Good afternoon, everyone, and welcome to today's webinar. The challenges of polysubstance use, treatment, and management of alcohol and opioid use disorder comorbidity, hosted by the provider's clinical support system in partnership with the National Council for Mental Wellbeing. Thank you so much for joining us. Before we get started, I'd like to cover a few housekeeping notes. Today's webinar is being recorded and all participants will be kept in listen-only mode. The recording and slides will be posted on the PCSS website within two weeks. There will be an opportunity to ask questions at the end of the webinar, so we encourage you to use the Q&A box located at the bottom of your screen to submit any questions you have. Today's presenter is Dr. Sarah Kawasaki, Director of Addiction Services at the Pennsylvania Psychiatric Institute and Assistant Professor of Psychiatry and Internal Medicine at Penn State Hershey Medical Center. Dr. Kawasaki is board certified in primary care and addiction medicine and has extensive clinical experience in both fields. She designed and currently directs an opioid treatment program at PPI, leads a Project ECHO teaching initiative for physicians and advanced practitioners on the treatment of opioid use disorder, and also serves as the principal investigator for the Appalachian Node in the Clinical Trials Network. Dr. Kawasaki has no disclosures. The overarching goal of PCSS is to train a diverse range of healthcare professionals in the safe and effective prescribing of opioid medications for the treatment of pain, as well as the treatment of substance use disorders, particularly opioid use disorders with medication assisted treatments. At this time, I'd like to turn it over to Dr. Kawasaki, who will review the educational objectives and begin the presentation. Thank you so much, and hello everyone. So today I'm going to talk about comorbid opioid and alcohol use, and hopefully at the end of the talk, you'll be able to understand the prevalence and health risks, identify various treatment implications, and examine the benefits of integrated care, as well as discuss strategies to support long-term recovery. Next slide. So I'm going to go over a case and then discuss the neurobiology of alcohol use disorder and opioid use disorder, the prevalence of the comorbidity of the two conditions, some medical considerations, evidence-based management for opioid use disorder and then alcohol use disorder, how opioid agonist therapy relates to alcohol use, and what to do in those situations, and follow up on the case, and finally, a summary. Next slide. So I'm going to start this out with a case. A 63-year-old man with chronic degenerative joint disease, chronic kidney disease, coronary artery disease, and a history of opioid use disorder on methadone treatment at a high dose of 180 milligrams daily admits to drinking 10 12-ounce beers daily. He cites pain as the primary reason for drinking. He doesn't have alcohol abstinence periods and denies a history of withdrawal seizures. For pain, he currently takes 200 milligrams three times a day of pregabalin, 60 milligrams daily of duloxetine, and 4 milligrams four times a day, oh, sorry, three times a day of tizanidine. His other medications include lisinopril HCTZ, 81 milligrams of aspirin, and metoprolol 25 milligrams daily. So how would we manage his alcohol use disorder in this circumstance? So dialing it back a little bit, next slide, I just wanted to talk about the different pathways, go over a little biology background of addiction, that there are three points of addiction, main points. There's the binge intoxication, which leads to the reinforcing neurotransmitters like dopamine. There's the withdrawal or negative affect. So the deep brain structures, the amygdala, the ventral striatum really create the emotional memories of not wanting to be in withdrawal. So there's an aversion to feeling sick. And then there's the preoccupation areas, the anterior cingulate that talks about the craving. So addiction is really focused on craving, the desire to continue the binge intoxication feelings and avoid withdrawal, next slide. So the alcohol receptor is the GABA receptor in the brain. And this is a chloride channel receptor, which means it's sort of shuts things down in the brain neuron, and that's why it is known as a depressant. There's several subunits to the GABA receptor and alcohol works on the alpha subunit. But benzodiazepines, barbiturates, neurosteroids also act on the GABA receptor, next slide. Opioids work a little differently. So opioids bind to the opioid receptor, which then inhibits the release of GABA. And GABA, as we learned on the slide before, is an inhibitory hormone. So when you inhibit the inhibitor, what happens is you get a release of dopamine in the adjacent neuron, next slide. So what happens in a functional MRI of the brain is when opioids are used on the left side, you see four areas of the brain lighting up, the anterior cingulate cortex, nucleus accumbens, the thalamus, and the periaqueductal gray. And these are the areas that release dopamine upon receiving opioids. And then on the right is a slide of the difference between a functional MRI of a normal brain and the functional MRI of somebody who drinks heavily. And you can see that there's less neural activity in the alcoholic brain, next slide. So how bad is the problem that we're talking about? Well, alcoholism, we can discuss it in a number of ways. And so I'll start by separating the two. And talking about alcoholism in