Pharmacologic Management of Substance Use Disorders Part 2 PDF

Pharmacologic Management of Substance Use Disorders Part 2 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... Pharmacologic Management of Substance Use Disorders Part 2 All righty, so here really is the for-real last slide...

Pharmacologic Management of Substance Use Disorders Part 2 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... Pharmacologic Management of Substance Use Disorders Part 2 All righty, so here really is the for-real last slide set of this entire semester, part 2 of the pharmacologic management of substance use disorders, speci!cally, relapse prevention therapy. So we will just get right to it. Relapse prevention obviously is very di"erent than acute medical detoxi!cation. And again, we certainly don't have pharmacologic strategies for relapse prevention for every substance of abuse. But we do have them for alcohol, and we have them for opioids. And those two are a big deal because they are among the very most common. So in case it slipped your mind, in case you didn't hear it 47 times when I said it in the !rst slide set, medication- assisted treatment protocols, I mean, they really are-- it's a comprehensive program. And the medication must be used along with counseling and support programs. Patients just aren't going to do very well without it, and we discussed that before. And I mean, I don't mean to imply that every patient is just drug-seeking and has no interest in relapse prevention because that's not at all true, even some who are the very best- intentioned. Like I said, relapse is part of the recovery process. You really have to anticipate it, and don't be surprised if it happens. It always bothers me when I see programs where if the patient has one positive drug screen that they discharge the patient from the program because part of preventing relapse is anticipating that there will be relapse and then identifying why that happened and what, if anything, you can do about it, which usually is a part of that nonpharmacologic piece. So anyway, relapse prevention is enormous. This is like the rest of your life. This is if you are familiar with Prochaska and DiClemente's theoretical-- the transtheoretical model of change, where they describe the various stages of change that patients are going through, whether it's stopping the use of a drug or alcohol or trying to have healthier lifestyles for weight reduction or smoking cessation or for that matter, even 1 of 14 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 2 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... taking a pill for high blood pressure or using an inhaler for asthma. Every intervention that we prescribe for our patient requires a change in their world in some way. And this transtheoretical model of change describes the !ve stages of change. And it helps us understand that change is a process. There are several stages people go through, and they need di"erent levels of support at di"erent points in the change process. And the last stage is maintenance, and that's the rest of their life. So you get through this whole process of implementing a change. In the world of substance use disorder, you actually get to D-day, where you stop using the substance. And now it's a di"erent challenge to not use it again for the rest of in!nity. And that's what relapse prevention is all about. So it's huge. I mean, it's obviously among the most challenging. Like I said, acute detoxi!cation, that's easy. Yeah, I mean, that's easy to medicate that and get people through it safely in a week or two. It's relapse prevention that is hard. So we have a few options, and that's the purpose of this discussion. Now to prescribe medication-assisted therapy, at least, to prescribe some of them, you need an X-waiver from the Drug Enforcement Agency. And the requirements for X-waivers are actually changing. It used to be that we had to have 24 hours of continuing education, very speci!c to substance use disorder management and relapse prevention therapies. But very recently, sometime in 2022, I believe that requirement was dropped. The CE requirement was dropped as long as you were managing less than 30 patients. And it's just because the need is so intense. But even if you don't require formal continuing education anymore to be an X-waiver provider, you still certainly want to know what you're prescribing, know how to use it. And that's why it's worth going through this slide set. So the !rst option discussed here is methadone. Methadone is old school. We'll tease it out in speci!c slides for the next few slides in the discussion. But methadone is one of the very !rst opioid relapse prevention therapies. And it still does have a role now. Since then, we have seen the emergence of buprenorphine and naltrexone therapies, which really have become more of the standard of care or the gold standard for relapse prevention. And there's all di"erent sorts of formulations available. And each of these are appropriate for di"erent people in di"erent circumstances. 2 of 14 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 2 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... And sometimes these are used for years. I mean, the whole goal is to keep people from relapsing. So if they need these medications to help them relapse, then we should continue it because it is absolutely better than having them relapse into an opioid use disorder. So don't feel compelled to put any particular time limit on this. I mean, of course, many people, at some point, may get to the point in their lives where they want to try to come o" medication-assisted therapy, and that's great. But there are people that need them for the long haul. And that's OK, too. So as I mentioned, methadone has been around for a very long time. It is an opioid, but it's a di"erent kind of opioid as compared to all the others. It is used for pain management sometimes in patients that need long-term opioid therapy. But the potential adverse e"ects-- [clears throat] --excuse me, have really limited its use in both opioid use disorder and chronic pain management. A couple of unique things about methadone, like the slide says, !rst of all, it has a very long half-life. So-- [coughs] Excuse me. If we're using it for relapse prevention, it can be dosed at once a day and that's su#cient to keep the patients out of any withdrawal phenomenon. And when you're using it for chronic pain management, remember, we said that for people that need it-- and believe me, nowadays if you're on methadone for chronic pain management, you really do need a long-term opioid. And so then again, a long-acting opioid would be the way to go to minimize that post- dose euphoria. You don't get euphoric with this. It's not a-- it's a di"erent chemical structure in that it does o"er some pain control. It's not as intense as some of the others. But it really does not produce the euphoria. And so that really, it's substituting one opioid for another. But this is one that allows people to be more functional and doesn't lend itself to abuse. The dosing for methadone varies enormously. Excuse me. Remember we were talking about how when people use opioids for the long haul, their tolerance just builds and builds and the doses go way, way, way up. And those formulations are unbelievable as compared to what an opioid naive patient would take. So in terms of dosing methadone for relapse prevention, we generally start-- oh, gosh, no more than 10 to 20 milligrams a day. 3 of 14 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 2 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... Absolutely, we don't start over 30 milligrams a day. But then we can escalate signi!cantly. I mean, there are people that are on hundreds of milligrams of this stu" a day. But one of the real safety issues to keep in mind is that it can prolong the QT interval at more than 40 milligrams a day. This is pretty well-documented. So anybody with any remote risk of dysrhythmia or cardiac toxicity, this really isn't a good choice for them. This also has to be distributed by SAMHSA-approved centers. This is not something that you can give a patient a prescription for, and they go !ll it, and then go home and take it on their own on a daily basis. They have to go to a distribution center on a daily basis to get this. On the upside, it is very inexpensive. It is very readily available. It essentially forces the patient to stay involved in a program because they have to go to the center every day to get it. And very often, it will require that if you go on Tuesdays and Fridays, you have to go to a group or something like that. So it is a"ordable. It does the job. Some people prefer this. And so there de!nitely is still a role for it, but it's the safety issues that have limited its use. You can still overdose on this. You can still abuse it. I mean, there are patients that will just dose up on this to try to get any opioid relief rather than a structured relapse prevention program. It is also interestingly a substrate of the cytochrome P450 1A2 isoenzyme, which is an enzyme that is induced by nicotine. So cigarette smokers tend to accelerate metabolism of this drug. And not surprisingly, people recovering from substance use disorder smoke more than the general population because cigarette smoking is like the last thing to get rid of it. Patients that are in programs and in relapse prevention often have to give up lots of other things. They're giving up alcohol, drugs, giving up the lifestyle and friends that made that stu" available to them. And for whatever reason, cigarettes seem to be the one thing that people hold on to. And it's the one thing that we don't-- I mean, we don't ever want people to be smoking. But we recognize that if they need that to get them through all of the other life changes they're making, we don't push it very long. So anyway, you will just !nd that a lot of your people with use disorders that are in recovery do tend to be smokers, which, of course, now will induce metabolism of methadone. I can actually share with you a brief story. This was a case study. I mean, it's not my-- it didn't happen to my patient. It was a case study that I found in literature once upon a time and use it to illustrate cytochrome P450 interactions. 