Hello everyone. To our session for today, we're going to get started in just a few. Let's give everyone the opportunity to get in and get settled. Feel free to use the chat box as an interactive space. Let us know where you are logging in from. Just say hello. All right, we have a lot to cover, and I want to make sure that everyone gets their questions answered. So. I'm going to get us started so good afternoon everyone and welcome to today's webinar titled co-occurring opioid and stimulant use disorders treatment and management approaches hosted by the providers, clinical support system in partnership with. The National Council for mental well, being Thank you so much for joining us today. Before we begin, I'd like to cover a few housekeeping items. Today's webinar is being recorded and all of our participants will be kept in listen only mode. The recording and slides will be made available on the PCS website within 2 weeks. And it will be an opportunity to ask questions at the end of the webinar. So we encourage you to submit your questions throughout the webinar in the Q and a box located at the bottom of your screen. So, this presenters are doctors, Craig Allen and Mark Fishman. Dr. Allen is medical director of rush for center and. Vice president of addiction services at heart for healthcare behavioral health network. And Dr. Fishman is a medical director at the Maryland treatment center. Just wanted to go over these. Quick disclosures, Dr. Allen has the following. And Dr. the overarching goal of is to train. Healthcare professionals and evidence based practices for the prevention of. Prevention and treatment of opioid use disorder, particularly. And prescribing medication as well as the prevention and treatment of substance use. This board. At this time, I'd like to turn it over to Dr. Allen who will review the educational objectives and begin the presentation. Thank you so, at the end of this presentation today, like, you to be able to describe. The broad context of co-occurring opioid and stimulant use and related overdose risk in the United States. Review the evidence base strategies for treating opioid use disorders. Promising practices for treating stimulant use disorders. Identify evidence based and promising strategies for treating co-occurring opioid. And stimulant use disorders and review psychiatric comorbidities associated with opioid and stimulant use disorders. Next slide. So, will I will start and talk about the scope of the problem then. Dr. Fishman will talk about the medications and psychiatric comorbidity. There'll be a patient interview and then we will go over some summary recommendations. And there'll be time for Q&A. There's also a couple of cases that we have. That we can present at the end, depending on the time. Next slide. So, this is the scope of the problem. What this cartoon shows is the number of opioid overdose deaths from the year 2000 on. Actually, this is all overdose deaths, but primarily they're opioid overdose deaths. And the dark red section shows when fentanyl, the synthetic opioid fentanyl, a very, very potent, 50 times more potent than fentanyl. 100 times more potent than heroin, comes on the scene. That's the maroon section. And you can see that to date, the primary cause of all overdose deaths is fentanyl poisoning. And certainly, a primary cause of opioid overdose deaths is fentanyl. In the state where I'm from, which is Connecticut, close to 90% of the overdose deaths are related to fentanyl. Next slide. So, this is not fentanyl that you get at the pharmacy or that is used in hospitals. This is illicitly manufactured fentanyl. The chemicals, many of the chemicals come over on the right-hand side as the chemicals coming over from China to South America, to Mexico, where they are manufactured into fentanyl. And the fentanyl comes across the border. As I mentioned, fentanyl has squeezed out other opioids. So, fentanyl squeezed out heroin back in 2015, around thereabouts. There were three waves of opioid overdose deaths, beginning in the 2000s with prescription opioids. That was followed by heroin, which was less expensive and more potent. And then that was followed by what's occurring now, fentanyl and other related synthetic opioids. They're much more potent. It takes a very, very small amount. People often talk about an amount that might fit on the end of the tip of a pencil that can lead to a fatal overdose. The added problems with fentanyl are that it is sometimes taken unknowingly. It can be manufactured into pills that look with illicit pill presses. These pills look like prescription medications. So, of pills that are illicitly made, these fake pills that are out on the street, six in 10 have a lethal dose of fentanyl. The number of pills that were seized from year to year are the red bar graphs in the middle. And they rise up to 2021 when there's 9.7 million. In 2022, double that amount of pills were confiscated. Again, I'll note some Connecticut data, which can generalize to the rest of the country. But Connecticut is one of the states that has a higher rate of these illicitly manufactured pills. Ranks 12th nationally. It's the oxycontin, the blue oxycontin 30s. There's a picture of those up in the upper left. The white two milligrams antibars. These are the most often illicit fake pills. And then down at the bottom, I have the 30 milligram Adderall immediate release. Methamphetamine is usually found in those fake pills. Next slide, please. So, not only is fentanyl getting into these fake pills, but fentanyl has gotten into the rest of the drug supply. And these pictures over on the left are different forms of methamphetamine. So, we have crystal there in the middle. Rock down on the bottom. Rock can be ingested orally. Crystals often smoked. And then the powder can be injected or insufflated, snorted. The powder there also can signify cocaine. And in my state, 15% of the cocaine or crack supply is contaminated with illicitly manufactured fentanyl. And a tragic case last January, actually January 2022, occurred when a 13-year-old took what he thought was cocaine into school and shared it with a couple of his friends. And they