particular, there are a lot of alcohol users in the United States, about 140 million. This is the National Survey on Drug Use and Health from 2021. And of the 140 odd million people who drink, about 61 million actually have occasional binge alcohol use, which is greater than five drinks in one sitting. And 17.7 million are heavy drinkers, which is greater than five out of 30 days, they will have greater than five drinks. This is the fourth leading cause of preventable death in the United States. And if you look at the graph on the right that looks at past month heavy alcohol use, you can see that the trends were actually trending downwards. And then something happened in 2020, can't for the life of me remember what, just kidding. And all of the lines start increasing, you can see the dots next to 2019 to 2020 start to creep up, next slide. So looking at it in a slightly different lens, for people with a past year of substance use disorder in 2020 from the same survey, there are about 40 million people in the United States that have substance use disorder that they identified in the past year. And so these are all sort of voluntary survey responses. And so about 28 million had alcohol use disorder and 18 million had other illicit drug use. And what we see as we go down, how many millions and hundreds of thousands of people are using other substances, including heroin, cocaine, methamphetamines, and pain relievers. Next slide. And so where do the two overlap? And so this is a study, this is the same survey from 2020 that said, okay, of all the people that are using alcohol and all the people that are using illicit substances, where's the overlap? And about six and a half million people are using both. Next slide. So what are the prevalence and patterns? Looking at it in another aspect. So the 2006 National Survey of Drug Use and Health found that of all drinkers, they were 70% more likely to have used opioids. And in 2014, greater than half of 4 million people using prescription opioids were binge drinkers. In 2017, among 2 million Americans with opioid use disorder, about a quarter had comorbid alcohol use disorder. So this is an extremely common phenomenon. In 2020, there were a couple, this article talked about how alcohol use is common in patients with chronic pain, that chronic pain patients with heavy drinking reported greater pain levels. And a Kaiser Permanente survey of 12,000 patients prescribed opioids found that a number of folks reported alcohol use, but almost a third reported concurrent sedatives like benzodiazepines, which the combination is really very dangerous and can cause respiratory depression. And 3% reported that all three were used. And then finally, in 2015, 30% of people on methadone treatment had problematic alcohol use. And these translated into a much higher healthcare cost than opioid use disorder alone. Next slide. So what are the dangers of this combination of drugs and alcohol? So in terms of mortality, there's an obvious increased risk of respiratory failure and death because we're talking about two central nervous system depressants. It's linked to opioid overdoses. Of the 130 people who die daily from opioid overdoses, a fifth involved alcohol. So that's not a small number. And an alcohol use disorder diagnosis predicts higher risk of opioid overdose accidents and injuries. So hugely problematic. In addition though, there's also morbidity. That it's associated with 20% of opioid-related hospitalizations in young adults. So that 20% number will come up over and over again. It's concurrent use, so alcohol and opioids together interfere with the treatment for chronic pain. There's a higher disease burden and higher rates of multiple medical comorbidities, not the least of which is hepatitis C, which we know is very high in the opioid-using population, drug-using population. And so if they're drinking on top of it, their risk for cirrhosis is much, much higher. And we should not discount chronic pain in all of this, benzodiazepine use in all of this to really sort of mess things up for these folks, as well as a higher psychiatric disorder comorbidity, including suicidality. Next slide. So what about methadone treatment and alcohol use? So now looking at people who are in methadone treatment for opioid use disorder, the study from 2000 looked at the number and causes of death at a methadone treatment program in Australia and found that of the drug-related deaths, that overall was 44% in the number of deaths that occurred. And alcohol use was the third most common reason after benzodiazepines and other opioids. So there was another study that was done in New York in 1985 that was longitudinal, and it looked at active and discharged methadone patients and found that excessive alcohol use was the cause of death 35% of the time for active participants. Also methadone initiation is a time of increased risk of mortality because it builds up in the system during induction, especially with concurrent alcohol use. So it's important to watch during that. Next slide. And so why the urgency to talk about it now? I think everybody has seen a version of this slide, but, you know, over the past year, we saw a 30% increase in overdose deaths, so it's really important that we screen for every substance use disorder that we can so that we can treat it appropriately and avoid these kinds of dramatic increases. Next slide. So next, I'm going to talk about the evidence-based treatments for both opioid use disorders and alcohol use disorders, and it's important that