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Worth a Shot? Evidence-Based Approach to Prescribi ...
Presentation and Q&A
Presentation and Q&A
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Hello and welcome. I'm Donna Rowland, the Director of the Psychiatric Mental Health Nurse Practitioner Program at the University of Texas, Austin, and the nursing expert for SMI Advisor. I'm pleased that you're joining us today for our SMI Advisor webinar, Worth a Shot? Evidence-Based Approach to Prescribing LAI Antipsychotic Medications. 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 the answers you need to care for your patients. Today's webinar has been designated for one AMA PRA Category 1 Credit for Physicians and one Nursing Continuing Professional Development Pharmacology Hour. Credit for participating in today's webinar will be available until May 2nd. Slides from the presentation today are available in the handouts area found in the lower portion of your control panel. Select the link to download the PDF. Please feel free to submit your questions throughout the presentation by typing them into the question area found in the lower portion of your control panel. We'll reserve 10 to 15 minutes at the end of the presentation for Q&A. Additionally, there are two points of the presentation where the speakers will ask for audience responses to discussion questions. Please use the questions area to respond. Now to introduce you to the faculty of today's webinar, Dr. Leon Raven. Dr. Raven is a board-certified psychiatrist who is currently serving in a position of Statewide Psychiatric Medical Director for the Division of Public and Behavioral Health, State of Nevada. He received his training in general adult and forensic psychiatry at the University of Pittsburgh Western Psychiatric Institute and Clinic. Dr. Raven has academic appointments with several universities, including his appointment as a clinical professor with the Department of Psychiatry at the University of Nevada Las Vegas School of Medicine. In addition to his clinical and academic responsibilities, Dr. Raven serves as a member of the Executive Committee of the Medical Directors Council of the National Association of State Mental Health Program Directors and is a member of the LAI Workgroup for SMI Advisor, this APA and SAMHSA initiative that offers researched, vetted, and verified guidance to the best resources on SMI. Since 2013, Dr. Raven has been a member of the Conference Committee for the National Psychopharmacology Update, the largest psychopharmacology conference in the U.S. Dr. Raven has presented at the national and international professional meetings on various topics focusing on delivery of psychiatric care, mental health laws, and medical ethics. Additionally, Dr. Raven has been one of the lead trainers for the Crisis Intervention Team training for the Las Vegas Metropolitan Police Department. Dr. Raven, thank you so much for leading today's webinar. Thank you, Donna, and thank you for this lengthy introduction. I also would like to thank SMI Advisor, the American Psychiatric Association, and the Substance Abuse and Mental Health Services Administration for the opportunity to have a conversation on oral versus long-acting injectable antipsychotic prescribing. My clinical experience with long-acting injectable antipsychotics comes primarily from working in outpatient settings. However, over the years, I have worked in traditional outpatient community treatment centers as well as specialized outpatient programs like Service Coordination and PACT. I have been providing education on long-acting injectable antipsychotics as a member of the SMI Advisor for the last couple of years, but my goal today is to stay away from my personal experiences and opinions and to share scientific peer-reviewed evidence on the effects of using long-acting injectable antipsychotics in treatment of patients with schizophrenia. I will have some disclosures. In the last couple of years, I have participated in certain activities that were sponsored by pharmaceutical companies. I am a member of Jason Neuroscience Mood Speaker Bureau that focuses on treatment of treatment-resistant depression. However, I have no relationships or conflicts of interest related to use of antipsychotics for treatment of schizophrenia. What is the subject matter of this presentation? So our goals for today are to review the APA take on using long-acting injectable antipsychotics in treatment of patients with schizophrenia and examine the state of current evidence comparing utilization of various formulations of the first and second generation antipsychotics. I want to acknowledge the constraints of the presentation and analyze data that did not allow us for in-depth secondary analysis of the research findings, including but not limited to use of different formulations of antipsychotics in various population subgroups, such as based on race, ethnicity, rural or urban settings, or other factors. Let me spend a few minutes discussing some of the acronyms that you may see in my presentation. FGA stands for first generation antipsychotics. The first representative of its class was chlorpromazine that was developed in 1950 and approved by the FDA in 1954. The second most known first generation antipsychotic, of course, is haloperidol that was discovered in 1958 and approved by the FDA in 1967. It's hard to imagine, but haloperidol is older than the average age of practicing psychiatrist in the United States. SGA stands for second generation antipsychotics. That's a class of medications that is characterized by exhibiting its antipsychotic action through various mechanisms, in addition to, instead of exhibiting D2 receptors. OAP stands for oral antipsychotics, PO is another way