were poisoned. And the one 13-year-old ended up dying. And the other two were in the hospital because of this poisoning. One of the surprise, caught the school system and even the EMS by surprise. They weren't looking for a 13-year-old to be overdosing on fentanyl. And in those cases, the school did, in that case, the school did not have naloxone or training on identifying signs and symptoms of opioid overdose. They do now, but they did not then. And even EMS may not have been aggressively looking for an opioid overdose at that time. Next slide, please. So, this is the prevalence of all substance use disorders. This is from the year 2019. And you see predominantly alcohol use disorder in the United States, followed by a category that has all illicit drugs. That includes different types of opioids. Heroin is listed on the bottom. It's actually a fairly small number, small amount. And then marijuana use disorder. Methamphetamine and cocaine, approximately a million people with those disorders. And then stimulant use disorder, which would be other stimulants at 500,000, to give you an idea of how prevalent this is. Next slide, please. So, this is looking at the, on the left-hand side, the methamphetamine use year-to-year in the United States. The red line is total use. And then the blue and the gray breaks it down into different age groups. So, you can see the methamphetamine use, although the level across the country is small, there has been a slight increase over the years. It starts in 2015 through 2019, a slight increase in methamphetamine use. On the right-hand side is cocaine use. And with cocaine, there's been a very slight decrease in the percentage of people using cocaine across the country. Again, the red line is the total number of people using across the country. And those other groups, you know, the blue group in both of these slides is the 18- to 25-year-old group, the most frequent users of both methamphetamine and cocaine. Next slide, please. So, hopefully you can see this slide, but I think you have access to these slides as well. This is showing the number of deaths attributable to methamphetamine on the left, cocaine on the right, and then the combination of methamphetamine and opioids and the combination of cocaine and opioids. So, looking at the left-hand side, the bluish line, the lighter colored line, are methamphetamine deaths alone, no opioids. The green line has to do with deaths that also involve opioids. So, you can see that the number of methamphetamine deaths from methamphetamine alone has been going up. Year to year. There's a much sharper rise in methamphetamine when there is also an opioid present, a much sharper rise in deaths. On the right-hand side, cocaine, the deaths from cocaine alone have not risen or have not risen very much. But you can see in that greenish line a very rapid rise in deaths from cocaine when opioids are present. Next slide. So, opioid and stimulant use together is common and increasing. The past month use of methamphetamine during this time period listed 2011 to 2016, methamphetamine use with opioids, or actually it's the use of methamphetamines in people in treatment for opioid use disorder, doubled during that period of time. So, it's not uncommon. And, you know, I think back to my formative years, having just graduated from high school, and one of the first, well, certainly a tragic death of John Belushi, who was using heroin and cocaine, called a speedball, using them together. But this has been done through the years, and there's a number of different reasons why people say that they do this. One is that opioids take the edge off of stimulants and help you to come down off the stimulants. And another approach is the thought that stimulants improve function and energy or wakefulness when someone's using opioids. And then this other idea, which isn't true and is dangerous, is that stimulants can be somehow protective against an opioid overdose. Of course, they cannot. The opioid overdose often occurs because of the binding of the immune receptors in the brainstem, and a stimulant would have nothing, no impact on that whatsoever. And I mentioned the unintentional deaths from fentanyl. I think at this, oh yes, one more slide here. Ah, we are actually going to switch over to Dr. Fishman at this point. Thank you, Dr. Allen, for that chilling view of the scope of the problem. I'm going to add one more scope of the problem slide, which is that in addition to various rationales and subjective reinforcement, and that people who use either of these substances are often polysubstance users and may have a higher risk of developing a drug-induced use them co-occurringly, some experts have conceived of a biological hypothesis where the whole is even greater synergistically, if you will, than the sum of the parts in which this kind of biological interplay between the two categories of substances are naturally and mutually reciprocally reinforcing. So the idea that with chronic opioid exposure, you have dopamine hyperactivity and receptor supersensitivity, but also with intercurrent withdrawal, which is a standard feature of opioid addiction, you're also in a persistent and chronic state of exaggerated dopamine deficit. And so people who are dopamine hungry and dopamine deficient may be even exaggeratedly reinforced by the dopamine production effect, the dopamine spike effect of stimulants. And then reciprocally, stimulants are thought to worsen opioid withdrawal, increasing the opioid negative reinforcement. And so it's a mutually exacerbating mess. This may or may not turn out to be accurate, but it's compelling, I think, and deserves further view. All right, so let's shift from scope of the problem to what kinds of solutions we might have in our treatment armamentarium. And I'll focus for a bit on medications. Obviously, there is enormous need. We've heard about how big a problem it is, but unfortunately, we don't have any stimulant specific home runs the way we do like for MOUD, where we have a nice portfolio of FDA approved medications. It's not for lack of trying either. People have been trying for decades. And anything you can name, I'm