All righty, I think maybe we could probably just get started. I'll introduce you. And like I said, then it's all yours. So thank you to Dr. Schulman for doing this grand rounds for us on the opiate use disorder. Dr. Schulman is a clinician scientist at the New York State Psychiatric Institute and assistant professor of clinical psychiatry at Columbia University. His research focus is on opiate use disorders, clinical trials, and the use of technology to enhance implementation, quality improvement, and treatment delivery. Dr. Schulman completed general psychiatry clinical residency at Northwell Zucker Hillside Hospital, where he was also the research chief resident. After residency, he completed a T32 research fellowship in substance use disorders and an addiction psychiatry clinical fellowship at Columbia University Irving Medical Center. So thank you for being here again, and we're really looking forward to your presentation on opiate use disorder. All right. Thanks for having me. It's great to be here. And I just want to confirm, most of the people in the audience are residents, psychiatry residents, also internal medicine, I heard? Yeah, I think you're going to have a lot. We certainly have a lot of psychiatry residents here, some psychiatry faculty and other medical physicians and staff as well. Okay. All right. So a mix. All right. So yeah, thanks for inviting me. And it's great to be here. I'm very happy that you guys were interested in learning more about opiate use disorder and treatment of opiate use disorder, which is my research expertise, and obviously a very serious problem facing the country right now. So, you know, the goal of this lecture is going to be two parts. Basically, the first part is going to be more of a background, historical, which I'll try to go through relatively quickly. And then I'm going to go through some of the large clinical trials that were done to try to get some answers, how to approach this problem clinically and some of the choices we have to make. So I hope that'll be of interest to the clinicians. And I hope we'll have time for discussion at the end. Throughout, I'm going to try to give you little nuggets on how to talk to patients when they have certain questions. There are some things that come up again and again, and hopefully we can just talk through how to approach them. So slides are actually advancing. Here we go. All right. So this is a lecture, which is supported through the Opioid Response Network, which is a SAMHSA-funded program. And they actually are available for local requests. If anyone has a question or some technical issue they want help with, you can always reach out. You can look up the website and put in a request. OpioidResponseNetwork.org. And there's the email. Okay. So I don't have any disclosures related to this lecture. Okay. So I talked about our objectives already. So here's the history part. And please, if you have questions, you can put them in the chat. I'll try to notice them as we go along. Okay. We got some students here. Thank you for telling me what you are. Excellent. Okay. So this should be good for different levels of students and clinicians. Hopefully it'll be of interest to everyone. Okay. So some history. So opioids have been sort of related to human society from the very early beginnings of civilization. So we have archaeological evidence that the Sumerians used the opium poppy and called it the joy plant. So they knew how it worked. They knew it did something happy. And we have accounts of opioid addiction as early as in the 1500s. So as technology developed, we started having more problems with opioids. So in 1806, morphine was isolated as a sort of independent pharmacological chemical. And soon after, we also had the invention of hypodermic syringes, which allowed people to be injected either intramuscular or intravenously. So those two things together, along with the Civil War in the United States, led to the first real serious opioid crisis we had here in this country. I don't know if many people know about this, but the Civil War, of course, was accompanied with a huge amount of suffering on both sides. And opioids were sort of developed, as I mentioned, to be delivered intramuscular, but also were just taken orally. And many of the soldiers and the people that were affected developed an opioid use disorder, we would call it now. This is a quote from a book at the time, written in 1868. It says, many people who suffered, many have found temporary relief from their suffering in opium. So this is a very longstanding problem. If you read some of the papers from the time, there's numbers given that 100,000 people were habitual users of opioids, which was a huge number in that time in New York City. And it was a London paper that said about one fifth of the people that were, less than one fifth of the people using opioids were using them for medicinal purposes. It was a lot of recreational use. So we even find opioids in children's remedies. This is Winslow's soothing syrup, had morphine in it. So as often happens in policy, when things are going too far one way, things swing back the other way. So in the United States, there was a law passed in 1914 called the Harrison Act. And we're still sort