Hello and welcome. I'm Tristan Grindow, Deputy Medical Director and Director of Education for the American Psychiatric Association. I'm pleased that you're joining us for today's SMI Advisor webinar, Adherence to Antipsychotics and Schizophrenia, Clinical Considerations. 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. Now I'd like to introduce you to today's faculty, Dr. Oliver Freudenreich. Dr. Freudenreich is Associate Professor of Psychiatry at Harvard Medical School and a psychiatrist at Massachusetts General Hospital. He serves as co-director of the MGH Schizophrenia Clinical and Research Program and directs the MGH Fellowship in Public and Community Psychiatry. Oliver, thank you so much for joining us for today's webinar. Tristan, thank you for inviting me to give this talk and thank you APA for giving us this opportunity to talk about things that matter for patients that I care for, patients with schizophrenia. In the spirit of disclosure, I'm going to show you here my slide. You'll see a lot of pharmaceutical companies listed because part of my role at Massachusetts General Hospital is clinical research, including drug development and improving existing regimens. I thought about three learning objectives when I put this talk together. After completion of this webinar, you should be able to list four important risk factors for non-adherence to antipsychotics. I would like you to be able to estimate adherence by inquiring about drug attitude, barriers, and compliance behavior, the ABCs, and I'll come back to that point, the ABCs of adherence. And then, of course, to be practical about it, I would like you to develop a patient-specific treatment plan to optimize adherence in your patients. Three broad sections of this talk, why does adherence to antipsychotics matter in schizophrenia, how do you assess antipsychotic adherence, and how can you enhance antipsychotic adherence. Just to warm us up here, I included a couple of slides. Here's a quote from William Osler, often considered the father of modern medicine. He said, the desire to take medicine is perhaps the greatest feature which distinguishes men from animals. You should laugh a little bit because you realize there's something to it, and yet it's not the whole truth. The quote at the bottom of this slide from an editorial or perspective in the New English Journal of Medicine 10 years ago now is titled, Thinking Outside the Pillbox, Medication Adherence as a Priority for Healthcare Reform. So you kind of see this tension. On the one hand, I think we are quite willing to take something, and yet it seems to also be problematic to do exactly that. And that's what this talk is a little bit about, to really show, I think, that taking medicines is actually a fairly complicated process in the end. Also in the spirit of disclosure here, I want to show, maybe to give myself a little bit of street credibility here, I don't do just research, I also treat patients in real settings. This is an older picture of the community mental health center that I work in, the Eric Lindemann Mental Health Center near the main hospital. So this talk really is for psychiatrists like me who treat real patients in real settings, patients with schizophrenia, who for the vast majority of them an antipsychotic is probably most people would say indicated. So let's go to the first section of my talk. Why does adherence to antipsychotics matter in schizophrenia? And in order to answer this question, I would like you to have a little thought experiment. What is actually a good outcome in schizophrenia, or put differently, imagine a type of patient where you think, well, the outcome is really not that good. And you may picture somebody with many hospitalizations, you know, not so sure if medicines are taken or not, there's a history of homelessness, maybe patients had a few rushes with the police. So there's a forensic history. And the opposite of that is, of course, somebody who lives at home, has involvement with family, has friends, is maybe working, doing things that are meaningful, having a time for leisure activities. So it's not that different, actually, a good outcome in schizophrenia from what you would expect for yourself or for your loved ones. And I say this because I think you easily see that the reality for a lot of our patients is not like that. They do struggle. And the question is, why do they struggle? What gets in the way of this outcome that we all hope for? And here's a premise. I'm going to be talking about a group of patients where antipsychotics are, in fact, a really critical part of the treatment plan. They are tools, they're not ends in and of themselves, but they're really not optional. This is a group of patients that fairly reliably relapses when maintenance treatment is discontinued. Now, that's not all patients with schizophrenia, but I think, depending on the setting that you work in, it's a very substantial number of patients. I have a premise here on the slide that reads, schizophrenia is for many a relapsing, remitting illness with accrued disability over time. I'm going to read that again because I think it's really important. This