sure it's been studied six ways from Sunday. And most of the time, we've come up short. But having said that, there are some, especially more recently, medications that, although not FDA approved, are promising, some even quite promising. And although not on label, they are well worth trying off label. Now, before I talk about cocaine and methamphetamine stimulant specific medications, I want to start with a big impact for this co-occurring problem of opioids and stimulants to make a plug for the use of plain old vanilla MOUD. And I bring that up, and this will be obvious to most of you guys who are experienced experts, but it can't be emphasized enough that people have tended to shy away from MOUD in circumstances of co-occurring other non-opioid comorbid substances like stimulants, like cocaine, like methamphetamine. And people say, listen, if they're using other medicines, MOUD might not be effective. If they're using, not other medicines, other drugs. If they're using other drugs, they may not adhere appropriately to their MOUD. And worst of all, if they're using other drugs, MOUD might not be safe. That is, if we add cocaine, methamphetamine to methadone, naltrexone, or buprenorphine, if we add alcohol, if we add benzos, that we might end up doing more harm than good. Well, it turns out that's not the case. And there's lots of evidence of that. But here's just one compelling study, a multi-state claims data set, looking at a year's worth of experience, looking at a subset of people who had co-occurring other substance use in addition to opioid use compared to those who had only opioid use. And the first thing they found was that there really was a substantially less use of MOUD in that comorbid population by quite a significant amount, as you see here, 30% only as compared to 47% for those that are opioid-only users. Of course, that it's only 47% for the pure opioid users is itself an indicator of how much room we have to improve the penetration of these life saving treatments, but much worse for those with comorbid stimulant use. And the other finding was that for those with the comorbid stimulant use, there was no increase of OD or poisonings. Now, that's a crude measure. We certainly are interested in more refined, more granular outcomes like lack of substance use, like lack of impairment, increased functional outcomes. But still, deaths are pretty good. Overdose is a pretty good outcome. And there was no decrement in safety or effectiveness. So the message here is for comorbid OUD and stimulants, start with MOUD. Those are very well established, very effective, very safe treatments. We should not shy away from them because people are also using other things. All right, so what about stimulant-specific medicines? Thinking about methamphetamine versus cocaine, many studies, you know the way research gets done in a kind of a narrow siloed way. So lots of these studies were either done for methamphetamine but not for both. But although the two substances are different in some aspects of their biology, I think they are more similar than different. Both are very high-potency stimulants. They have somewhat different profiles but very overlapping profiles. Those of you from different areas of the country will recognize that there are lots of regional and cultural differences, more cocaine use in the mid-Atlantic and Northeast, more methamphetamine in the West and the South and the Southwest. But there's a mix everywhere. And so whereas the research that's been done has been done with both substances, more of it has been done for cocaine over the years than for methamphetamine. But overall, I think a take-home message should be that medicines that are promising for one are very likely to be promising for the other. And at least at the crude level of beginning and emerging knowledge that we have now, I think it is safe to say that if trying the medicines that have been studied for cocaine on methamphetamine and worth trying the medicines that have been studied for methamphetamine on cocaine. So what are the medicines that have been studied? And here's a partial list. I use this kind of as the greatest hits. The best evidence probably is for an agonist substitution strategy. And that won't be surprising to you guys. It's a strategy that's been used in lots of addiction pharmacotherapy, most centrally in our use of methadone and buprenorphine for opioids. It's been used and tried in other substances too. But it's been proven to be relatively effective for both cocaine and methamphetamine. So that's been using prescription stimulants, the ones that are used on label for ADHD, are lower potency than either methamphetamine or cocaine, but are acceptable, safe, and partially efficacious. I won't say they're home runs the way our MOUDs are home dose effect sizes. But nevertheless, a fair bit of evidence across the board that they are helpful. Could that be mixed amphetamine salts? That's the one probably that's been studied the most. Also dextroamphetamine, also modafinil. But it could be any of the prescription stimulants. In general, we tend to use long acting agonist substitutes rather than short acting agonist substitutes. But you guys know the drill. Another medicine that's been studied primarily for cocaine, but again, you've heard me say that there should be cross efficaciousness for methamphetamine is topiramate. And the combination of topiramate plus prescription stimulants has been studied. And probably, for cocaine at least, in my mind, is probably the best. There are limitations logistically, which we can talk about, how people are comfortable. It's harder to do two medicines if people won't even adhere to one prescription stimulants people sometimes feel reluctant about, given diversion and the like. But when you have a patient who will adhere and can be cooperative, this has been shown to be effective in a multi-site study that I think is well worth noting. Naltrexone has had mixed results. But the combination of bupropion plus naltrexone has shown efficacy studied for methamphetamine, big splash came out about a year and a half ago in the New England Journal of Medicine, not