I'm not sure if you can hear us. I think I see a message saying connecting to audio. So I don't know if we just need a couple of minutes to, to connect. Yeah, I had emailed him letting him know that we were finishing up the last one. So I'm wondering if he's just waiting in the space still. Give me a second, I'll email him again. Okay, no worries. Thanks. Hi there, can you hear us? Hi, is everyone, can you hear me? Yes, we can hear you. Can you hear us? Yeah, yeah, yeah. All right, so do we have a quorum? Sorry. I think we've got pretty much everyone here. My name's Dr. Khan. I'm the program director at Inspira Health. Thanks for joining us. We have two residency programs here with us. So a lot of trainees, PGI ones through four, pretty much. Great. And everyone's very excited to hear your talk on substance use disorders as it relates to alcohol use. I was just gonna kind of give a brief intro to you from what Courtney gave me and then kind of let you take the floor. So is that okay? Okay, so we have today Dr. Benjamin Shreve, I hope I said that correctly, who is a double board certified psychiatrist with additional training expertise in substance use disorders. Coming from, also from Columbia University where he's an assistant professor of clinical psychiatry in the division of substance use disorders and is adept at treating a broad range of psychiatric illnesses with state of the art treatments. And will be talking to us today about alcohol use disorder treatment, which we're very excited about because we see so much of this. So, we thank you for your time and we'll kind of let you take the floor. I'll be here in the background. Dr. Hirsch is also, he's our chief resident. So he'll also be in the background if you need any help from us. Okay, cool. So thank you for having me. As Dr. Khan said, I'm Ben Shrevasto. I'm an addiction psychiatrist on faculty at Columbia. And so, yeah, so this is sort of a broad overview of substance use disorders. Which screen can you see? Your slideshow. So it's the good, do I need to switch it or is it the? No, no, it looks perfect. Okay, cool. All right, so this is actually adapted from one made by Siddharth Wakulu, who's a senior addiction psychiatrist at UT Southwestern and has, you know, a very experienced clinician. And so, you know, I just, I made some slight changes, but this is all from him and, you know, a great colleague and a great resource that I've known for some time. All right, so this is just stuff about SAMHSA, the Opioid Response Network. We're basically a large organization that provides on the ground assistance, mostly focused, it's SAMHSA funded, mostly focused on opioid and stimulant use, but all substance use disorders. And their focus is on guidance and implementing evidence-based treatment and prevention for substance use disorders. And what we do is we provide locally geographically based consultants to help on frontline clinicians in addressing these issues with complex cases or more like infrastructure type things. And, you know, we, and anytime you wanna reach out, the ORN is glad to help. So, you know, whether you do substance, you focus on substance use disorders or not, it's always a resource. And then this is just information. It's sort of run through the American Academy of Addiction Psychiatry. Okay, so we'll talk about the elements of addiction treatment, shame and stigma, epidemiology, diagnosis and treatment, and psychosocial interventions and pharmacotherapy. Right, so that's from Dr. Waklu. All right, so when we think about, we think about addiction, and this is actually why I got interested in it when I was a medical student, and, you know, even more so when I was a resident, is that there's like different phases. I mean, it's true, you know, in lots of different things in psychiatry and medicine, but with like this carrot, you know, there's just very different, there's just sort of very different things, and they all kind of flow together. And you, you know, and they all kind of flow together, and you most of the time need to address all of them. So there is the intoxication, withdrawal, like how do you manage that, which is oftentimes, you know, at least from a, you know, strictly medical standpoint, the most straightforward thing to do, but then, you know, that's just a very small part of treatment. And then there is, okay, well, what do you do next? There's, you know, invariably there's going to be a psychosocial component, and whether that's residential treatment or inpatient. And then in, depending on, you know, what the severity of the illness, most people who require some level of treatment will need ongoing care, and whether that is continuing therapy or mutual support group like AA. And then, you know, in addition to that is the additions of medications. And there's sort of this, I think it happens in all of psychiatry, but especially true in the substance use disorder world, nothing is mutually exclusive, right? It's not like, okay, someone can't go to AA and also be on naltrexone. Just similarly, like why people benefit, you know, the evidence suggests, again, depending on severity, people benefit from medications and psychotherapy for depression. And, you know, again, if you think about other areas of medicine, like people need PT after surgery. So, you know, we need to, you know, my whole sort of philosophy is think what does the rest of medicine do? And, you know, why, you know, how can we think along those lines, right? Okay. All right. So again, as I was saying, so it does, treatment does work. Again, as I said, some people require multiple treatments. It saves lives. Again, addiction is a family and public health problem. And, you know, people will talk about the cost of treatment. But again, if someone is like constantly getting hospitalized for liver failure, as I'm sure you guys saw in your intern year, or for those of you who are interns are seeing now when you're on your medicine months, like again, if you can get people sober, then that brings down the cost of medical care, right? And then, you know, this last point is there is a thought and it's still sort of a pervasive thought, unfortunately, that, you know, everyone needs to be, everyone with it who meets criteria for a substance use disorder needs to be abstinent. And that's not true. In fact, most people can probably do some form of harm reduction. Now