Hello and welcome. I'm Dr. John Torres, the Director of Digital Psychiatry at Beth Israel Deaconess Medical Center and technology expert for SMI Advisor. I'm pleased that you're joining us today for our SMI Advisor webinar titled Approaches to Conversations About Long-Acting Injectable Antipsychotics. SMI Advisor, also known as the Clinical Support System for Serious Mental Illness, is an APA and SAMHSA initiative devoted to helping clinicians implement 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 the questions you need to care for your patients. Now, I'd like to introduce you to the faculty for today's webinar. We have an outstanding lineup for you. We have Donna Rowland, we have Sarah McLaurin, Eric Atches, and Rob Cote. So I'm going to introduce each of them because they're each impressive in their own and together, you'll see why this is a terrific panel. So first, Donna Rowland. So Dr. Rowland is a Clinical Associate Professor and the Director of Psychiatric Mental Health Nurse Practitioner Training at the University of Texas with 23 years of experience in psychiatric nursing. She is co-leading interdisciplinary graduate training initiatives with the Schools of Nursing, Medicine, Educational, Psychology, Social Work, and Pharmacy with funding from Health Resources and Service Administration and the Texas Higher Education Coordinating Board, aiming to expand a culturally diverse workforce for underserved populations. She serves as Co-Director of the Institute for Domestic Violence and Sexual Assault, working alongside Schools of Social Work, Law, and Bureau of Business Research. Next, we have Sarah McLaurin. Sarah McLaurin is a Psychiatric Mental Health Nurse Practitioner at the Freedom Trail Clinic in Boston. She is the Director of Community Health Integration for North Suffolk Mental Health Association and the Massachusetts General Schizophrenia Clinical and Research Programs. In this role, she has developed the mental health and medical prevention services through which the clinic provides guideline-coordinated care and moves towards population-based management of disease. Sarah worked closely with the Department of Mental Health, specifically engaging the residents at two Department of Mental Health homeless shelters. In this role, she advocates for systemic change and supports the education of psychiatry residents and Department of Mental Health staff. Next, we have Eric Atchis. Dr. Atchis is a staff psychiatrist and researcher holding appointments at Pine Rest Christian Mental Health Services, Cherry Street Health Services, and Network 180, all located in Grand Rapids, Michigan. He is currently an Assistant Professor of Psychiatry and Director of the Division of Psychiatry and Behavioral Medicine at Michigan State University College of Human Medicine. Dr. Atchis' main research interests include improving treatment for patients with schizophrenia and depression. He has served as an investigator on more than a dozen clinical trials, including NIMH, NIAA, and NIDA-sponsored studies, and his work has been published in the Journal of Dual Diagnosis, Drama Psychiatry, in the Journal of Clinical Psychopharmacology, the British Journal of Medicine, and the Journal of the American Medical Association. Last but not least, we have Dr. Rob Cotis. Dr. Cotis is an Associate Professor at Emory University School of Medicine in the Department of Psychiatry and Behavioral Science. He has significant expertise in clozapine, characterizing persistent symptoms of schizophrenia, understanding cardiometabolic side effects of antipsychotic medications, and first episode psychosis. Additionally, he is Director of PSTAR Clinic, which stands for Persistent Symptoms Treatment Assessment Recovery, Project AERO, which stands for Achievement Recovery Through Resilience Optimism Wellness, and Open Dialogue Atlanta at Grady's Outpatient Behavioral Health Clinic. Dr. Cotis is also Associate Director of Psychiatry Residency Education in the Department of Psychiatry and Behavioral Sciences at Emory. Thank you all for leading today's webinar, and over to you. Thank you. Today, we'll be focusing on the use of long-acting injectable antipsychotics and how to have these discussion with our patients, including the risks and benefits. We'll use prepared scripts for collaborative discussions with patients and families about the options and troubleshooting anticipated patient challenges, and we'll utilize best practices of shared decision making when having these conversations. Next slide, please. First of all, I'll start by talking about the existing research on the use of long-acting injectable LAIs, antipsychotics risks, benefits, and ambivalence. First of all, from a patient perspective, what we often think about as pros or benefits would be primarily relapse prevention, and I think aligning with patients around the shared goal of not returning to the hospital, to the hospital, of preventing interruptions and education or employment fall under that. And regarding the ease of use and improved relationships, I think of those two often as going together and talk with especially younger patients about not having to fight with their parents or caregivers about remembering to take their medication, kind of taking that piece of the treatment dynamic out of the picture. Also, some people identify the stigma and confidentiality can be a benefit of long-acting injectable medication instead of having pill bottles around the home, you just, I have a doctor's appointment to go in for. On the flip side, some concerns that people have, they worry that there's less control, especially around dose adjustment. We'll talk further about how that can be addressed in conversation. Some people have needle phobia and worry about pain at the injection site. Also, for some people who may have had trauma in their past, the location site can be something to consider if it needs to, if it's an injection that needs to be given gluteally. Just as we said for the addressing stigma can be a pro, it can also be a con. Some people don't like having to go to a clinic, especially if it's a kind of well-known or clearly a mental health clinic. Next