Hello and welcome. I'm Dr. John Torres, SMI Technology Expert for SMI Advisor and Director of the Division of Digital Psychiatry at Beth Israel Deaconess Medical Center. I'm pleased that you're joining us for today's SMI Advisor webinar, the American Psychiatric Association's Guideline for Treatment of Patients with Schizophrenia. SMI Advisor, also known as the Clinical Support System for Serious Mental Illness, is an APA and SAMHSA initiative devoted to helping clinicians implementing evidence-based care for those living with serious mental illness. Working with experts from across the SMI clinician community, our interdisciplinary effort has been designed to help you get answers to care for your patients. And I'd now like to introduce our faculty for today, Dr. George Keepers. Dr. George Keepers is the Department Chair at the Department of Psychiatry at the Oregon Health Sciences University, OHSU. His research interests include psychopharmacological treatments of schizophrenia and side effects of those treatments, such as acute pyramidal symptoms, tardive dyskinesia, and other aspects of neuropsychiatry and neuropsychopharmacology. His current clinical and research interests continue to be in the field of neuropsychiatry, and he is the Director of the Complex Neuropsychiatry Clinic and Director of the Adult Attention Deficit Disorder Clinic. Dr. Keepers is also a member of the APA writing group responsible for the Schizophrenia Guidelines, which is what we're talking about today. So Dr. Keepers, we're thrilled to have you here. Thank you for leading today's webinar. So please take it away. Thank you very much, Dr. Torres, and welcome to our audience today. The work that I'll be presenting is the result of efforts by a large group of people who composed the APA Schizophrenia Writing Group. These writing groups are structured in the following way. The core group of writers are paired with APA editorial staff and an employed expert academic psychiatrist writer who generate the draft text. Dr. Laura Faulkman, who is that person, the academic psychiatrist writer, deserves great credit for her efforts in producing this guideline. The guidelines are developed using a process intended to be consistent with the recommendations of the Institute of Medicine, the Council of Medical Specialty Societies, and the requirements of the AHRQ for inclusion of a guideline in the National Guidelines Clearinghouse. In developing the Schizophrenia Guidelines, an AHRQ review was commissioned. Existing guidelines from the APA and other organizations were examined. Additional relevant literature, including articles suggested by members of the writing group, were reviewed. Guideline statements drafted by the methodologist were discussed and modified, and the implementation text also drafted by the methodologist were extensively reviewed and revised. These meetings were conducted online and by telephone. I have no disclosures that would bias the content of this presentation. In fact, if I said so much as a sandwich from a pharmaceutical company, the APA would not have let me participate. These are our learning objectives today. We'll identify successful psychopharmacologic treatments of patients with schizophrenia, explain the most successful methods for the management of the adverse effects of antipsychotics, and describe clozapine utilization methods to successfully treat treatment-resistant schizophrenia. Now, I have a very vivid memory of the very first patient with schizophrenia that I ever encountered. I was a freshman in college at the University of Missouri. It was a pleasant fall day. Class had started the week before, and I had walked across campus to see my high school friend, David Hamilton. He'd rented a house on the north side of campus not too far from the university medical center, but more relevantly, it was close to what everybody in town called Mid-Mo, the state psychiatric hospital and clinic. A few minutes after I had arrived, there was a knock on the screen door. We'd barely gotten up from David's tattered secondhand couch when a short, roundish woman with a Prince Valiant haircut opened the door and shuffled in. She didn't seem aggressive, but we could not understand what she wanted. She talked, but didn't make any sense, and her expression never varied. We eventually made out that she wanted to use the telephone, but she was incapable of successfully dialing the seven-digit number. In those days, of course, no area code was needed. David dialed the number for her, and we reached her parents. She was clearly in trouble, and we expected that her parents would want to come and get her. We were astounded that her parents wanted nothing to do with her and left us with that problem. Schizophrenia is arguably the most severe condition and the most complex condition that psychiatrists treat, affecting a bit more than 1% of the population. With an onset in the late teens and early 20s, it frequently leads to a lifetime of disability. The human cost to the patient, family, and society is terrible, and the economic cost is staggering. The cause of schizophrenia, although a lot of progress has been made, remains unknown, and curative treatment is unavailable. We are, as a result, limited to empirical treatment methods about which considerable knowledge has been amassed, but gaps in our evidence base hamper our ability to make rational treatment choices. Now, the APA has undertaken the task of providing guidance to psychiatrists in the treatment of the major psychiatric conditions. The APA asked me to lead one of the three APA writing groups charged with updating and developing treatment guidelines. The new guideline for alcohol use disorders was published last year, and we are finished with the treatment