there are people, you know, maybe, you know, of the people who meet criteria for substance use disorder, maybe about 30% who do need to be totally abstinent and who cannot succeed at harm reduction. But most people can do okay with harm reduction. And then we think about things like quality of life. Okay. And again, you know, again, going back to, because it's always about the money, you know, incarceration is extremely expensive, medical hospitalizations are as well. All right. And again, I know we all know this, it gets repeated, but it's always, you know, it's always helpful when you have patients to reiterate this to them, that it is a medical condition. It's not like a moral failing. And because, you know, it doesn't make, you know, there's, I like the line, you're not a bad person, you're a sick person. And, you know, that's not to say like people, you know, there's obviously a strong comorbidity between substance use disorders and antisocial personality disorder. But, you know, for the most part, like viewing it as an illness is a way to reduce stigma, right? And, you know, and then, you know, empathy, these are, as I'm sure you've experienced, these can be very difficult patients. Confronting them, judging them is not helpful and usually counterproductive. So, you know, be, but, you know, you do have to, you know, you do have to be firm at times, emphatic, and then avoid stigmatizing language, right? So, you know, we talk about, if they're doing the 12-step programs and they identify as an alcoholic or addict, it's fine to, you know, talk about those things, but, you know, talk about it as substance use disorders for people who aren't. And then, you know, sort of explore, you know, why people may be hesitating at stopping. And then, you know, offer them hope, like, hey, we can get you, you know, we can work on your recovery and getting you better. And, you know, there's sayings from, you know, AA, like don't stop until the miracle happens. And then, you know, find strengths, right? So it's a lot of motivational interviewing is a common thread here. All right, so key elements. So again, let the, you know, as is fundamental to all of medicine, open-ended questions, get the patient to tell their story, you know, the, and just, you know, just sort of respect them coming from where they're coming from. And then, you know, these are just things that, you know, obvious stuff like, you know, get down to eye level. Again, as I said before, do not confront them, you know, do not accuse them. It's never helpful to say, you know, no matter what service you're on, like you had, you know, why was your drug test positive in sort of a, in sort of an insulting manner. Now, if you have a long-term relationship with a patient that you're seeing in an outpatient practice and you develop some rapport and a mutual understanding, that may be a little bit different, but like, especially as you're more green and getting used to this type of thing, again, non-judgment, empathy, things like that. Okay, words have immense power to wound or heal. The right words catalyze personal transformation and offer invitations to citizenship and community and service. The wrong words stigmatize and disempower, right? So if you come across as paternalistic and you use, you know, sort of harsh language, and it's very tempting to do it, especially like you're on a, you know, whatever type of practice you're in and someone is, you know, being very painful and stuff. You know, if you're, you know, as a psychiatrist and, you know, substance use disorders do fall under our purview, there's, you know, obviously you've heard of addiction medicine that's around largely because a lot of, you know, our specialty has, you know, sort of ignored or pretended that substance use disorders are in ours, but they fundamentally are within our realm. So, you know, you need to, you know, when you have patients with substance use disorders, I personally think it's part of our, whether you do an addiction fellowship or not, it's part of our professional responsibility to, you know, be responsible with how we phrase, we talk to them. Okay. Again, they have a lot of shame and stigma. They're stigmatized by family, other healthcare professionals. You know, so as the point of contact, you can make a big difference. And then, you know, there's different levels, obviously like drug addiction, specifically opioids, IV drug use, women, and then, you know, stigma is also a barrier to engagement and recovery. And so, you know, this is, I won't read through all of these, but these are, you know, just language so that, you know, there's the slang words, which can be more derogatory, you know, and again, some of the slang words can be helpful if, you know, you're, if someone understands that you understand the vernacular and they say it and, but, you know, then you can, you know, but again, realize that there are parallels with the medical language. Okay. So there's a huge gap. So actually most of what I do is translational neuroscience addiction neuroscience, but there's, you know, which is great in the theory setting and what, you know, may come to fruition in terms of treatment, but, you know, in terms of what we have to offer, despite, you know, offering hope, despite we do have evidence-based treatment, there is a huge gap in what is practiced or what we have available and versus, you know, what the science is. And even with what's available, most of, you know, fewer than 10% of people with substance use disorders even get adequate treatment, right? So again, this comes as, you know, people viewing it as a social problem. And then again, much of what passes for treatment is not up to standards of other things in psychiatry, for example, you get, you know, now with the, I think last year, the buprenorphine was not the way the X waiver went away, but I personally thought that whole thing was ridiculous. And when I was a resident 10 years ago, I had to like go through hoops to get a waiver for, to not pay $400 for a waiver training. And it was, you know, so there's like, there's all these types of things, right? And then, you know, right. So this is a good example. You go to the hospital with chest pain and you're found that to be, you know, what if you're found to be having a heart attack? It's, and you get told it's your fault because of your choices, you're denied