is from Dr. Venner, a neurologist at Mass General, who pointed out the similarities between multiple sclerosis and schizophrenia, so I adopted this from him. Again, schizophrenia is for many a relapsing, remitting illness with accrued disability over time. Relapse is really important to consider, particularly the cost of relapse and schizophrenia. Maybe there's a small group of patients where relapse is no big deal, but I would argue that for this disorder, relapse is potentially disastrous. I use the term that relapse has psychosocial toxicity. Just imagine, patients that you know, what happens when somebody becomes psychotic and gets hospitalized, they might lose their jobs, education gets derailed, there might be criminal problems, the risk of suicide is higher, and there's a loss of reputation. Simply imagine that you become psychotic and at night you cause a ruckus outside because you may be naked in the street. It might spread that Dr. So-and-so was taken away by police. And this is real. The other issue is that relapse might be biologically harmful. I mean, there's some evidence for that in trials, I'll give you one reference here, that emergent treatment non-response happens in a significant minority of people, 16% in this one sample. But I think it's hard to argue with the idea that relapse is psychosocial toxicity because it has face validity. So if we think then, what is it in the end that contributes to poor outcomes? There's no question that unresponsive biology is critical. We all can imagine a patient, we've tried everything, the patient is taking the medicine, is getting ECT, clozapine, and yet the patient is simply not responding to the treatments that they do have. Such patients exist. But the vast majority of patients with treatment can do substantially better. And so we have to ask, why is it that overall not more patients are doing better or even well? And I think that's, you see this listed on the right side, it's time spent psychotic in hospitals or idle at home is one of the contributors. Lower access to treatment and no care, substandard psychiatric care, and poor engagement in ongoing care and poor adherence. I highlighted those three because that is kind of my argument here, why we need to really think very hard how to improve adherence in our patients, substance use, comorbid medical disorders, and of course the social determinants of health, poverty, are clearly also important. And this has been shown, this is a slightly different way of looking at it, if you compare people who are adherent versus non-adherent or treated, non-treated, every variable that you look at, going from left to right here, suicide attempts, arrests, violence, victims of crime, substance use, relapse, and hospitalizations, those people who are non-adherent have higher rates compared to adherent patients of those things. So a slogan that I stole from HIV care is treatment as prevention. If you believe me that sustained remission is in fact the basis for accrued treatment benefits over time, then relapse prevention is a key goal of schizophrenia care. And part of relapse prevention then is to really take adherence very seriously, and that's what I hope, it's a lengthy introduction here, but I think it's important for you to appreciate why this is such an important issue and not really optional. It's particularly tragic, I think, because we have very effective medicines to prevent relapse in patients with schizophrenia, that type of schizophrenia that reliably relapses if untreated. We have over 50 years of evidence now, this is a meta-analysis by Stefan Leucht, and this is just a one-year relapse rate that clearly shows a very substantial risk reduction from being treated as opposed to not treated. For a different talk, of course, there are issues, what kind of treatment, for how long, are we always talking about decades, sometimes maybe less, is it a little bit more, maybe treatment has some side effects that are not fully appreciated, including getting in the way of function. And yet I think that the idea that I showed you, that relapse actually psychosocial toxicity, and that is a good reason to try to avoid it, to my mind has at least some face validity. So let's say, well, the problem is solved, right? We do know that no or suboptimal treatment is a major cause of poor outcomes. If the treatment is highly effective, and yet, and yet, then we do know that all chronic conditions have high non-adherent rates. So adherence is clearly a very real problem in clinical care. In a meta-analysis of main compliance rates, it's pretty much about 50-50 for endocarditis. Different analyses show different numbers, but broadly speaking, I think that that feels about right. It's not limited to antipsychotics, but includes other medications and also medicines taken for medical reasons. In Scandinavia, one cohort study showed that in young patients after their first hospitalization for schizophrenia, only 50% of them used the antipsychotic for over 30 days. That's against all guidelines. In a more chronic sample, typically looking at people who were admitted and then discharged, a significant minority of