guidelines for schizophrenia, which have now been published. The AHRQ review was the foundational document for the development of these guidelines and sought to answer the questions noted on this slide for medications and for psychosocial treatments. Unfortunately, many questions that are important to guide clinicians in their treatment of patients were not answerable in the context of this review. Supplementary information from a variety of sources was reviewed, but it rarely qualified as adequately strong evidence to form the basis for a statement. Instead, much of that material is incorporated in the implementation sections of this document. Now, guideline statements are phrased as either recommendations, which is the highest level of statement, or as suggestions. Each statement includes a rating of the quality of evidence that supports it, and each statement is also followed by extensive text that is divided into these sections. Implementation, benefits, harms, patient preferences, balancing benefits and harms, differences of opinion among writing group members, review of available guidelines from other organizations, and quality assurance considerations. It should be noted that each of the statements presented today required an explicit voting process by members of the group. Any negative vote and the rationale for it are recorded in the section differences of opinion among writing group members. One of the most difficult aspects of developing guideline statements is repeated encounters with the limits of our reliable knowledge. Much of what we think we know about treatment is not supported by an adequate evidence base. Now, when I was a resident, we didn't have such doubts. Instead, giants in the field of psychiatry favored us lowly trainees with the revealed truth, which was handed down to us almost like the Ten Commandments. Those days are long past, and we live in the era of the ascendancy of evidence-based medicine, and there are new commandments by which we must live. These are the Ten Commandments of evidence-based medicine as I have modified them, and I would ask you especially to attend to Commandments 1, 3, 7, 8, and especially to 10. Thou shalt be skeptical of all you are taught, even that which you have heard from me. Of course, in our imaginations, constructing clinical guidance for our colleagues becomes a precise exercise in summarizing the clinical research literature in mathematical terms. But of course, that's just a fantasy. Instead, the real process looks more like this. Time again, we encounter clinical practices that have become common, but for which on examination there is not adequate knowledge to make a recommendation or even a suggestion. Instead, much of the accumulated knowledge and practices actually contained in the implementation sections of this document rather than in the statements themselves, which are required to be rigorously supported by the evidence. The guideline material I'll be presenting today is final. The writing group's efforts were published for extensive public comment and revised and were approved by the APA Assembly. The guideline has been published by the APA Press. Now the first statement is on the assessment of possible schizophrenia. The APA already has a guideline for psychiatric assessment, but this statement was included to emphasize that a complete evaluation of a patient is important. The implementation section includes a more specific discussion of assessment methods, both initially and during treatment. In the evaluation of the potential for self-harm and harm to others, access to firearms is specifically called out. Guidance includes measurement of the BMI at every visit for six months and quarterly afterwards for second generation antipsychotics, measurement of the hemoglobin A1C and lipid panel at four months after starting treatment and annually thereafter, an EKG at baseline and on-dose increases for chlorpromazine, haloperidol, coperidol, thioridazine and other medications that affect the QTC and for patients with cardiovascular disease. Although a discussion of differential diagnosis is beyond the scope of the guidelines, its importance is emphasized and examples of conditions that can mimic schizophrenia such as neurosyphilis, velocardiofacial syndrome, Huntington's disease, Wilson's disease and anti-NMDA receptor encephalitis are given. With this emphasis on evaluation, we are seeking to avoid this. A general feature of this guideline is the encouragement of the use of quantitative measures to accept symptomatology and clinical condition. We wanted to avoid language which would limit such measures to traditional rating scales because future quantitative measures may include other methods. Computerized assessments, real-time monitoring of behavior and remote physiological monitoring may in the future prove to be useful. We did not feel it appropriate to recommend a particular patient or clinician rated scale, but the implementation section for this statement includes the discussion of many of the useful and popular rating instruments including the PANS, the clinician rated dimensions of psychosis, symptom severity, which is included in the DSM-5 and some scales for specific symptoms like the Bush-Francis Catatonia rating scale and several options for patient rated scales. Now, the goals of treatment planning encompass efforts to promote and maintain recovery, to maximize quality of life and adaptive functioning, and to reduce or eliminate symptoms. To achieve these aims, it is crucial to identify the patient's aspirations, goals for treatment, and treatment-related preferences. The comprehensive treatment plan will recognize that both psychopharmacologic and non-pharmacologic treatment and interventions will be required to optimize