of living with the repercussions of this act today. It was restricted opioids and cocaine a lot. As most of you probably know, cocaine is actually not Schedule 1. There are some legal uses for cocaine. But it restricted the use of opioids and cocaine at the time. And important thing for our discussion today is that it was interpreted to be understood that clinicians couldn't use opioids to treat someone with an opioid use disorder. So you had a soldier that was recovering and developed an opioid addiction, opioid use disorder because of injuries. And then later on, they're coming back and their injuries may have resolved. The doctor says, well, you still need to continue using these opioids. You're going to get very sick. That was considered illegal. And there were some physicians that were prosecuted. There's discussions. If people are interested in the history, there are a lot of good books on the topic. So this sort of restricted how we would be able to treat opioid use disorder. And things only changed much later. We'll talk about that. But to sort of talk about the problem as opposed to the treatment for now, before the second opioid crisis, which happened in the early 2000s, doctors were pretty nervous about prescribing opioids. And actually, when I was in medical school, it's just, you know, the dark ages. But when I was in medical school in the mid 2000s, this is where things were starting to shift. But it was still sort of in the height of where opioids, the way people looked at opioids were changing. And there was a lot of talk about how we were under prescribing for pain. We're not addressing pain enough. We have to believe people when they talk about pain. That was all a reaction to the fact that for many years, people were concerned about using opioids. They knew they were addictive. They knew they were dangerous. And they were only really used for cancer pain, and rarely for chronic pain, and usually for lower doses. Unfortunately, there was industry involved. And medical society, I think, probably failed to really stay on top of this, possibly because of industry money. But around the early 2000s, Purdue and other companies developed synthetic opioids. So these are man-made. They don't exist in nature. So OxyContin was one of the earlier ones. And Purdue pursued a very aggressive marketing campaign, even though they knew there were risks. And if you look at the doses that they were suggesting, it was huge doses of opioids. And the studies that they cited were studies of much lower doses, but they failed to mention that, where they talked about how opioids were safe and they could be used safely. And they were very successful in making a lot of money. In 2001, there was a sale to $1.1 billion. So this sort of kicked off, unfortunately, the problems that we're still having today many years later. So I'll just talk through the history. So you can see in this, this is a chart showing overdose deaths. And can everyone see my pointer? Yes. So this line is the line which is referring to prescription opioids. So you can see that in the 2000s, it starts going up. And then it kind of plateaus in the late 2000s. And around 2011, that's when I think society realized we're starting to have a real problem. But we saw that there's a huge number of people that were having a problem with prescription opioids. There were pill mills. And it was driving a serious opioid epidemic. Now I lost my place. There it is. Unfortunately, what happened was the cartels moved in and were able to substitute prescription opioids in the drug supply for illicit opioids, heroin, which was an old opioid that was used for many years. But they were able to sort of spread the supply throughout all of society in the United States. And overdose deaths for heroin started to rise. And then now we're really living with the most devastating, in a way, part of the opioid overdose epidemic. And that's the synthetic opioids, which I'm sure you're all aware of. Fentanyl, which is extremely potent, really small amounts, can lead to an overdose. Easy to transport, sorry. That kicked off an even sharper peak in terms of overdose deaths. And we've had really horrible years in the past couple of years in terms of the numbers of people who die from overdoses. And much of that is driven by fentanyl. And actually, even more recently, we have a problem with fentanyl being used along with psychostimulants like methamphetamine. So that's kind of the history. That's where we stand. It's unfortunately been a pretty tragic story. And there's been a lot of suffering because of opioids. But there are treatments. And we can actually do it. And I think that society has moved into trying to get these treatments out into the community. And I'll try to be hopefully optimistic about some of the things we can do and the ways we can help people to deal with this problem. So three medications for opioid use disorder that are approved. People are aware of this, I guess. We have a broad audience. I'll just go over them quickly. The oldest of the three medications is methadone. Methadone is actually a full agonist opioid. Full agonist opioid means that it acts on the opioid receptor just like any other opioid. It's acting on the receptor just like