slide, please, Cindy. Ayers et al looked at the specifically patient perceptions of advantages and disadvantages. They did the study in Canada using focus groups and identified four main themes, awareness and knowledge of LAI antipsychotics as an option, perceptions about this as a treatment option, cost and convenience, kind of practical factors, and the issue of a coercive context. I think it's notable that nine out of 34 of the focus groups participants had not heard about long-acting injectable antipsychotics, didn't know that that was an option. Also, coercive context is something that often comes up. People's experience with injections have been in more of an acute setting. It's also here you can see patient differences based on whether or not they've actually had it, they've used LAIs themselves or not. Mindy, we'll go on to the next slide, please. Next slide, please. And this talks a little bit further about this, but specifically focus is on those in the early phase of their illness. Das, Malik, and Haddad looked at people within the first three years of their diagnosis and treatment for schizophrenia and included purposive sampling of patients from diverse backgrounds and included people who were on oral medications, LAIs, or no medication at all. And similar to the other study, the attitudes characterized here included the therapeutic alliance and relationship with the prescriber, knowledge and beliefs about long-acting injectables, and the patient's views about the appropriateness. Again, concerns about coercion come up, misperceptions. And I think it's important to note that similar to the other studies that attitudes were almost more positive in people who were receiving long-acting injectables already. Again, the kind of common positives noted were convenience and to avoid forgetting, and pain and coercion were the primary concerns. Next slide. In considering how we think about who would be a good fit for a long-acting injectable, think about eligibility and selection, patient preference, their history of tolerability of various antipsychotics, efficacy, the risks associated with relapse, and what does somebody's decompensation look like? Is there violence? Is there hospitalization? What kind of relational ruptures could exist? And I think, again, it's referencing before the risk of rehospitalization is significantly less for people on long-acting injectables. You can see here, any LAI, it's 19 and smallest for those on the second-generation antipsychotics, but both first and second-generation antipsychotics remain very effective. And now I'll pass it along to Donna. So clinicians commonly have hesitancies about LAIs as well. And we'll look here at these two research studies that examine clinician attitudes and the impact of our conversations with our patients about LAIs. Patel and colleagues in 2020 surveyed 136 European psychiatrists across six countries looking at their prescribing attitudes for long-acting injectables. And what they found were that physicians were less likely to discuss LAIs than oral antipsychotics with their patients. However, 60% of those who were surveyed did indicate that their rate of prescribing LAIs had increased over the past five years, showing some progress. Also, negative attitudes about LAIs from colleagues were reported to influence their decisions in initiating LAI treatment. There were also concerns over cost of reimbursement, as well as side effects. And the most concerning side effects reported in this study were injection site, granuloma, inflammation, and pain, as well as the risk of NMS and hyperprolactinemia, common side effects of antipsychotic treatment, but not limited to LAIs. And the other study was by Wyden and colleagues in 2015. They completed a qualitative discourse analysis of the actual conversations and transcripts of psychiatrists recommending long-acting injectables. This was a U.S. study, and there were a total of 33 psychiatrists' transcripts analyzed here. Providers presented LAI option as an imposition was one of their main findings, meaning that this information was conveyed in a negative light, if you will. Prescribers here also felt like potentially recommending LAIs could impact their therapeutic relationship with their patients. And thinking back about the history of court-ordered long-acting injectables and acute situations like Sarah had mentioned in inpatient facilities, they didn't want to force their patients, if you will, to take injections. So overall, these two studies illustrate in different ways how the presentation of LAIs in our conversations impact whether or not patients will consider them. Next. So I'll look similar to what Sarah was presenting from the patient perspective. I'll look at the clinician perspective pros and cons of LAI use. And we share this relapse prevention goal with our patients as a pro. We also have assurance of adherence since we can track and actually observe the administration of the long-acting injectables. And consistent drug serum levels can be achieved with LAIs as opposed to oral antipsychotics. And on the con side or the risk side, we do have some decreased flexibility in making dose adjustments, starts and stops, as well as site requirements. And Sarah had mentioned some of the site limitations for certain patients. Frequencies and intervals of dosing vary from long-acting injectable. And it's important that clinicians be knowledgeable about those intervals. These conversations with patients can be challenging, and they really do require some preparation. None of us want to coerce our patients to do anything. And we certainly realize that rapport is essential in maintaining, and we don't want to disrupt that. Next. So we'll look at a couple of studies that talk about mortality in using long-acting injectables. First, there's a Swedish registry study of a cohort of nearly 30,000 patients with schizophrenia. And overall, their mortality risk is 40% lower when taking antipsychotics in general than when not taking antipsychotic medication. And comparing long-acting injectables to oral antipsychotics, and comparing long-acting injectables to oral antipsychotics, mortality