treatment. The fourth statement begins our discussion of antipsychotic medications. An algorithmic approach to antipsychotic selection is not possible due to the heterogeneity of clinical trial designs and few actual head-to-head comparisons of antipsychotic drugs. Thus, there isn't a reliable strategy to predict response in patients who have not been previously treated. Nonetheless, it is important to account for the side effect profile and metabolism of the drugs, particularly in relation to drug interactions, the use of nicotine, the use of cannabis, the patient's age and ethnicity. The likelihood of some side effects such as dystonia can be estimated on the basis of drug properties and patient risk factors. Now, the guideline includes very useful tables for suggested laboratory and the use of measurement-based care systems within the EHR to monitor compliance, response, and side effects is encouraged in the guidelines. Clinicians will generally agree that patients who have responded to an antipsychotic continue to take antipsychotic medications because of the demonstrated benefits. However, patients, of course, encounter multiple obstacles to adherence, including routine forgetfulness, financial barriers, cognitive difficulties managing complex regimens, side effects, substance abuse, and stigma. A patient-centered nonjudgmental approach to adherence may be aided with patient rating scales, pharmacy records, collateral history, and technological innovations such as electronic pill bottle caps. Some patients will benefit from long-acting antipsychotics, but the harms of these treatments must be carefully considered. Now, it would seem common sense to continue a patient on a medication that has been effective for that patient, and the available evidence supports this approach. Switching from an effective antipsychotic to one of unknown efficacy for a particular patient carries three risks, patient discontinuation of treatment, ineffective treatment, and adverse side effects of the new agent. Unfortunately, patients are sometimes forced to switch medication based on their insurance coverage and financial considerations, an outcome that we would like to avoid. Evidence for the effectiveness of clozapine for treatment-resistant schizophrenia is robust, but the definition of treatment-resistant remains variable. Thus, the indication for initiating clozapine treatment is not entirely clear. A typical definition of treatment resistance would be that a patient's symptoms have shown no or an inadequate response to two antipsychotic medication trials of at least six weeks. This would also include optimization of the treatment with a dose of 300 to 450 milligrams a day to obtain adequate levels of clozapine and noreclozapine at approximately 350 nanograms per mil. There's no systematic support for augmentation, although some open trials do suggest this, and the treatment response should be monitored for adverse effects. ECT is supported in multiple studies as an augmentation treatment for schizophrenia. Although the benefits of clozapine treatment do outweigh the potential harms, significant harms of this treatment must be carefully considered, including leukopenia, cardiomyositis, orthostasis, sedation, and anticholinergic side effects. Monitoring for these potential side effects is extremely important, and I would mention one additional one that has recently come to light, which is a condition in which the patient has paralysis of the bowel. There have been reports of fatalities from this side effect of clozapine. Because of these problematic side effects, monitoring to confirm effectiveness and efforts to maximize effectiveness are extremely important. Measurement of serum levels and noreclopromazine, as I have indicated, to assure an adequate dose are extraordinarily important. And if there is a response that is inadequate, that is if clozapine doesn't work, clozapine should be discontinued in patients who have not responded for six months. 50 percent of patients with schizophrenia will attempt suicide, and 5 to 10 percent of these patients will die by suicide, schizophrenia being one of the most lethal psychiatric illnesses. In individuals with schizophrenia who are at significant risk for suicide, the use of clozapine is associated with lower rates of self-harm, suicide attempts, and hospitalizations to prevent suicide. Meltzer in 2003 was the first individual that I am aware of to document this in an article in the Archives of General Psychiatry, Clozapine Treatment for Suicidality and Schizophrenia. There have been multiple other studies that have confirmed this since that time. Many of the risk factors for aggressive behavior are the same in patients with schizophrenia as in other disorders. But persecutory delusions and command hallucinations may increase the risk. Evidence for the reduction of aggressive behavior in schizophrenia with clozapine suggests its use if reduction of modifiable risk factors and treatment with other antipsychotics fails to adequately reduce the risk of such behaviors. We also suggest in Statement 9 that long-acting injectable antipsychotic patients be reused to treat patients if they prefer that treatment, or if they have risk factors or a history of uncertain adherence to treatment. This was a statement that was suggested by the public review of the initial draft of this document and a review of the evidence suggested by that public review does suggest that this is appropriate for many patients. The next several statements concern the management of neurological side effects of antipsychotic drugs. These adverse effects and others affecting organ systems are the major harms against which the benefits of antipsychotics must be balanced. The implementation sections