heroin does, morphine does, oxycodone does. But I'll talk in a minute about why it's used as a treatment as opposed to, so you could say, well, how is that a treatment to give someone more opioids if they have an opioid use disorder? Well, we'll talk about that in a minute. Buprenorphine, which is quite an amazing medicine, was developed and approved. It was developed in the 1970s, 1980s, but only used clinically later in the 1990s in other countries. And in the United States, there was a special law that was actually passed to allow the use of buprenorphine because, as I mentioned, the Harrison Act says you can't use opioids to treat an opioid use disorder. But there was a law passed, the Data 2000 law, that allowed people to prescribe buprenorphine outpatient. And that really changed things. How does buprenorphine work? It's a pretty amazing drug in that it starts to act on the opioid receptor at lower doses just like an opioid, but it's only a partial agonist. When you get to higher doses, it no longer has more effect, no longer has an additive effect. So a person can take quite a bit of buprenorphine and really there's very low risk of overdose. They can only get so high on the buprenorphine. But it also acts to treat withdrawal. It helps people reduce their cravings. So it's really quite an amazing medication. And it's right now the most commonly prescribed and used treatment for opioid use disorder. And finally, we'll get to the last option, which works totally differently, and that's naltrexone. Naltrexone is also a relatively old drug in the oral form. And naltrexone blocks the opioid receptor completely. So if a person is on naltrexone and they take an opioid, then the opioid receptor doesn't react. So, you know, I didn't feel anything. Unfortunately, in the oral form, it was problematic that people just weren't consistent in taking the medication. So there's a pharmaceutical company developed a long-acting injectable form, which is marketed as Vivitrol. But that form was approved for use of maintenance of opioid use disorder. So people should know you're going to use naltrexone orally. You're not using it as an FDA-approved form. And it may actually increase risk. Not to say you should never do that, but treatment is really in the long-acting injectable form, which is about a month's shot. So every month people come and get a shot. So those are the medications for opioid use disorder. We're going to talk about these. And if anyone has any questions on these, please put them in the chat. And we can discuss them. But I'm going to talk a little bit about some of the details. Start with methadone. So here's a myth, and here's something you can talk to patients about. A little nugget about how to talk to people if they bring this up to you. So people may say medications like buprenorphine and methadone, they just replace one drug for another. They keep you from reaching true recovery. So I don't want to take that. That's not helpful. So how would you talk? Has this come up for anyone? Anyone have any answers for that? Or I say what I want to say? All right. No volunteers. No one's brave. Okay. So I'll tell you how I would approach it. So with regards to methadone, I explain to people that really when you're taking the dose of methadone at a steady state, so it's not changing, so then the methadone is basically turning off the opioid receptor. It's not acting. So it's like, consider this is a picture of Alex Honnold in a Talbot rail cab. So this is a rock climber who climbed straight up a rock face. And so that was quite impressive. That was a really big deal that he was able to climb in two hours this huge rock face in three hours. Somebody who walked up or maybe was just hanging out at the top, it really doesn't have any meaning. It doesn't mean anything. So that's kind of how the body reacts with opioids. So here's a nice graph trying to demonstrate this. So with the methadone, if a person is taking methadone, their blood levels kind of remains about the same. It's a very long acting medicine. Stays in the body for 72 hours. So if the person is taking it every day, their blood level kind of goes up and down a little bit, but pretty much stays at about the same level. So the person doesn't experience the euphoria that's associated with methadone. The person doesn't experience the euphoria that's involved in when you change the dose of an opioid from a lower level to a higher level. That's when a person experiences the euphoria. They also don't experience the withdrawal that's involved when a person stops having an opioid in their body. Because again, the level isn't going down. And if you look at the jagged line, which just looks like peaks and valleys up and down. So that's sort of how heroin works in the body. People are using multiple times a day, maybe twice a day. And so right after they use, maybe they feel really good, then they feel bad, and they have to go back and use again, and it creates a cycle. So methadone is, even though it's a full agonist, it really turns off the receptor and the person is able to achieve recovery. It's tried and true. We'll talk a little bit about some of the evidence for methadone, but it's tried and true. It was developed in the 1970s in