of describing oral antipsychotics. LAI, of course, stands for long-acting injectable antipsychotics. The APA is referred to as American Psychiatric Association, RTC, randomized controlled trials. More needed to treat is the number of people that we need to give a drug or intervention to in order for just one person to receive a benefit. Alright, enough with definitions, suppose the LAIs have been studied in recent years, but comparing them to oral antipsychotics is not always an easy task. We have to recognize that the studies, the way how they are designed, don't always represent the traditional patients we see in our clinical settings. Randomized controlled trials usually have very specific criteria of which patients are selected for the study and don't always account for substance use, medical comorbidities, absence or presence of polypharmacy. We also have to recognize that various studies look at different outcomes, so you cannot always compare the studies. Some studies focus on treatment discontinuation, some look at time to the next hospitalization, relapse or arrest. The APA published the treatment recommendations for treating patients with schizophrenia. As it comes to recommendations on use of long-acting injectable antipsychotics, the APA clearly states that we need to offer the treatment choice to any patient who is interested in long-acting injectable antipsychotics, which implies that pretty much from the moment we established diagnosis of schizophrenia, we have to discuss with our patients availability of long-acting injectable antipsychotics. The APA also recommends use of LAIs in patients with a history of poor or uncertain adherence. It may come as a surprise to you that we are not, or may not, that we are not necessarily very good in estimating patients' adherence to treatment. I'll give you some more data on that in a little bit. The APA also acknowledges advantages for our patients when we use long-acting injectable antipsychotics. Some of those advantages are described as decreased risk of mortality, which sounds pretty important to me, also reduced risk of hospitalization, decreased rates of treatment discontinuation. Additionally, there is a greater convenience for our patients as a result of needing to take fewer medications daily, having fewer conflicts with family members or other persons of support related to medication-related reminders. While the risk of injection-site reactions remains a concern for us, the APA states that discomfort can always be minimized by using water-soluble, second-generation, long-acting injectable antipsychotics as opposed to oil-based, first-generation LAIs. And finally, the APA emphasizes the importance of early discussion of the LAIs that needs to be done with individuals who have increased risk for poor adherence due to limited awareness of needing of treatment or co-occurring substance use disorders. All right, so let's dive into the world of data. This study looked at the subjects of 20- to 63-year-old treated for schizophrenia that were followed through Medicaid medical services and pharmacy claims for a period of 90 days before each hospital admission and for 30 days after discharge. What was interesting is that 41% of patients were able to receive a follow-up visit within the first week of hospital discharge. That's pretty good because remember that the first couple of weeks post-discharge are very critical for patients because that's the time when we commonly see decompensation in post-discharge period. By day 30, the percentage rose to almost 60%, which may be good news. The bad news is that 40% of patients did not receive follow-up care in the 30 days post-discharge. Now, I promised to give you some information on medication adherence. This study looked at patients taking their medications using special technology. Essentially, there was a sensor built in the patient's pill bottle, and every time the patient would open up a bottle, it would register the event as patient taking their medication. If you look at the patients who were taking their medication 70% of the time, which was in the study acceptable as an adherence threshold, 57% of chronic schizophrenia patients were non-adherent. Now, it's interesting that when the patients were asked to estimate their non-adherence, they only estimated it as 5%, and prescribers estimated patients' non-adherence as 7%. You could see that there was significant discrepancy between what the patients were reporting, what prescribers were thinking about patients' non-adherence, and what the real rates were. This is a somewhat similar study, and again, in this study, non-adherence was counted if the patients took less than 80% of their medications. Now, this is kind of a side comment, but I don't think any of our medications have been studied for efficacy if they're taken 70% or 80% of the time. We always hope that our patients take their medications every single time, but even with 80% adherence that was considered to be good enough, only 48% of schizophrenia patients took their doses, four times out of five, essentially. As you can see, less than 20% of patients were taking less than 20% of their antipsychotics. As you can see, even when we hope that they take majority of the doses of our medications, patients still quite often don't do so. This study came from the United Kingdom, and it was pretty interesting because it looked at the patients who identified as treatment-resistant schizophrenia patients, and in them, 35% of patients had plasma levels of antipsychotics that were sub-therapeutic, and of this, 34% of patients had their medication plasma levels as undetectable, so obviously, it's hard to respond to treatment if the drug is not in the system. This is just a headline from the study. Those