4 of 14 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 2 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... It was about a male patient who was-- he was a veteran. He was a patient of the VA. And he had-- excuse me. [coughs] He was on methadone for chronic back pain. [coughs] Excuse me. And he was on a pretty high dose for a long time. He was a smoker. And I forget what the dosage was on, something like 80 milligrams a day. And then, out of the blue-- at the time, it seemed like out of the blue, he basically became obtunded. I mean, he just, sort of, a pre-comatose, stuporous state. And so his family unit got him to an emergency room. And it was an opioid overdose basically. And yet the providers that managed him were certain that he was not abusing it. He had had a long history of being stable on his methadone. The family indicated that there was nothing going on that would change that. There were no concerns. And so he was, all of a sudden, after years of being stable on methadone, he was methadone overdosed. And !nally somebody !gured out that what happened was he had quit smoking. He was !nally at that last stage of his use disorder recovery where he was !nally ready to give up the cigarettes. But when he stopped smoking, he stopped inducing the 1A2 isoenzyme. So he stopped inducing the enzyme that metabolized methadone. So he didn't metabolize methadone as e#ciently, and it built up in serum. And that's how he became methadone toxic. And it was just because he stopped using the thing that accelerated metabolism of methadone. So they held it for a while. He got better. And then his maintenance dose of methadone was just decreased because he didn't need that much anymore because he wasn't inducing metabolism of it. So I mean, like I said, it still has a role. It's not a !rst-choice drug anymore. But there are times when you'll see people on it. We don't throw out the baby with the bathwater. Just because we have things that are more contemporary or more trendy, it doesn't mean there's not a role for methadone. Next up though is the 21st century golden child of opioid relapse prevention and that would be buprenorphine. So buprenorphine-- I mean, it is also an opioid. So it can also be abused. It's not like it is the total gold standard, and you can't abuse it. Like methadone, this can be abused, and that's why it's so important to make sure that our 5 of 14 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 2 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... patients aren't in-- they are in their comprehensive program. We don't just give out buprenorphine. We prescribe it in conjunction with the nonpharmacologic components of medication- assisted treatment. So you do need the X-waiver to write an order for buprenorphine or dispense it. So the DATA 2000, that was the Drug Assistance Treatment Act that was passed in the year 2000. And that's what developed the X-waiver that you can apply for from the DEA. So to prescribe controlled substances, you need a DEA registration. And you'll have a DEA number that begins with two letters. One of them is the !rst letter of your last name and then the other one designates the level of provider that you are and then a series of numbers that I forget where they come from. But anyway, they're very speci!c to you. And then if you qualify for the DATA 2000 waiver, you will have a second DEA number that instead of the same two letters, one of those letters becomes an X. And that's what tells the pharmacy that you are authorized to prescribe these substances, and they can !ll your prescriptions. And like I said, up until very recently, you had to have a SAMHSA-approved 24-hour CE program to be eligible for it. But just this year, I believe that they have removed that requirement. Anyway, buprenorphine really is the golden child of relapse prevention for opioid use disorder right now. And it comes-- I mean, there's all formulations available. There's all sorts of ways you can take buprenorphine. Buprenorphine's mechanism of action is really very straightforward. All opioids bind to mu receptors. That's how they control pain. And so some opioids are very potent. When they bind to mu receptors, they produce a great deal of pain relief and typically, associated euphoria, and other opioids, less so. Buprenorphine again-- I mean, buprenorphine is a pain management drug That was its origin. It is an opioid agonist. But the things that make it very useful for relapse prevention is that it has a very high a#nity for opioid receptors. So if there's a couple of di"erent opioids on board like heroin and buprenorphine, buprenorphine is going to get to the receptor !rst. I mean, they're both competing for the same receptor. Buprenorphine is going to win because of the higher a#nity. At the same time, buprenorphine is only a partial agonist. So it just doesn't give as much e"ect. So if someone is taking buprenorphine and they're on a buprenorphine relapse prevention program, and they happen to relapse and try and use heroin or fentanyl or oxycodone or whatever is their opioid of choice, with the buprenorphine on board, the other 6 of 14 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 2 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... opioid can't bind to the receptor and can't cause the response. That's the idea behind this partial opioid agonist. And it's the combination of the high a#nity, but the partial agonism, that makes it a good choice. But it is an opioid. It can be abused. So like I said a few slides ago, patients really have to be invested in the entire medically-assisted treatment program because they still need to have those nonpharmacologic aspects of treating a use disorder. It's not just about the buprenorphine because it is potentially subject to abuse. It's not as-- it doesn't make people feel as good, and it doesn't make people feel as high as another opioid. But it's better than nothing, basically, is what the patient response to this will be. So here's a visual of what it does. Let me see if I can grab my little laser pointer here. So before anybody takes anything, they have no e"ect, no e"ect and no dose on board. The x-axis here is the dose, the higher the dose you give, and then the y-axis is the greater e#cacy. So opioids bind to mu receptors. They are agonists. Remember again from the !rst week of class, we talked about agonist and antagonist. And I'm sure that was a review of your more generic pharmacology course. Anywho, both buprenorphine and all the other opioids are mu receptor agonist. If you take heroin, you get a complete agonist. You get lots of binding, and you get high. If you take buprenorphine, you only get partial agonism. So no matter how high you go with the dose, you're just not going to get that much e"ect. There is a ceiling e"ect. There comes a time when even the higher dose is not going to make any di"erence. And so this is-- again, it's substituting one regularly scheduled opioid administration for another. It's substituting buprenorphine for the opioid of choice, which is better than not being in a treatment program at all. But it's still an opioid. It's still a pill the patient has to take every day, and it is still subject to abuse. It's just a lot better than the other opioids that get abused. And that's the whole concept behind buprenorphine. It is again the combination of high a#nity for receptors as well as the fact that it is only a partial agonist. So if you're using buprenorphine and then you happen to relapse into heroin or fentanyl or whatever, you just don't experience the euphoria. And this is just another way of looking at it. Now on the $ip side, if you are high, if you're very new and you've just decided that you're going to go into a treatment program, and you still have a signi!cant serum level of the last opioid you took, we have to be very careful about introducing buprenorphine. 7 of 14 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 2 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... Now as time has gone on, we've gotten more and more aggressive about establishing it early. The general rule of thumb is to not begin buprenorphine until the patient is experiencing some level of withdrawal symptoms. And the reason is-- I mean, think about the mechanism of action we just talked about. If you've got a lot of heroin on board and you're just feeling good and you're high, and right then, you take buprenorphine because buprenorphine has a higher a#nity for mu receptors, it is going to displace the heroin and you put the patient into precipitated withdrawal. It's just counterintuitive to the whole treatment plan. So we want to wait until the patient is already in withdrawal. Not till they're-- not to the point that they are so uncomfortable they just want to go back to using. But we do need to wait until withdrawal is established, and then we introduce the buprenorphine, which will give them a little bit of relief, but more importantly, prevent it from getting any worse. Like at this stage of the game when they're just starting to have withdrawal symptoms, their primary pharmacologic treatment for that, remember, is acute medical detoxi!cation. They'll take something like clonidine. But we introduce buprenorphine here, and then it's going to become the long-term relax prevention drug. And the general rule is to not begin the buprenorphine until the patient's COWS score-- remember, that's the Clinical Opioid Withdrawal Score, until that is greater than 8, which evidences some level of withdrawal, but it's not intolerable. Now I mean, this is an evidence-based guideline. You will de!nitely see di"erent twists on that in clinical practice. But that is if you're new to practice and you don't have any experience with this, and you take a job and you take a position where treating substance use disorder is a signi!cant part of what you do, then you can never go wrong by starting with evidence-based guidelines and see how it works for your patient population. And in that circumstance, you would not introduce buprenorphine until the COWS score is greater than 8. Some centers will say greater than 10. Others will say even down to 6. There's a little wiggle room there. But generally speaking, we don't start until the COWS score is 8. Once you decide that you're going to put the patient on buprenorphine for medically-assisted treatment, then you have to decide how you're going to administer it. So it comes in numerous formulations. There are oral forms, oral !lms. There are injectable forms. There are long-acting forms. There's also combination forms with naloxone, which is an opioid antagonist. And that really generally tends to be preferred. 