patients, 16%, never initiated treatment after discharge. And only about one in five persisted at six months. So these are striking numbers that are really a challenge, I think. So adherence is a key variable, I believe, for good outcomes. So we need to assess it competently at each visit. And yet it's not rocket science, that's what I'm going to show you. You can do this very naturally and quickly and easily, I believe. We all guess the patient's adherence. Somebody walks in the room, you think, oh, this is Larry, and you have an idea of how adherent the patient is. There are common errors in thinking. There's overconfidence on both sides. It's a phenomenon that we all believe we are above average. So my patient's adherence is better because I'm a better clinician. We all, I think, deep inside, believe this. And it's been shown that it's simply not true. So it's on both sides. It's us overestimating how good the patients are. And patients themselves. And I don't think it's ill will. It's simply patients want to be nice to us. They believe, I think, in their heart that they're doing a good job with their medicines. And so they forget that they did not take the medicine the last three days. So overconfidence on both sides. Second, we underappreciate partial adherence and the pernicious effects of partial adherence. I don't want to go over this in detail other than pointing out that while we don't really know what's an ideal level of adherence other than simply saying 100%, it's 90% OK or 80. It might depend on the individual circumstances. But very quickly, you end up, seven days, two or three pills missed, you end up in the range of only 50-50. So 50% of times. And then you increase. This has been shown very nicely in many studies. You increase the risk of having symptoms. Where you inappropriately might then add medicines to treat those. Or you increase the risk for actually re-hospitalization. And the third error is we do underappreciate the lack of persistence over time. I showed you in an earlier slide that this has been shown very nicely in a follow-up study of hospital of post-discharge patients. Sometimes we use this idea of insight to kind of claim we understand adherence. I don't find this particularly helpful except in the extreme. And this is a shorthand. But I think clinicians know what I mean when I say the patient has zero insight. To talk for a different day, insight, I just want to say here, it is more complex than yes or no. It's a multidimensional construct. We're talking about awareness of symptoms, acknowledgement of illness. And then perhaps unrelated, the first two, an acceptance of the need for treatment. Important. Illness insight is neither necessary nor sufficient for adherence. There are those patients who, to use this shorthand, who lack insight that may very reliably actually take their antipsychotics. So the patient who doesn't really know why he has to come to the clinic is sent by the group home and is really taking in his mind the medicine for insomnia, the antipsychotic in this case. Similarly, patients with insight, they may choose a non-medication approach so this is a variable that is, in the end, I find not that helpful. It is important to recognize that insight may not improve when symptoms improve. Sometimes something we hope for, we believe. And unfortunately, in quite a few patients, it may actually not improve with more therapy. Families love this idea that you, as a psychiatrist, you just talk to your patient more and more and more therapy. And I certainly have a core group of patients that it doesn't really work. So insight, I think it's important as one aspect, and I talk about adherence, but I want to show this to you in a different way, which I think is more practical. And this is the most important slide. It's also one of the learning objectives. I want you to appreciate the ABCs of adherence. Adherence is two things. It's both an attitude and a behavior. And we'll go over those two things. And there's a third piece, there's barriers that kind of block from the good attitude that you might have towards taking medicine from actually implementing in the real world. A, B, C. So A for attitude, B for barriers, and C for compliance. I had to put compliance here, so the ABC works. But as you know, adherence is, I think, a term with less baggage. So we should stick with that. So A, the assessment of the attitude towards taking medications. That's a really, I think, helpful construct that's also used in clinical research. It's the kind of thing that I think intuitively you know what it is. Because you all have a drug attitude about certain things. We learned this growing up. We know when we are sick as children, and we have a fever, and mom gives you a colorful pill, that this might be a good thing. So you actually learn that for particular problems, pills might be a solution. And when it comes to antibiotics, I think we fundamentally have a good drug attitude towards this class. Because we kind of know that for certain types of problems, they can be highly affected. Unrelated, whether you're an optimist or pessimist, I think it's simply something that you have