clinical practice. The first methadone clinics in the United States were in New York City, and it's really all throughout the country. It's very highly regulated, so people have to come every day to the methadone, to a methadone program to get their methadone. But it is quite a good medication, and you can tell people if they ask, it's going to turn off your receptor. It's really, you're not going to feel anything when you use an opioid after you have the methadone. You're just kind of, you're living on top of a mountain as opposed to jumping up and down and skydiving and climbing back up. You're just staying there, so it's not going to really affect you at all. Okay, so any questions on this? I mean, a lot of reactions here. Okay, I'll keep plowing on. So next topic is the question about how we approach someone who comes for treatment. So someone comes with an active opioid use disorder. They come to an emergency room. They come to an outpatient program. They come to a medical hospital for, let's say, for infection. So historically, unfortunately, the way this was approached was, well, let's treat their withdrawal. Let's just take care of the fact they're not feeling well. So let's treat their withdrawal so they can be off all opioids, and then we'll just let them go, and they'll figure it out. We'll send them to maybe an NA group. Maybe we'll send them to recovery. And so basically, the medical system was focused on withdrawal management, but the reality is that was just a patch, and it really wasn't solving the problem. So that was – we'll talk about this now. I'll show you some of the evidence about why this is a problematic approach. So if you just approach – so this is a study that was done in Boston, and it was published in 2020, so it's relatively recent. It just tries to show you – it's an association. It just shows you followed people and how they did, but it shows you some pretty concerning numbers in terms of if you just provide withdrawal management. So everyone in the study – more than 30,000 patients came in and were treated for their withdrawal. So they came into these units where they're focused specifically on, okay, let me treat this person's withdrawal. Let me get them off opioids. Then what happened next? So if there was no treatment after they left, two of the 100 people – of 100 people died in one year. So it was about 1 in 50 people didn't survive, unfortunately. When people were willing to go into residential treatment, which is just living in a controlled setting, so there was a pretty strong decrease, 37%, third decrease in the risk of all-cause mortality, but with the addition of medication, MLUD, that's how we say a medication drug-reduced disorder now, you get a 66% decrease in overdose, and if you have both, you get an 89% decrease. So you have a real significant decrease in the risk of death. If people are just treated with medication, that's why we call this medication for opioid use disorder, we don't call it assisted treatment anymore, we don't call it just a bridge or anything, it's really the treatment for opioid use disorder is to put people on medication. Here's a randomized trial which showed, I think pretty clearly, the importance of keeping people on medication for the long term. This was prospective, so it wasn't just an observational trial like the last one, and this was done in the 2000s, so it was where there was a focus on prescription opioid use disorder, but it included people that had prescription opioid use disorder. It was 10 different sites. They did a two-part trial. So the first part of the trial was they took people who were coming for treatment, they put them on buprenorphine, and then they randomized them to, everyone was taken off their buprenorphine, but half the people got a very strong therapy and psychosocial approach, and the other half just kind of got their regular approach, and then for anyone who relapsed during that first part, they got to a second part, second stage, where they put everyone who was in trouble back on buprenorphine. So the question, sort of the big takeaway from this trial, is what happened in stage one. So what happens when you take people off of their buprenorphine early on in treatment, you know, maybe after a month or two. Any guesses on the number of, how many people would have gone back to opioid use disorder, or opioid use, if they, they're off, they're taking off their buprenorphine early? Anyone want to guess on the chat, a percentage? 75%, okay. 70, 75, everyone's thinking the 70s, okay. All right, close. Anyone else? 66%. 