we stay on the same page for this throughout. And in order to do that, just a reminder of the difference between addiction and dependence, that addiction is really a neurobehavioral problem that is evidenced in the mesocortical limbic tracts that we saw in that earlier slide that really revolve around craving and the desire to use despite legal consequences, health consequences, et cetera, whereas dependence means if you stopped a medicine, you would get sick. So a lot of people depend on different kinds of medication to stay healthy for different chronic illnesses, such as blood pressure medicine, diabetes medicine, and we should think of it in the same way when it comes to medications for opioid use disorders and alcohol use disorders, that whether people would go into withdraw or not, if they depend on those medicines to stay healthy, then it is an important medicine for them. Next slide. So what are the evidence-based treatments for opioid use disorders? We know that there is the full agonist, methadone, which is most chemically similar to illicit opioids on the street. There is the partial agonist, buprenorphine, and the antagonist, which is naltrexone. Next slide. And so what does success mean in the medical literature on whether these medications work? So the litmus test is really, does the medication keep people alive, does it keep people in treatment, does it keep people out of jail, and does it keep people from engaging in high-risk behaviors that can cause HIV and hepatitis transmission? So if those four criteria are met, it is a well-worthwhile medication to be on. And so this is a study from 1990, and every single one of the studies I'm showing for methadone treatment has, you know, 10, at least 10 others backing it up. This medication has been around for decades. And so this question asks, does methadone keep people alive? This is a study that looked at, that followed people over eight years and compared methadone treatment versus 115 that got counseling alone or detox and counseling, and found that the untreated patients were more likely to behave, you know, as if, if they had counseling alone, it didn't matter. They died a lot more frequently than the, than the folks that were treated with methadone. And the graph on the right asks the question, how long should patients stay on methadone? And the answer to that is really as long as the patient really needs to, and it should be a shared treatment agreement. So the top line looks at voluntary discharges, patients that wanted to taper and had an agreement with their practicing provider or medical director, and they started tapering of their own volition and did well on discharge versus if there was an involuntary discharge for whatever reason, they behaved as if they never got any medication at all and died just as frequently as the untreated control. Next slide. So does methadone keep people in treatment? Absolutely. This is a study from 1979 that looked at heroin addicts randomized to detox and versus maintenance and found there was 76% retention rate at 32 weeks in the treatment arm versus 10% in placebo, 56% retention at three years versus 2% in placebo. And I just wanted to, I guess, remind all of you that if we were talking about cancer treatments, it would no longer be ethical to test anything against placebo after evidence like this. But unfortunately for substance use disorders, there were several placebo controlled trials conducted after this, and in some instances still exist today. Next slide. Does it keep people out of jail? Yes. So this is a suite study from 1969, small, that randomized folks that had recently been released from jail to methadone treatment and control. And almost everybody in the control arm were reincarcerated versus a quarter only of the people that were given methadone treatment. It was clear that methadone was actually improving lives. Next slide. And then does it reduce disease transmission? So this is a meta-analysis, 8,000 methadone patients and found that it significantly reduces high-risk behaviors of HIV transmission and seroconversion. So there is a comment that says these studies are awfully dated. So for methadone, I actually did that on purpose to just remind everybody that methadone is a very old treatment. So we have a lot of evidence that still is valid today because it was studied so long ago. So methadone treatment is actually very settled science and that is the point of showing these older articles. Next slide. Next slide. So buprenorphine is a newer treatment. It was FDA approved in 2002. And does it reduce death rates? Absolutely. This was a study that looked at how buprenorphine reduced the death rates in Baltimore City through a 15-year period and found that after the release of buprenorphine on the street, it reduced opioid overdoses by 60%. So pretty steep reduction. And then on the right is similar results in France. Next slide. Does it keep people in treatment? Absolutely. Out of 255 patients, 56% were retained at one year. And those with polysubstances were actually more likely to adhere to treatment and people did very well. Next slide. Did it keep people out of jail? The answer to this one is no. So this was a comparison of methadone treatment initiation and buprenorphine initiation and found that drug-related charges did not change with buprenorphine initiation, whereas they were significantly reduced in the methadone population. That may have to do with the fact that people were getting prescriptions for buprenorphine instead of getting daily