too shabby. And that showed a very impressive result. Again, not the effect size that you'd like to see, not the effect size that we get for MOUD, but still far better than not using anything. Disulfiram has had mixed results for cocaine. Mirtazapine has had some mixed results for stimulants. And interestingly, buprenorphine has had some cocaine demonstration of efficacy. And surprisingly, the combination of buprenorphine plus naltrexone. Wait a minute, that sounds a little odd. How do you do that? Well, you can't start people on buprenorphine and then add naltrexone. Obviously, you'll get precipitated withdrawal. But if you start with naltrexone and add buprenorphine, you can do it safely in that order. And that's had some suggested benefit in one multisite study and is now going into the field with a bigger, broader multisite study that uses the injectable extended release versions of both of those medications. So stay tuned. Now, the idea of perception stimulants makes some people worried. There's lots of history about the misuse, the diversion of prescription stimulants. For sure, some of our patients are vulnerable to excessive use. Certainly, there are people who have primary addiction to prescription stimulants. So we're worried about it. We're also somewhat concerned about profiles. They can worry mood, especially trouble person mood, especially for people who have pre-existing affective disorders. They can cause insomnia. They can cause anxiety. They can cause autonomic instability. But those are things that can be monitored. Those are things that are manageable. And so, for example, my approach is if you're going to start this with a person, you don't give them a month's supply and six refills. You give them a week's supply. You see if they'll come back. You see what their urgency, how they manage it. And you can do it. It does take medical staffing. It does take a shift in attitude. It might not be for everybody, especially people who have a known history of diverting prescription stimulants. Maybe OTP-style direct administration is a potential strategy for consideration. But I would recommend that this is certainly something worth pursuing and getting some experience with and can be very effective. And then you can add topiramate. Or I often start with topiramate and then add prescription stimulants. But either way, as I mentioned, that combination seems to have some very substantial effectiveness. The idea of extended-release naltrexone for stimulant disorder, remember I mentioned the combination extended-release naltrexone plus bupropion in a study for methamphetamine. There may be limitations in the real world about what insurance coverage will there be. Because places where extended-release naltrexone, which is expensive, is approved. It's typically for an MOUD indication. Will they approve it for off-label use when it's not FDA approved? Who knows. In this particular study, they did Q3 week dosing. Is that going to be approved? Again, the issue of the intensity of medical staff is subjectable. But again, to the extent that you get some experience trying these things, that's the key. The key is to know that there is a tool chest. And we should not feel disempowered. We should feel empowered to try stuff, to be aggressive, to give patients the option of tools and to see what might help them. There are also psychosocial treatments. One particular brand of cognitive behavioral therapy is called the matrix model. It's quite intensive. It's an IOP-based model. To the extent that people will adhere, it has lots of multi-component modalities and structure and has demonstrated efficacy for methamphetamine. Contingency management, which as you guys well know, probably our highest effect size psychosocial treatment in our entire counseling repertoire. Of course, it hasn't been moved with big uptake from research to the real world for all sorts of reasons. One of them being logistical and economic, who's going to pay for it? Another being regulatory suspiciousness, CMS still kind of is coloring it as perhaps a flavor of fraudulent behavior. So hopefully we'll have some progress on that. But the idea of using contingency management, that is motivational incentives, targeting urines for either methamphetamine or cocaine is a reasonable high effect size treatment, both in the context of stimulant use alone, but also well-studied in the use of, in the treatment of comorbid OUD plus stimulant use. For example, adding contingency management to methadone treatment for OUD or adding contingency management to buprenorphine treatment to OUD. So if you can figure out a way to do that implementation, not trivial, but if you can do that, this is a robust treatment. All right, let's shift from medicines direct treatment to the idea of psychiatric comorbidity, because that's a different flavor and a very important flavor of treatment for these conditions. I want to start with depression in OUD. And this is a very common presentation. When people are in crisis, they often report very high rates of depressive symptoms. But then what happens? Part of the question of chicken and egg, do you treat an independent psychiatric disorder? Do you wait for resolution? This is a secondary analysis we did of the X-BOT study, looking at Hamilton depression scores across time over six months of treatment, either with naltrexone or sublingual buprenorphine, those two methods not separated here. And the key is that for most patients, this is a growth mixture modeling analysis in which you look at predominant trends. This solution showed three particular clusters representative of the whole population and the 85% bottom dashed line. Most people, when you treat them with OUD, their depression resolves, but not all people. And there's in particular, this 5% dashed red line and a middle 10% blue line of people who don't do as well despite MOUD have persistent depression and one of the punchlines is those people are much more likely to drop out of MOUD treatment and relapse. So that comorbidity or minority, it's hard to predict at the outset. So we're still stuck with the puzzle of how do you make a decision