learned over time. And I think this is also what Osler basically is talking about, that we as human beings, as opposed to animals, we actually kind of learn to associate pills with improvement in symptoms and feeling better. So drug attitude as a kind of definition would be the sum of subjective medication risk and benefit assessment. So a good drug attitude then would be something that I think you would say is necessary, but not sufficient for adherence. Put differently, if somebody has a bad drug attitude, okay, medicine is not the solution, I don't like this medicine, it only has side effects, I think it's highly, highly unlikely that that person will take medicines. A good drug attitude exists for medications if a medication is perceived as warranted, I need it, it's effective, it works, and tolerable. Okay, I don't have too many problems with it. In many trials, including a first episode trial in Europe, the UFES trial was shown that if you actually just simply ask, inquire about the drug attitude, and this is a scale, I don't want to belabor this point too much. You can predict treatment effectiveness because it really shows who's likely to take medicine or not, at least potentially likely to take medicines or not. You may have just like, you know, with Insight, you may have a good drug attitude for the wrong reasons a little bit, the idea of taking an antipsychotic for insomnia, you might love your antipsychotic at night because you feel it's really critical for you to get better sleep. Not really my view, but that does happen, as you know. Assessing a drug attitude is not rocket science. You can easily elicit a drug attitude by talking about a patient's worldview of their illness and treatment views and their health beliefs. So, when, think about yourselves, when do you accept treatment? The health belief model, I think, nicely shows this. You accept treatment if you believe you have a problem, a medical disorder, and it has to be severe enough to actually warrant treatment. You know, there's a lot of conditions where we think, eh, I'll just toughen it out without seeking help. And when you believe that the treatment is effective, you accept treatment. When you believe that the treatment actually addresses the problem, like a pill, you might say, well, I don't need a pill, I need physiotherapy. And where the benefits outweigh the risks. It's really hard to do something where you feel, eh, you know, not sure if it works, but it sure has a lot of side effects. In the language of the health belief model, you look at the perceived vulnerability, the perceived threat, the perceived benefit, and the perceived cost. And critically here for this, this is from the patient's perspective, not your perspective. They might, you know, be in parallel or contradict each other. Let me show you this health belief model in a slightly different way. A common error that we and our patients make is that we assume that medication adherence in and of itself leads to an increase in, and I'm using quality of life here, as something that we value. So on this slide here, going from the left box to the right box. And this is problematic because this thinking also justifies them to make adherence in and of itself. You know, if this were true, then adherence would be just something that you have to insist on. But if you're honest, you recognize that there's actually two competing pathways towards improving quality of life. So if you adhere to medicine, and this is the top pathway here, you reduce positive symptoms, the negative number, then you will actually, with a reduction in symptoms, you will increase another negative number. You will increase your quality of life. So that's the idea of effectiveness if you have troublesome symptoms. This is counterbalanced, however, by medication side effects. So taking medicines for benefit comes at a price. And the price that you pay will actually reduce your quality of life. And we all make this judgment when we take a pill, let's just stick with something we can all relate to taking an antibiotic. For a treatable condition, we might feel better quickly. But then we might also develop GI problems and, you know, stomach hurts every time we take the antibiotic, which I think is a big reason why nobody ever finishes 10 days of antibiotics, just enough to feel a little bit better, but not take the brunt of the side effects. So assess the attitude. It's easy to do, you know, just by chatting with somebody, how they see the role of medicine and what they have. And a good drug attitude, if you can elicit that, shows you at least a likelihood of adherence. Because if somebody says, you know, this makes sense to me, why would they then not take the medicine? Of course, then we have barriers to implementing, you know, a good drug attitude, if you will. Sometimes there's administrative barriers, prior authorizations, medicines are not on formularies, the financial, the co-pay is too high, there might be drug use, cognitive difficulties. The environment might be something that's hard to overcome. If a family member or peers are anti-medicine for whatever reasons, you might kind of believe