8 of 14 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 2 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... Combining it with the opioid antagonist minimizes the risk of abuse. So it's not like you're just taking an opioid agonist, even a partial one alone. So there are many excellent formulations to choose from. An experienced patient who has been through this before may request that they have a formulation that does not have naloxone in it. And there's really no good reason to do that unless-- well, I guess really-- I mean, there really is no good reason to do that. It really is just about provider preference. So buprenorphine comes as Subutex or Subutex, which is the buprenorphine alone, and Suboxone, which is in combination with naloxone. You probably !gured out that out by the name. And most of the injectable formulations and the alternative formulations are primarily buprenorphine on its own. So there's just di"erent options for di"erent circumstances, and that's for you to decide. In terms of adverse e"ects, buprenorphine is an opioid. So the adverse e"ects potentially are similar to other opioids. The risk of respiratory depression is less because it is just a partial agonist. But like methadone, this can prolong the QT interval, although methadone in higher doses is really more of a concern for that. And buprenorphine can precipitate anxiety, which is a bit of a concern because anxiety can lead to relapse in some patients. So this is not a magic pill or a magic !lm or however you use it. This isn't something that you just take it, and that's the end of that, which is why, again, it's so important that this just be part of a comprehensive program of relapse prevention maintenance. It's not just about the pill. It's not for everybody because of some of these adverse e"ects, and it requires ongoing monitoring. These are a couple of the combinations that are available. So again, I'll have to read to you. We have combos that are available-- as !lm combos that are available as sublingual tablets. And again, keep in mind that naloxone is an opioid antagonist. So it is perhaps even more important to make sure that the withdrawal is !rmly established. Now the last bullet point here on your slide says that the combination with naloxone is not recommended for induction therapy, meaning not like in the very beginning when they just hit a COWS score of 8. That's a little bit dated. More contemporary places are using the combinations now for induction therapy just because the belief is that abuse and relapse prevention is enhanced by the introduction of naloxone. It's just really most important to make sure that they are !rmly established in 9 of 14 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 2 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... withdrawal or these medications would actually precipitate it. Now naltrexone alone is also used for relapse prevention maintenance, and it does come in daily oral forms. It comes in injectable forms, and this is a pure opiate antagonist. So obviously, the bene!t there is that it is not a drug of abuse. It has no opioid agonist activity. It's not something that people can abuse. The downside is it is contraindicated in patients taking opioids. And I know that you're probably thinking, well, isn't that the whole point here is that patients not take opioids? And that's true, except that there are circumstances where people with an opioid use disorder in remission do from time to time need to take opioids, if they have an abdominal surgery, if they have a traumatic accident, like a femur fracture or some other very painful thing, maybe now they have to have their-- and this does happen. People that have use disorders, they fall o" the grid. They don't take care of themselves. And then when they go into recovery, they start becoming aware of various physical ills and go have them taken care of. And one of the things that is very often left alone is the mouth. So people start to feel better and then realize that their mouth hurts, their teeth are a mess, and sometimes need really exhaustive dental work. So these are all circumstances where patients may really very legitimately require an opioid for pain control. And if you're on naltrexone, you can't take it. So there is that. I mean, it is de!nitely the exception than the rule, the signi!cant majority of people in opioid relapse prevention maintenance will not be taking opioids. That's the whole point. But there is that risk that if something unplanned and traumatic and unexpected happens that they can't take an opioid for pain control while they're on naltrexone. So it's a discussion that you have with your patient. And you and the patient decide what's the better option. I mean, it is a real plus that these are not drugs of abuse. As with buprenorphine, there are various formulations available, their oral formulation, ReVia. There's the injectable formulation, Vivitrol. And these are pure opioid antagonists as I've mentioned. And they also are e"ective for alcohol relapse prevention. You notice the last bullet point here says the mechanism of action is not understood. We see that, unfortunately, more often than we would hope when looking at medications. And so right now, the mechanism of action is not well-understood. But the relationship is observed. People who are on naltrexone relapse prevention, they do have less relapse to alcohol. 10 of 14 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 2 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... So just like aspirin and many other old school drugs, we might not know how it works at this point. But we know it safely works. So we use it and then maybe 50 years from now, somebody will research it and !gure out why it helps prevent it. So the oral formulation is marketed as ReVia. And so this is-- now when you read about this in your book, it will tell you that if you're using it for opioid relapse prevention, in the beginning, you'll want to do a naloxone withdrawal test. And you give the patient a small dose of naloxone and make sure that they don't have any withdrawal symptoms. You want to make sure the opioid is !rmly removed from their body, yeah, the naloxone challenge test. And then once they do not have a reaction, once there are no withdrawal symptoms with naloxone challenge test, then they can be maintained on this. It's titrated to 50 milligrams at bedtime, and that's the daily form. And so the advantage to the daily form is that if you need to stop using it, it washes out of the system pretty quickly. The downside is A, the patient has to remember to take it every night, and B, they actually have to take it every night. So I mean, there's a certain patient for whom this is appropriate and another patient for whom it is not. Conversely, Vivitrol is the injectable formulation of this. This is given once monthly by a health care provider. So you can see the risk bene!t analysis here. The fact that it is given by a health care provider ensures that it is given. This isn't something that a patient can forget to take. On the downside, this is-- if you need emergent opioid therapy, like if you're driving home from your injection and have a car accident, it's going to be very di#cult to achieve pain control, so there is that. So like with every drug in every class of every disorder that we talk about, we virtually always have multiple options within a drug class. And you just have to evaluate the risks, bene!ts for each patient scenario. Obviously, you can see how there are some persons for whom the injection is preferable and other patients for whom the oral formulation is preferable, but they're the same thing. So that's opioid relapse prevention. And then as I say, naloxone or naltrexone alone is also used for alcohol relapse prevention. Now we do have some other options for alcohol relapse prevention as well, and they're on the next few slides. So well, naltrexone, we've already talked about. And so that really is the majority of the slide, isn't it? 11 of 14 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 2 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... But also notice here at the top, we have acamprosate. This is marketed as Campral. This is an old school drug. It's been around for a long time. And it always catches my eye when I look at the dose formulation. There's just something about that 666 milligrams three times a day that I wish was any other dose formulation, but it's not. And that's the dose. And so downsides and upsides here, the downside obviously is the TID formulation. It's hard to remember to take any drug three times a day, much less something that you're going to have to take for the long haul. But it does have a di"erent mechanism of action. It is an option both for patients in whom the opioid antagonist is not indicated for any reason, or sometimes it is used in combination with naltrexone injectable like you can see by the last bullet point there on the right. But its mechanism of action is di"erent. And it's another one of those mechanism of action is unclear, one of my favorite phrases. But like almost all other medications in psychiatry, it is theorized to restore normal or near-normal balance