is reduced 33% when patients receive LAIs compared to oral agents. And the chart gives a visual of this. The green LAIs have the lowest mortality on the left, and the yellow oral antipsychotics do promote better reduction of mortality than the red indicated for no medication. There was a Finnish registry study where they looked at 62,000-plus people with schizophrenia, and in their study, they found no significant difference between long-acting injectable and oral antipsychotics. However, the authors note that LAIs are utilized more commonly in Sweden than in Finland, and in Finland, clozapine is utilized more heavily. Next. Next. And back to the Patel study, there are four key decision points in treatment planning. This graph illustrates the discrepancies at each point when psychiatrists consider oral in red and LAI antipsychotics in blue. First, they consider prescribing. Then they discuss medication options with the patient. Attempt to consent is the third step. And then the actual point of prescribing. You can see that the orals lead LAI antipsychotics at each point, yet they run parallel until that final point where LAIs drop significantly at the prescribing step. All of these steps can be targeted points of intervention in attempting to increase LAI utilization. Next. And I will hand it over to Eric. Well, thank you so much, Donna. And it's great to be with everyone this afternoon. I'm going to share a little bit of data from a study that was published last summer in JAMA Psychiatry on the prelapse trial. And this was an investigator-initiated study led by John Kane. I was fortunate to be on the central scientific team that helped conduct the study. Next slide. Next slide. So, the prelapse study is an investigator-initiated study that was sponsored by Atsuka and Lundbeck. The funders participated in the formulation of the study. But had no influence on the conduct of the trial and were not involved in data collection or analysis or in the writing of the manuscript or the decision to submit it for publication. Prelapse stands for prevention of relapse. The primary question that we were trying to address was, can the use of a long-acting injectable medicine, in this case, aripiprazole monohydrate, prevent or delay the need for inpatient psychiatric hospitalization for individuals with schizophrenia who were early in the course of their illness? Next slide. The target population for this study was determined to be early phase schizophrenia. So, this was defined as less than five years of antipsychotic treatment. We aimed to recruit roughly equal numbers of participants who had either one episode of psychosis and less than one year of antipsychotic treatment. So, they had to actually have both of those. Or either more than one psychotic episode and or more than one year of antipsychotic treatment. So, we really tried to recruit both a true first episode group and an early phase group. Next slide. Next slide. So, the challenge with designing this study was to design a study that provided the rigor of randomization and yet engage people in real-world clinical settings. The solution that the team came up with was to conduct what's called a cluster randomized, randomized controlled trial. So, sites rather than individuals were randomized. And in sites that were randomized to offer the long-acting injectable, patients were offered access to aripiprazole monohydrate. And in the group that was assigned to usual care, which we called clinician's choice, the prescriber could use whatever medication they wanted. It could include an oral medication or a long-acting injectable medication. Individuals consented to the treatment that was offered at their clinic. And prescribers at the AM sites received additional training on the use of aripiprazole monohydrate. Consistent with large, simple trials, rating scales were done by centralized raters via two-way video only at baseline 12 and 24 months. We did interview participants every other month to assess for data on hospitalizations and ER visits. And the reason for this was to provide a light touch and avoid some of the study effects that have been seen in other randomized trials of long-acting injectable medicines. Next slide. So you can see here how the sites were randomized. There were 19 sites randomized to deliver or offer access to aripiprazole monohydrate. And then 20 sites were randomized to be clinician's choice. In those sites, in terms of patients, there were 234 patients who were in the aripiprazole monohydrate sites and 255 in the clinician's choice sites. It's notable that all 39 clinics agreed to randomization and none withdrew after learning their assignment. 19 different states were represented across the country. 28 had no academic affiliation. 30 of the sites had no formal first episode treatment programs. And the sites represented urban, suburban, and rural settings so it really was a good representation of real-world sites across the United States. Next slide. Okay, so here you can see the baseline demographics and the patient characteristics who entered the study. The average age was approximately 25 years. About three quarters were male and that's very common in studies of schizophrenia, especially early phase schizophrenia. And the mean number of hospitalizations was three in the AM arm and 3.4 in the clinician's choice arm. And then if you click forward for me one more time, it should highlight a section of the slide. Thank you. So the other thing that I wanted, oh, sorry, if you can go back one slide, please. There you go, thank you. So I wanted to point out that at the time of consent, in the aripiprazole monohydrate sites, a total of 36 patients were already on aripiprazole monohydrate at the time of consent. Another 36 were on a different LAI. And we had similar numbers in the clinician's choice arm. So a total of 70 individuals in the clinician's choice arm were on an LAI at the time of consent. Here, only 10 were on aripiprazole monohydrate and 60 were on a different LAI. Next slide. Sorry, there seems to be a little lag here. There we go. So in terms of patients, then this is looking at patients at the aripiprazole monohydrate sites. You can see a little bit the flow of patients. 