about who 15% in OUD treatment who need additional support, additional treatment for comorbid depression. With stimulants, we see similarly high rates of depressive symptoms, high rates of ADHD, high rates of psychosis, anxiety, insomnia, bipolar disorder. And part of the question is what about acute agitation? Those of you who have seen these patients present in the ED or on the streets or in specialty substance use disorder treatment recognize that agitation can be a major part of presentation. So treatment is symptomatic. Some people favor benzos, some people favor antipsychotics. When people are autonomically hyperactive, beta blockers and sometimes antiarrhythmic agents and antihypertensives can all be very helpful but you gotta get safety, right? When people are acutely agitated and violent and possibly psychotic or delirious, obviously stabilization is a primary goal. As I said, a part of the question is how do you decide? Are you going to wait for the possibility of spontaneous resolution of symptoms if a person cuts down, if a person gets abstinent? If you do that, you will have better diagnostic precision. Say you wait two weeks, wait three weeks, wait four weeks hoping for reduction in use or abstinence. You will have less possibility of unnecessary treatment. You will have not given them antipsychotics or antidepressants that they might not have needed otherwise and could cause side effects but you will have lost an opportunity for early and effective treatment and they might not come back. On the other hand, you could move ahead with a presumptive diagnosis, not waiting for precision and you would in the end have less specificity but you'd have more sensitivity. Although you'd be risking overaggressive treatment, you'd have a better opportunity for earlier and more effective treatment and capturing people who otherwise might have disappeared and not had the advantage of getting their treatment at all. Is there a right answer? No. Is there a biomarker or a gold standard? No. So everybody's got to develop their own set of kind of practice approach, balancing sensitivity with specificity and deciding what are the kinds of indicators that will help you make this decision like previous treatment experience, family history, past response to treatments, severity of symptoms and all of those things. Psychosis is very common in stimulant use disorder both in acute intoxication where 50% of stimulant users develop psychotic symptoms but also with a significant subgroup, the minority but a substantial minority having persistent psychosis perhaps 15% of people after 30 days having residual psychotic symptoms, sometimes indistinguishable from an indefinite syndrome of a schizophrenia like illness. There's probably some underlying genetic vulnerability. Schizophrenia incidence is five times greater in those that present with meth induced psychosis. So there's probably some vulnerability. We of course don't know how to measure that in any meaningful bedside clinical way but I think that in general, the idea is that we should be aggressive about the treatment of comorbid psychiatric problems, whether it's ADHD, whether it's insomnia, whether it's psychosis and that helps patient engagement. If you can reduce their suffering by addressing in an effective way, their psychiatric symptoms, the likelihood that they'll keep coming back for your psychosocial or your pharmacotherapeutic treatment is greater. I tell you one trick of the trade is focusing on insomnia as a symptom not because you necessarily know that they have a persistent psychiatric syndrome even if it's just for symptomatic relief. One of the things, unlike many of our psychiatric medicines which take a long time to work and are painfully slow with needed titration, you can generally get insomnia quickly. And so you've engaged a person, you've helped them with their distress and encourage them to keep coming back. Whether you're using a simple over-the-counter like diphenhydramine, whether you're using trazodone or quetiapine, which also may help with a psychotic syndrome if it's there, whether you're using mirtazapine which also might have a anti-stimulant primary pharmacotherapeutic effect, but whatever you're using address insomnia which is a common feature of both OUD and stimulant use disorder. So summary of these medicines and of our approach to psychiatric comorbidity. Although none of these medicines themselves are home runs and none of them FDA approved, I think to use a kind of a tired baseball metaphor, you got some solid doubles, especially in the absence of anything better, right? We ought to be trying something. And I would not say, oh, our research, yes, of course we need more research, but I wouldn't put off the decision to try stuff. I think they are ready for prime time. I think if you can figure out a way of testing these hypotheses and these treatment tools with individual patients, I think that's very worthwhile doing. Does the effect for one stimulant that is methamphetamine generalized to cocaine the other? I think in broad brushstrokes, yes. Real world conditions still need to be worked out. You've got to find out how it goes in your own practice setting. And as I said, psychiatric comorbidity can't emphasize enough how that should be applied. And now we've got a patient interview that we want to show you. This is Jonathan Steinan, Education Coordinator for Recovery Leadership Academy at Hartford HealthCare. I've been talking with Jonathan today about his struggles with addiction to opioids and stimulants. By 2015, Jonathan, you had eight years of recovery. You'd built up a successful business as a contractor. You were married. You had two kids. You owned your own house. What happened then? So there were kind of a lot of contributing factors. I had been through some rather significant periods of depression over that eight years and kind of white knuckled it, relying on supports of AA and similar, you know, peer support programs in the community and hadn't really re-engaged with therapy or anything else like that, was not taking any kind of medication. The stress of having a newborn at home, running a