of neurotransmitters. And in this case, the neurotransmitter is glutamate. Remember that glutamate is the most common excitatory neurotransmitter in the brain. And it is believed that Campral modulates the e"ect of too much glutamate activity that occurs after the patient withdraws from alcohol. So remember, when you stop using alcohol, alcohol is a sympathetic nervous system suppressant. It is like a GABA agonist. It actually depresses sympathetic nervous system activity. So when you stop using it, your sympathetic nervous system wakes up and goes into overdrive. And it is theorized that a primary neurotransmitter that modulates that is glutamate because glutamate is an excitatory neurotransmitter. So after you stop using alcohol, you become hyper-glutamatergic, interesting word, glutamatergic. And so Campral is theorized to modulate that, and that's how it works. And so it can be used alone, or it can be used in combination with Vivitrol. The formulation is 333, but you have to take two of them three times a day. So it's a cumbersome and clumsy drug in that respect. But sometimes it is the drug that people just do best with. You just don't know why some people do better with one than the other. But this de!nitely has a role. There are some people that do very well with it. And they just structure their day in such a way that they get in the habit of taking it three times a day, and that's great. So that's it. Let's see. If you miss it, you don't want to double this one up. This is just if you miss a 12 of 14 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 2 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... dose, you miss a dose. You just stick with your regular schedule next time around and then try to !gure out why you missed it. And if it's something that you can correct for the future, you do. But this isn't something you double up on. There are-- like every medication, there is the potential for adverse e"ects. They are conveniently located here on this last slide. And so not comfortable but they're also not fatal. And they're not as bad as having an alcohol use disorder. And so you know the next phase here, risk bene!t analysis. It is always about risk bene!t analysis. And the last relapse prevention drug I wanted to talk to you about is disul!ram, which is marketed as Antabuse. This has a di"erent mechanism of action. This isn't a medication that is supposed to attenuate craving or desire. This is $at out aversion therapy. This is a medication. It's taken once daily. It blocks the oxidation of alcohol, allowing toxic metabolites to accumulate. So if patients drink alcohol while they have a serum level of this medication, they will get very, very sick. They report profound headache, nausea, or a signi!cant and repetitive vomiting if they drink alcohol while they have it on board. So again, you can see it is for a very particular type of patient. It's not real, real common anymore. But I use it sometimes in people who just-- they drink out of boredom more so than a true physical craving, just drink out of boredom or a habit. And in any event, you want to make sure that the alcohol is-- there's no alcohol in their body when they start. You start at a higher dose and then down titrate it paradoxically. Usually, people settle at around between 250 and 500 milligrams a day. And if there is an occasion in which they plan to drink, and I know that that's not the evidence-based textbook approach to treating a use disorder, we don't ever want them to use a substance again. But the fact is people do. And so we do want people to know that if you are going to take a break from Antabuse, then you've got to give it time to wash out. If you look it up, many references will say give it up to two weeks. I have found that it doesn't take that long to wash out. Usually, patients are OK after a couple of days. But they de!nitely-- it's not like, oh, I'm not going to take my pill today so I can drink tonight. They de!nitely have to give it at minimum a few days to be out of the system. And that's it. Those are our aversion and relapse prevention therapies. 13 of 14 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 2 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... And so in summary, substance use disorders, there are a whole bunch of them. Opioid- use disorder and the opioid crisis is the one that's most famous right now. But there certainly are others out there. And it's part of our job to be screening for this, be on the lookout for this, and recognize that especially with opioid use disorder, medication- assisted therapy is more-- it really is more promising than anything else out there. We do have some evidence to support multiple, multiple advantages to it, decreases in undesirable behaviors, increases in desirable behaviors. But opioid-use disorder isn't the only use disorder we can medicate. We also have pharmaceutical approaches to help people conquer a benzo-use disorder and an alcohol-use disorder. Always, all of these are best served if the patient is also in a nonpharmacologic program to include group therapy and usually, individual counseling and sometimes transition to independent living. And then what we didn't talk about here and we will talk about in another course are those use disorders for which we do not have speci!c drug therapies. There's a whole lot of them out there. And we need to think about those, too. So tune in on, I think, 6970 to talk more about that. All right, that's it. In fact, 6970 will probably happen in another week or two because right now, you are at the end of the psychopharmacology course. And I will see you in your next class, whichever theory class you are starting with. Print this page 14 of 14 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 1 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... Pharmacologic Management of Substance Use Disorders Part 1 Well, here we are for the last week of this semester. This week, we're going to talk about pharmacologic management of substance use disorders, but you probably !gured that out by the title slide. And while it is a very rudimentary picture, it does highlight the nucleus-- the relationship between the VTA, the nucleus accumbens, and the prefrontal cortex. And the area that really is signi!cant physiologically in substance use disorder is the nucleus accumbens because that's like right dead center in the reward center of the brain. We've talked in a few di"erent-- few di"erent units this semester about how dopamine is the neurotransmitter of reward. It's the thing that makes us feel good appropriately when we engage in some sort of rewarding activity, whether it's paying attention to a lecture or eating something that's really awesome or getting a new puppy or whatever the case may be. And we've talked about the consequences of too much dopamine in other circumstances, like if you have too much dopamine at certain receptors in the mesolimbic pathway, you can wind up having hallucinations or delusions. Well, that can happen in the nucleus accumbens as well. I mean, that is part of the mesolimbics. But the thing about use disorders is that whatever the substance is-- and even if it's not a substance, I mean, I'm getting a little far a!eld here because in another semester, we'll talk about non-drug related addictions like gambling addiction, food addiction, sex addiction, stu" like that. In substance use disorders, we're really talking more about opioid addiction, alcohol addiction, benzos, stu" like that. Methamphetamine, cocaine, et cetera. But all forms of addiction. One of the ways in which they draw people in and keep people addicted to whatever it is by the mesodopamine dump in the nucleus accumbens. Depending on what it is, like what is your choice of use substance or use activity, there will be exponential increases of dopamine in the nucleus accumbens. And if you keep 1 of 19 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 1 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... using this substance or keep doing this thing, you get used to just having that as your baseline. And it's interesting-- I mean, there are-- you can get links online. In fact, I have to see if I can !nd a really good one to link into this unit. Where you can look at dopamine concentration in someone who is like eating a meal that they love. And there would be like a little more dopamine than usual and compare that to the dopamine concentration of someone using fentanyl or heroin. And the dopamine amount is way higher in the fentanyl user. The highest is in the methamphetamine user. The amount of dopamine that concentrates in the nucleus accumbens is like 10,000 fold greater than the typical reward system. So the nucleus accumbens is a big deal and we'll talk about that later. I think, depending on how this goes and how long it takes me to get it all out, we will either do this in one slide set or maybe break it down into two. It really is about-- like the physiology behind substance use disorders, that's one topic of conversation and I've actually just addressed half of it. And so that leads to acute medical detoxi!cation like certain substances of abuse if you withdraw them abruptly, they can be, if not exceedingly uncomfortable physically, can be downright dangerous and that needs to be medicated. So there's acute detoxi!cation and then after the patient gets past that, which is really the easy part, then we have relapse prevention. That's like the long haul that's keeping them from going back. And in addition to all of the non-pharmacologic interventions, we do have some medications that can help with relapse prevention for certain substances. So the two topics of conversation this week are about the physiology and acute medical detox and then after that relapse prevention. So it's going to be either one or two slides, that's depending on how long it takes me to get through the !rst part of it. So with that said, it's time to go. Time to go on to the !rst part. You know, !rst we can't really talk about substance use disorders in general