It's much more easy to do as opposed to sending a patient to a lab a third company sends nurses or venipuncturists out To patients. So anyway, there are all these moving parts so that's another complexity prescribers just think well, which of these do I choose and You know that kind of thing So What was the other point I wanted to make I guess You know, the main thing is merely that I think that there are many reasons why this isn't used even in Canada at the level at which it should be I've just named some of them and What you said earlier about physicians being Deskilled I think is important too because we did a survey at baseline to see what the physicians thought about prescribing Clozapine and many of them admitted that as residents they had seen a couple of patients on clozapine They had never initiated clozapine or certainly in a community setting And so we have to make sure that residents get exposure to this. I think that's really important Thank you for that the It's rare that I see it here advantages of the US over Canada's health care system. But but I was I Was vaguely familiar with this three different, you know monitoring systems there and that is one good thing about REMS Is that all you know, all the companies pay into a single system to support the REM system in the u.s Which makes that a little easier My name is Azim Shasabar, I work at But in Baltimore, Maryland, I wonder do you have any data about? rate of or incidence of prescription of clozapine among different states For example, I work at the you know, it's very interesting why I'm asking. I worked in Connecticut for about 10 years ago. I realized the incident in my experience and observation was far higher than when I moved to Pennsylvania and Maryland. I realized you don't see so many prescription of clozapine. So I was wondering, do you know any differentiation between different states who prescribe it and what's their outcome? Do the states that prescribe more, they have better outcome versus the state that they don't and they are more conservative? The second thing is a great question and I do not know the answer about differential outcomes among the states. We do have in repeated studies in the US using Medicaid data variations in use. It varies. I think there was even a slide here that showed pretty substantial variations and that's been persistent over time. And you know, is it, I don't know what drives it exactly. I mean, to some extent, Medicaid policies could drive it but it probably has to do with the training of the psychiatrist and the comfort levels. I think the university and also the culture of there also influence the way that do that. As I mentioned, in New Haven, Connecticut, I saw it a lot but then you move to other area, you don't see it. Maybe once a year or twice a year. That's the, do you want to tell about that, yeah. Yeah, so, sorry. So in this slide, it's a little hard to make out but what it shows is that, let me just see where I have it. There are four states where 10% or more of the patients were prescribed Clozapine. That's the purple. Yeah, that's the dark, dark purple blue. And 15 states where between two and 3.9% were prescribed Clozapine and then everything else is between four and 9.9 that were prescribed Clozapine. With regard to area variation stuff, I mentioned we were looking at use of Clozapine after suicide attempts in New York State and one of the ideas there was to identify where it was being used well and not being used and to try to improve that. The rates of use were so low that it was really hard. There is variation but this was my, you know, the hypothesis was that there were gonna be certain places where there were champions or something that were using it and we could learn from them but we're still working on that. Yes sir, I have a question about the utility of Clozapine blood levels. When do you do that, every three months, six months? When clinically indicated? When? I'll hear what the others say. I would do it when it's clinically indicated. The way we suggest it, you know, you prescribe Clozapine, you titrate till people are better. If a dose that you might expect to work doesn't work, then you check a level and then you monitor it but just routine levels, you know, don't seem indicated and they, you know, there is a threshold, you know, above which you would want a guy, I think it's 350 nanograms per milliliter. I would try to aim for that if possible. Many people respond with lower levels but, you know, people with really high levels, if they're not having side effects, I don't know that's a big concern. Rapid changes seem to be a problem though for seizure risk. Hi guys. For those who are not the foreign front, my name is Sheryl Iyer. I work with the New York State Office of Mental Health and I think this slide in particular highlights it but also I think the data that you presented about racial differences is pretty critical as well and if you see on this slide for those who are familiar with the United States, you could probably pick out pretty quickly that the states that are blue with the highest rates of Clozapine prescribing are also the ones that are the whitest and the ones that are red in the south in particular are the ones that are more racially segregated. So you have to wonder a little bit about where that plays into it and so that also gets to the issue of, you know, Clozapine prescribing being pretty clearly racially different and disparity, pretty significant racial disparity and likely a structural disparity from that standpoint as well that relates to other kind of things that relate to the racial differences in the United States but I have to wonder a little bit about where us as prescribers are default. I think we probably underestimate the effects of implicit bias in prescribers when we see a patient sitting in front of us and that person is of a certain skin color and we make a determination about how well they will adhere to labs or how well they'll do the appropriate titration and et cetera, et cetera and so we give them an LAI with high side effect profile which is also shown in the literature that people who are African-American, people of color get higher rates of LAIs, the first generation LAIs at that. We give them a first generation LAI instead of give them Clozapine even though they're by far the appropriate candidate for Clozapine. So how do we overturn the implicit biases because I think the idea of raising Clozapine prescription rates as a whole is great and, you know, highlighting the New York State