contain an extensive discussion of this topic. It should prove to be a major resource for clinicians. Although the statements concentrate on the neurologic side effects of antipsychotics, there are many other adverse side effects that are discussed in the implementation section and for which patients need to be monitored. Statement 11 is about dystonia. Acute dystonia is less frequently seen since the advent of second-generation antipsychotics. I think there are some residents who have actually never seen a case. Fortunately, there are some good examples of dystonia and other movement disorders available on YouTube. This slide actually included a link for a particularly good site on this. Interestingly, one of the writing group members disagreed with the recommendations stating that antipsychotic discontinuation or dose reduction would be preferable to treatment. Given the acute pain and sometimes life-threatening nature of dystonia, the rest of the group felt very strongly about the need for prompt treatment. The treatment recommended are anticholinergic agents diphenhydramine, venstropine, and trihexyphenidyl, and in the acute situation, should be given parenterally. There are certainly life-threatening cases of laryngeal dystonia that should be immediately treated. I have seen cases of this sort before, both on the inpatient wards and in the community mental health clinic. In many cases, the staff are not aware of this side effect from antipsychotics, and I've seen it missed in the emergency room as well. This is an important one to mention and to treat immediately. Statement 12 concerns the treatment of drug-induced Parkinsonism. Although the first options mentioned for drug-induced Parkinsonism are dose reduction and switching antipsychotics, the risks of recurrent psychotic symptoms have to be carefully weighed in that decision. Anticholinergic medications are not benign, particularly when used on a chronic basis and in the elderly. They include adverse effects of blurred vision, constipation, tachycardia, urinary retention, thermoregulatory dysfunction, and cognitive impairment. The risk for these adverse effects is especially prominent in the elderly. One writing group member felt so strongly about these risks that he disagreed with including anticholinergic as a treatment option. His disagreement is recorded in the recommendation. Amandadine is mentioned in the implementation section as a possible alternative to anticholinergic agents, but the evidence for treatment with amandadine was not strong enough to include it as a definite recommendation. The treatment of achesthesia is more problematic than the treatment of dystonia or of Parkinsonism. Similar considerations apply to the dose reduction as a strategy for managing achesthesia. Anticholinergics have not been shown effective for achesthesia, but there is low-quality evidence that supports the use of benzodiazepines and propranolol. Both agents carry some liabilities. There is some evidence reviewed in the implementation section that supports the use of mirtazapine for this purpose. Achesthesia is another antipsychotic side effect that sometimes escapes notice or escapes diagnosis because it can be confused with agitation or anxiety. Particularly for inexperienced clinicians may be difficult to diagnose. It's therefore important for clinicians to be educated about the manifestations of this side effect and to be careful in assessing patients for it. Next, we will talk about tardive dyskinesia. Tardive dyskinesia, of course, is the long-term, sometimes permanent movement disorder side effect of antipsychotic agents. It can occur with the second-generation antipsychotics, as well as first-generation antipsychotics. There are certain risk factors such as the presence of a mood disorder and advanced age and female gender that predispose to it. Patients should be carefully monitored for the development of TD on a regular basis through clinical examination, and more formally with the use of the aims. In our implementation section, you will find recommendations about that, that patients should be monitored at every clinical visit with clinical examination for the development of this side effect, and periodically with the use of a formal examination. We did not recommend particular scales in this area, since there are others besides the aims, but a formal evaluation is important. Many cases of TD are mild, but some can be quite disabling to patients. There is a moderate level of evidence that supports the use of DMAD inhibitors in treatment. Specific agents are mentioned in the statement, since there are a limited number available, and we wanted to alert psychiatrists to the availability of these treatments. Table outlining their use is included in the implementation section. Tetrabenazine is the oldest agent for the treatment, and has been around for a number of years. I recall treating patients with it a decade ago. Tetrabenazine and valbenazine have been developed since and they are much easier to use than tetrabenazine, which cures a heavy adverse effects load. This is a slide demonstrating the mechanism of action of DMAD inhibitors. We move now into non-pharmacologic treatments for schizophrenia and I will say that it was very important to the writing group that these be included in the treatment of schizophrenia. You'll find in the actual document itself, statements that on every recommendation, that the treatment of schizophrenia must be comprehensive in nature and must include pharmacologic and non-pharmacologic needs. The first of these concerns the use of a first episode coordinated specialty care program. For individuals with a first episode of psychosis, team-based multi-component treatment programs have been developed that