dose, but also that buprenorphine is that partial agonist and isn't as chemically similar to street opioids as methadone is. Next slide. And does it reduce the high-risk behaviors that can cause HIV and hepatitis transmission? It absolutely does. This was a great study that looked at four high-risk Asian communities and found that when people were on buprenorphine maintenance, that they stopped their high-risk behaviors. And once they did stop the medicine, unfortunately, those high-risk behaviors no longer reduced and everybody went back to their old behavior. So it's important to stay on this medicine. Next slide. So naltrexone was a medication that was released a little while ago in the injectable form. It was released about 10 years ago for alcohol use disorder, but then it started to be used in 2016 for opioid use disorder after the release of this study that looked at people that were incarcerated getting their first injection prior to release, and then getting six additional injections out in the community. And so of the people that continued on the injections, the overdoses were zero. And so everybody got really excited about this, except that, you know, people that are incarcerated, it's a much more controlled environment and people weren't using. And many of us may know that it takes a seven to 10 day washout period of all opioids to actually be able to start naltrexone safely. So in a general population, next slide, this is what naltrexone really looks like. This was another study from 2016 that looked at all comers with 171 patients at the first injection, and by the sixth injection, only eight patients remained. It was a steep drop off. Next slide. There's no evidence that it can keep people out of jail because it's hard to even keep people in treatment. And that's what this slide basically says. Next slide. And there's really no evidence that it reduces the high risk behavior that prevents HIV and hepatitis transmission. So it's really important from a public health point of view, if that's what you want to reduce in your community, that you use the medication that works. Next slide. So what about comparison studies? So this was a 2014 Cochrane review that compared buprenorphine versus methadone and found that methadone was better at retention and treatment versus buprenorphine. But buprenorphine was better than placebo. So buprenorphine is a great medicine, better than nothing, but head to head methadone and buprenorphine for treatment retention, methadone had an edge. Next slide. And the comparison between buprenorphine and naltrexone is that, so this is a randomized control trial that randomized people to the buprenorphine arm versus the naltrexone arm. And they found that the folks that were able to be inducted on naltrexone compared favorably to buprenorphine or equivalently, but there was a 30% dropout rate in the naltrexone arm before they could actually do that. So that is important that there was a 30% dropout in the naltrexone arm. Next slide. So switching gears to alcohol treatment, there are three, it looks like four, but it's really three, FDA approved medications, acamprosate, disulfiram, an oral and intramuscular naltrexone. Next slide. So how does acamprosate work? So acamprosate, it's not exactly clear how it works in the treatment of alcohol use disorder, but there's a theory that it helps tamp down the glutamic receptors that actually cause anxiety and agitation. And so the idea is that GABA receptors, glutamate receptors actually work like a seesaw and that GABA sort of calms everything down and glutamate actually revs everything up. So if somebody is in a detox situation and they've stopped drinking alcohol and they're getting really agitated and anxious, they can take acamprosate and that calms down that part of the brain. This is a theory of how it works, but just so you know, it's only proven for relapse prevention. It actually cannot be used if the person is still drinking. It is expensive and it's hard to get paid for, and it is three times a day dosing, which is hard to keep up. Next slide. Disulfiram is a very old medication. This is an acetaldehyde dehydrogenase inhibitor. So it works on the liver and causes intense flushing after drinking. And it is a good medication to use in a directly observed therapy setting. But if you are going to send a patient home with a prescription, the likelihood that they're actually going to take it is low. So again, only 20% of those who finished the study were compliant. So 80% dropout for people that take disulfiram to prevent drinking. Next slide. So oral naltrexone, it certainly looks like it helps. This is a forest plot from a Cochrane review that showed that oral naltrexone was better than placebo in reducing the cravings. And yes, it is an opioid receptor antagonist. So why does it work in alcohol use disorder? And the answer is really that alcohol is kind of a promiscuous drug. So it does primarily work on GABA, but it also works on the opioid receptors. And so for some people, it actually really helps reduce cravings and reduce the joy one may get or euphoria one may get from drinking. Next slide. This is the studies for extended release naltrexone in alcohol use and found that in men, it actually significantly reduced the heavy drinking days. And what's interesting about naltrexone is you can actually give it to folks while they're still drinking. They don't need to stop before doing it. And it actually helps reduce those drinking days. Next slide. So that's the FDA approved medications, but