were observational studies in Finland that showed that LAIs compared to oral formulations of the same drugs were associated with a significantly lower risk of re-hospitalization drug discontinuation. This study is also known as PRIDE study, looked at two groups. One group that was prescribed palipiridone, long-acting injectable antipsychotic, compared to another group that was randomly assigned to seven acceptable pre-specified oral antipsychotics. The groups were followed for 15 months, and the outcomes were looked at treatment failure that was described as arrest, incarceration, psychiatric hospitalization, suicide, treatment discontinuation for any reason, or other issues that increase psychiatric services to prevent hospitalizations. When comparing those two groups, there was evidence that there were fewer treatment failure events in palipiridone LAI group, and it was superior to oral antipsychotics in delayed time to the first treatment failure. The median time for all-cause treatment failure was 416 days for palipiridone LAI compared to only 226 days for oral antipsychotics. And if you look specifically to median time for psychiatric hospitalization or arrest or incarceration, the median time for all the palipiridone LAI was never reached in the study. It was 274 days for oral antipsychotics. Now, this study was performed using a representative sample of patients in Canada who were newly treated with long-acting injectable antipsychotics. And when compared to themselves, those patients who received the first treatment with LAIs had fewer hospitalizations, pretty much half the number of hospitalizations compared to being treated with oral antipsychotics, three times fewer inpatient days, 40% fewer ER visits, and more than 50% less in healthcare cost. What was also remarkable that while both the first and the second generation long-acting antipsychotics demonstrated benefits, the second generation long-acting injectable antipsychotics performed better than first-generation LAIs across the board in reduction of concomitant use of oral antipsychotics, reduction in inpatient days, and the cost of care. This was a review of nine published papers focusing on antiaggressive effects of long-acting injectable antipsychotics in patients with high risk of violent behavior. The article provided analysis of three cross-sectional charge reviews for its respective studies, two prospective and randomized trials. And the results indicated positive clinical antiaggressive effects of LAIs in patients with high risk for violent behavior. Without doubt, the authors suggested that LAIs may have a particular niche in treating patients in forensic psychiatric settings. Now, if I'm allowed to have a favorite study, I would say that would be the one, because not only of the sheer number of patients whose records were reviewed in the study, but also because of, in my mind, one of the most important outcomes, which is mortality for patients with schizophrenia. And it was a linked, prospectively-gathered, nationwide register-based data collected from 2006 to 2013. In Sweden, they looked at all adult patients with schizophrenia between 16 and 64 years old, and patients, on average, followed up for about five and a half, six years, during which about eight and a half percent of those patients died. You could see that adjusted risk of death was 56% lower during the use of any antipsychotics compared to no use of antipsychotics. The amount of patients with schizophrenia LAI use was associated with approximately 30% lower risk of death compared to oral antipsychotics. So the way how to interpret this graph on the right is, consider one is kind of standard hazard ratio for dying, and the further to the left the different group is, the more likely patients were to experience reduced risk of death. So as you can see, the top line for second-generation LAIs is the most to the left, which means that the patients who were receiving second-generation long-acting injectable antipsychotics has the lowest mortality risk, followed by first-generation LAIs, then second-generation orals, and first-generation orals. Somewhat similar way to interpret this graph, and again, the more to the left the line is, the better outcomes were for the patients in respect to decreasing mortality. And as you can see, all the top spots go to the LAIs, except for oral epiprazole, who performed quite well in that particular study. Now, that's the last slide that I want to show you from this study. And I know that you may not recognize the names of some of the medications, but it's a European study, so they have a little bit different formula than we do. However, what I want you to see is, so on the dotted line, this is a hazard ratio of one. That's when patients were taking their oral antipsychotics. The kind of maroon color, red color line is them being prescribed medications, but not taken. So as you can see, not taking medications of any kind was definitely associated with increased risk of mortality, but if you look at the blue lines demonstrating long-acting injectable antipsychotics, you could see that they were much better across the board compared to oral medications compared to not taking medications of the same activation. So this is really comparing apples to apples. All right, let's move on to this study that examined probability of re-hospitalization for any cause at 30 and 60 days after the initial hospitalization. And essentially, look at the difference between patients who were prescribed either LAIs or oral antipsychotics at the time of discharge. And you could see that there was a decrease in re-hospitalizations for oral antipsychotics. All patients on LAIs compared to oral antipsychotics. This is a somewhat similar study, the conducted retrospective