without highlighting certain use disorders speci!cally. And of course, opiate use disorder is among them. It is the one that everybody is talking about. It is the foundational discussion of the opioid epidemic and you can't turn on the news without seeing how, very speci!cally, fentanyl has become at the very center of the opioid crisis. So there's a lot of interest in trying to manage opioid use disorder. There's a lot of federal money and resources available to manage opioid use disorder. And so 2 of 19 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 1 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... consequently, we know more about it than we knew about some of the others. And it is also interesting that there are those who blame us as health care providers for the opioid epidemic. I really hate to see that. I mean, I think it is certainly multimodal and while there are those, of course, who have prescribed inappropriately, there also were a lot of us-- and throw myself in here, who were prescribing according to standard of care at the time. Those of you that have been in nursing for a while may realize this and those of you that didn't become nurses until like into the 21st century might not know it. But in the '80s and '90s-- and 1995 speci!cally, JCAHO identi!ed pain as the !fth vital sign. I mean, before that-- in the '80s and the early '90s, we recognized pain as a real problem in hospitals and there was an absolute push for patients not to have it. We were hugely encouraged to just keep giving opioid, opioid, opioid so that the patient would not be in pain. The philosophy was there is absolutely no reason for patients to be in pain. So just keep upping the dose. And unlike many other medications, there is not believed to be a dose ceiling for opioids. In other words, as much as it takes-- as much as it takes and the more people take it, the more tolerant they get of it and the dose needs to go up and up and up. And as long as you could use it without suppressing respiratory status, we were just encouraged to keep going up. And !nally, in 1995, JCAHO identi!ed pain as the !fth vital sign. And-- I mean it was crazy how we were just encouraged to use it. And this even was like part of accreditation evaluations and even like patient satisfaction scales and stu". If after discharge patients complained that their pain wasn't well managed and they didn't get enough medication, they would complain on their surveys and then we would hear about it. Like we were incentivized to medicate people and deincentivized not to treat their pain aggressively. So shocking no one at all, the result is this opioid epidemic. In health care, it just seems like things-- there's this bell curve. We have real extremes and have di#culty settling there in the middle. So we got to this place where we were just medicating everybody because it was the standard of care and then lo and behold, the opioid epidemic emerged. And I think-- I know I go o" on the occasional tangent from time to time, but it just lends some context. Here back in the day when pain was the !fth vital sign and nobody 3 of 19 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 1 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... was supposed to have it, there was a real emphasis on managing people who had to be on long term opioids with long-acting opioids. So like people that had chronic back pain, chronic whatever pain. Chronic cancer pain, chronic non-cancer pain, whatever the case may be, if it was anticipated that you were going to be on opioids for the long haul, we were discouraged from prescribing short- acting things like Percocet or hydrocodone and we were encouraged to prescribe long- acting agents. And the rationale for that was, that if you give somebody a long-acting medicine once or twice a day, they achieve a steady state of pain control. They don't cycle up and down. And also that there is a decreased incidence of post-dose euphoria because opioids do-- excuse me. Opioids, they bind to opioid receptors, which is what attenuates pain, but they also bind to sigma receptors in the brain, which actually produces euphoria. They're two separate things. So if you're taking a short-acting agent four times a day, not only are you up-down, up- down, but you're also getting a little euphoria boost. Every time you take one, it really invites abuse. So for all those reasons that made perfect sense back in the day, we were encouraged to get people on a long-acting opioid. And that's when OxyContin was born. OxyContin was the long-acting version of oxycodone which is the active ingredient in Percocet, right? So oxycodone, it was a powerful Schedule II, controlled substance opioid. And OxyContin was marketed as a long-acting version of this and wouldn't it be great. And so there was just a huge marketing push and billions of pills of OxyContin were put out there. But unfortunately, what happened was those who would abuse them would start crushing, snorting, mainlining. So what they were doing was taking a sustained release capsule with a concentrated amount-- or caplet pill kind of thing. It had a concentrated amount of drug that was intended to be distributed in the body over like a 12 to 20-hour period. And they were like crushing it and snorting it up their nose. So deaths occurred. Lots of deaths occurred. And that's what really brought it to the forefront. And so OxyContin since has been pulled from the market, there are other long-acting opioids out there and there are people that do need them. And that's a whole di"erent. That's your regular pharmacology course that you did as part of your 3Ps. But that's really where the opioid epidemic is credited with coming from. And so all of a 4 of 19 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 1 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... sudden, all of a sudden in the 21st century, we were having an opioid crisis and we were hugely encouraged to stop. Stop long-acting opioids and stop opioids use as much as you can. In 2016, the Centers for Disease Control put out guidelines for chronic opioid prescribing. And I think, 11 or 12 principals of opioid prescribing for chronic pain. And they all begin with a phrase like, don't use them, but then if you have to, do x, y and z. Don't use them, but if you have to, plan your discontinuation as soon as you can. So like they really, really discourage it. And they also discourage long-acting opioids. It's a classic example of how the pendulum does. Just go back and forth. I've probably said it to you before, I always tell all of my students just stick with what you learn in school and never change your mind because every 20 years, you'll be right again. Because we just seem to go from thing to thing to thing. But where we are right now is in an opioid crisis and we have rampant opioid use disorder. And that's where it comes from. And then, of course, other problems that happened were once-- it just really overnight. It seems like there was such a push to not prescribing opioids. That many providers in fear of their licenses just stopped doing it. And on a side note, I mean, I will say, that yes, every state has rules and laws. Administrative regulations about opioid prescribing and we should be judicious with it. And we have to follow the law. But there are people that need them. And if you prescribe them appropriately and follow the law in your state, nobody's going to take your license away or lock you up in jail. So for patients that need opioids, we still want them to have them. Unfortunately, providers are just human. And many of them were just like, nope, not doing it. I know one oncologist who left the world of cancer management because she was just so disgusted by the amount of regulation that was involved for prescribing these things for people that need them. I will say that many states in the last couple of years have amended their laws and become a little bit more realistic about it. So if you're-- I mean, I know this isn't an opioid-prescribing lecture. If you're going to prescribe opioids, be sure that you know what the laws are in your state. And if you're not going to prescribe opioids, you probably don't care so much about that. But in mental health, you may very well be the one managing. Recognizing and managing the opioid use disorder. And one of the many problems with opioid use disorder was not-- I mean, not only 5 of 19 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 1 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... were we having deaths occur from opioid excess, but then when providers abruptly stopped prescribing them, the people that still needed them both for pain and to satisfy an addiction, which very quickly becomes blended, they couldn't get them from their prescribers so they started getting them illicitly. And that's where they're buying the stu" on the street that's laced with fentanyl. So we would have deaths related to that. And then also the patients who suddenly had their opioids stopped, they would go through a physical withdrawal which in itself won't kill you. I mean, opioid withdrawal is really an awakening of the parasympathetic nervous system. So while it's very uncomfortable it's, not fatal. But what happens is you, very quickly, revert back to like a treatment-naive patient. So the person who has been using opioids whatever-- oxy, heroin, fentanyl, all of the above for weeks, months, years, their tolerance becomes really, really high. And then if they go through withdrawal for even a couple of weeks, they have no tolerance again but don't realize it and go back to using the same dose that they used before and then they OD. So I mean, it's crazy. In the beginning, as we were all normalizing to this, we saw deaths occur from overdose because people didn't realize their tolerance had dropped. So they would use what they used to use and die that way. And then we had people who would commit suicide because keeping in mind that one of the theorized origins of opioid use disorder is people who were medicated for pain. And