576 were judged to be eligible based upon the screening interview. And of those, only 14% refused to participate in the study because they might receive a lung injectable medicine. There were a number of others who didn't participate for other reasons. And ultimately, 328 were consented. Upon completing full eligibility, there were 234 that were enrolled and had baseline interviews. And of those then, only four decided not to receive a lung acting injectable when it was offered to them. So once patients were consented and had done their baseline interview, 91% of those patients agreed to at least one injection with aripiprazole monohydrate. Next slide. Okay, so in terms of hospitalization events, when we looked at the aripiprazole group here, 52 or 22% of the 234 patients had at least one hospitalization. On the clinician's choice side, 91 or 36% of the 255 participants had at least one hospitalization. Now of these who had a hospitalization, 40 of them were on AOM at the time of hospitalization. And 22 of the individuals in the CC group were on an LAI at the time of hospitalization. Now in this group, there were a total of 208 hospitalizations and there were only a total of 133 hospitalizations in the AOM group. Next slide. In terms of the main outcomes, which was time to first hospitalization, the blue line represents those on aripiprazole monohydrate and the red line are those in clinician's choice group. And as it turns out, the mean time to first hospitalization in the AOM group was 614 days, somewhere out about here. And the mean time to hospitalization in the clinician's choice group was 531 days. So somewhere about here. That translates into an odds ratio of 0.56 for the AOM group or a 44% reduction in time to first hospitalization. I'll note also that the length of follow-up was similar across both treatment conditions, 594 days for the AOM group and 573 days for the CC group. Next slide. In terms of secondary outcomes, 234 AOM participants had a total of 133 hospitalizations. 255 CC participants had a total of 208 hospitalizations. The total number of hospitalizations had a similar decrease in rate, 36% for AOM relative to CC as the decrease in rate for AOM relative to CC for that first hospitalization, which was 44%, as I mentioned. But this decrease overall was not statistically significant. Next slide. In terms of other secondary outcomes, the quality of life scale and the BPRS, estimated change from baseline to 12 months or months 24 did not differ between the conditions for either the QLS or the BPRS total scores or their respective subscores. There were two deaths that occurred in the study. One in the CC, one CC participant died due to suicide and one CC participant died of unknown causes. There were four participants in each condition who made suicide attempts. Next slide. In terms of tolerability, they were very similar. So in terms of side effects between the AOM group here on the left and the Clinician's Choice group on the right, I'll highlight the ones where there was more than a 5% difference. So when we look at worsening of psychotic symptoms, it was 40% of individuals in the Clinician's Choice arm had that compared with 23% in the AOM arm. In terms of weight gain, 19.5% of those in the Clinician's Choice arm compared with 14.4% in the AOM arm. In addition, there was an elevated hyperprolactinemia, 12.9% in the Clinician's Choice arm compared with just 4% in the AOM arm. And then in terms of anxiety, 12.2% in the AOM arm compared with 6.2% in the Clinician's Choice arm. And down here, restlessness, 6.3% in the AOM arm compared with 0.8% in the Clinician's Choice arm. Next slide. So in summary, in this study, a large number of individuals with early phase schizophrenia were agreeable to receiving aripiprazole monohydrate. Aripiprazole monohydrate compared with standard care increased the time to first psychiatric hospitalization, and that difference was both statistically significant and clinically meaningful. For the prevention of one additional hospitalization, the number needed to treat is seven. And again, I would emphasize that the results may have underestimated the effects of LAIs on hospitalization due to the relatively high utilization rates of LAIs in the control condition. Next slide. Okay, so now we'll move on to share some of the shared decision-making and motivational interviewing tools that we use to train the clinicians in the AOM arm on how to talk with first episode and early phase patients about using a long-acting injectable. Next slide. Next slide. I think the first critical thing is to overcome our own barriers to talking about this with early phase patients. And both Donna and Sarah talked a little bit about this. And we published actually this list of at least 11 reasons why LAIs may not be widely used in early phase schizophrenia. And I can confess that I'm guilty of at least four of these. I think the first one there, clinician overestimation of the patient's degree of adherence, I'm probably guilty of that. We all like to think that we're good clinicians, that our patients like us, that they do what we ask them to do. And probably we overestimate that. The second one is bias against injections as being invasive, punitive, or overly painful. And I think that often stems from our training. I mean, we typically have not used, at least I didn't use LAIs early in the course of treatment. I reserved them primarily for patients who prove themselves to be maybe non-adherent. And I think what we've seen is that when presented in a way that's more positive, that patients may be willing, in fact are willing to accept trying an LAI earlier in the course of treatment. I think I have a lack of appreciation for the advantages of, or I had a lack of appreciation for the advantages of LAIs for patients and families and healthcare providers. So that's another one that I kind of relegated it to a treatment of last resort approach. And then I also had the belief that LAIs were maybe not appropriate for first episode or early phase patients who had not already clearly demonstrated