treatment because you did it to yourself. You're given a list of cardiologists and cath labs to call with the time being tissue. You're only given aspirin if you agree to go to counseling and then you're kicked out, right? So again, this is, you know, there's, it's not a, you know, there's some leaps between, you know, acute presentation and substance, but, you know, fundamentally this is a, this is a useful heuristic to think about, right? I used to call people, then into emailing, then texting. Now I just ignore everyone, okay. All right, so alcohol use disorder epidemiology. So it's about, so 30 million people meet criteria for an alcohol use disorder and you kind of see the age distribution. It's skewed more towards above 25. And then, you know, historically it was more adolescent boys were likely to drink and binge drink. That trend has reversed. And then you see the narrowing of the, in the gender gap. Again, it's typically thought of as like more men have the problem, but it's narrowing, you know, and especially in COVID, this became more true and, you know, huge amounts of deaths related to alcohol. Men have greater morbidity and mortality. All right, and then so 40 million people have unsafe alcohol use. Alcohol liver disease is the most common indication for liver transplant and 50% of all liver disease deaths are attributable to alcohol misuse and 25% of pancreatitis cases and even 5% of cancers. And increase intense, and we've seen a trend of increase of intensity of binge drinking and ED visits and hospitalizations in the last 10 years. And again, as I said, fewer than 10% of people with alcohol use disorder get any kind of treatment and fewer than 4% receive any kind of pharmacotherapy. And again, huge healthcare costs, $250 billion. This is Dr. Wakalu's at UT Southwestern. And so this was a figure from Texas, 19.1 billion for Texas and three quarters is related to binge drinking and 10% of children live with a parent with alcohol use disorder. And so you can kind of see this is where the trends are going in terms of alcohol related deaths. This is a little bit dated data. This is from the NISARC, which is a huge epidemiological survey. And so you can kind of see some trends or a lot of trends are just going in the wrong direction. Obviously it's been a huge problem in Native American populations for years. And you see that like, especially, whether it's Caucasian, Latino or African-American or it's still like, the trends are still going up. Okay, all right. And then, so this is just a geographic distribution of age standardized rates of alcohol induced death among non-Latino white individuals. So you can start to see that like in this, sort of what is, this is 2013 to 2016, like you start to see the deaths go up especially in the West Coast in some of these areas. So yeah, so I guess that it looks like the trends are going in not a great direction. When I read about the evils of drinking, I gave up reading. All right, so diagnosis and assessment. So difficult to treat, there's memory issues, especially in the elderly, falls, injuries and motor vehicle accidents. Difficult to treat, sorry, depression, anxiety and insomnia, hypertension. Again, if someone is not responding to their SSRIs or whatever, and they're drinking all the time, then you kind of go back to. Even if you're convinced that there's two independent diagnoses, again, if someone is binge drinking all the time or then, and they're having panic attacks and then they want more Klonopin or whatever, we kind of have to look at the drinking, right? And then these other things, so, unexplained arrhythmias, I just had a patient, I like, there's a reason why now in my outpatient practice, I make people see me in person, at least for the first visit, and he was like drinking very heavily, and I listened to him and I'm like, that sounds irregularly irregular, right? And so, there's that, recurrent infections, domestic violence, chaos, and then various other medical problems. You know, hematologic problems, GERD, etc. All right, so GGT is, so then you have the lab markers again, you know, this is hopefully this is review. GGT by itself with like a normal ALKFOS, normal because it's released from the liver. Microsomes is specific to alcohol, is specific to heavy alcohol use. Again, the classic AST to ALT ratio, 2 to 1, low BUN. There's hypovolemic, hyponatremia, hypokalemia, hypomagnesemia, again, electrolyte deficiency, elevated lipids, anemia. Generally, like with alcohol, you would see like a high MCV, but you know, if someone is malnourished or iron deficient, obviously, you can see a microcytic anemia as well. And then we have the testing, the ETG, ETS testing. Those are metabolites that are detectable usually around 3 to 4 days after the last drink. PETH is usually 3 to 4 weeks, and those are available. Usually, these are mostly used in forensic settings, though a lot of liver doctors are actually now starting to use these. Okay, so psychosocial intervention. So, the classic model is sending people to residential treatment. Again, you know, how feasible and effective that is, is sort of debatable, but that's sort of what has done classically along, you know, decades ago, insurance would pay for right now. That is less common, but now there's out, you know, outpatients tend to be a little bit more common. So, partial hospitalizations where people like live and then go in sort of sober housing and go to groups every day, then intensive outpatient programs where people live at home, but then are in group and in treatment for a significant portion of the day. Then we think about mutual support groups, the classic, the prototype was Alcoholics Anonymous and other 12-step programs, but then there's others like non-12-step based like Smart Recovery, Celebrate Recovery, Mantra Recovery. There's also the Buddhism-based ones like Dharma Recovery. So, you know, there's lots of different, and then, you know, there's lots of different 12-step programs for various other addictions, but, you know, so that's, that can be an important component. Oops. All right, so AA a little, so AA, I actually really, you know, I find it a really fascinating organization. So, it was founded in 1935. Bill Wilson was a New York stockbroker and on, and basically on his third, and he was like end-stage alcoholic, and then he had the sort of the spiritual experience