there are actually some off-label treatments that get better evidence for it than the FDA approved medicine. And these include gabapentin, topiramate, and baclofen. Next slide. So there've been a number of studies looking at gabapentin to treat alcohol dependence and found that when someone is on gabapentin, the abstinence rate is 17%. In other words, you can give it to somebody who is still drinking and 17% will achieve abstinence. And the heavy drinking, which is again, greater than five drinks someone's sitting, greater than five days out of 30, was reduced by 44%. So that's pretty powerful. We're talking about 600 milligrams, three times a day dose. Next slide. You can combine gabapentin with naltrexone. And it was used as 400 milligrams, three times a day with 50 milligrams daily oral naltrexone. And it found that it was significantly superior to naltrexone alone to use both. It's longer delay to heavy drinking, less total heavy drinking days and less drinks per drinking days. So that is also very promising and actually relatively easy to use outpatient. Next slide. Topiramate is also a great medication to use in this setting. So it can be 25 milligrams to 300 milligrams per day over five weeks. The final dose 300 milligrams per day divided. And you can see that in the naltrexone, the topiramate arm, there was fewer heavy drinking. Next slide. Next slide. Baclofen also shows similar promise, although there is a risk of withdrawal seizures with it. So it tends not to be my first line when I treat people. But it's good to know that it's there in case it's needed in any way. Next slide. So how does opioid agonist therapy impact alcohol use? Initiation of opioid agonist therapy is a very delicate time. So especially with methadone, it can build up in the system very quickly. And there's some sort of mixed reports that initiation of opioid agonist therapy, whether it be methadone or buprenorphine was associated with reduction in alcohol use, but then the long term results resulted in increased consumption. That was one study. And then in a different study in 2008, showed that opioid use disorder and alcohol use disorder was associated with a reduction in alcohol use, but buprenorphine was more efficacious. But then a meta-analysis of 15 studies showed no clear patterns. That initiation of one medication for one substance use disorder did not seem to impact the other substance use disorder. Next slide. So what about opioid therapy and alcohol treatment? So what is the uptake of alcohol treatment in folks that are on opioid agonist therapy? First of all, treatment is widely ignored. There was one OTP in New York City, about 20% had alcohol use disorder, but only 5% had engaged in alcohol detox and only 7% in psychosocial intervention. Also, what's important to note is if you start somebody on opioid agonist therapy and then realize, hey, they need to go inpatient for detox, many programs will require termination of the medication for opioid use disorder as terms of acceptance. They are worried that somebody is going to overdose, especially if they're going to give them a benzodiazepine or phenobarbital to detox from their alcohol if they're on an opioid. But the risk, the magnitude of this risk is actually overblown. And also it should be known that phenobarbital and methadone interact in the way that methadone actually increases, or phenobarbital, I should say, increases methadone metabolism. So somebody might actually go into opioid withdrawal if you give them phenobarbital instead of the other way around. All people on medication for opioid use disorders should be offered treatment for alcohol use disorder. Next slide. So there was actually one study that looked at disulfiram that in 1988, they made methadone contingent on taking disulfiram. So if you took your disulfiram, you could get your methadone that day. And that was very effective. And disulfiram worked in that setting. But if you just said, hey, here's your disulfiram, we'll dose you methadone every day, go ahead and take it. It was not effective. Next slide. Extended release naltrexone is actually a one-two punch potentially in this group. And it was feasible and safe in an HIV clinic. But there was only eight individuals in the pilot. Next slide. And there's also lots of non-pharmacologic therapy. So collaborative care intervention. So this looked at 377 primary care patients with either alcohol use disorder, opioid use disorder. And they had six sessions of brief psychotherapy versus treatment as usual, referral to community programs. And those in the intervention were twice as likely to get treatment and had greater rates of abstinence. However, rates of those with both use disorders were low. And they failed to report numbers or any subgroup differences. Mindfulness has been shown to be very effective in polysubstance use and pain. And cognitive behavioral therapy is effective in alcohol use and substance use disorders. Next slide. But what's the prognosis? Ultimately, comorbidity may reduce the efficacy of all available treatments. Opioid misuse is tied to poor alcohol use treatment outcomes and vice versa. There are no specific treatment approaches, pharmacologic or non-pharmacologic that effectively treat comorbid alcohol use disorder and opioid use disorder. It can complicate treatment of chronic pain. And the research is lacking in all of it. So, you know, you may wonder, hey, why is she posting articles from the 1980s? Oh my gosh, if there was a more recent article, I'd let you know. But these