a pattern of non-adherence. And I think what we'll show you in some subsequent slides is that for many of these patients, it's really not a matter of if they will become non-adherent, it's a matter of when. Next slide. Okay, so we had a prescriber training program as part of the pre-lapse study and all of the sites got these elements. So we talked about the reason for the study, characteristics of early psychosis patients, recruitment and retention strategies, good clinical practice, all of those things that are important to conducting a clinical trial. In the aripiprazole monohydrate sites, we had some specific training around role of non-adherence in relapse and hospitalization, the rationale for LAI used for selection of AM in early phase patients. We talked about shared decision-making principles, how to discuss with patients and their families, prescribing guidelines for aripiprazole monohydrate, talked about the effectiveness of LAIs, optimal ways to transition to an LAI. We did role plays, which I think is an important part of flexing your own muscles in terms of talking with patients. And then we suggested overcoming some of the barriers in terms of LAI logistical concerns. Next slide. Sorry, there's just a little bit of a lag for me here. There we go. Okay, so then one of the very first things that we emphasized was engaging patients and their family or friends in a shared decision-making process. So this is a process where clinicians and patients work together to make decisions about their care, utilizing both the best clinical evidence and the patient's informed preferences. And I think that's really key is understanding that both parties bring different but equally important knowledge and expertise to the process. Whereas the clinicians bring diagnosis, treatment options, prognosis, disease etiology, outcomes, we bring that to the table, but patients bring their experience of the illness. They are the experts in what it's like for them. And they also bring opinions about their preferences, values, differences, social circumstances that might affect their choices, and then attitudes towards risk, which all are important. Next slide. Next slide. So we want to move away from kind of authority and coercion that we talked about early. We still want to provide education, but having this be the only thing that we do, we want to move to emphasize patient autonomy and collaboration with their treater. We want to evoke the concerns that patients have and really emphasize those. So this is about building a partnership. It's about helping the patient understand that they have resources to change and that we help elicit that change. And it really is, I think, honoring the patient's right to self-direction. And we affirm that, but then also provide education and input. Next slide. Next slide. Okay, so what if you've got a patient who's ambivalent about trying a new treatment, such as an LAI? I think in these situations, we would encourage the use of motivational interviewing. And many of you may be familiar with this, but it's a style of dialogue between two parties, which is intended to motivate one party into making positive changes by compassionately challenging the status quo and helping them explore alternatives. So in order to practice motivational interviewing, we obviously have to listen and connect with our patients. We listen actively. So we reflect back to individuals what we're hearing them say. We try to understand their values, fears, their skills, their goals. And we're, of course, always nonjudgmental. We're collaborative. We may be challenging, but we're genuine, we're flexible, empathic, and respectful. And the idea is to help the patient work through the stages of change. Next slide. Okay, so what are those stages of change that we may identify in motivational interviewing? So there's pre-contemplation, which, really, the patient does not recognize there's a problem at this stage. The responses, I won't, I can't, those type of things are the things that we hear when somebody really doesn't recognize that something isn't an issue. Then there's the contemplation stage, which is a stage in which they may be ambivalent. And this is really where motivational interviewing has its biggest impact. And people are trying to weigh the differences between, do I make a change, do I not, what are the reasons for making a change, and what are the reasons for not making a change? And we're hoping to move them to the preparation stage where they want to, and then we help them overcome any barriers they might be facing, and move to the action stage, doing it, and then the maintenance and relapse prevention stages. Next slide. Okay, so why is non-adherence a concern in early phase schizophrenia? Well, I think it's important to discuss with patients and really normalize that most people have trouble taking medications regardless of the illness. I often use an example that if I have to take antibiotics for two weeks, even though I'm on top of it, by the end of that two weeks, I've usually got a few pills left, and I don't know where it happened. But somewhere in the course of taking those antibiotics, I missed a dose or two. We want to discuss the importance of avoiding relapse, re-hospitalization, missing school and work, and avoiding missing friends. And many times, especially for early phase or first episode of patients, they and their families do not have a track record of experience with relapses and re-hospitalizations. And what often happens is after the first hospitalization, they can go back to school, maybe they're with their roommates or others. But after the second hospitalization or the third, those supports, especially friends, tend to kind of filter away. So it's really important for us to try to keep people well as long as possible. Next slide. Another key element, of course, in discussing this with patients is really finding out what their goals are. So we talked about using the gain model. So this idea of goal setting, really discovering what the patient's life goals are, talking about their current treatment, what's good, what's bad, what's worked, what's not worked. Really