they, sometimes, still have chronic pain, they still have it. And now, if the opioids aren't there anymore, they're still having pain and they're thinking that they're never going to get any relief from it. And so that precipitated suicidal. So obviously, in many ways it was a big problem. But now, we recognize opioid use disorder and, of course, like any other disorder in health care, the best approach is prevention. The best approach is primary prevention. Keep it from happening. The second best approach is screening the high-risk patient and intervening before it becomes a big problem. And then, of course, tertiary prevention is, treating the patient with opioid use disorder after it has developed and is recognized. Just so that we're all talking about the same thing and on the same page, the terminology depends on who's book you look at. And it can get a little bit confusing. Remember that ICD-10 terminology. And you'll talk more about that. I know I always say that every week, but it's because it's true. You'll talk more about that in your 6 of 19 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 1 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... diagnosis and treatment classes. ICD-10 codes are codes that we use to identify symptoms and diagnoses. And then the DSM is, of course, our Bible and mental health for diagnostic criteria. But they don't always completely match when it comes down to terminology. So the ICD-10 terminology includes terms like use disorder, opioid abuse, and opioid dependence. And the DSM calls it substance use disorder, and we'll characterize it as-- you can see on your slide. Mild, moderate, severe, in remission, et cetera. I mean, really, picking the right term isn't as critical as-- that's the thing that academics argue over what's the right terminology. But just to put it in context, opioid use-- a patient who is using an opioid to treat fractured femur-- they're opioid use. It's not necessarily a problem and it doesn't need to be treated, but you would identify it on a chart because it can have an impact for screening and preventing an abuse disorder later on. Abuse, of course, is di"erent. Now, we are using the drug in a way that's not consistent with how it was intended or we're using too much of it or-- then it's atypical. And then dependence doesn't necessarily mean that somebody is abusing it. People who are prescribed opioids for even like say, cancer, that seems to be the one thing that everybody still agrees. Patients should be able to get their opioids as the patient with terminal cancer. You can have a patient who is appropriately medicated with an opioid but after a while, they will develop a physical dependence. So there are di"erences among the three and we just want to make sure what we're talking about. It's not so much for separating over the term but understanding the di"erence. A patient who is coded as opioid use may not be a problem at all. It is a short term intervention for an acute painful situation, but we want to document it because we want to be on the lookout. We want to prevent a use disorder developing down the line. Abuse is di"erent. This is something that we don't prescribe for as prescribers. We want to try to intervene in a healthy way, get them into our program. And we want to code it to alert other providers to its presence. And then dependence, again, is just acknowledging that there is a physiologic dependence on the drug. It doesn't, necessarily, represent an abusive situation. It's just a physiologic one. Or it may. They're not mutually exclusive. Dependence may occur with use or it may occur with abuse. And then the DSM-5, there are criteria. I think 7 of 19 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 1 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... there's 11 separate items that we look at when we're evaluating any substance use disorder and based on the number of criterion that the patient have, we will characterize it as mild, moderate, severe. But I only mention it because sometimes it gets confusing, especially, when you're studying and it's new to you and you see all these di"erent terms and what do they exactly mean. That's the best I can do on one slide. So since we're talking about-- we're going to talk about pharmacologic management of substance use disorder and, in this case, opioid use disorder, we're really most interested in what the use disorder itself is. And, I mean, any substance that's out there that people use can develop into a use disorder, whether it's ca"eine or opioids or alcohol or diet pills or cocaine or heroin or fentanyl or methamphetamine or hallucinogens or all the things people abuse. I can't even keep up with it. Every time I think I have a handle on it, something else pops up that people are using. So substance use disorder, by de!nition, you can see the bullet points here, I don't suppose I need to read it to you word for word. But I will point out, that like any other psychiatric disorder, notice the last bullet point, there is some element of social or occupational dysfunction. All of these other things will likely be there or at least one of them. But it interferes with social or occupational dysfunction in some way. Oh, so I guess these are the criteria. I did list them out here for you. I really never intended for this to be a diagnostics course or a diagnostic lecture. I just, sometimes, have trouble separating the two. So we will, probably, revisit this again in another course. But because it's here, these are the items that I told you about. These come right from the DSM-5. So if you are trying to evaluate whether or not there is a use disorder, these are the things that you're looking about. And notice not all of them are there and for some patients that you wouldn't necessarily think they're having a use disorder, you'll look and see that a few of these elements are there and it constitutes mild substance use disorder. So it's interesting. Things aren't always as black and white as our intuition might suggest. So you can see. Larger amounts, persistent desire or failed e"orts to control it. Most people with a use disorder do, typically, recognize that there's a problem and want to do something about it. They just have been unable to. Spending a lot of time getting the substance-- using it or recovering from it, I said I wasn't going to read to you. So I won't read item 4. Let's see. Anything else we have to highlight here? 8 of 19 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 1 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... Well, there's your social or occupational function. Yeah. Well, 5, 6, and 7 are all the social or occupational function piece. And one of them-- one of them or one of the others will certainly be there in a use disorder. Yeah. Yeah. That's it. And then, of course, the number 11 is withdrawal. Occurrence of that characteristic withdrawal syndrome. Some drugs do have a physiologic withdrawal, some drugs don't. That's why you don't necessarily have to have a physical withdrawal to have a substance use disorder. So notice the table here at the bottom. To diagnose a substance use disorder, if people have two to three of those criteria. So two at-- as little as two, that is considered mild substance use disorder. Now again, you're also looking for social or occupational dysfunction. So one of those items should be there. Four to !ve elements. Moderate disorder. And six or more then you're talking about a severe substance use disorder. But if you go back and look at them and just pick out two-- and one of them might be spending an inordinate amount of time, getting the substance or recovering from it. And then one other thing that would constitute a substance use disorder by this DSM criteria. I can tell you on a side note that for a couple of years, I worked as a consultant to the Nevada Board of Nursing. I was the APRN investigator at the board of nursing. So whenever there was a complaint about an APRN, it came to me to evaluate. And in that role, I, on more than one occasion, saw nurses and nurse practitioners that had been reported for potential-- suspected being under the in$uence on the job or if they had a DUI and disclosed on a renewal. And if that happened, if they disclosed a DUI on their renewal, then we would discuss whether or not it might be necessary to do an evaluation. Have a trained professional do an evaluation for a substance use disorder. And with one DUI, probably not so much, but the second DUI, virtually, guaranteed that you would be mandated by the board to have a substance use disorder assessment and if you have two or more of these criteria, if you have two criteria, it was considered a use disorder, which then meant that for the next three to !ve years, you were going to have to go to meetings, be on a program, be on a board-mandated program to ensure that you were managing your substance use disorder. So those little two to three criteria, they really can-- depending on your profession, they really can come back to have a major impact on your life because it's considered a use 9 of 19 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 1 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... disorder. OK, enough of that. So successful use or-- successful, not successful use. Successful management of virtually any use disorder condition is multimodal. But like I said, opioid use disorder is really well explored, really well studied, and we have some very speci!c interventions. For best outcomes-- and I mean, recidivism is very high. One of the real emphases in treating any use disorder is that we have to recognize recidivism is part of it. It's most unusual for people to have a use disorder. Go into treatment, stop using it, and never have a problem again. So you just have to consider that relapse is part of the treatment plan and it needs to be supported and the reason explored and then our interventions restructured to try to address that. So with all of that said, yes, it is always going to be multimodal-- both pharmacologic and