evaluation of 240 men and women, all adults between 18 and 65 years old, diagnosed with bipolar schizophrenia or schizoaffective disorder and discharged from inpatient state hospital over a two-year period. And again, it compared patients discharged on LAIs compared to patients discharged on oral antipsychotics. And patients who were discharged on LAIs had significantly longer survival time compared to those who received oral antipsychotics at the time of discharge. And what was also interesting was that patients who received LAI administration with frequency of a month or longer had significantly longer survival time without transmission compared to those who received LAIs of a shorter duration. So again, to summarize, any LAI was better than oral in increasing survival time, but the LAIs that were spaced out at particular length periods of time performed even better. This study gave us important comparison of patient outcomes when long-acting injectables were initiated early in treatment rather than later. So the retrospective analysis looked at, again, adult patients with new episodes of schizophrenia, and they put them in two mutually exclusive cohorts. One of them initiated a long-acting injectable within the first year of receiving diagnosis. The second group initiated treatment with LAIs after 12 months from receiving the diagnosis. And as you can see, the group that was early initiators did significantly better compared to those who received LAIs later in treatment. It was evidenced by both decreased or delayed hospitalizations, but also the adjusted psychiatric health care costs. Again, I will be kind of pointing out a few things that are related to price as well, because sometimes we hear that long-acting injectables may be more pricey, but if you look at the patient outcomes, there could be real savings there. This study examined which patients with schizophrenia were more likely to be prescribed long-acting injectable anti-cellulitis on discharge. It's a relatively small study from one teaching hospital. What was interesting there was that less than half of eligible patients were prescribed LAIs, and most of those patients who were prescribed were males. And no other factors like gender, employment status, living arrangements, length of hospital stay, or even concurrent substance use were at play to decide whether or not patients would receive LAI at the time of discharge. This is a pretty interesting study where patients got a chance to be compared to themselves. It was a so-called mirror image type of study. It's a naturalistic study that looked at the patients before they received the treatment with RAP Prozol LAI to the time after they received treatment. The comparisons were done for four months, plus or minus the index date, and six months before and after. As you could see, all patients experienced a significantly lower psychiatric hospitalization rate after switching their treatment to the LAI, than compared to themselves before they started being treated with RAP Prozol LAI that was used in that study. This was a double-blind active control non-inferiority study. I know we often want to hear whether or not the new formulation works better than what we have before, but this study was not powered to assess whether or not the LAI formulation of RAP Prozol was better than oral, but it was powered enough to show that it was at least not worse than oral formulation of the same drug. This study, also known as pre-lab study prevention of relapsing schizophrenia, was pretty interesting in its design. Instead of randomizing patients, this study randomized 39 mental health centers in 19 United States. The sites either were encouraged to use RAP Prozol once monthly injection, or leave it up to the provider to decide what treatment patient would receive for treatment of schizophrenia. That meant that the clinician choice groups still could receive RAP Prozol for the longer injectable antipsychotics. But what you can see is that for early phase schizophrenia patients, there was a 44% reduction in incidence of first hospitalization, but in patients who were steered towards RAP Prozol LAI compared to clinician choice treatment, and the number needed to treat was seven to prevent one hospitalization. This was a meta-analysis of five randomized controlled trials, so four prospective observational studies and four retrospective observational studies. What was interesting is that if you look at the randomized controlled trials, oral medications in certain studies did better than LAIs in other studies. LAIs did better than oral medications. There was no apparent benefit of DIPO over oral formulations in those particular studies. However, as we move forward to prospective and retrospective analysis, those observational studies demonstrated significant advantage of DIPO formulations in both prospective and retrospective studies. You see all the benefits on the left side were the ones that favored a long-acting injectable antipsychotics. Now, there could be some explanations why randomized controlled trials look differently than observational studies. One thing is that randomized controlled studies definitely are the best strategy to estimate treatment effects from a statistical perspective, but remember that there is quite a vigorous selection process as far as which patients would enroll in the studies and which ones won't. The patients who are enrolled in those studies are not necessarily the patients that are scheduled in the office on a regular day. Another thing to consider is that patients in randomized controlled studies usually receive much closer follow-up, and therefore those treatment settings are not necessarily as realistic as they are for observational studies. However, in observational