integrate a number of evidence-based interventions into a comprehensive treatment package. Where I am in Oregon, for example, the EISA program, which stands for the Early Assessment and Support Alliance, is an outreach program for youth with early symptoms of psychosis for which we provide psychiatric services. There are many others with some of the best efforts developed in other countries, particularly Australia. The demonstrated benefits of these programs include lower mortality rates, lower rates of relapse, a better quality of life, and better chances of remaining in school and in employment. The use of CBT for individuals with schizophrenia has a number of potential benefits, including improvements in the quality of life and global social and occupational function, as well as reductions in core symptoms of the illness, such as positive symptoms of schizophrenia. The overall approach with CBT-P, which is what this therapy is formally called, includes developing a collaborative and non-judgmental therapeutic relationship in which patients can learn to monitor the relationships between thoughts, feelings, behaviors, and symptoms and evaluate the perceptions, beliefs, and thought processes that contribute to those symptoms. Through that dual focus on monitoring and evaluation, patients can develop beneficial coping strategies and improve their functioning with behavioral self-monitoring. This behavioral self-monitoring can serve as a basis for graded task assignments and for activity schedule, so familiar methods in CBT. There's a link on this slide to video examples of the use of CBT-P, which are quite good and are recommended for viewing by those unfamiliar with this particular treatment. We also recommend psychoeducation, elements of psychoeducation are really an integral part of good clinical practice. However, formal, systematically delivered programs of psychoeducation have been evaluated through clinical trials. These psychoeducational programs have varied in their format, duration, and scope. Some psychoeducational programs are delivered on an individual basis, whereas others are delivered in a group format. Often in conjunction with family members or other individuals who are involved in the patient's life. To give you an idea of the scope of these research studies and clinical trials, the 12-session program of psychoeducation has been the norm. However, there have been briefer trials that comprise 10 sessions. Typically, psychoeducation is conducted on an outpatient basis, but elements of formal psychoeducation programs can also be incorporated into care on inpatient settings. Statement 18 recommends supported employment services. Imported employment differs from other vocational rehabilitation services in providing assistance in searching for and maintaining competitive employment concurrently with job training, embedded job support, and mental health treatment. Most studies of supported employment involve individual placement and support. In addition, there's a focus on the rapid attainment of competitive employment. Individualized long-term job support and integration of employment specialists with the clinical team are frequently found in these programs. The evidence consistently shows that supported employment is associated with greater rates of competitive employment than either transitional employment or pre-vocational training. ACT, or Assertive Community Treatment, sometimes referred to as programs of Assertive Community Treatment, PACT, is a multidisciplinary team-based approach in which patients receive individualized care outside of a formal clinical setting. Thus, individuals may be engaged in their homes, workplace, or other community locations. Continuity of care is enhanced by this because individuals work with an assigned team, which has 24-7 availability rather than being assigned to a designated clinician for care. The team members typically include a psychiatrist, a nurse, a social worker, or case manager, peer specialists, vocational specialists, and clinicians with expertise in substance abuse treatment are often part of this team as well. Studies of ACT suggest that it is associated with comparable symptom improvement to other treatment delivery approaches, but that individuals who receive ACT are more likely to have a home, to be living independently, working, and less likely to be hospitalized as compared with patients who receive treatment as usual. We also suggest that patients with schizophrenia who have ongoing contact with family receive family interventions. Good psychiatric treatment often involves family members and other individuals who play a key role in the patient's life. Now, our writing group's use of the word family is intended to include a broad range of individuals as shown here, who may have important roles in the patient's life. In addition to spouses, parents, children, or other relatives, such individuals may include people who reside with the patient, intimate partners, or close friends who are an integral part of the patient's support network. These individuals benefit from discussion of topics such as diagnosis and management of schizophrenia, types of support that are available, and ways to access help in a crisis. Most patients are accepting of family involvement. Some health professionals may worry about the legal or regulatory aspects of sharing information. General information that is not specific to the patient can be provided, that is common approaches to treatment, general information about medication and their side effects, available support and emergency assistance, since these are not protected health information. Even when a patient does not want a specific person to be involved in their care, the clinician can listen to information