while he was detoxing on Atropine, and his friend who had got sober through this Evangelical Christian program sort of gave him these spiritual principles, and then he was on, and then he was trying to like relay them to other alcoholics, and no one was listening, but he was able to stay sober until he was on a failed business adventure in Akron, Ohio, and he was about to drink, but then he said, I need to find another alcoholic. So, he called some people, and then he met Dr. Bob, who was a colorectal surgeon, very bad alcoholic, and they started talking, and eventually, you know, they were able to both stay sober, and they met a third guy, and then, you know, it sort of blossomed from there. So, it's basically a fellowship of people who share their experience, strength, and hope with each other that they may solve their common problem and help others to recover from alcoholism. That's like their mission statement. Misconceptions. There's many, many misconceptions. I have to argue these with some of my colleagues. It's not a religion. It's not a cult. It's based on spiritual principles. It's actually, they make it clear that they are not religious, and, you know, even in the 30s, they were talking about we pretty much welcome anyone as long as they want to stop drinking. Huge heterogeneity of people in it of every religion. They welcome atheists and agnostics even though they, you know, many people, you know, are able to overcome that, and it's basically, the reason why I like it is because, and we'll talk about this, so basically, what the idea is is that, you know, there's a list of 12 steps. The first one is the only one that mentions alcohol, admitting powerlessness over alcohol. The best, the rest of them are just about, you know, their idea. The idea is that, and this is part of my research, is that, you know, when you're drinking a lot, your brain becomes what I call, what we would call homeostatically adapted to heavy drinking, and they even talk about this. They say, I love this quote, their alcoholic life is the only normal one, and so every time you try to remove alcohol, as they describe you, they become restless, irritable, discontent, right, and then what do people do when they're not feeling great? They drink, and, you know, part of my research involves looking at this brain stress circuitry that may be underlying that, but, right, and so they're saying, okay, well, what do, what can you do to, what's the substitute for drinking, right, and they show this spiritual program of action that they call the 12 steps that involves taking inventory, making amends, prayer and meditation, things like that, and part of staying sober is, as Bill did to Dr. Bob, is carrying this message, and so the idea is that you get a sponsor who takes you through these 12 steps, and then you start sponsoring other people, and, you know, there's been a lot, the thing that gets me really annoyed, sorry, I'm opining, is that people will say, well, there's no evidence that AA worked, that's actually false, like, there's actually been a lot of very high quality evidence since the early 1990s that, you know, it does work, it's hard to study because, and, you know, you can't randomize people and tell them to go to AA, but in 12-step facilitation, which is a form of psychotherapy that is essentially 12-step oriented, and eventually the idea is that people go to AA, there's a Cochran interview published in 2020 that it outperforms other therapeutic modalities, so there's definitely a signal, I'm an evidence-based medicine person, there's a signal in the literature, right, so that's, you know, that's AA, it's large, it's ubiquitous, it's free, you know, people have to want to do it, but, you know, I always talk it up for people who need to be abstinent, right. Smart Recovery is also a mutual support group, self-run, self-management and recovery, it uses sort of motivational interviewing and CBT techniques, it's, you know, some people find it helpful, it's a little bit less accessible, though now with remote Zoom meetings, it's probably more so, and it emphasizes, you know, again, so CBT training for alcohol use disorder is mostly skills-based, so, you know, coping with urges, problem-solving, lifestyle balance, so a lot of those things, it's just, you know, outside of a formal treatment setting. All right, so now we'll talk about pharmacotherapy, so we have the, you know, there's the main FDA-approved ones, we have, you have disulfiram, oral naltrexone, injectable naltrexone, which is vivitrol and acamprosate, then you have the non-FDA ones, and these are some of the most commonly used ones, gabapentin, topiramate, baclofen, and prazosin. So disulfiram, its effects were, it's been around forever, so it was, it was first observed in the 1930s when workers became ill after, in the rubber industry, became ill after drinking alcohol, and then it was accident, like everything in psychiatry, a serendipitous discovery in Denmark, and then they did studies with very big doses of disulfiram, and they, and then that came, and out came antabuse, and so what does it do? So alcohol is metabolized to, by alcohol dehydrogenase to acetaldehyde, which of course is the toxic compound that causes hangovers, which is then metabolized to aldehyde dehydrogenase into acetate, which is vinegar, which you just, which is just excreted out. So disulfiram inhibits that second enzyme, acetaldehyde dehydrogenase, and then what can happen? So the idea is that if people drink on this, they can get very, very sick, like the worst hangovers of their life, flushing, tachycardia, extreme nausea, vomiting, headache, like horrible, horrible feelings. Most are self-limited, lasting, you know, 30 minutes to several hours. For people with bad medical comorbidities, you can, they can die from it, or have liver failure, and then with the, so there is that potential, we always tell people to avoid, like, food cooked with alcohol, cosmetics, things like that. The key is, and then it can rarely cause, there's rare side effects like optic neuritis, peripheral neuropathy, and the liver toxicity is like very rare, like one out of 25,000. So basically when you dose, you get baseline LFTs, and then you check them, like, it's an idiosyncratic drug reaction. So this is a common misconception. If someone has a transaminitis from alcohol use disorder, whether acute or chronic, it's