Office of Mental Health's good efforts from that standpoint, hint, hint, is great but I think we're still perpetuating the fact that, you know, the implicit bias remains, the prescribing bias remains. How do we overturn that? So I think a lot of, there's an educational strategy that we could do, right, and make it more kind of consistently applied that education about just that this exists, this is a problem showing people the data and then some of the interventions that do help are encouraging people to, A, is just to, again, educate them that this is a problem and so that they're more aware of it and then, of course, they can do implicit bias training in general but in specifically related to kind of prescribing use, things like using a decision tree, whether that's in your institution, whether you have, you know, clinic system or whatever, so having a medication algorithm and encouraging people to sort of follow that and then when they're departing to, you know, discuss with their colleagues or their teams about why, that can help and then once people are understanding and sort of remembering and considering implicit bias in an application of that algorithm, that can help to improve and we've seen demonstrated effects of improved kind of prescribing patterns as less biased prescribing patterns when people are using medication algorithms, for example. The same thing with diagnostic criteria when people are sort of misunderstanding symptoms, using strict, kind of more strict criteria and also cultural formulations, so making sure that people really understand what a symptom is, not your understanding of what the symptom is but with the patient's understanding of what the symptom is and how that presents and so using those kinds of tools, cultural formulations, diagnostic algorithms, medication algorithms as well, I mean, sorry, diagnostic instruments like more standard instruments and medication algorithms, those are things that have demonstrated success in terms of less biased diagnosis and prescribing, so those are kinds of things that you wanna use and then in your institution, you wanna make sure that that education isn't done once but just continues because it needs to be reinforced regularly so that people are sort of aware that this is a problem and that doesn't sort of fall out of their head as they're just moving through their day. That's a great answer, Jean-Marie. I'm glad you had some solutions there. I mean, because the complaint is that we've been describing disparities but now we've gotta do something about them. One specific thing that I'm aware of is, she mentioned the cultural formulation interview. We've got another study we're about to do now that isn't about prescribing, it's about diagnosis. There is this thing about the over-diagnosis of primary psychotic disorders of people of color and one way we're gonna try to address that is working with Roberto Luis Fernandez and Neil Agarwal to actually do an intervention using an adapted version of the cultural formulation interview for psychoses to try to make sure we have, it's just using a criteria-based but with culturally informed to try to address this what has been well-documented over-diagnosis of psychosis in people of color, primary psychos. Go ahead. Hi there. My name is Jacob. I'm a psychiatrist working in nursing homes in Illinois and I inherited a very large clozapine population. There's an infamous psychiatrist who lost his license and so I inherited many of his patients. I'm sure to have a pharmaceuticals he knows about. But so I have a large population of clozapine patients that have been on clozapine for many of them over a decade and what I've been finding is that we haven't had any patient discontinue clozapine due to ANCs and so it makes me wonder, obviously we have to follow the guidelines and everyone's registered in REMS and all, but it makes me wonder, are we doing something wrong in the US by requiring such frequent ANC monitoring and are there any efforts to change those recommendations based on what the rest of the world is doing? And is there anyone that's looked at the kind of more permissive, the more permissive kind of dispensing that occurred during COVID to see, did we have increased mortality by, they weren't my patients in nursing homes. It's very easy to get blood draws. I'm really lucky, but I know that in the community, a lot of patients went without and did they have higher mortality risks by not getting the blood draws? I don't know if anyone has looked at that. I think you're absolutely right that the risk of agranulocytosis is heavily concentrated early in the course of treatment and that's why even in the US, it was every week forever at the beginning and even now it's more permissive. The idea of dropping it off together, I've heard it suggested. I don't think it's on the verge of happening in the US. I'm actually not aware. Maybe there are other countries where it drops off after a couple of years. I'm not sure. I don't know what the current system is here. Is there a reduction in the frequency? It goes to monthly after six months. It stays at monthly. Okay, all right, yeah. So it's the same in Canada. It's so different. Did you have more to say? Can I just say one more thing and then I'll, oh, you're from another country? Oh, go ahead. Hi, I'm from Holland. I'm a psychiatrist over there and first I have a question because we use the HemoQ. That's a very easy thing for your finger and we use that when it's on monthly base and I was wondering, is it also familiar here to use it or? It doesn't even involve a finger prick. It's just a. Yeah, it's just a very easy system and it's easier for patients because it's less than a finger puncture. And second, sometimes when it's really difficult for a patient to even use the HemoQ, we do like an informed consult with the family and relatives that we consider not to do it like every month but to do it like once a year or two times a year. But that's always after consultation with family, with relatives. Right, but that's a great example of just how it's different in different places and easier and can facilitate prescribing and use of Clozapine. That was a question earlier that you had and it just shows you. And other countries don't require the degree of frequency of monitoring and then the extension ongoing indefinitely as well. So, yeah. Actually, we, in Canada, we can occasionally get exceptions made by appealing directly to the drug company to have the frequency of monitoring reduced. They will allow that sometimes. I