provided by that individual as long as confidential information is not provided to the informant. Illness self-management and training programs aim to reduce the risk of relapse through the recognition of signs of relapse, development of relapse prevention plans, and the enhancement of coping skills. Recovery programs focus on patients' self-determination and personal goals, and on sharing coping strategies with other patients. Although studies of these interventions are limited, they do suggest improved quality of life, empowerment, and recovery from illness in individuals that participate. You will note that the level of evidence for these programs did not permit them to be a recommendation, but instead a suggestion. We also suggest that patients with schizophrenia have a therapeutic goal of enhanced social functioning. That to have a therapeutic goal of enhanced social functioning, receive social skills training. The use of social skills training in the treatment of schizophrenia can improve social function, core illness symptoms, and negative symptoms more than usual care. Reductions in relapse rates, including rehospitalization rates, have also been noted in some studies. Supportive psychotherapy is commonly a part of a treatment plan in individuals with schizophrenia, although the evidence related to its benefits is limited. When compared to treatment as usual, no advantage was seen for supportive psychotherapy in terms of global or social function. Now, those findings are difficult to interpret, and we had a long discussion about this, given the frequent use of supportive therapy techniques as part of usual care. When compared to insight-oriented psychotherapy, a small number of early studies suggested that supportive psychotherapy might be associated with a better outcome on coping skills, adherence, and relapse. Supportive psychotherapists, of course, foster goals which include reassurance, praise, encouragement, explanation, clarification, reframing, guidance, and suggestion, and the use of a confrontational and non-confrontative communicative style. Many of these are the common elements in all effective therapies, and they are common elements in usual care. We think that that is why the studies don't show dramatic differences between usual care and supportive psychotherapy. Nonetheless, the evidence for this treatment grows only to the level of a suggestion. Now, the writing group is very well aware that for many of the recommendations and suggestions that are in these treatment guidelines, implementation in many localities will be very difficult because of the lack of the availability of services and the personnel required to deliver them. Although there are many inadequately answered questions about the genesis and treatments of schizophrenia, one of the great tragedies of our times is that people with this devastating disease do not have access to treatments and systems that we know would help them. So we hope that the publication of these guidelines will be adopted in many mental health care systems and health care systems as a standard of care, and that the treatments outlined in the guidelines will become available to many more patients. That is sadly not the case currently. Here in Portland, Oregon, for example, we have a new wonderful acute care psychiatric hospital with 107 beds and 50 psychiatric emergency beds that is a major training facility for our students and residents. In Oregon, we have two brand new state hospitals that are truly wonderful facilities, staffed in part by university faculty and also being training facilities. We have three major metropolitan mental health centers that provide traditional and residential treatment services. However, the capacity of our system is not nearly enough for the population of Oregon, which is relatively small compared to most states, and rural Oregon has very limited services. Additionally, patients eligibility for services is remarkably fractured. For example, Medicaid patients can be seen in our child clinic, but until recently not in our adult clinic. We'll come in as no surprise to this audience that we have a broken system. Here in Oregon, NAMI gives us a C-grade with regards to our mental health system. Nobody gets an A in the United States. What we do with our residents is to send them to Vancouver, BC to have a look at a better functioning mental health system that allows access to all and provides the treatments that they need. I would like to thank again the members of the APA writing group who have produced this extensive and comprehensive treatment guideline. Their work was done over a period of some years. Again, I'd like to mention Dr. Laura Hoffman, who was responsible for all of the drafts of the guideline statements and the implementation text. I'd also like to thank the APA staff who are listed here under the systematic review group whose tireless efforts and the production of this guideline were very much appreciated, and without whom we would not have been able to do this work. At this point, I am ready to take any questions that you might have. Thank you so much for such an interesting presentation, Dr. Keepers. Before we shift to question and answer, I want to take a moment and let you know that SMI Advisor is accessible from the Internet as well as your mobile device. You can use the SMI Advisor app to access resources, education, upcoming events, complete mental health rating scales, and even submit questions directly to our team of SMI experts. You can download the app now at smiadvisor.com. Now we'll take a couple of questions and we'll go through as many if we have time. One, Dr. Keepers, is, is there a reason for recommendations for CSC or, of course, coordinated specialty care programs that's