articles are old and there's very little research being done on the topic. Next slide. So to follow up on the case discussion, again, this is a gentleman on 180 milligrams of daily methadone in drinking 10, 12 ounce beers daily on pregabalin, duloxetine, xanadine, and methadone, and then other medicines for his medical comorbidities. And so how did we manage his alcohol use disorder? Next slide. So because he was on methadone and because he was on pregabalin, we couldn't use naltrexone and gabapentin. He was continuing to drink, so a camprosate was out, and disulfiram, I was worried he wouldn't even start. So we initiated topiramate and we titrated that up to 100 milligrams daily, and we offered broad community support, including counseling and peer services. And he reduced his drinking to two beers a day, which is not abstinence, but it was better than what it was before. So we achieved some success with this gentleman. Next slide. So ultimately, I hope that you heard that alcohol and opioid therapy is really understudied together, and it's also under-tested and under-treated. But treatment can and should be given simultaneously, and determining the best treatment milieu is really important. Different substance use disorders call for different treatments, and it's really important that you can start screening for alcohol use disorder in the UDS. So in your urine drug screens, you can test for alcohol and really engage in that conversation with your patient. I doubt that alcohol screening is happening enough, and given that what we see in prevalence in these different clinics, that it's a very common problem and one that should be talked about and engaged with. So that's actually all I have, and I'm happy to answer any questions. Thank you so much, Dr. Kawasaki, for that presentation. It was very comprehensive and informative. We have been receiving a lot of great questions throughout. So I'm gonna start off with the first one. Methadone is a fantastic tool. Do you have any suggestions on opening up access to utilizing it more in primary care instead of just within OTPs? Ah, what a great question, the $64 million question. So methadone is absolutely underutilized it was actually made legal in the early 70s as part of the Controlled Substances Treatment Act. So it was allowable, but sort of in the most narrow way where it had to be subjected to federal and state licensing and also federal and state regulations. You know, now that we know that there's this huge need and certainly with the rise of synthetic opioids taking over and causing a ton of overdose death, it's important to figure out how to expand access and to do it safely. There are a lot of safety concerns about offering methadone treatment in primary care unless there are capabilities of dosing daily. But right now the ground spell is to see it managed through local pharmacies. That pharmacies actually have the licensing to dispense controlled substances and they can dispense it daily for folks so that it can actually remain within reach and not have so many geographic gaps in methadone clinics. And so that will likely require an act of Congress to change and amend the methadone, the Controlled Substances Treatment Act. And this is not a revolutionary idea. Canada and the UK currently use pharmacies in treatment. And so, you know, a lot of the logistics need to be worked out. Like what is, what does payment look like? What does billing look like? You know, who collects urine? Should counseling be required? Kind of questions that need to be answered. So that's being actively worked on on several different levels and hopefully we should see some movement on that soon. Great, thank you so much. Guidelines still suggest that opioid agonists should not be offered to someone with ongoing heavy alcohol use for safety concerns. Do you have any thoughts on this? So it really depends. So opioid agonists for people that are on, that are heavily drinking. Yes, that's the question. Yes, that is correct. So it really depends. I think at a certain point you have to put on your harm reduction hat. You know, if this is somebody who's not using illicit opioids and they have back pain and you're wondering whether to prescribe a heavy drink or oxycodone, the answer is probably no, right? But if you're talking about somebody who is using a lot and likely has, you know, maybe they're using intravenously, maybe they're using fentanyl, maybe they're using heroin, and you can presume that they have a high tolerance for opioids, starting them on something like buprenorphine, which is a partial agonist, would greatly lower their likelihood of overdose. So you really have to meet the patient where they are, you know, discuss what they would like to do. Certainly if they're a heavy drinker, maybe detox is the milieu they should start in. And then, you know, with the idea to continue treatment in the outpatient setting. But, you know, it really depends on the patient and it depends on what they're using and it depends on what their treatment goals are. Great. If a new patient meets the criteria of both alcohol use disorder and OUD and both are severe, how would you manage this? Which disorder would you prioritize? So you have to prioritize both. I would be worried more acutely about which one is going to kill someone faster. And an opioid overdose can do it pretty quickly. So you really need to engage with that person on that. And the trick I think is to develop a therapeutic rapport that they keep returning. If somebody's reluctant to go