studies, the downside is that there is some possible lack of control for other confounding factors and possible selection bias. Now, this study is really remarkable because it gave us a very important glance on how both first and second generation antipsychotics performed as individual groups compared to oral antipsychotics. Majority of the studies that I quoted to you up until now were focusing on general LAI versus oral kind of comparison. Here you see three groups. So you see a group of first-generation long-acting injectables, second-generation long-acting injectables, and how they are compared to oral treatment options. What was really important was that antipsychotic polypharmacy was more common in patients treated with first-generation long-acting injectables and less common in patients with second-generation LAIs. Second-generation LAI patients had higher odds of adherence at 12 months, while first-generation LAI patients had 48% lower odds of adherence relative to oral antipsychotics. Second-generation LAI patients were more likely to be persistent in treatment than patients treated with oral antipsychotics, but the same was not true for patients treated with the first-generation long-acting injectable antipsychotics. So in conclusion of that study, patients initiated on second-generation LAIs demonstrated better treatment adherence and persistence compared to oral antipsychotic-treated patients, and patients treated with first-generation LAIs did not show significant improvement in adherence or persistence and had more antipsychotic polypharmacy compared to patients treated with oral antipsychotics. So these findings definitely suggest the potential value of second-generation LAIs in treatment of schizophrenia. And the final study I want to show you is very new. It was published just last summer. It was a large observational study using VA pharmacy database, and it looked at more than 37,000 outpatient veterans with schizophrenia. And it looked at a couple of outcomes. One was all-cause antipsychotic discontinuation, and another was psychiatric hospitalization. And the authors of that study used oral olanzapine as a reference group. So, as you can see, olanzapine is kind of somewhere right in the middle with median time for discontinuation. And the best results, and probably more evident on the following slide, is that patients who were treated with clozapine had the longest time to treat discontinuation. So the solid line with hazard ratio of one, that's olanzapine that was used for reference. And all the medications listed to the left, kind of on top of the table, those are the ones that had longer time to discontinuation compared to oral olanzapine. And everything that is listed at the kind of lower part of the table with green dotted line to the right, that was compared to olanzapine as it came to treatment discontinuation time. Now, there is one of the possible explanations why patients on clozapine stayed on that medication particularly longer. For once, they may have tried many other medications, and clozapine was more or less treatment of last choice, so there was not much to switch patients to from clozapine. Also, as you know, patients who receive clozapine usually have much tighter follow-up. They require periodic blood draws, more frequent doctor's appointments. So there's possibility that those factors also contributed to patients staying longer on clozapine. But if you look at other medications that perform better than oral olanzapine as it comes to time to discontinuation, almost all the spots belong to long-acting injectable antipsychotics, with exception for antipsychotic polypharmacy. And this is the slide from the same study, but in this particular case, it looks at the risk of hospitalization, and no medications were associated with decreased risk of hospitalization. You may not see the olanzapine LAI, and it was not actually considered for the study because it was so infrequently prescribed in the VA system. And the authors of the study also acknowledged a couple of things. First of all, this was done in the VA, and VA patients with schizophrenia were more likely to be older males with higher incomes and better psychosocial support compared to the patients who are commonly seen in Medicaid treatment settings. And the additional limitation was that the assumption that all-cause discontinuation is an indication of oral effectiveness measure, but the study did not include any clinical measures such as assessment of patient symptoms and functioning. So you cannot necessarily say that just because somebody stayed longer on the medication meant that they did clinically better. It may or may not have been a relationship, but the study was not able to look at that. All right, so let me summarize what we've learned. Patient self-report or physician estimates of patients adherence to treatment are extremely unreliable. We do know that oral and long-acting injectable antipsychotics are both approved for treatment of schizophrenia, and we have those options available at our disposal, and we need to educate our patients about those treatment options. Our patients treated with LAIs when compared to those treated with oral antipsychotics demonstrated lower risk of treatment failure, re-hospitalization, drug discontinuation, gaps in therapeutic plasma concentrations, violence, or death. Patients treated with LAIs when transitioned from oral antipsychotics had fewer hospitalizations, fewer inpatient days, fewer ER visits, decreased hospitalization costs, decreased all medical costs, and decreased total health care costs. Now, LAIs demonstrated non-inferiority compared to oral formulations and compared to clinician choice of care. LAIs in early phase schizophrenia produced significant