that you ought to be taking the medicine, but you will have a hard time explaining this maybe to your mother. A common struggle, I think. There's the side effect burden. People might be skipping pills, so this is a little bit of a barrier, if you will, if you want to put it under the B side. And pill fatigue. Those are some really real-world obstacles to actually implementing a good drug attitude. And even in those patients where, as you go through this, good drug attitude, no clear barriers, you still have to look at the actual behavior then. You know, what is actually taken, despite, you know, what the patient says, and despite there not being any barriers. I put here in Russian. Maybe some of you speak some Russian. I don't, so I have just a translation. Trust but verify. It's something that Ronald Reagan liked to say when he negotiated with Gorbachev about nuclear weapons. So how do we assess actual compliance behavior, adherence behavior? Again, the C, so that the ABCs work. There's no gold standard. Already kind of talked about the self-report and the limits of self-report. Collateral information is helpful. You know, what does the group home think? What does the family think? How good adherence is? And there are some objective things that we can try. There's, we can count pills. We can look at pharmacy records. The medication possession ratio, MPR, that should be on the slide. Something that you can calculate by looking, you know, how many days the patient actually in theory even have medicine. If you gave a prescription for 30 days and the patient comes back after three months, he simply didn't have enough pills to be 100% adherent. I'm going to talk about therapeutic drug monitoring and digital medicine in a few slides. To structure the self-report a little bit, this is a scale, the brief adherence rating scale, the bars that was used in Katie. You can ask how many pills or capsules do you take each day over the past month? How many days did you not take the medicine? And over the past month, how many days did you take less than prescribed? These questions are just an attempt to kind of make an estimate based on the patient report. And you can look at the percentages here at the bottom. I find a question more helpful that is a little bit more concrete. How many pills did you forget the last five days? And the answer should be zero. Anytime there's a little bit of hesitation or one, then you need to probe a little bit more and find out why that is. Antipsychotic therapeutic drug monitoring, or TDM, has a long history in psychiatry. You're very familiar with lithium monitoring. Tricyclics used to be monitored more closely than the SSRIs. But in that regard, it's currently underutilized. I believe there's more interest again. If you're interested in some summary about it, I have a reference here from a German task force. It's in English, so you can look that up. It really reviews the evidence for therapeutic drug monitoring antipsychotics. I think it's actually pretty straightforward. Why might it be helpful? Because it allows you to have an informed decision regarding the root causes of treatment complications. And in the context of this talk here, if somebody has a poor response to antipsychotics, and that's a significant number, at least a quarter according to this review, you really need to find out if it's what I call pseudo-refractoriness because of non-adherence, or if the patient is, in fact, refracted to treatment. It will give you a little bit of an idea about the relapses that have been shown in the Katie sample. I think in the end, you're really mostly interested in extreme value. It's particularly zero or close to zero or surprisingly low antipsychotic blood level for a given dose. There might be genetic reasons for that and drug-drug interactions and all kinds of other reasons. But let's not forget that the most likely culprit here is, in fact, partial adherence. Now, not surprisingly, new technologies get applied in medicine, including for adherence monitoring, falls under digital medicine. We have now a host of new acronyms that we have to learn. How does, for example, a DMS, a digital medicine system, work? It's basically a pill. In it is embedded a sensor. A patient ingests that. It's called an ingestible event marker, the event the patient took the pill. There's a wearable sensor patch somewhere on the body that captures the stomach acid-activated signal from the IEM. Then the signal is sent to a mobile device app that perhaps then even connects to the cloud. And the patient, whoever else has granted access to this system, reviews data. The first system approved in the U.S. is a generic aripiprazole with an embedded event marker. Now, this is all good. The question at this point is a little bit, does it actually improve adherence in real patients? And with psychosis, both in the short and long term, we don't actually know this. A colleague of mine from cardiology, Lisa Rosenbaum, wrote a very nice article asking the question, how palatable is it for paranoid patients to swallow a spy? I think practically for me, the question is, will my average patient with serious mental