inpatient, for example, and you're saying, well, I'm not going to treat you unless you go inpatient. And then they just walk out the door. They could overdose and die that night. You know, whereas if you can tell them, okay, we're going to start treatment with methadone or treatment with opioids, we're going to start treatment with methadone or treatment with buprenorphine, and then we'll discuss alcohol use or today we'll initiate both medications if we wanted to. That would be fine. Again, like it really just depends on the patient, depends on the circumstances and what that patient wants to do. Great. It's definitely important to always involve the patient in the treatment decisions as well. There's one person asking gabapentin they heard was going to be added to the controlled substance list because of a potential for abuse. Has that been a topic of consideration when it comes to prescribing? So gabapentin is already a controlled substance, I think in several states. And, you know, it has been abused. I've seen it be abused, but from a harm reduction point of view, I haven't seen the adverse consequences like I do with benzodiazepine withdrawal in gabapentin. So there's several ways to think about how to write for gabapentin or really any medicine safely. And, you know, you can write for small amounts, you can see the patient back frequently, you can do random pill counts to make sure that they're not selling it and taking that too. I see the comment by that logic, we should add clonidine too. I agree, I agree. But that is, I think it's a medication for concern just like any medication is. But if you're taking a person from heavy alcohol use to gabapentin use, you know, if they're taking it as prescribed, it's a win. If they're taking too much of it, but they're not drinking anymore and there's less of a risk for seizure disorder, you know, consider increasing their dose so that they don't have to take too much or seeing them back more frequently. Great. This person had a number of patients who stopped injectable naltrexone because of discomfort at the injection site. This was especially among patients who were thin. Do you have any thoughts on avoiding this? Great question. I think that injections are, you know, different for different people. And some people have comfort with them and some people don't. The naltrexone injections are great because they don't undergo first pass metabolism. And so when somebody who's drinking, you don't necessarily have to worry about liver enzymes as much, especially if they have hepatitis C. But, you know, for thin people really reporting pain, we can't make them continue these injections if they don't want to. Everything is voluntary. So, you know, in that setting, maybe thinking about oral naltrexone or if there's another medication that they'd rather take for alcohol use. Great. Would you recommend a breath alcohol test prior to dosing methadone? So that is actually a federal regulation that there are random breath alcohol tests prior to methadone dosage for folks. And if there's any suspicion, you can check BAC through breathalyzer. But every opioid treatment provider every opioid treatment program that dispenses methadone is required. You carry one and do those tests randomly. Great. For a patient with a history of alcohol use disorder and has received a liver transplant for secondary alcoholic cirrhosis and a kidney transplant, secondary to liver transplant complications, would you be able to use naltrexone? And if not, what medications would you recommend? Oh, that's a great question. So I think if I were to use naltrexone, I would use injectable naltrexone. There's less of a chance of metabolism there and you'd want to do some monitoring. You'd also want to check in with their transplant doctors and make sure that whatever medication you prescribe, it doesn't interfere with the anti-rejection medicines that they might be on. But I would think that injectable naltrexone would be fine. In the case... This discussion, after your pay dose, considering how alcohol can have profound effects on methadone half-life reduction and alcohol use can result in greater methadone accumulation. I'm sorry, you cut out for some of that. Can you repeat it? Sorry. What happened to the patient's methadone dose after his drinking reduced? His methadone dose remained the same. Okay, so this person is considering the alcohol has profound effects on methadone half-life and reducing alcohol use could result in greater methadone accumulation. Was that a consideration? No, not for this patient. He was actually much more comfortable. Could you also talk a bit about why primary care settings would be ideal for treating substance use disorders? And do you think that this requires shifting away from addiction-only specialty care? So I think it's a great question. I think primary care is a great place to start substance use disorder treatment for sure and continue it, absolutely. You know, I think it's like any chronic medical illness, blood pressure, diabetes, you know, this is bread and butter primary care. And certainly with your trusted doctor, or primary care provider, if they're able to do substance use treatment right in the office, that's so great for one-stop shopping. I do still think that specialty care centers should exist just like endocrinologists exist and, you know, nephrologists exist for those patients where they're really struggling to do well at their level of care that maybe they need a little more close supervision. And so that's where that