reduction in incidence rate of first hospitalization. Remember that randomized clinical trials did not show apparent benefit, but there was a significant advantage of depot formulations in prospective and retrospective observational studies. Finally, we're comparing patients treated with oral antipsychotics patients with second generation LAIs were less likely to need antipsychotic polypharmacy, while those treated with first generation LAIs required multiple antipsychotics. If you treat patients with second generation LAIs, they had higher odds of adherence at 12 months in contrast to first generation LAI patients who had lower odds of adherence, and second generation LAI patients were more likely to have no gaps in treatment compared to patients with oral antipsychotics or first-generation LAIs. So this is the bibliography. You should be able to find that in the handouts. And with this, I am going to pause here and see what questions we may have. Thank you for such an interesting presentation and for all this data. Before we shift into Q&A, I want to take a moment to let you know that SMI Advisor is accessible from your mobile device. Use the SMI Advisor app to access resources, education, and upcoming events, complete mental health rating scales, and even submit questions directly to our team of SMI experts. The app now at smiadvisor.org slash app. Now we can move into some questions. And audience, feel free to submit any more questions in the question area. So, Dr. Rabin, our first question, this reduced mortality for LAIs over oral antipsychotics is striking. Do we or the researchers of those studies understand why this is? I don't believe they specifically look at causation. It was a review that just looked at the nationwide registered data. So I don't think it was specifically powered or designed to look at specific factors associated with that and just looked at who were patients who died during that about six-year time period and who were the patients who did not. And again, patients who were in treatment of any kind did better than not being in treatment. So I guess that kind of corresponds to what we commonly see in practice. But what was particularly remarkable there that could demonstrate that using long-acting injectable antipsychotics, in particular, second-generation long-acting injectable antipsychotics, produced the lowest cumulative mortality rate. Great, thank you. OK, is there a chemical reason behind the choice of solvents for the first-generation versus second-generation LAIs that you're aware of? I am not really experienced enough to speak on that. So I can imagine that maybe many years of research allowed the companies to develop new ways of delivering medications. And now we have nanocrystal technologies and other ways of delivering medications as long-acting injectables. But I don't know of any formal explanations why first-generation antipsychotics, why sesame oil-based and new ones seem to be all water-soluble. Yeah, thanks. I think it gets trickier and trickier. Microspheres and nanocrystals, and one is a prodrug. And every time I listen to an explanation on a new LAI, it's kind of dazzling how this technology has really advanced. Very complicated as well. Well, at least I'm glad to see that we have brought a variety of options, because it certainly gives patients more choice of treatment options. And nowadays, when we have patients who only have to be compliant with treatment twice a year, that certainly makes a difference. And I think patients appreciate the difference between taking medication twice a year as opposed to twice a day. Right, right. More options are always better. Let's see, we have a related kind of question. As we move toward LAIs with wider spacing intervals, for example, Trenza and now Hafeera, we are starting to see patients in our clinic who get worse toward the end of their dose interval. Do you have any data on this? Manufacturer data seems to say it shouldn't be the case, but it seems hard to explain away as a chance in clinic. So, Paul, I certainly have seen similar instances. And I want to be clear that now I'm speaking from my clinical experience rather than from the data. And I have spoken to a variety of clinicians and pharmacists who suggest that sometimes you may shorten the intervals for those LAIs. Definitely, just because you administer long-acting injectable antipsychotic, it does not mean that that interval between injections should dictate how frequently you see the patient in your office for reassessments. And you can make your clinical judgment as to what factors could possibly be contributing to patients experiencing less efficacy of the medication as it gets closer to the next injection. You could consider measuring antipsychotic plasma level and the best time to do so is right before the next scheduled injection. And you could see whether or not it kind of falls within the bell-shaped curve where you expect your patient to be on a given dose of the antipsychotic. Thank you. That's a great response. And let me see, I had another question about plasma levels. Since you mentioned that, the plasma level data for oral antipsychotics is striking. You presented 35% at sub-threshold levels and with 34% not detectable at all. How does this compare with the LAI plasma levels in your experience? Well, again, it may sound like I'm making an assumption, but I think the reason why the antipsychotic plasma level was undetectable in those treatment-resistant schizophrenia patients in UK was because patients were not taking medications. But not because they had super high clearance rates. If it's undetectable, it is undetectable. One thing that we know is when you give injection with long-acting injectable antipsychotic, the medication is going to