illness actually be able to use this technology? And as always in medicine, patient selection is key. Which patient group might benefit the most? Maybe people with active substance use, with memory problems, people with no routines. I think there's going to be a role at some point for monitoring of court-ordered treatment if you want to really reduce catastrophic outcomes in selected patients, very selected cases. And I do think there is the possibility you will actually increase autonomy in community-treated patients who need some medication supervision. I don't want to be bright-eyed and bushy-tailed about this. I think there's real issues and risks with this technology too. Is a technological solution always progress? I think it's inevitable that we use it. Maybe there's even a generational divide about this. But I do think there are risks to medical privacy. There's a risk of increasing health disparities with the new technology. Misuse and lack of access, using it only in certain groups of patients. And only certain groups of patients actually have access who might benefit from it. And the biggest concern as a clinician is that technology could easily replace meaningful other interventions. If we work with the patient to help them come to terms with their illness, to maybe consider taking medicines, to try them, to develop a good drug attitude, seeing that the medicine might actually be part of the solution for them. If we want to increase health literacy, we actually need to understand patients. We might need to spend time with them. And I think we have to actively work with patients towards accepting evidence-based treatments like clozapine and long-acting injectables. It's not clear to me that this is necessarily the biggest benefit from these technologies. So we'll have to see how this shapes up. So let me summarize this last section. It's also one of the learning objectives, the risk factors for non-adherence. But in your mind now, I think you should group them into A, a poor drug attitude, and B, the barriers. So these are risk factors for efficacy, a high side effect burden, lack of insight. You know, I don't have a problem. And then the barriers like chaotic lives, cognitive difficulties, the cost of the medicine, drug use, and family and friends as being opposed to perhaps to taking medicines. So the last 10 slides here are going to talk about how you can enhance antipsychotic adherence. Because in the end, the assessment is good. And we kind of have some sense where patients are. But what are we going to do about it? Valegan and colleagues have now, almost a decade ago, have pointed something out that I think is not fully appreciated in its usefulness, a model that's a public health prevention model for adherence-enhancing interventions. So here we grouped interventions based on the risk for non-adherence. And the way this works is this universal intervention. All patients get it regardless of risk. And I think we do. Psych education about the medicine falls under this. Any system-based intervention that everybody gets without asking questions about the patient. Selected intervention, that is the type of intervention that you would choose for patients who are taking medicines, but are at high risk for non-adherence or partial adherence. So anything that you think about adding to make it more likely that patients take medicines like pillboxes and degrees of monitoring and supervision, this is this group. And then there's indicated intervention, which is for those patients currently non-adherent. Motivational interviewing, of course, I think one approach. Directly observed therapy. And digital medicine to some extent. So one way of just thinking about the various interventions that you have. At a more practical level, how do you kind of create a treatment plan for your patient? One approach does not fit all. I think that's something to just appreciate. Taking aside here the idea of universal interventions that all patients get, you really have to tailor the intervention to the problem that the patient actually has, to the reason for adherence problems. And you could group this into patient-centered strategies, environment-centered strategies, and treatment-centered strategies. Well, times have changed. This is a while ago now. I was working at the time in a state hospital. You see here is a bin for a smoke break. Most places now are smoke-free. This person has gotten a bad reputation for good reasons. And my point here is that times have changed. And I think the idea that the patient is more of a partner, there has to be a real effort to work on the alliance to align with the patient's goals and work on those things is really rightly prominent today. And I want to use the term shared decision-making. So we have moved from the age of paternalism to the age of shared decision-making. There's different ways of looking at this. This is a useful way, I believe, because it points out that not all decisions are equal. There are preference-sensitive decisions where the patient really should decide which way to go. There are best-choice decisions where this patient still decides, but you