business and trying to make sure that I was providing for the guys that were working for me, you know, keeping the work moving so that they could get a paycheck was really important. And really what ended up happening is the stress built up. I found myself in another period of significant depression. Didn't make any effort to reach out to address that. One day out of the blue, you know, I live close to some areas where drugs are commonly found and a gentleman that was asking me for work all the time, I had employed him to come mow my lawn because I was busy and had estimates to do and, you know, I knew that he was somebody who was using himself and almost without thought, I asked him if he could get any substances and he did. He purchased something for me off the street and I was off and running. So tell me about the substances you were using and how you used them and how they affected you. I started off actually a little bit before that, where I was drinking periodically and I had been totally absent in the previous eight years and, you know, I found that I didn't really enjoy the alcohol too much but kind of wanted to be, you know, a little bit more high, quite literally. And so initially it started off with this one incident where this gentleman, you know, procured the substance for me. I tried sniffing heroin, didn't get the high that I wanted to and that same day I was back to IV drug using. From there, it quickly escalated, you know, the opioids would bring me down. I had a business to run, I really needed the energy and I quickly ended up turning to cocaine. I was using cocaine, IV and smoking that as well. Within a short period of time, it was pretty much anything I could get my hands on but the stimulants to bring me up, get the work done during the day and the opioids to kind of bring me back down and level me out at night. So during your struggles, you had interactions with the medical field. Can you tell us about some of those experiences? Yeah, absolutely. What ended up happening because I was using such a large amount of cocaine on a daily basis is that I ended up developing something of a psychosis and I was pretty well convinced that I had a parasitic infection of sorts and I presented to several different emergency departments throughout the state, at least three of the larger hospitals. And on every instance, when I went in, you know, at this point, I was noticeably kind of getting worn down by the drug use. I had visible track marks on my arms and my neck, some significant weight loss, you know, and certainly not taking care of myself. And on all of those encounters, with no exception, you know, they ruled out the possibility of any parasitic infection and kind of left it at that. There was never any issue brought up about the substance use, even though to pretty much everybody on the outside, it was visibly apparent. So you ended up actually getting some treatment, getting some help. You used a number of different medications at first. Can you tell us about the medications you used and how those treatment episodes went? Absolutely. Starting to come back into recovery and trying to gain a little bit of traction and get treatment. Early on, I used Vivitrol, which was very successful in reducing cravings and kind of keeping me focused. Unfortunately, I experienced some side effects from that that made it really uncomfortable and not productive for me to use and try to maintain the business and run the business that I still had at that time. So because of that, I ended up discontinuing the use of that, and I ended up experiencing another relapse afterwards. And coming back into treatment, in the course of a 28-day program, inpatient treatment, I started Suboxone, and I stayed on Suboxone for a period of time, which was really fantastic and effective for me. That was coupled with antidepressants at the time. At this stage, I'm no longer taking the antidepressants, but I've also been engaged in therapy, and I have a lot of other recovery practices that I implement in my life on a regular basis. Thank you so much for your time today. Really appreciate it. Absolutely. Thanks for having me. So we were, here we go. This is our, these are the stimuli use disorder medications. I think that Mark just covered these. You know, we can move on to the next slide. There's another summary slide, but we also have a case presentation. Mark, I want to ask you, do you have any comments on Jonathan's story before we move into the case here? Well, I think it's a very nice example of a person who struggles. We reminds us, no surprise to people here today, that recovery is often, in fact, most often, not a unilinear monodirectional nirvana, right? I mean, people come in and out, people lapse and relapse and remit and- Process, not perfection. And process and progress, not perfection. And he's an example of somebody who didn't give up and an example of somebody for whom treatment providers did. And the idea of leading with MOUD and continuing with other treatment responses, including attendance to his comorbid depression, psychotic-like. Interesting clinical vignette of his psychotic state. Sometimes we talk about this as delusional parasitosis. Those of you who have not seen it directly in patients, it's amazingly vivid and disabling. Some call it the methamphetamine bugs or the cocaine bugs. And for those of you who haven't seen it, people are delusional about being infested with bugs or parasites. It's often cutaneous, thought to be because of activation of the sympathetic nervous system around hair follicles. And people have a sensation of activity and motion and itching and discomfort. And they mistake, they will pull pieces of skin and say, here, doc, don't you see? It's right there. And I've seen patients who remove a full thickness skin layer from their scalps. Anyway, we needn't go on, but it can be quite disabling. And he gave an example of that. But at the end, I take it as a very encouraging of we'll get better. Yeah, yeah. That's great. I think those are really illustrating a number of the things that we were talking about and that you were presenting. We can take some questions or