specific to people experiencing first episode psychosis rather than anyone experiencing psychosis? The programs that we reviewed to make this recommendation were programs that concentrated on first episode psychosis. Background of this is really programs in other countries, particularly Australia, as I mentioned, that have attempted to reduce the, really by treating prodromal symptoms, have attempted to reduce the onset of schizophrenia in patients, and have attempted to reduce the morbidity and mortality that is associated with frank psychosis and hospitalization. That, of course, is still being studied as to whether or not that's possible to do to prevent the onset. But I think the data do support the idea that you can prevent much of the morbidity associated with schizophrenia by early treatment and the prevention of hospitalization. There is good evidence that when you begin to approach patients and patients' families early in the prodromal phase or early in a first episode psychosis, that the patient's compliance with treatment is better and that there is a reduction in the need for hospitalization. Now, whether these types of programs would be useful later in the course of schizophrenia, I think is an open question. It seems to me common sense that they would be, but the programs that I know about and that we reviewed have not addressed that issue. That makes sense. And this question, I'm going to combine two questions about CBT for psychosis. The first one says, I realize CBT for psychosis is one of the recommendations you covered, but it's so hard to access. Do you know of any ways to access it? And then also related to kind of hard to access CBT for psychosis. Why is the question says, could there be or should there be a mention of psychodynamic therapy after someone completes CBT-P? We have no evidence that psychodynamic psychotherapy would be helpful to patients with schizophrenia after CBT-P. That would be something that people would need to study, but we don't have any evidence to that effect at this point. To address the access issues to CBT-P, that's absolutely right. That's one of the problems that we have in the treatment of schizophrenia. And it's not limited to the issue of access with CBT-P, but it is also a factor in the provision of some of these other treatments. And I'll speak to a couple of them, which I think people should be aware of. It's not only non-pharmacologic treatments in which access is limited. It's also pharmacologic treatments. So the use of clozapine in the United States is tremendously underutilized. There are many more cases of treatment-resistant schizophrenia than there are patients who are taking clozapine. And so that's an issue of the ability of our systems and our clinicians to be able to deliver a treatment that we know is effective and that will help many people. And it's something that we need to address in our healthcare systems and in our mental health systems. With CBT-P particularly, there are not very many people who are specifically trained in this modality. And so what we can do with these guidelines, I think, is to encourage systems to train more clinicians who can deliver this kind of treatment. That makes a lot of sense. And one question is, are there any workbooks or articles that you would recommend around CBT-P? And I'm also going to cheat and take an answer saying, for the person who submitted this, we're going to have a consult slide coming up. And that's a great one where our experts and SMI advisor can also send you some resources. But Dr. Keepers, any resources or handbooks come to mind on CBT-P? And if not, again, no worries. We do have a reference to CBT-P within the guideline. I'm not going to try and look it up right now. But we can certainly answer that question and send out the answer to the reference for you. And the slide that I showed actually has a link. I don't know if the links come through on these slides, but there is a link to an actual CBT-P session. And actually, there's more than one of them on that YouTube presentation with an explanation of what the therapist is doing and actual footage of the therapist treating a patient. Got it. This question will switch off from CBT-P and say, would you recommend titrating an atypical antipsychotic beyond the FDA maximum when it's been moderately affected at the maximum dose for switching to a different antipsychotic? Not something that has been studied, so I will only be able to comment from the standpoint of my own practice with patients with schizophrenia, which has been extensive over the years. The FDA guidelines, dosing guidelines, are based upon studies. And so those studies, of course, have a limited dosing range and are designed to demonstrate the effectiveness of an agent in a group of individuals who have the disorder. They don't address the individual patients who may have specific needs based upon either their metabolism of a drug or based upon the pharmacodynamics of the drug and their central nervous system. And so it is perfectly reasonable to advance the dose of a drug over the FDA limits in an individual patient, particularly if there is evidence of a response and there are not adverse side effects. Now, there are caveats with that recommendation, of course. You wouldn't want to do that with bupropion, for example, because you risk giving the patient a seizure if you do that. And similarly with clozapine, you've got to be very careful about the dosing of clozapine because of the adverse effects, including seizures, that you might encounter with clozapine. So with those caveats, I would say that it is reasonable to try. The fact that the patient had some response to the agent suggests that they're going to be responsive to it. And I personally would not