might disagree with whether this is the best way of doing it. So this is a little bit as a plan A that would be great, but the patient is only willing to implement plan B, which from a physician's side might not be ideal. And then there's life-or-death decisions where it might include court-ordered treatment where there's actually not a choice that we as a society decide. At this point, we need to decide for a patient. The critical point here is, and this is not a talk about shared decision-making, but I want to point this out, that we have to be extremely careful to not start to blend best-choice decisions and life-or-death decisions just because we think this is not the ideal decision does not make it a life-or-death decision. So we really, I believe, have to be sure to hold that line. Environmental interventions are those interventions that support motivated patients getting the treatment plan implemented correctly. The pillbox is such a tool. Anything where the patient doesn't really have to think about it, but it just happens automatically, like automatic refills. Some pharmacies deliver to patients. It's convenient. Some aspects of digital medicine that are noted in motivated patients, they might like this idea of tracking their adherence with an app. I think it works best for such patients who have a little bit of cognitive impairment and have a hard time with routines. In the extreme, of course, you would need more support. It does not work if non-adherence is intentional. And I often see this kind of overlooked that people work very hard in environmental interventions and somebody where basically the idea is that I don't want to take medicines. Another environmental intervention at a little higher level is supervision with all the various degrees of supervision, including directly observed therapy, a term that might sound familiar from tuberculosis care. And there's different people that you might involve, meaningfully family members, group home staff, visiting nurses. So the patient-centered interventions are those interventions that we tend to focus on as clinicians prescribe the medicines. We try to keep the regimen simple. We try to choose the most effective regimen. That might mean, for example, proposing clozapine for a refractory patient, because the patient rightly will say to all these other medicines, well, they don't really work. We work, I think, hard to address tolerability to the extent that we can. That can be hard. If somebody needs to be on clozapine, the sedation and weight gain that tends to come with it is a real struggle. And I've shown you, I think, in the health belief model and the risk-benefit judgments, it's not so obvious that the benefits outweigh the risks. And the risk to defend our patients a little bit includes premature death from medical causes, at least partially related to our treatments. And then long-acting injectables. I want to add this last slide here about this, an extra slide about long-acting injectables, because if you think about who should get something that they take once or twice, once a month, or even space it out even more, well, those people need maintenance treatment for something. Why struggle every day with taking pills, not forgetting, picking them up, if you have a preparation that could be taken less frequently? So I would argue that it makes no sense to not propose long-acting injectables for those patients who need maintenance treatment for a chronic disorder with a high cost of relapse, because it's highly effective. And this has been shown to be highly effective in first-episode patients who have a lot to lose in this critical phase of their illness from getting readmitted immediately after their first admission for a first episode of psychosis, but also for multi-episode patients, any multi-episode patient, but certainly particularly for those where there's a forensic history, coma with substance use, where it's really difficult to implement a treatment plan that's based on all medications. I am not brighter than a bushy-tailed naïve about long-acting injectables as a tool to solve all non-adherence. It does require, of course, a certain willingness on the part of the patient to really give it a try. I do believe, though, it has advantages. It does allow for an open discussion of adherence, including a drug attitude that might be biased towards, you know, I don't really want to take medicines. It clearly avoids family conflict, and I think that that is something that is greatly beneficial in young patients. You want parents to be parents and not, you know, not the nagging kind of our eyes and ears in the community police. So by taking over that part of treatment with a long-acting injectable, I think we actually open up family to do the things that they ought to be doing. It also avoids the risks of unrecognized partial adherence. I alluded to this earlier, but if you don't recognize that adherence is partial or poor, what you end up doing is you use higher doses of antipsychotics. You use more medicines. You add medicines to augment the partial response. And in the end, you have poor symptom control and relapse. So there's many