still okay to start antabuse. You just have to trend the LFTs because the, one, the hepatitis, the drug-induced hepatitis is extremely rare, it's idiosyncratic, and, you know, you would just follow, you would just follow the LFTs. So you just need baseline, and then follow them, like, a week and a few weeks later. Okay, so it lasts a long time, 60 to 120 hours, but it's more, more relevant is how long the enzyme stays blocked, which is theoretically up to two weeks in real life. So you always tell patients, like, if you're gonna drink or if you decide to not take this, realize that this can last in your system up to two weeks. In real life, it doesn't usually do that. 250 to 500 milligrams, it's never, you know, it's not really clear if it's above that. This is for patients who, as I said, this is for patients who need to be abstinent. They need to be, before you start them on disulfiram, they need to be abstinent for at least 12 hours. If you remember, alcohol is metabolized via zero-order kinetics, so you think about 20 milligrams per deciliter per hour. 12 hours is pretty good, unless, you know, they have a BAL of 600 or something, which, in which case, if they're alive, then, you know, that's kind of crazy, which I've seen, but anyway. So, and then again, as I said, the two-week rule, hidden alcohol, and then, you know, you can't start the, these are sort of guidelines, but again, if they have, like, a mild or moderate transaminitis, the liver trans, so the liver transplant, I've talked to liver people about this. These are guidelines, like, with a male model of end-stage liver score disease or moderate discriminant function. It's more that they're already, you know, because they're so hepatotoxic, they're just very, very sick, and then, you know, chronic therapy, you may have a slight transaminitis. Again, it's a very, very rare, and it's idiosyncratic, the transaminitis. So, the meta-analysis, this is a very good paper, compared disulfiram versus controls, and for obvious reasons, this, it really only has been shown to work in open-label studies, when in a randomized controlled trial, they've all been, you know, compared with either placebo or other medications, they've been negative, because it's contingent, the disulfiram works because it's contingent on the fact that people know they're taking it, and the idea is, is that for a motivated patient, right, and that's the big thing with disulfiram, is people don't want to take it, or they, or even if they're being, then you need to have someone supervise them, and they may be cheeking it, or spitting it out, or whatever. So, for people who are motivated to take it, and want that guarantee, then it can be very helpful, right, but it's contingent on them knowing that they're taking it, right, and so, if you're in a clinical trial, and you know you're taking it, versus if you may be getting a placebo, and then, or, or another drug, and then you stop taking it, or whatever, it sort of makes sense that it hasn't been shown to work. All right, so, yeah, and then, if you, just another comment, is that I tend to think of antabuse as a psychotherapy, and I'm not the only one, you know, a lot of people who've been doing this a long time think about this, because it's, it's, you know, you, you learn probably for step one in the PRITE, that it's like an aversion therapy, it's really not. So, if someone is take, is motivated, and they're taking it, they're going to be, they're going to get cravings, whether it's they're walking by their favorite bar, or they see a commercial, or, or stress, like, you know, they're getting back to that restless, irritable, and discontent, their boyfriend, girlfriend, whoever, friend, husband, wife is irritating them, there's a work problem, they're low on money, whatever, and then, you know, their natural response is to drink, because drinking changes the way it makes them feel, but what antabuse does, is it basically, if they're motivated, they, then it will say, okay, I'm not going to, you know, I'm in this stressful situation, but if I drink, I'm going to get very, very sick, I have to find some other way of regulating, and so that way, it's a lot like exposure and response prevention, right? And so, you know, I think of it more, you know, there's this whole thing of, you know, does it work in the central nervous system, because there's this whole thing with dopamine beta hydroxylase, which I don't think is that relevant, which converts, which it inhibits that step, which converts norepinephrine to dopamine, or dopamine to norepinephrine, but I think it's more like on a higher level, like, okay, you know, people are essentially being forced into abstinence, they have to learn how to sort of manage these things, and it's sort of like learning a foreign language, like, what's the best way to do that? You go to a foreign, you learn the basic grammatical structure, you go to a foreign country, you don't speak English, right? You force yourself into learning whatever language it is, right? So same thing. So that's, that's antabuse. So naltrexone is a full mu opioid receptor. It's approved for opioid use disorder, obviously, receptor antagonist, sorry, and kappa and delta, but mu, at least for naltrexone is the important one. It, so basically, you have, you have GABAergic projections to the nucleus accumbens that have mu opioid receptors, and then alcohol activates endogenous opioids like enkephalin, dynorphin, etc. And those bind, and then they increase, this is, this is all theory, you know, about how, how naltrexone would work, but that increases striatal dopamine release. If you give it, then what happens is that naltrexone blocks that, and then you don't get the, this sort of striatal dopamine release. And so what that translates into clinically is that you get that it's used as a harm reduction agent, basically. So for people in whom it works, you, they, if they take it and they drink on it, rather than drinking a bottle of wine, they may have a glass and they'll describe, like, I have a full stomach feeling. I've seen this work a handful of times, maybe, and most people, they'll just say, oh, it didn't work. And that's sort of the problem you get, like in clinical trials, it does work, but then in real life, you know, these are fault, small effect sizes, right? So in some people, it can be extraordinarily helpful for harm