abandon that drug until I was sure that they were not able to get an adequate response. The other issue in this, of course, is the time that the patient has been on the dose. So the response, we're accustomed in the acute care setting these days to discharging patients after a few days and after they've attained an initial response to an antipsychotic agent. But we do have to remember that the full response to an antipsychotic agent takes weeks to develop. And in patients with chronic psychosis, it may take as much as 12 weeks to show a full response. So you've got to be careful to go slowly enough that you're seeing the full response to the dose that you're giving. That's very good advice for everyone. This is a question different saying, what about music therapy? Clearly, the evidence may be less, but did you guys come across any evidence to support music therapy or have thoughts on it in general? Well, I am a fan of music therapy, but we did not encounter systematic evidence for its effectiveness in the treatment of schizophrenia. I will say that this kind of therapy that is directed towards patients' artistic interests is frequently a component of some of the treatment programs that are offered to patients. I think that from the standpoint of the patient's personhood, of treating them as an individual who has individual interests, abilities, talents, that music therapy and artistic therapy of various kinds are a big plus for those patients. And I would not abandon them simply because there's not systematic evidence about them. That makes a lot of sense. This question says, can advocacy for patients on individual clinical system or policy levels be included as a treatment recommendation in some way as an addendum, i.e. recommendations and directions for individuals, families, and providers to advocate for these evidence-based services and treatments, some way to incorporate advocacy into any guidelines as part of a comprehensive treatment plan? Well, that's a very interesting suggestion. Of course, the APA itself is a very strong advocate for patients' rights, their right to effective treatment and the resources to do so. So the APA's position on this is very clear. And the APA spends a lot of money lobbying legislatures to try and assure that. I'm not sure about the inclusion of that kind of statement within a treatment guideline. I will say that if you read the APA's discussions of the AMA's ethical principles, there's a discussion, you can find it on the APA website, of the discussion of the AMA's ethical principles, that there is a strong role for advocacy discussed in those discussions of the AMA's ethical principles. So it's certainly something that the APA endorses. Whether it belongs in a treatment guideline, that would be kind of up to the APA itself. That makes sense. And I would say to that individual, if they are a member of the APA, that they do have avenues available to them to advocate for that kind of a statement. This is a broad question, but clearly these guidelines were developed, or most of the work was before COVID. Is anything, do you think, substantially different in offering care via video visits and telehealth? Or that you found you would go, oh, if we had known this was happening, we would have thought a little bit differently about any of these recommendations? Well, who knows? I can tell you that we here at OHSU, we converted our practice from a, basically, we did do a lot of telepsychiatry since 2007. We've been doing it since then to remote sites. But we converted the rest of the practice to telehealth in about three weeks. After the advent of the COVID pandemic. And we've had very good success in delivering our treatments with telehealth. There are some patients who find the video, who find video visits very adverse. And who avoid them. For example, I've got patients who won't do video visits. They'll only do telephone visits. And of course, there are some treatments that you can't deliver with telemedicine. LAI, for example, are one thing that you can't do. We have people coming in for their injections, of course. Vagal nerve stimulation is another one you can't do remotely. So I think there are some adverse effects of not being able to see patients directly. And I will say that in our clinics that have a heavier load of patients with various persistent, severe and persistent mental illness, that the use of telehealth is at a lower volume in those clinics than in our other ambulatory services. So we might have had, we've been writing this during the pandemic, included something in the guideline as a forward about the use of telemedicine. And of course, we didn't have that opportunity. Perfect. I'm actually going to break it. We'll go to the next slide for consults. We're out of time. But if you have any follow-up questions or we weren't able to get to all the questions or to a specific topic about evidence-based care for SMI, our clinical experts are available now for online consultations. Any mental health clinician can submit a question and receive a response from one of our SMI experts. Consultations are free and 100% confidential. And SMI Advisor is just one of many SAMHSA initiatives that are designed to help clinicians implement evidence-based care. We encourage you to explore all of the resources available on the Mental Health Addictions and Prevention TTC, as well as the National Center of Excellence for Eating Disorders and Suicide Prevention Center. These resources cover a broad range of topics from school-based mental health through the opiate epidemic and more. Thank you for joining us. Thank you to our guest, Dr. Keepers. Thank you for everyone for wonderful questions. Until next time, take care.

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