non-pharmacologic interventions. And now, the most successful approach to opioid use disorder is described as MAT or medication-assisted therapy. Some folks call it medication-assisted treatment. It is very well explored on the SAMHSA website-- the society-- or Substance Abuse and Mental Health Services Administration. And there may even be a link in your recommended readings or external links for the week. So medication-assisted therapy is exactly that. It's medication assisted. The non-medication piece is critically important. And so I mention this especially because you don't want to prescribe the meds if the patient is not in a multimodal treatment plan. Not only does it not work as well, but also there is a potential for abuse of some of the medications that we prescribe. So notice the abstinence rate without medication-assisted therapy is-- so we're talking abstinence here. We're talking success. Less than 50% at six months out and less than 15% at one year out. So if I come to you with an opioid use disorder, and you diagnose me with an opioid use disorder and I go into some form of treatment that is not medication-assisted, in other words, not multimodal, chances are more than half of the patients will be reusing again at six months and 85% will be reusing, again, at one year. And remember, I mentioned this before. The risk of overdose and death by overdose following abstinence is very high because people just lose their tolerance and then when they relapse as the overwhelming majority will, they don't realize that their tolerance has fallen and go right back to the dose that used to get them high before. And now it can cause death. So what is medication-assisted therapy or medication-assisted treatment? I can feel the 10 of 19 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 1 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... question oozing through the slide set here. So this is what we're talking about. Opioid treatment programs, speci!cally, MAT like, it is the name of the treatment modality. It's like capital MAT. And as I say, they have to be-- those programs are approved by SAMHSA and they are very well de!ned. And notice the last bullet point here. MAT markedly underutilized. There really isn't a whole lot of real, real quantitative substantive research on this because it's just hard. It's hard to do follow up studies, certainly with people that do relapse and with substance use disorders in general because I think a higher than average proportion of the opioid use disorder population begins as either homeless or wandering, staying from place to place. So it's just hard. It's hard to establish relationships and do good follow up. But in general, it is believed to be very under-utilized. Yes, again. The whole person approach. Not just medication, medication-assisted therapeutic modality which includes group therapy, it includes individual therapy. It may include family therapy. Like intensive outpatient programs, integration back into the community. It is a multimodal approach. And although it is hard to research this, it's hard to get really good data. There is a little bit out there. And I've tried really hard because I feel like whenever I present anything in an academic setting, I'd like to have some data. There are data to suggest that medication-assisted therapy not only decreases opioid use which, of course, is a primary purpose here but also decreases opioid-related deaths. Decreases overdose deaths. Also decreases the incidence of criminal activity in the opioid abuse population because the trajectory often is such that patients, as they fall further and further into their addiction, will start engaging in various forms of criminal activity to get the money they need to buy their drugs or just to get their drugs. I mean, not necessarily-- really violent crimes although it may be that. But things like prostitution, burglary, robbery, then selling things, that kind of stu". People, as they fall further and further into addiction, the incidence of that goes up. And then the other thing that medication-assisted therapy is purported to decrease is the transmission of infectious diseases. Those that are transmitted primarily by contaminated needle. So medication-assisted therapy doesn't just decrease opioid use although that is a big deal and it's important. But it has these other bene!ts as well. And one of the better studies that's available is 11 of 19 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 1 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... the one that I've mentioned here. In Baltimore, there is some quantitative research on this. There is a study that was done out of Baltimore that reported that the use of-- the incidence of heroin overdose deaths fell by 37% after buprenorphine became available to the population. And buprenorphine is actually a big relapse maintenance drug that we will talk about in the second slide set. In addition to the things that medication-assisted therapy decreases, it also o"ers some improvements. It can improve social functioning. Remember, social and occupational dysfunction is always part of diagnostic criteria. These patients often, by the time their addiction really gets to that point where it consumes their lives, they have often-- if they had a job, they lost it. Have lost family relationships. So medication- assisted therapy can improve that and keeps people in treatment and improves outcome for pregnant women, which is hugely important. Because not only does it improve outcomes and decrease consequences for the pregnant women themselves, but also can decrease the incidence of neonatal abstinence syndrome, which, of course, is a whole other consequence of opioid use disorder. So lots of purported bene!ts to medication-assisted therapy. Like I said, it is considered the gold standard for managing opioid use disorder and it is hugely important to be sure that you might be the prescriber but you want to make sure that the patient is in the other elements of the treatment plan too. Because it's not-- unfortunately, it happens that some of the medications we prescribe them, they can also abuse. And so you will have people that come in and say, "I need a re!ll on my Suboxone or I need a re!ll on whatever." And then you say, "OK, well, you know, how's group going? Have you seen your therapist?" And sometimes, there's always a reason why not. There's always-- couldn't get there. Didn't have transportation. Car broke, like always something. But yet, they can still come to you for a re!ll of the Suboxone. And that's like a big no. You don't want to give them medication if they're not engaging in the entire medication-assisted program. What else? OK, so now that we know what it is, the !rst piece of medication-assisted therapy-- and this isn't necessary for all drugs of abuse. This is the part that is important when the drug of abuse can cause a physiologic withdrawal phenomenon. I think I mentioned before that physiologic withdrawal can range from being either a 12 of 19 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 1 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... very uncomfortable to fatal and in any event, even if it's just physically uncomfortable, sometimes it is a deterrent for people. They just don't want to go through it. So they keep using to avoid the physiologic withdrawal. So the purpose of acute medical detoxi!cation-- easy for me to say. The purpose of acute medical detoxi!cation is just what your slide says. Number 1, safe withdrawal from the substance. We want them to safely withdraw from the substance of abuse. Again, not necessary for all substances. In fact, not necessary for most substances of abuse. There are a few substances of abuse where we do need to attend to acute medical detox, but most of them, we don't. And then your handout says, commonly performed in an inpatient setting. I would actually edit that a little bit to say that it is performed in the least restrictive environment. A real trend in health care in general-- psychiatry being part of that and in substance use disorder, speci!cally, the trend is, least restrictive environment. Some people really do need to be in an inpatient hospital setting and then that's what we do. And then other people can go through acute medical detoxi!cation in an intensive outpatient program. Depending on the drug and depending on their resources in the home environment, some people can go home at night. And then there are others who can medically detox even in a less restrictive home environment. So it's really an assessment of the substance. Close monitoring of the physiologic response to withdrawal and the substance of abuse. And in acute medical detox, drug therapy is the primary modality. When we're talking about substances that lend themselves to a physiologic withdrawal phenomenon, the primary way to get them through it safely is pharmacotherapy. And the substances to which this most applies are opioids, which we've been talking about, alcohol and benzodiazepines. And the reason is that those are the ones that directly suppress some aspect of the central nervous system. They actually both suppress arms of the autonomic nervous system. Remember, the autonomic nervous system you have your sympathetic and parasympathetic side. Feel like we just discussed this for some reason that I can't remember now. But anyway, you have your sympathetic and parasympathetic side. The sympathetic nervous system is your fear of $ight-!ght. That's your tachycardia, tachypnea, everything that jacks you up to get ready to !ght a stressor. The parasympathetic side is the vegetative side. The GI motility, the digestion, the elimination, the urine, the 13 of 19 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 1 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... bradycardia, remember? So alcohol and benzos, when you take them, they directly suppress the sympathetic nervous system. Benzos are like pill form alcohol to the sympathetic nervous system. They are both GABA agonists, they both directly