reduction. And then the other problem is, is for people, then people are like, well, that's kind of stupid. Why do I just want one drink? I can't get drunk. I'm just not going to take it. So there's compliance issues too. But for motivated people who want to be in a harm reduction and for whom it works, it can be helpful. Some people, Dr. Wakulu likes to start at 25. I usually just give people 50. It's a stylistic thing. You can give it up to a hundred milligrams a day. There is a black box warning for hepatitis from 300 milligrams. That was, no one does that. In some of the literature, there's a signal that a hundred milligrams may cause liver problems. So you would, if you're doing a hundred, you'd want to monitor liver, liver function. And then the other thing is, is that, you know, some people will report that it does decrease their cravings. So even if they're abstinent, like I have some patients who are abstinent, but like naltrexone, because it helps with cravings. Okay. So it has an active metabolite, 6-beta naltrexol, half-life, four hours, 13 for 6-beta naltrexol. Has a pretty quick time to peak, an hour. And then I think the liver functions, I don't get them for 50 milligrams. And if I were to prescribe someone a hundred, I would get them. And again, these are the sort of baseline LFT rules. These are in the guidelines. Again, you know, I think they're at least for 50 milligrams, I would consider them kind of loose because again, you have to balance like, okay, if someone is continuing to drink, that's definitely going to cause liver problems versus antabuse. You have this rare idiosyncratic reaction, naltrexone, really the, it only causes problems when you're at mega high doses. So, you know, those are all things you have to, what I would convey is do not let a slight elevate, do not let a slight transaminitis or even a moderate transaminitis be a barrier to treatment. You just have to understand what you're doing. Okay. So the Deponaltrexone, the Vivitrol, it's really, it's embedded within a polymer that's supposed to last about 30 days. Same with opioids, 380 is the approved dose. It peaks at about two hour, you have a peak plasma concentration, two hours and then three days. And then the elimination half-life is five to 10 days. You have after 14 days, so that's about the T max levels tend to decline. And then some for patients, sometimes they'll, you know, they'll, the effects will start to drop off, and this is true for opioids too, at about three weeks. Ideally, what you would do is give more frequent dosing because that would decrease the peaks and troughs, but then the problem with that is insurance usually. So again, this helps for compliance with treatment, technically hepatically safer since it bypasses first pass metabolism. It helps with decreased alcohol use and abstinence. And then this was the pivotal clinical trial, now done almost 20 years ago, that people in the 380 milligram group did the best and were able to reduce their heavy drinking. Or reduce their heavy drinking. All right, so Acamprosate has been shown, this is approved in the US based on European trials. It has never been shown to work in a trial done in the United States. It's thought to modulate glutamate and GABA. We don't really know how it works, but the idea is that you have this chronic GABAergic glutamatergic dysregulation, like you have the acute ones, but then you have this persistent dysregulation that may be contributing to this, protracted withdrawal phenotype. And then so for people who are already abstinent, GABA, or sorry, Acamprosate may be helpful in preventing relapse. And so, and then also helping with some of these, by helping some of these negative affect syndromes, it doesn't have liver, it's renally metabolized, so you don't have to worry about liver problems. I have honestly never seen it work. I don't prescribe it. I think it's still, you know, it's this, it's the TID regimen, ominously 666 milligrams. I don't, you know, I talk to patients about it. It's not my go-to. I think I prescribed it a handful of times and I've not seen it to be helpful, but it is a tool, it is FDA approved. So, you know, if you can get insurance to pay for it and all these other things, and someone is willing to take it three times a day medication, may be useful. All right, so you don't need to dose adjust for mild renal disease, but for moderate disease you do. Severe disease contraindicated. You can have nausea, lose stools. Again, only been shown to work in European trials, American trials negative, right? And then, so again, it's abstinence. It's an abstinence-based treatment. And then the combined study failed. This was the landmark. These were the landmark American trials. They failed to find efficacy. All right, and there's various theories about that, why that is, but yeah, so that's a camper's aid. Gabapentin is an interesting medication. We use it a lot in psychiatry, as you've probably discovered a lot off label. It's approved for neuropathic pain. Despite, there's still this misconception. It does not, but the sort of total, the totality of evidence would suggest that it does not act on GABA or glutamate for that matter in any way. It's an alpha-2, it's an alpha-2 delta subunit binding voltage dependent calcium channel blocker. So it inhibits neurotransmitter release, but it does not act on the GABA receptors in any way or change levels of GABA. So it's non-plasma protein bound. It has a very fast half-life, five to seven hours, very fast time to peak, two to four hours. There's a lot of literature on it in the alcohol use disorder world. So the 12 to 1800, even we had a study with 3,600 milligrams it can both produce, it can reduce consumption, improve sleep and cravings. And it works in combination with naltrexone. And then also this was a study published a few years ago that it can help, it may be particularly helpful in people who have had withdrawal histories, thought that, okay, it works on this idea of protracted withdrawal, negative affect. And the recent meta-analysis showed that it's usually helpful for people, that it can be helpful more for reduced heavy drinking rather than abstinence. But I think it's good. It's renally clear, you can keep increasing the dose so long as people aren't sedated. Again, we published on 3,600 milligrams. So I've used it somewhat successfully. And again, you