be there. Now, as far as factors that may impact antipsychotic plasma levels, you definitely want to consider if the patient is taking any concomitant medications. Maybe they also prescribed various medications, but their primary care physician that may impact 2d6 or 3d4 clearance of the medications, either increasing or lowering the levels. If your patient is a smoker and you prescribed medication that is clear to 1a2 system, keep in mind that if somebody smokes a pack a day, that could hypothetically lower their medication plasma levels by as much as 50%. So all that needs to be a consideration as well. But one thing that at least gives me comfort that I'm yet to see a single patient who overdosed, particularly intentionally, on long-acting injectable antipsychotics is just simply not an option. So if you have worries about the patients who are taking medications not as prescribed or maybe possibly taking a handful of pills or those who seem to take their oral medications less frequently because they feel they're doing better, and then when the voices add up, they just double the amount of medications that they take on their own without ever consulting you as a physician. That is a concern. And long-acting injectable antipsychotics actually allows to have that consistent presence in patient's plasma without having significant peaks or throats. Thanks. And I know you said you were making an assumption, but I think we all probably can safely assume that the LAI is getting into the system, at least much more consistently than the oral versions. And important points about interactions with other medications as smoking as well. So thank you for that. The next question, any updates on what LAIs are in the pipeline? Either orals developing their first LAI or existing LAIs developing wider spacing intervals? Yes, unfortunately, I'm not able to give you that answer. It was not covered under the scope of the current studies that I presented. And I am not involved with any pharmaceutical companies that are focusing on developing new medications in the pipeline. So I simply don't have that knowledge. Yes, so if you want to, whoever asked that question, submit a consultation, we might be able to answer that in the consultation system. I happened to hear just last week that there is another subcutaneous risperidone coming out from a different company that will have the abdominal or upper arm subcute sites and also more dosing range. But that's the only thing I've happened upon hearing recently. OK, let's see. That's actually done pretty interesting that the company is now looking at subcutaneous options so for injections. I have heard from some physicians working with patients who have pretty extreme rates of obesity. And getting through that fat tissue into the muscle is quite challenging. So having subcutaneous injection in the fat tissue could be quite beneficial for that particular patient population. That's an interesting point. And since the other subcute LAI hasn't been out for all that long, I haven't heard a lot from colleagues about whether they're seeing that last longer or work better for certain types of patients. But we shall see. OK, so going back to way early in your presentation when you were talking about what typical patient adherences and their reports and clinicians reports, why do you suppose that clinicians estimate or guess that of their patients oral med adherence was so high at 93% or 7% non-adherent? Well, I guess all of us have good faith in our patients. All of us want to believe that the patients will do what is in their best interest. But the reality of life, well, that it's not. And we cannot just take it at face value. And we also need to be reasonably considering what patients understand as adherence. Because for them, taking medication every once in a while may mean that they've taken the medication. And so if you just simply ask them, hey, are you taking your meds? And they say, yeah, sure, I do. That gives you that false sense of security. For me personally, I always ask patients to bring all the meds they have at home. Sometimes they bring big plastic, like supermarkets, plastic bags filled with meds. And some of them could be six, seven, eight years old. And they still keep them around just in case, as they say. So it is certainly concerning. Last week, we had a patient at our clinic. And our patient was prescribed an oral antipsychotic. And the patient was prescribed oral antipsychotic last month, came back this month for follow-up, and told us that he took one pill and decided to stop. So that was an estimate of spending about $2,000 for one pill that the patient decided not to stay on. And the patient did not even contact our clinic. So if you're looking at expenses associated with treatment, I think it's pretty evident that spending $2,000 for one pill of oral antipsychotic and getting zero bang for the buck is really not the best of health care economics. Not to say anything specific about each patient outcome. I'm betting that many of us have had an experience like that, with abrupt discontinuation and already having that cost incurred. Okay, a couple more questions here. You mentioned that 40% of patients did not receive follow-up care in one of the studies you presented within 30 days of hospital discharge. Do you have any recommendations in preventing this kind of gap in treatment or thoughts about this? So I can tell you what our facility does here. We actually have a dedicated nurse who contacts the patient within seven to 10 days post-discharge. And usually just a brief assessment, making sure that the patient still remembers when their post-discharge appointment is, so that they were able to fill their prescription if it was meant to be filled in outside pharmacy, if