reasons why long-acting injectables just conceptually make sense for a group of patients at risk for relapse. In the United States, long-acting injectables are, compared to other countries, underused. So I just ask you to actually check your own attitude towards it. And if you are against using long-acting injectables, you know, question yourself a little bit why that might be. So let me summarize what I spoke about in a slide that I put together a while ago now that groups patients as adherence prototypes. And it uses this idea of drug attitude and worldview as kind of organizing principles. You might disagree with the names that I picked for each of those prototypes, but let me just give you examples here. So you have the true believer that there's a type of patient with a good drug attitude, and he has this drug attitude for the right reasons. So the worldview with regards to medicines is biomedical. That patient basically says to you, yes, I have schizophrenia, which is a disorder that puts me at risk for psychotic relapse. And I'm taking this effective antipsychotic to prevent relapse down the road. The adherence threat for such patients is, of course, you know, lack of efficacy. You're assuming here this works for patients. And pill fatigue, you know, after many years of taking something to prevent something from happening, even the truest of believers will question, do I really need the medicine? We have the clinic trooper in the Eric Lindemann. I think there's a lot of patients like this with a good drug attitude that's in part driven, also having a really good relationship with the clinic, maybe even with me. Their worldview with regards to meds might be a little bit idiosyncratic. You know, some understanding of having a psychiatric illness, not really necessarily schizophrenia. The medicine sometimes is not really used in a preventive fashion, but more in an active way, like the proverbial, you know, taking the antipsychotic for insomnia. The threat here is really complacency. Nobody pays attention and then somebody tends to forget. And honest mistakes are made. So that such patients might, you know, be helped with a little bit of the environmental support. The reluctant recruit is the starting position for young patients. They're ambivalent about our drugs and psychiatry. The first episode patient's never taken a psychotropic. So as I said, that patient actually has to learn, you know, what it means to take medicine, how they work, what they work for, what they might not work for. You know, medicine doesn't give you a job. It just allows you to not be psychotic so you can then go to a job interview. And their worldview is often uninformed and ambivalent. They don't know. What they know is from the news. So there's a lot of things that you can do well in this group, psychoeducation, addressing poor efficacy from the patient's perspective, and clearly making sure that the patient develops a good drug attitude by avoiding side effects. And a dystonic reaction is something that if you ask patients who were treated, you know, decades ago, they all remember that. The coffee guy is a name I picked to honor a patient that I knew from the state hospital that I showed you early in my career. I got admitted several times while I was there. Usually police were involved. I got some medicines at night, and in the morning he was essentially better. Didn't really care about medicine or not. Maybe some lip service. Was really unable to verbalize, you know, what it is that got him there and what role the medicine or illness plays. And his chief complaint actually often was, I just came for coffee. Such a patient needs a certain degree of supervision for things to work out. And then we have the last very difficult group, the talk in and of itself, what I call the constitutional combatant. Those are people who have a fundamentally negative or hostile attitude towards psychotropics and antipsychotics. Their worldview with regards to meds and psychedelics is incompatible with our view, and it's really hard to have an alliance. Very little to work with sometimes. So I'm going to finish with one slide, and I'm going to hand it back to Tristan for some discussion. My favorite philosopher said, however beautiful the strategy, you should occasionally look at the results. That's Winston Churchill. And how does this relate to this talk? Well, you know, you might be prescribing and fiddling with the medicine and adding medicines. So your beautiful strategy, you know, advanced psychopharmacology, please do consider that you might actually overestimate the patient's adherence. And hopefully in this talk I gave you some very concrete, helpful ways of assessing adherence, looking at the barriers, and then thinking about interventions based on the ABCs, the drug attitude, the barriers, and the compliance behavior, the ABCs of adherence. So thank you for listening in. Thank you.

Dr. Oliver Freudenreich

adherence to antipsychotic medications

patients with schizophrenia

medication adherence

drug attitude

barriers to adherence

compliance behavior

interventions to enhance adherence

individualizing treatment plans