listening actively and reflecting on their experiences. And then developing some small achievable goals and steps to those goals, concrete steps they can take. Exploring the patient's life goals. Concrete steps they can take. Exploring delays and then really compromising where you can. So I think that's important in terms of establishing that treatment relationship and that rapport. Action planning. So again, listening actively to patient's fears, describing the link between use of LAIs and achieving their goals. And we'll share an example of that in just a minute. We always wanna elicit support from family and caregivers. They can be our best resource in terms of emphasizing positive choices for the patients. So I think that's really important. And then in initiating treatment, it's very important to explain the process and what they can expect. Listen for any negative perceptions that they might have regarding an LAI. And then normalize things like the flu shot, vaccinations, getting insulin, elicit feedback and how the treatment is going. Exploring any side effects or negative experiences is really important so that we can address those concerns quickly. Celebrating positive things that may happen. Graduations, other things that may happen in their life, getting a new job, relationships, things that would be very important to them. And then identifying any other aspects of the total treatment plan that we could help them with. So perhaps if there's case management available, we're assisting them with housing, maybe finding a job, talking to school counselors, things like that. And of course, we've got to reassess those goals and repeat. Next slide. Okay, so now we're going to jump into some of the prepared script we have and some of the role plays where we illustrate some of these clinician-patient discussions. And I know I'm being joined here by Donna again. And this is an example of an interaction that we actually used in training sites for the pre-lapse study. And in this particular interaction, I'll serve as a prescriber and Donna will serve as my patient. Next slide. Okay, so Donna comes into my office and I may say something to the effect of, I think that you should be on an injection to avoid getting sick again. I don't want to change my treatment. Oh, why is that? I prefer oral medications and I really hate needles. Oh, well, but I'm your doctor and I really think you should be on an injectable medication. No, thank you. Next slide. So, you can see the style of communication. It's kind of an obvious sample, but the style of communication is very important. Taking a my way or the highway approach often does not work well with patients and we really want to foster more of a collaborative approach to care. Next slide. Okay, so good afternoon, Donna. How are you doing today? I'm okay, I guess. I've been struggling at my job lately and my boss says that I'm my last strike. Oh, no, what's been happening? Why is your boss upset? Well, I keep coming in late sometimes. Oh, tell me more. I haven't really been sleeping well lately. Oh, no, that's awful. Any ideas what's been keeping you awake? Well, sometimes I've been hearing more voices in the evening. More voices? Oh, that doesn't sound so good. Do you think your medications are working all right? Yeah, I think so, but it's when I remember to take them. Sometimes I get up in the morning and I'm really rushing around to get to work and I just forget to take my pills. Hmm. Well, I know keeping your job and apartment are really important to you. Do you think that missing your medications in the morning might have some effect on your symptoms in the afternoon and evening? Hmm, I hadn't really thought about that, I suppose. Next slide. Well, have you ever thought about taking a once-monthly injection? No, not really. I'm afraid of needles and that sounds pretty scary to me. May I share something with you? Sure, I suppose so. Research and my own experience have shown that once-monthly medications are often more effective than oral medications in keeping people from experiencing a recurrence of their symptoms. People who try these kinds of medications reported very little discomfort, only about two to five on a scale out of a hundred possible points. Many prefer once-monthly treatments over daily oral treatments once they give them a try. It may allow you more nights without symptoms so that you can keep going to your job and we even have a program available here to allow you to take a once-monthly medication at no cost. I'm not so sure, this is all a bit much right now. Well, I can certainly understand that considering a change can be a bit unsettling. Yeah. Would it be okay if I give you some information about our program and you take it home and think about it some more, talk about it with your family and I'd be happy to discuss it with you more at our next meeting if you'd be interested. Yeah, thank you. That sounds good. Next slide. So, yeah, you can see, you know, we've had a much more positive interaction talking about this. We're linking it to the individual's goals. They want to keep their apartment. They recognize, perhaps, that symptoms or we're trying to help them see that symptoms may be impacting that and hopefully, you know, we're giving her some time to think about it, talk about it with her family. We're trying to collaborate around care and hopefully this will result in a different outcome. So, at our next visit, I'll say to Donna, have you had a chance to look at the material about the once-monthly medications that I gave you and do you have any questions about it? I did take a look but I have a few more questions. Sure, go ahead. Aren't injections for the failures? Don't you really get stiff and sick when the meds enter your body all at one time? Well, I'm glad that you're bringing up this concern. Actually, taking once-monthly medication means that you would take less medication overall but still be at least as well covered as when taking a hundred percent of daily medications and doing a hundred percent of anything is difficult, if not impossible, for all of us. Do you have any additional questions or concerns