can help. Great. Are any of these medication services offered with support, like recovery support services, or any other types of supportive services? Yes. So in opioid treatment programs, it is a federal regulation that each patient needs to engage in counseling at least two and a half hours a month, sometimes more, it can be group setting. There's a level of treatment that's determined. And so intensive outpatient is required for folks that are getting a treatment through opioid treatment programs. There are some states that require counseling with buprenorphine prescriptions, but many states do not. The evidence is actually mixed, that combining counseling actually leads to better outcomes with buprenorphine in particular. So there are, but there's no requirement. And I think that you're going to find variability and quality wherever you go in whatever field you're in. So it's important to end up in a practice that you would send family members to, so that you would feel comfortable sending your patients to as well. Great, and then just a clarification, are there any non-clinical supportive services as well? So we have case management that helps with, so our counselors are also case managers, so they'll help with things like job placement, housing, food security, clothing security, other sort of resources within the community. And there are, we work with a peer recovery service, so people with lived addiction experience who have been in treatment for a long time and in sustained recovery, they actually can connect folks to different levels of care and also like help them go inpatient if needed and connect them to peer support services as well. Great, have you ever used buprenorphine for alcohol use disorder, either with or without a history of OUD? So I've never used buprenorphine for alcohol use disorder. I have had patients with opioid use disorder, after I start buprenorphine, they have told me that they no longer have a desire to drink. Now this is anecdotal, so I don't know what that means exactly, but I think for folks with opioid use disorder who also drink, for some of them, the buprenorphine has really worked and it might be sort of the same underlying reasons why naltrexone works in some people, right? That alcohol can act on the opioid receptor. Great, just a couple more questions, I think. What is the main drawback of utilizing oral naltrexone initially? The main drawback, so I think with any injectable medicine, everybody needs to start oral medicine just to make sure that they're not allergic because you can't take it back once you inject it to give to a patient. So everybody needs to start on the oral medicine, but I think the thing you worry about is that somebody would stop taking naltrexone. And so if they don't like it, they would just stop it, and then it just wouldn't be a big help. And so it's really adherence that people worry about and maybe not showing up again to appointments. Great, I think maybe one more question. Have there been any off-label studies using caraprazine, I believe, for alcohol use? Let's see. Capazine. I haven't, so there's carisopradol, and I haven't seen any studies on that. And I'm not sure that there are studies on that medication. Okay, no worries. Maybe one more question. For your case patient, would changing to xanadine tobaclofen be helpful? Perhaps, that's a great thought. And certainly something to keep in mind, back pocket. I would be worried about the interaction between baclofen and methadone. So I think for me, this man is miraculous that he can be on so many medications and walk upright. So I think that doing one medication at a time is a good approach, just to make sure that we don't tip him over into anything dangerous. But certainly, that is something that we would consider, for sure. There was another question about what I saw about his aspirin use, given the new guidelines, but he already has a diagnosis of coronary artery disease, so we would not stop his aspirin. Great, thank you so much. Unfortunately, that's all the time we have for questions today, but I would like to, again, thank Dr. Kawasaki for presenting and answering so many amazing questions. We're very appreciative of your willingness to share your knowledge and expertise and time with everyone today. Just as a recording for everyone, the recording, reminder for everyone, the recording and slides will be posted on the PCSS website within two weeks from today. And finally, to close out, I'd like to make you aware of two resources offered through PCSS. The first is the mentor program designed to offer assistance to anyone in need of more one-on-one interactions to address any clinical questions you may have. You can either request a mentor from the directory or PCSS will pair you with one. PCSS also offers a discussion forum comprised of those mentors and other experts in the field who can help provide prompt responses to clinical cases and questions. There's a mentor on call each month who can address any submitted questions through the discussion forum. Here is the list of lead partner organizations that are part of PCSS. And finally, the PCSS website, contact info and social media handles if you would like to find out more about their resources and trainings that they offer. So thank you all again for joining today's webinar and we hope you have a great rest of your day and week.

polysubstance use

treatment

comorbidity

integrated care

opioid medications

substance use disorders

neurobiology

alcohol use disorder

opioid agonist therapy