wanted to mention, someone brought up the Clozapine levels. A good resource to look at is the 2017 Treatment Resistance, I always forget the exact title, Treatment Response and Resistance in Psychosis Working Group Consensus Guidelines. Those are an excellent resource. And we kind of follow those so that the guidelines suggest a Clozapine level twice during the first 12 months, 12 weeks or so of treatment with Clozapine to ensure you reach the therapeutic level and also to ensure adherence and then subsequently as needed. But we check them pretty often. We find them quite helpful, especially when patients are using tobacco and their tobacco use fluctuates. It can be helpful in that circumstance too because as their tobacco use grows up, their levels will often drop off. Thank you. I just wanted to speak to the comment on the frequency of blood draws and the pandemic. I do think this is the right time to look at this and see if those who couldn't get a blood draw, we've had plenty of our outpatients that were unable to get blood draws and we were still able to prescribe and dispense Clozapine. And that's an option on the REMS website right now. It would be interesting to see if there is any worsening of outcomes or any increased rates of Neutropenia, which I doubt there were. So I do think this is the right time to ask that question and to consider whether or not the parameters could be loosened. Yeah, untangling that will be a challenge, but it's probably doable. But there was a paper that did show higher rates of mortality of people with Schizophrenia during the pandemic. But how much of that had to do with agranulocytosis is probably minuscule. Hi, my name is Yulan. I'm a psychiatrist here at San Francisco Kaiser. I have a few Asian patients that prescribe Clozapine too. And I was calling for a colleague and her patient died from intestinal obstruction. I was just wondering, I'm a bit uncomfortable with sort of bowel regimens and which, like do we, should we get ahead of it by using a more vigorous bowel regimen and just wanting your comments on that. I mean, I think yes. I think they're encouraged to ask about at every early visit continuing and then using the standard bowel regimens I think do work. I think there's a cautioning it's using any kind of bulking agent. I guess that's not indicated for Clozapine, but other things, yes, ask about it and get ahead of it as much as you can, hydration in particular. I also think this is a great topic because it's not as discussed as frequently as agranulocytosis and myocarditis. But yes, there are fatalities and we don't have clear guidelines on how to best treat it. So I've noticed that it can vary what bowel regimens are recommended per institution. But I do agree it's best to get ahead of it and have this as part of the visit, like a routine questioning, including like using the Bristol stool scale and really encouraging the patient to discuss what their bowel regimen is like. Yeah, and I wanna underscore that last point, especially because unlike some of the other side effects, a patient doesn't necessarily associate this with the medication. And so you really wanna make that a routine as Laura was saying, a part of the visit and follow that along. And highlight to the patient that this is something that we wanna make sure we're concerned about. So we wanna make sure that what's happening with you. Any other questions? Can you tell us about the consultation? Yeah, it's a consultation service. It's just, you know, every psychiatrist in the New York State Office of Mental Health has our phone numbers for these weeks and they can just call us up and we just answer questions that come around. It really doesn't come up that much and we've been doing it for almost 10 years now. And I guess I'm on every fourth week approximately. And you know, the questions vary from people who have little experience using clothes being trying to start it. But often it's dealing with side effects and complications and you're restarting clozapine. It's, I don't get many calls. Maybe people wait for the other people to call because they're more helpful. But it's just a resource to try to decrease any barriers that people might have. And really to try to decrease stopping clozapine when it's not necessary. You know, for example, I mean at the beginning we would, one of the reasons we discourage people from taking blood levels unnecessarily is because people would be doing it every six months or every year and occasionally one would come back, you know, the clozapine level's 1,000 and they'd get these panic blood level results. And it was, well, how's the patient doing? And usually there was nothing going on and we'd just say don't worry about it. But it's, yeah, I think it is helpful for reassuring some people and maybe helping people get started some. I'll just do it from the outpatient perspective. It's great. So if. You must call other people. So we have a phone number to call and if there's a question that comes up, it could be like a medication interaction or just something that if we talk amongst each other we couldn't really figure out. It's very reassuring to know that we can call someone and then yes, it usually leads to the patient remaining on clozapine. So I think it's an excellent service that New York State provides. Thank you. And I do think it's a good model, actually, if you're able to implement it in your institution or area just to have that availability. Again, with the providers who are sort of nervous about prescribing this, whether it's because they haven't had that experience or exposure, enough training, or just because of the side effects and monitoring that's required, this can help to alleviate those concerns. Well, I was interested in your model. We actually are doing this too, but we have a different model. We have a biweekly Zoom drop-in. So we open up a Zoom and anyone can, we've sent the links out to clinicians and they can just come on and ask me or one of my colleagues questions. And are people Zooming in? Yeah, we usually get a couple of people each time. And we just have an interchange. Sometimes we can have two, three, four people all just sharing information. Should we stop? Any last question or comment? All right, well, thank you all so much for coming. Thank you.

Clozapine

Racial disparities

Ethnic minorities

Treatment-resistant schizophrenia

Neutropenia

Implicit bias

Healthcare access

Prescribing practices

Benign ethnic neutropenia

Comprehensive care

Clinician education

Systemic barriers