we can go into this case. Let's see. Why don't we do that? Why don't we let people ask some questions, have some discussion if, I think there's, we see in the Q and A, plenty of room for that. Here's a methodological question. How is a methamphetamine death defined? Most of these overdose death studies define it by presence of a substance in the system at autopsy. So rather than complicated post-mortem analyses of which was the predominant substance, it's what's in your system. Craig, you pointed out a dangerous misperception on the street that maybe stimulants are protective for overdose death. Quite the opposite. They synergistically make opioids much more dangerous and the likelihood of having a overdose with the addition of opioids plus methamphetamine or opioids plus cocaine, or as you also know, opioids plus alcohol or opioids plus cocaine, makes the likelihood of death much worse. Here's a TMS for stimulant use. It's being explored. I think it's a promising idea. I wouldn't say that we are quite yet ready for prime time, but very exciting. Yeah. You know, Von Steele is one of the researchers who did a study on opioid use. He's one of the researchers here at Harvard HealthCare and the Institute of Living. And he came from John Hopkins where he was doing some, actually, he was doing some research out there at the NIH, TMS with cocaine. And he's looking at it with OUD, opioid use disorder now. But promising results, as you say. Yeah. Here's a question about comorbid ADHD. Yes, I think that's exactly right. And also, I'll comment later, I saw about comorbid PTSD. Both of those are very prevalent in our escalation in comorbid stimulant and opioid use populations. Earlier conjecture that maybe people with ADHD were stimulant preferring has been mixed and hard to hold up. I'm not sure I would jump to that conclusion, but there are certainly plenty of people with stimulants who have ADHD. And it might be that prescription stimulants are a twofer in that case, both treating a comorbid psychiatric disorder having primary anti-addiction effect for the stimulant. So that's a possibility. Bupropion also is good, both potentially good for stimulants and potentially good for ADHD. So I think that's quite reasonable. Addressing PTSD, as in- Let me comment on the ADHD first, Mark. I just wanna, as a child and adolescent psychiatrist, want to point out that the data, the data that I look at supports treatment of ADHD and that actually treating as a child, as an adolescent, probably decreases your risk of developing a substance use disorder and probably for multiple reasons. So that's one comment. The other one is, as a child and adolescent psychiatrist, to see a lot of young adults who are going to college, the question of ADHD that develops when a kid's a freshman in college and out from under their parents' oversight has to be looked at, I think, rigorously, because there's a lot of things that can cause inattention and poor academic performance in a young adult, particularly in the college environment. And you really wanna see evidence of ADHD prior to getting to their freshman year at the local university. For sure, for sure, because certainly other substance use and substance use disorders can be a primary cause of symptoms of inattention, distractibility, and academic decline. Absolutely. So just because a person says they have Adderall deficiency doesn't necessarily make the diagnosis. That's right, that's right. And here's about the use of stimulants to treat stimulus use disorder and their risks. We mentioned that. Gotta go slow. You've gotta be careful. And yes, stimulants are benign. They have both the side effect of overuse, misuse, loss of control, and a side effect profile. So short durations, monitoring for effect, and you can always stop if you think it's going awry. The patients won't be happy necessarily that you stopped. That's part two. We negotiate all the time about what's an appropriate treatment. This isn't just McDonald's. I think I've had this conversation, well, every single day. Every single day. You were gonna talk about post-traumatic stress disorder. There you go. Here's a question about anacetylcysteine. That's a very interesting question. For those of you who, anacetylcysteine is a medicine that we've used a variety of applications in medical treatment. It's acetaminophen overdose antidote. It's a treatment for secretions in cystitis, but it's also been used as a anti-addiction medicine, perhaps made the biggest splash in treating cannabis use disorder in youth, maybe not so effective in adults, maybe a strange developmental impact there, but it's also been looked at for alcohol. It's also been looked at for stimulants with mixed results. And some people have found efficacy. Other peoples have not. Myre, and there was most recently in 2021, a fairly well-executed study out of Australia that showed no results for methamphetamine use disorder. So I don't say it's not worth trying, but I don't think it has the evidence base that some of these other treatments have, but listen, you got stuff and more shall be revealed. Very few side effects with anacetylcysteine. And very few side effects, except the patient's complaining about dirty socks. That's a nuisance side effect, not dangerous. Is it better to treat stimulant with medications first or treat OUD with medications first? If people- You answered that one already. What's that? You answered that earlier. Well, let's say, let's talk about it again, because I think in part it depends on the patient. So there might be patients who have a more severe presentation of one versus the other or more preoccupying concern and impairment from one than the other, or be more motivated to take one set of medications than the other, and that can steer you. But in general, I would say MOUD, both because of its very high effect size, because you can get quick bang for your buck, doesn't work all the time, but when it works, it's impressive. And the risk of opioid overdose is so catastrophic that that is probably our primary target for initial intervention. And then we work with multiple other treatment goals from there. But you