they have any questions about medications, if they have any side effects of treatment that may require them to see a provider sooner. Then they schedule the appointment. We did discover that some patients lose their follow-up information. Some patients feel that they're doing quite fine and don't think like they want to keep an appointment. And if they miss their appointment, then it's getting much harder for them to find the next available slot in the community. So Nevada has a lot of underserved areas. So definitely missing an appointment can be problematic for the patient to get a timely follow-up. So we started this as a performance improvement project many years ago at our facility. And we noticed that we have better outcomes for our patients. So we decided to make it a procedure. And now we have that staff member, that nurse who does those follow-up phone calls routinely post-discharge. Wonderful. I love to hear the nursing involvement. Okay, one final question. Why do you think that LAIs that last a month or longer, that you mentioned in a study, prevented re-hospitalization better? I don't have an explanation. The study did not provide that information. So I wish I could give you an answer that would be backed up by data. So the difference was about 60 days between the patients who were receiving shorter administration frequency LAIs compared to the ones that were administered a month or further apart. But the study itself did not provide any explanation to that. Okay, thanks. We could speculate that it might be non-return for the next injection, but just speculating. Okay, well, thank you so much for answering all of those questions. Very good questions. Just a few wrap-up slides and information before we finish up today. I mentioned the consultation system earlier. If you have any follow-up questions about this or any topic related to evidence-based care for serious mental illness, our clinical expert team is ready and now available for online consultations. And even if you have a question specifically for Dr. Raven, please indicate this in your consultation request. Any mental health clinicians can submit a question and receive a response from one of our SMI experts. And consultations are free and confidential. On behalf of SMI Advisor, I'd like to invite you to learn more about APA's 2022 annual meeting. The in-person conference takes place May 21st to 25th in New Orleans, and the virtual meeting takes place June 7th to 10th. During the live conference, clinical experts from SMI Advisor are leading a variety of sessions on how to improve care for individuals who have SMI. Topics for these sessions include the basics on how to use Clozapine, digital navigators, and making technology work, and how to improve physical health in patients who have serious mental illness, and more. I encourage you to take a moment right now and browse the agenda at psychiatry.org slash annual meeting. To claim credit for participating in today's webinar, you'll need to have met the requisite attendance threshold for your profession. Verification of attendance may take up to five minutes in the system. You'll then be able to select next to advance and complete the program evaluation before claiming your credit. Please join us next week on March 11th as Anita Manley presents Dialectical Behavioral Therapy for Serious and Persistent Mental Illness. Again, this is a free webinar and it will be on March 11th, 2022 from 12 to 1 p.m. Eastern time. Thank you for joining us so much and until next time, take care.
Video Summary
The video is a recording of a webinar titled "Worth a Shot? Evidence-Based Approach to Prescribing LAI Antipsychotic Medications," hosted by SMI Advisor. The webinar is introduced by Donna Rowland, the Director of the Psychiatric Mental Health Nurse Practitioner Program at the University of Texas, Austin. SMI Advisor is an initiative by the American Psychiatric Association (APA) and the Substance Abuse and Mental Health Services Administration (SAMHSA) to provide evidence-based care for those with serious mental illness.<br /><br />The webinar offers one AMA PRA Category 1 Credit for physicians and one Nursing Continuing Professional Development Pharmacology Hour. The presentation discusses the benefits of long-acting injectable (LAI) antipsychotic medications compared to oral formulations in patients with schizophrenia. It explores various studies and meta-analyses that have shown LAIs to be associated with lower risk of treatment failure, rehospitalization, drug discontinuation, violence, and mortality. It also highlights the advantages of LAIs, including convenience, decreased conflict with reminders, and reduced healthcare costs.<br /><br />The presenter, Dr. Leon Raven, a board-certified psychiatrist and Statewide Psychiatric Medical Director for the Division of Public and Behavioral Health, State of Nevada, discusses the benefits of LAIs based on scientific, peer-reviewed evidence. The webinar concludes with a question and answer session. The video includes slides from the presentation, which are available for download in the handouts area of the webinar interface.<br /><br />Note: This summary is based on the provided transcript and does not include any additional comments or information from the speaker that may have been conveyed during the webinar.
Keywords
webinar
LAI antipsychotic medications
schizophrenia
studies
meta-analyses
convenience
healthcare costs
Dr. Leon Raven
question and answer session
Funding for SMI Adviser was made possible by Grant No. SM080818 from SAMHSA of the U.S. Department of Health and Human Services (HHS). The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement by, SAMHSA/HHS or the U.S. Government.
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