suppress the sympathetic nervous system. And so we put them together when we talk about withdrawal phenomenon. Benzos and alcohol. The opioids directly suppress the parasympathetic nervous system. So our approach to them is a little bit di"erent. In either case, whether you're talking opioids or alcohol/benzos, abrupt cessation of the substance is going to result in acute rebound of whatever system it suppresses. So let's talk about opioids !rst because that's what we we've been talking about up until this point. If you abruptly stop using opioids, you abruptly stop suppressing the parasympathetic nervous system. So what happens is the parasympathetic nervous system wakes up with a vengeance. It cranks up. And that's where you get the nausea, the vomiting, the diarrhea, the profound abdominal discomfort because of the accelerated GI tract. These patients often vomit, their volume contracted. A lot of times, they're not in the best health to start with. They're having diarrhea, so they feel sick, they are diaphragmatic. There is some element of compensation here when you become volume contracted and vomit constantly and have diarrhea. Heart rate will actually go up. So it can be a little bit confusing. But the real issue there is parasympathetic rebound. So while it is exceedingly uncomfortable, it's not usually dangerous. If you can provide acute medical detoxi!cation, it certainly is much more comfortable for the patient and it supports going without-- it supports abstinence because they feel better. But if they don't-- if you can't medicate them for this, it won't kill them. The only time that there's really any concern about true danger to life and health is in the pregnant woman we worry about the fetus. But other than that, I mean, like I worked in a county jail, I'm sure I shared with you, for eight years. And it was very common to get people that, as a consequence of being incarcerated, had to abruptly withdraw from opioids. And it was just the policy of this jail that we did not medicate that. I mean, we didn't give them true medical detox. We gave them Motrin for muscle pain and extra $uids with a meal to try to combat volume contraction. And so lots of times, there were some 14 of 19 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 1 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... very sick inmates in the medical unit asking for things like antiemetics and things like that. The one exception was the pregnant woman. Pregnant women, we put on methadone. So that's an example of waking up the parasympathetic system. If you abruptly stop using benzos and/or alcohol, then you abruptly stop suppressing the sympathetic nervous system. And you put the patient at risk for sympathetic nervous system rebound. This is the dangerous one. This is the one where your fear of $ight-!ght response suddenly wakes up with a vengeance. These are patients that will become acutely tachycardic, hypertensive. Depending on their own tendency and the amount of drug that you're suddenly withdrawing, they will sometimes become delirious, they can have CVAs. This is called delirium tremens when they hallucinate. And that really is the more dangerous one. So abrupt cessation of alcohol and benzo, that could cause serious, serious health injury or death. And acute medical detoxi!cation is absolutely required for that. Even in the county jail where there was not a lot of sympathy for a lot of this kind of stu", we did medicate benzo and alcohol withdrawal because it can be unsafe. So then the next question you might say to yourself is, self, what can we use for acute medical detoxi!cation? Well, funny you should ask. So we have some options that aren't necessarily directly necessary to acute life saving but that they are supportive of the patient, for instance, thiamine and folate. Patients who are withdrawing from alcohol. And alcohol, speci!cally, is when we use thiamine and folate because typically, alcoholics that have gotten to that level of alcoholism usually have nutritional de!ciencies. So the thiamine and the folate really are to help. Like this is the proverbial banana bag if you were ever a medical surgical nurse or an ER nurse or in any environment where you saw somebody acutely detoxing from alcohol be given the banana bag which included the thiamine and folate, one of which is yellow. I forget which one. But it made the $uid look yellow. So that's for alcoholism. For anyone who is withdrawing from alcohol or a benzo, we do use seizure prophylaxis and there's a couple of options listed here, because we are worried about this abrupt elevation or abrupt waking up of the sympathetic nervous system can predispose the patient to seizure. And also the B vitamins-- the thiamine and the folate. We also are concerned about 15 of 19 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 1 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... Wernicke-Korsako" psychosis in our patients who have been using alcohol in the long haul, which really can make you $at out psychotic. Now, also for the patient that's withdrawing from Benzos or alcohol, we do, for the short term, use a benzodiazepine to help taper them o". We obviously-- they're withdrawing from Benzos, we don't want to have them on it forever, but we do need them to come o" of it safely. So the actual evidence-based approach to benzodiazepine acute medical detoxi!cation or, for that matter, alcohol acute detoxi!cation is to use a long-acting benzodiazepine. Like if the patient was abusing Xanax, which is short-acting, we're going to convert them to a long-acting form. Alcohol has a very short half life and now going to convert them to a long-acting benzo. So chlordiazepoxide is Librium and that's been classically used, but lorazepam is Ativan, that's more contemporary. And then oxazepam is Serax, it's marketed as Serax. It's not, typically, your !rst line drug for benzo withdrawal but because it spares the liver, sometimes in patients with more severe liver disease, that would be the benzo of choice because it doesn't really a"ect their liver, they don't rely on the liver for metabolism of it. But really, I mean, it's typically Ativan which is lorazepam or Valium or Librium. And it is a tapering schedule. We're not trying to keep the patient on their addiction, we're not trying to keep them high, we just want to keep them safe. So we slowly and steadily put them on a taper that usually is somewhere around-- it depends on how bad things are. But usually, somewhere around a week or so. And I think I mentioned this before. The mechanism of action benzos, it is a GABA agonist. GABA is the most common inhibitory neurotransmitter in the brain. It directly suppresses sympathetic activity and that's what it does. I mean, it's why it's so e"ective as an angelic. But if you become-- if your brain becomes dependent on it and then you suddenly stop it, like I said, your brain rebounds into overdrive. These drugs-- I mean, they are intended for things like anxiety attacks, panic attacks because they really do block the physiologic arousal symptom. They're not as useful for worry. People will still worry but they just don't get the tachycardia, tachypnea, and stu" like that. If you are absolutely terri!ed to $y on a plane and you have to, for some reason, and you take a short-acting benzodiazepine like a Xanax an hour before the $ight, you will not panic about that $ight. You might still be on the plane going, gosh, I sure do hope we don't go down. Gosh, I 16 of 19 6/26/24, 10:11 PM Pharmacologic Management of Substance Use Disorders Part 1 Transcript https://alt-5c5afaf83f339.blackboard.com/bbcswebdav/pid-2425045-dt-... sure do hope there's not turbulence and you look out the window and go, hmm, interesting. When you're perpendicular to the ground, what it looks like. But they don't feel that physiologic anxiety so it just becomes very tolerable. It is the bomb drug for a panic attack, but it really is not intended for long term use. This is another one of those drugs where it's a shame because if you use it the way it's supposed to be used, it can be really helpful for people. But the tendency to abuse it has just made it harder for everyone. So anyway, those are examples of acute medical detoxi!cation pharmacotherapy for people that are withdrawing from sympathetic nervous system suppressants-- alcohol and what do you call it benzos. Now, on the $ip side, we have clonidine. And we can actually use clonidine for everything. But clonidine is really helpful in opioid detoxi!cation because even though you're waking up the parasympathetic nervous system, the parasympathetic nervous system gets so jacked up that the sympathetic system will actually try and compensate a bit. I mean, it's not like a benzo withdrawal, but there is some sympathetic activity as well. And remember, clonidine is a centrally acting anti-adrenergic agonist. So clonidine calms down everything from the brain down. So it can calm down anxiety that occurs during detox, it can help people even, perhaps, feel like they may sleep again some day. So you can use it in all forms of withdrawal, including opioid withdrawal. It, actually, will help slow down the GI tract, which is one of the biggest contributors of symptoms. And yeah. So that's when you're thinking about acute medical detoxi!cation for an opioid, remember, I said, we don't have to-- people, usually, will survive this without any real consequences, but to try to facilitate some level of comfort and the ability to sleep when you're a detoxing from opioids. That's what good old fashioned clonidine is still good for. It's such an old school drug. And for hypertension, it's really gotten dissed in recent decades. But it is very e"ective in helping a patient get through opioid withdrawal. Some of the other things we have is more ancillary medications. Hydroxyzine, this is an antihistamine, this is Vistaril. And this can be used to help with the anxiety that often accompanies any-- really detoxing from anything, including opioids. Trazodone is commonly used for insomnia because people that are