about the once-monthly medication option? Yeah, I guess, doesn't the drug build up? What if I want to stop? Next slide. Well, actually, the once-monthly medication does not build up continuously. After you've received a few monthly treatments, the medication reaches its desired level and this level is generally lower than that with oral medications. Really? Yes, and if the once-monthly medication needs to be stopped, it leaves the body more slowly than oral medications. If side effects are present, it can generally be managed well. Well, that sounds less scary than I thought. Yes, I really think that since you've been doing this well lately, it is of utmost importance for you to stay well. Staying well is related to having enough, not too much or too little, of a medication that works for you. This way, you have the greatest chance of meeting the goals that are important to you, like keeping your job and staying in your apartment. That would be good. Well, what do you think, Donna? Do you want to give the once-monthly injection a try? I think so, sure. Thanks for taking the time to explain it to me this way. You're very welcome. Next slide. Okay, so we want to emphasize for people that it's not just them. We think this is an optimal way to treat everyone. We want to help them stay well, is the main thing. If they work with us, we'll hopefully be able to help them do that. We want to emphasize that we have a lot of experience with people just like you. I think this is important for first-episode and early-phase patients to let them know that we've been there before. We've worked with a lot of people who've experienced symptoms similar to theirs. Emphasize, then, that it's great if we can get their illness under control early and keep it under control long-term. Then, the other thing that we'll sometimes say is, well, why not just start with one injection and give it a try and see how it goes? A lot of times, once people get that initial injection, they're willing to keep going. Next slide. This is a slide about addressing common concerns. You can click through it. The patient might say, injections are a hassle. You'll say, well, you don't have to remember to take it every day. That's actually nice. Someone always nags me about taking my pills. Well, that's not going to happen again. It means I'm sicker. Well, it actually means you're more likely to stay well. What if I want to stop? You can stop any time. If you do, there's less chance of a withdrawal reaction. It feels like control over me. Well, we're not trying to control you. We really are trying to help you control your illness. Let's start with that one injection and see how it goes. Next slide. I'm going to try to move fairly quickly, so I apologize. With akathisia, there are treatment of emergent side effects that can develop. Akathisia can usually be treated by beta blockade or benzodiazepine. You may also consider a dose reduction. Sleep disturbance, we, of course, emphasize really good sleep hygiene, so exercising, reducing caffeine. If not sleeping, get out of bed and do something for a while. We don't take naps. You may try progressive relaxation. Then, if needed, there are medications that can be helpful, things like melatonin, diphenhydramine, triazodone, or benzodiazepines. Then, don't forget to consider a sleep referral if somebody is snoring. They may have undiagnosed sleep apnea, which can be very challenging if they don't recognize it. Then, if someone continues to be sedated during the daytime, you may consider modafinil or another stimulant. Extrapyramidal symptoms, of course, we could add an anticholinergic or antihistamine or benzodiazepine. Dose reduction, of course, may be helpful. Weight gain, we would encourage diet and exercise, meeting with a dietician, and consider metformin or topiramate if needed, or a statin for hyperlipidemia. Sorry, next slide. I just show this one really quickly, and I'll sometimes share this with patients. Side effects typically peak in the first month, but by the time you get to that second or third injection, side effects are usually quite manageable. I think this also helps people if they're struggling with some side effects to let them know, hang in there, your body's going to get used to this, and the side effects should improve over time. Next slide. There's also less, this is a slide of kind of the optimal treatment window for individuals on long-acting injectables. This happens to be for aripiprazole. You can see that with oral aripiprazole, there is more peak blood levels with oral dosing, especially if you're getting up to 20 and 30 milligrams a day. You really want to stay in this therapeutic window, and that's often easier to do with a long-acting injectable medicine. Next slide. Okay, so what other challenges might there be? So transportation, getting to the clinic for injections, if you can offer bus, subway tickets, cab rides, that can be helpful. Meeting with the family if they have concerns, that can be very important. And I'll jump down, just getting help, so directing patients to appropriate resources for therapy, just getting help, so directing patients to appropriate resources for things that I may not be able to fix, such as housing, finding a PCP, other things. Next slide. This was another study by Peter Widen, which showed that the longer people go without medications, antipsychotic medications, so this is gaps in medications, the more likely they are to be hospitalized. Next slide. And this was looking at cumulative relapse on and off of antipsychotics, and you can see four studies looking at one year on antipsychotic, this was, the relapse rate was low. As soon as you're a year off of your antipsychotic, your relapse rate is 77%. In two years, it's almost 90%. Next slide. This comes from the 2020 APA guidelines for the treatment of schizophrenia. Some of the benefits of LAIs for patients, a sense of better symptom control, again, fewer opportunities to miss medication doses, which is really important, and reduce conflict with family members, and we talked about that already. And I think really for the prescriber as well, you are no longer guessing about