always have to weigh risk, benefits, availability, all those other things. So yeah, so that's gabapentin. Tapiramate, it was originally an antidiabetic. It's mostly used for migraines and epilepsy. It's renally cleared. It works on GABA and the GABAergic and glutamatergic systems. So it reduces, it's been shown to reduce heavy drinking and decrease abstinence. The problem is the side effects. The meta-analysis show it works, but you have to increase it to basically 300 milligrams. And what do you hear in the neurology service? They call it Dopamax because it basically makes people stupid. And then you can get, there's acute angle closure glaucoma and metabolic acidosis. Those are a little bit more rare, but the cognitive one are the more, are the more problematic side effects. I tend not, and again, it's a slow titration just because of side effects. I tend to not use it in actually a lot, and just for a lot of those reasons, it's definitely not my go-to. Other people like it. I will, again, I will always talk about it, but it's an option. Yeah, baclofen is also interesting. It's a GABA-B receptor agonist. So again, alcohol and benzodiazepines act on the GABA-A receptor, which is nicotinic. GABA-B is muscarinic. And it's been shown, the evidence is sort of mixed, but it's been shown basically at low doses to work on, right, with reduced lapse to drinking and greater likelihood of abstinence during treatment at doses under 60 milligrams. There's a recent study where they looked at sex differences and really the effect was seen at women at 30 milligrams with a marginal significance for men at 60 milligrams. That was published a couple of years ago. Frazacin is, as you know, an alpha-1 blocker. It's used in PTSD for nightmares. It's very short-acting, works quickly. It's shown for, you know, it's been shown both for patients with and without PTSD as a promising pharmacologic treatment, specifically for working on abstinence, reduced affect, and heavy drinking as well. Right, and so you have, the way they did these trials is increased it to 16 milligrams over the course of a couple of weeks. And rates of drinking and heavy drinking showed a greater decrease in Frazacin compared with placebo and then side effects, drowsiness, and edema. Again, alpha-1 blocker. All right, so psychedelics, these are interesting. So this was published 2022 or, yeah, 2022. You may have seen it with psilocybin where they compared people, where this was a randomized controlled trial and there was a significant reduction in heavy drinking. So that's something new. There's an ongoing trial with LSD. You know, obviously in all of psychiatry, this is a new, old idea that has been around forever, but now, you know, there's a psychedelic renaissance. Ketamine, there's now a couple of clinical trials showing that ketamine infusion combined with mindfulness-based therapy is associated with abstinence. You know, these are all sort of things under investigation, the Neurokinin-1s. And then also the other thing that, you know, is the GLP-1 agonist or the GLP-1 receptor agonist like Ozempic, Wacovia, the semi-glutides. There was a trial with Exenatide, which is an older generation, which was negative actually, but that has a 50% homology to human GLP-1, whereas Ozempic, Wacovia are like in the nineties or close to a hundred or semi-glutide. And actually, if you look at the glycemic in the diabetes literature, they do get better glycemic control with semi-glutide than Exenatide. And so there's, I think last I counted like four or five ongoing randomized controlled trials with the GLP-1 agonist. And, you know, just anecdotally people have said, like even people without alcohol use disorders have said like, wow, I don't want to drink anymore. So there may be something there. Again, there's a reason we do clinical trials because anecdata is nice, but at the end, it's just anecdotes. Okay, so this is Dr. Waklu's algorithm. He bases it off of like MELD score, but, you know, he likes a camper's aid, but, you know, this is just an example algorithm. So, you know, I think it's up to your own, you know, I tend to ask, well, what are your goals? If you're abstinent, I think if you can convince people to take Antabuse, that's, you know, the gold standard. If you're, if they want to do a harm reduction and you talk about Naltrexone, then I think about, okay, you know, other things, Gabapentin, Baclofen, I think are more of my go-tos. And then, yeah, and then from, and then going from there. And obviously you treat psychiatric comorbidity too. Okay, and then these are just resources in the, in your area, in the, so right, the New Jersey Society of Addiction Medicine has treatment resources, and then this is from, the treatment atlas is from the New Jersey Department of Health. Okay, and then these are just some references. Okay, all right, so we have some time. So does anyone have any questions? Thank you for that very informative, thorough talk. I have one question, then I'll turn it over to the trainees, which is, you know, a lot of times when we're on like a consult service in the hospital, they're on the, you know, the medical floors, we get all kinds of, you know, very frequently get consults on like withdrawal and alcohol use for patients, right? Some medically compromised and whatnot. And I think one of the things that we always kind of talk about is like, I guess, sort of, in your practice, in your experience, what the data says, when do you feel is the right time, you know, to kind of start some of these treatments like you've talked about with naltrexone or otherwise, you know, like at what point is it in the withdrawal, a few days after the withdrawal, like what is your sort of suggestion? Because we don't often know like where they're going post-hospitalization. We don't know if they're actually gonna follow up, you know, with the substance use program, even if we get them the right referrals. So just kind of your thoughts on that. Yeah, so there's a, I mean, the classic model is you detox them first, which, you know, is mostly a fairly straightforward process. And then, but you know, there's not absent any strong contra, medical contraindication. Like once the alcohol is out of their system, there's really not a pharmacologically logic reason. Now it's not conventionally done. This is just my take on things is that there's not really a, there's