also make a very good point. And I was saying, well, of course it's MOUD, but you make a very good point. The most effective medication is the one that's indicated and the patient wants to take. That's right. Like all treatments, the best treatment is the treatment a patient will do. Right. Right. You may not know this, Craig. He asks, this participant asks, can you share what side effect that our interviewee had with Vivitrol? Do you know? Do you remember? He had shakes. He had tremors in his hands. And that's not one that I have heard of very often. I don't know if you have, Mark, but he's a finished carpenter. And at the time that was his livelihood. And so it was unacceptable. When he was talking about that, actually in the interview, as I saw it again today, I thought about, you know, he was on the medication, right? He was on the medication that works for opioid use disorder and there's evidence that show it could be effective for a stimulant use disorder, cocaine use disorder. And he was on the long acting form, perfect, but he developed a side effect. Yeah. And that addresses in part, this next question, how did Jonathan's use of buprenorphine and antidepressant address both OUD and stimulant use disorder? And it may not have been directly targeted at that. It may have been an MOUD forward approach, but as you say, there's mixed evidence of naltrexone effectiveness for both cocaine and methamphetamine. So that could have added benefit. Additionally, the antidepressant to stabilize a co-occurring psychiatric condition, as we talked about, can also promote engagement, promote stability and promote a synergistic effectiveness of direct anti-addiction pharmacotherapies. But if you're asking, what about in a hypothetical patient like this interviewee, what about the addition of an additional anti-stimulant medication? That could have been an alternate approach and very reasonable to try. Yep. Didn't necessarily work in this case, but certainly reasonable. Yep. With all the medication tampering with fentanyl, I've never understood why people, drug dealers, take the time to lace all of these medications with fentanyl. I know they want people addicted to drugs, but why fentanyl? Well, I can't read the minds of the gangster marketers, but I can conjecture that because fentanyl is so reinforcing, because it is so potent, because you get such a bang right away, that the likelihood of recruiting customers is a reasonable idea if your goal is to distribute and sell more and more addictive drug. I will tell you that as chilling as it sounds, and all of you may have experienced this in your local communities, you'd think, well, if there are overdose deaths in the supply of a particular dealer, won't people avoid that dealer? Isn't that a bad business practice? And on the contrary, although, that means that that dealer has the really good stuff. And if you kill a few people, you attract business, as horrible as that sounds. I'm throwing an advertisement in here for naloxone. It's important to flood naloxone into your communities. There was a question or comment about fentanyl and really potent synthetic opioids. Naloxone still works. Yeah. Still works. You may have to do it twice. You may have to provide CPR, but it still works. So always naloxone. Use naloxone. Here's a question about methadone. Is it safe to continue increasing the methadone dose to higher doses to combat fentanyl use while still also using stimulants? Great question. The answer in short is yes. As most of you certainly know, now in this era of fentanyl, we presumably have been underdosing our MOUDs. Our MOUD dosing strategies come from the era of heroin. So this applies to methadone, buprenorphine, and naltrexone. We don't really have a lot of play with naltrexone dosing as much as we do with methadone or buprenorphine, but the accumulating that higher doses of methadone and higher doses of buprenorphine are appropriate. And there is no reason to suppose that that makes a stimulant use disorder worse or less safe. So press on with a primary MOUD strategy, titrating to effective dose. Awesome. Thank you. Thank you all so much. That's all the time we have now for questions. But I'd like to thank you, Drs. Allen and Fishman for presenting today. We're really appreciative of your willingness to share knowledge and expertise with everyone. As a reminder to everyone, the recording and slides will be posted on the PCSS website within two weeks from today. Okay. I wanted to speak to this mentoring program and program slides to make you aware of two resources offered through PCSS that may be of interest to you. First, the PCSS Mentor Program is designed to offer mentoring assistance to those in need of more one-on-one interactions with one of our colleagues to address clinical questions. You have the option of requesting a mentor from the Mentor Directory or PCSS can pair you with one. For more information, please visit the website, the PCSS website noted on this slide. Second, PCSS offers a discussion forum comprised of PCSS mentors and other experts in the field who help provide prompt responses to clinical case and questions. There is a mentor on call each month who is available to address any submitted questions through the discussion forum. You can create a new login account by clicking the image on this slide to access the registration page. This slide lists the consortium of lead partner organizations that are part of the PCSS project. And that is it. So finally, the PCSS website, contact info, and social media names are listed here if you'd like to find out more about the resources and trainings offered. Thank you all again for being part of this webinar today. Again, thank you to Dr. Allen and Dr. Fishman for such a comprehensive presentation and we hope you all have a great rest of your evening. Thank you. And I'm sorry we couldn't get to all of your thoughtful questions. Thanks for your engagement and discussion. And I hope that was helpful. So long, everyone. Thanks, bye.

co-occurring

opioid use disorders

stimulant use disorders

treatment

medications

dangers

overdose

psychosocial treatments

addiction

resources