adherence, you know whether the patient's getting their medications because you can check whether they're coming in monthly. And so that helps you with your clinical decision making. If somebody is having breakthrough symptoms in spite of guaranteed treatment, you know that you may need to do something to switch or augment your antipsychotic. Next slide. Okay, so just very quickly to summarize, the mental health system and treatment is confusing for early phase patients who have limited experience with accessing care at the risk of relapse. Maintenance treatment and preventing relapse is critical to achieving their goals and yours as their treater. Non-adherence is a major reason in terms of risk for relapse, and maximizing that can help the acute and long-term effectiveness of pharmacotherapy. The percent of time spent experiencing psychotic symptoms in the first two years is the strongest predictor of long-term symptoms and disability. So again, getting people well, keeping them well is a really important message. And with each subsequent exacerbation, treatment response tends to decrease. I think that's important to let people know. They come in, the antipsychotic works really well, they decide to stop it, and all of a sudden the symptoms come back. We put them back on and it doesn't work quite as well as it did the first time around. There can be neuropathologic brain changes with each new episode. And then those personal and societal implications of relapse can be devastating for a young patient and their family. Next slide. All right, so I just had a couple of concluding comments about best practices in using long-acting injectables. If we go to the next slide. So the first question here is, how do you determine which patient might be appropriate for a long-acting injectable? And I think that this is a pretty straightforward one, that really anyone may benefit from a long-acting injectable. And it's really important to provide people the information using a shared decision-making framework, and then they can make the best decision for themselves. Next slide. And we just had a couple of ideas specifically about using long-acting injectables with young people with first episode psychosis. But in fact, you could really think about these sort of principles for anyone. And I think that one of the big points of the talk is that the medication may be a way for people to accomplish their recovery goals. And it's important to have a genuine interest and curiosity in understanding what people's recovery goals are. As what happened in the scenario, it sometimes takes time and the conversation needs to be revisited over several visits, but it's important to keep that momentum. Understanding the reasons that people may have reluctance is also important. And then finally, engaging the family can be a key way of getting people on board perhaps with taking a long-acting injectable. Thank you all for such an interesting presentation. Before we switch to question and answer, I want to take a moment to let you know about the SMI Advisor and how we're accessible now via your mobile device. You can use the SMI Advisor app to access resources, education, and upcoming events, complete mental health weighting scales, and even submit questions directly to our team of SMI experts. You can download the app now at smiadvisor.org. We have a little bit of time for questions, and maybe I think to facilitate it, we can try to give abbreviated responses because some of these are large questions. The first one, Rob, being how has your experiences changed around COVID-19 in terms of LAI? So a huge question, but if you had to give the 30-second answer, 30-second answer, what's new with COVID? Yeah, thanks, John. I think one of the main things is it's important to make sure that people don't fall through the cracks. And I know that several people have developed ways to keep track of the individuals that have been receiving long-acting injectables, maybe through various spreadsheets. And then we had a lot of success using a mobile integrated health team that would actually go out into the field and administer long-acting injectables. But that might not be a resource that everyone has. Sometimes visiting nurses may be able to help. So really, it's sort of an organization-specific type question, but I think I'll probably leave it there. And Sarah, one, would you consider starting someone on LAIs during the pandemic? I think similar to what Rob was saying, it would depend kind of clinically what made sense. I'd rather have them on a potentially new medication if it were to be more effective than end up going into the hospital and having, or decompensating and having other consequences. And just one last thing to add on to what Rob said, we also had a good bit of success transitioning people transitioning people to longer versions of long-acting injectables. So from Invegas, Sustana to Trinza or Aristata 62 to 1064. Got it. So I think that was a very quick question answer because you all shared so much fantastic information with us. So if anyone has follow-up questions on this or any related topic about evidence-based care for people with SMI, our clinical experts are available now for online consultation. Any mental health clinician can submit a question and receive a response from one of our SMI experts. Consultations are free and confidential. SMI Advisor is just one of many SAMHSA initiatives that are designed to help clinicians implement evidence-based care. We encourage you to explore the resources available on mental health addiction and preventative TTCs, as well as the National Center for Excellence in Eating Disorders and Suicide Prevention Resource Center. These initiatives cover a broad range of topics from school-based mental health through the opiate epidemic. Thank you for joining us. Thank you to our fantastic panel and to all until next time, take care. Thank you.

Dr. John Torres

Director of Digital Psychiatry

Beth Israel Deaconess Medical Center

SMI Advisor

Long-Acting Injectable Antipsychotics

Clinical Support System for Serious Mental Illness

Donna Rowland

Sarah McLaurin

Eric Atchis

Dr. Rob Cotis