not a medical contraindication for starting some of these things, as long as the alcohol is out of their system. And, you know, there's not some other medical reason why they can't be started on them. Like while they're, now, if they're in DTs, that may be like a separate issue. You'd wanna get that. But if it's like mild withdrawal that, you know, they're on a basic benzotaper, then it's, you know, I would say it's fine. The problem is always going to be follow-up, right? Like, you know, even if your hospital system will pay for the Vivitrol shot, like, you know, again, you can, again, as long as there's no opioids on board, you can probably, you know, there's, they would, they do recommend a test dose of like either naloxone or oral naltrexone before you get the Vivitrol shot. But that's more for opioids, not so much alcohol, but, you know, that could be something to even try. I would, you know, I would still try like oral naltrexone, like one dose of oral naltrexone first, but yeah. So, I mean, I think sooner rather than later, but again, the problem is always going to be follow-up motivation, things like that. But yeah, no, as long as they're like coherent and, you know, they understand, you know, the implications, I think it's fine to, you know, begin the conversations, even if they're having some withdrawal symptoms. All right, thank you. Yeah, go ahead. Hi, I'm Donna. I'm a psychiatry intern in Spirit Health Network. Thank you for your great talk, by the way. I really appreciate it. The question I had was that when managing alcohol withdrawal, I know there's different styles of CIWA protocol, the neuron taper, and I was curious if you had thoughts on which, you know, like, yeah. So, this is a very hotly contested issue that I don't think should be. So, there's more of a philosophical point of everyone wants everything protocolized for, you know, good reasons, because it's supposed to make things, you know, like idiot-proof, but that's not always the case. So, one, alcohol withdrawal is a clinical diagnosis, right? So, as the physician, you have to, you know, make sure it's not opioid withdrawal, make sure it's not like malignant hyperthermia or whatever else, right? So, you have to make the diagnosis, right? And then, I prefer to treat symptomatically, right? So, I don't even, I think, I mean, so CIWA has been shown to work with experienced nurses in like detox, in clinical trials and detox settings in terms of fewer, faster detox time, fewer benzo requirements. When I was a resident at Wash U, people just kind of, when I was an intern, people just kind of did their own thing. Then they tried implementing a CIWA. When I was a PGY2, it was a total disaster because the medicine floor nurses weren't trained on it. And that, like in psychiatry, like on the psych floor, they like all knew how to do it because that's, you know, that was it. But so, you know, I personally don't, I don't use cows. I don't use CIWA because like I get there, I view them as research tools, the cows especially, you know, and this is like heresy if I were to, you know, say this out loud, but this is just my opinion, is that, you know, you want to have someone on getting regular benzos. And for alcohol withdrawal, you're not going, most of the time, you know, it's very hard to give them too much, right? And then if it seems like their symptoms still aren't controlled, they need to go to the ICU. Now, for example, at like Mass General and San Francisco General, they prefer phenobarbital based or barbiturates where they, you know, at Mass General, they basically give them a mega loading dose and send them out, which pharmacologically may be better. I mean, there's not a, you know, there's not, their data is all retrospective and you need a randomized controlled trial to show it's better. But I mean, and, you know, barbiturates are, you know, a little bit more complicated, but I think if you have like benzos have been shown to reduce seizures and DTs, they're not that hard to use. And I prefer Valium because you get, it's a faster, it's the most quickly absorbed. You have long acting active metabolites. It's very easy to dose. You can give it parenterally if someone has like malabsorption problems. The whole thing with, you know, I know you learned that, you know, if someone has liver problems, you're supposed to avoid, you're only supposed to use lorazepam, oxazepam, and temazepam because they bypass phase one oxidation and go in or metabolite or phase two oxidation and are metabolized hepatically or renally. You know, I mean, I don't think that's as relevant. You can give Ativan if you want, but I generally go with Valium. I just think it's the, I just think it's the easiest. You, I personally think, again, this may be in violation of like, you know, these protocols and things, but, you know, as a physician, you always, you know, you're not wrong if you think, you're not wrong if you're thinking about mechanism, right? So what is the mechanism? You have a glutamate, you have a glutamatergic GABAergic dysregulation. What does the evidence say? Benzos work. Benzos are GABA agonists, right? So, you know, I think you do that, you know, and if you have a CWA and you're not sure of the nursing staff, I would keep an eye on it because they may miss doses. They may not be doing it at night and the CWA is supposed to be done every, you know, however many hours. And if they miss doses and I have seen this happen, the patient wakes up and they're delirious and then you have a DTs and then they have to go to the unit, which could have been preventable, right? So, you know, you always, what I guess my, what I'm saying is, you know, do not just click the CWA box and say, this is what I did. You wanna be paying attention to it. I think that's not if we do have more questions, are you okay if we send an email or yeah, of course. Of course. Yeah. Any email me with any questions, clinical or otherwise related. Yeah. Okay. I really appreciate your time and giving us this talk. It's really informative and helpful for our practice. So, so thank you. Awesome. Yeah. Thank you so much for coming. Yeah. Thank you. All right.

alcohol use disorder treatment

pharmacotherapies

Clinical Institute Withdrawal Assessment for Alcohol

symptom-based approach

emerging therapies

individualized care

Dr. Benjamin Shreve

substance use disorders

patient goals