56, okay. That's lower, it's got to be higher. So the answer is actually that it was almost 95% of people who were taken off of, were taken off of the buprenorphine, ended up using opioids again, pretty quickly. When they put people back onto buprenorphine, about 50% were continuing with opioid use. So it's not that buprenorphine is perfect, people do use opioids while they're on buprenorphine, but it was a difference between 95% and 50%, which is obviously a huge difference. And even if someone's using buprenorphine, it's protective for overdose. So, so that was, you know, there are many trials that demonstrate this, but this was a trial that was done with my group, the Clinical Trials Network, the NIDA Clinical Trials Network. So it's just a great example of how important it is to tell people to stay on buprenorphine for a significant amount of time. You can't just stay on for a month or two. All right, that's trial number one. I'm going to move on to trial number two, if no one has any questions. I don't see any questions in the chat. So now we'll talk about, so hopefully I've convinced you that it's important to use some medication for opioid use disorder for any patient you ever see anywhere that you see has an opioid, an issue with opioids and opioid use disorder. So let's think about how to approach those patients. So how do we think about the three medicines? Does any one work better? You know, how do we consider them? So here's a trial that was done soon after buprenorphine was approved in the United States. The FDA was interested in the question of how does the buprenorphine affect the liver? So, yeah, we're going to, great question, Donna. Donna, is that how you pronounce your name? Or Dana? A great question. I'm going to get to that. That's the last part of the lecture. But that is a very important question. What should we tell patients in terms of coming off? So you have, but anyway, this, getting back to this trial. So this trial randomized patients that are coming for treatment for opioid use disorder at a methadone program. So OTPs, places where people were coming to be given medication every day. And they said, okay, so half the people are going to be getting methadone and half the people are going to getting buprenorphine. And let's see how each group does in terms of the primary, the main question was how they do it for their liver health. But we were lucky that we got some clinical information about how they also did in terms of opioid use and how they did in terms of retention. And I'm not going to go through the details of the trial beyond that. So the main outcome was that there's no difference in terms of their physical effect on the body. And generally, these medications are actually not too, they're usually can be used with people that are having liver issues. There is a researcher in Yale who does a lot of work on that. She's shown that it's generally safe. It's usually safer to give someone a medication rather than worry about their liver because opioid use disorder is so devastating that it's just better to focus on that and treat that. That's the primary outcome. The secondary outcome was really very important. They found that people that were on methadone were much more likely to remain in treatment. So it's not just tried and true. It's a medicine that we know works really well and keeps people engaged. It was almost, you can see it's a pretty large, it's about a 20% difference here, right? Of the people who were randomized to methadone versus the people that were randomized to buprenorphine. So you can argue that, well, these are people that were coming for methadone treatment, they come every day. But all things being equal, we have some evidence that methadone may be better in terms of retention. In terms of opioid use, they weren't that different. So there wasn't really significant differences. All right. Another really important takeaway from this trial for clinicians to think about, and this is one of the things that we're still looking into, but this is an associational point from the trial, is that in both the case of methadone and the case of buprenorphine, higher doses did much better in terms of retention. So this is a graph showing the milligrams of buprenorphine. So people, I don't know if people know, but the dosing range for buprenorphine is, if you look at the FDA package insert, it says, well, it's usually about 16, you can go up to 24. But a lot of people are maintained on much lower doses. So you can see here that if people are on zero to 10 milligrams of buprenorphine, their percent completion is 11%. But if they're on the higher range, the 30 to 32 milligrams, their completion rates were almost about a third. So you get a triple, almost triple the retention if you increase the dose. So we actually have a trial that's running right now. It's a really quite large trial. It's in its final years now where we're randomizing patients to sort of 16 milligrams versus 32 milligrams to and also versus a long-acting injectable of buprenorphine to see if this is going to hold true if we do it prospectively. But I would say clinically, if someone's not doing well and you put them on buprenorphine, don't be bashful with your dosing. Just go to 24. The risks of people having really getting into real clinical problems with 24 and 32 are really not that high. It's, again, it has like a peak effect in terms of risk of overdose. There is a concern for diversion, but we can talk about that if people are interested in that. But I think generally, all things being equal, it's better to push the dose higher. If someone's overusing their buprenorphine, if someone's still using opioids on their buprenorphine, you may have this reaction where you're not getting better. Let me kick you off. Don't do that. Raise the dose. Keep the person in treatment, and then eventually, hopefully, they'll get into a stronger recovery. And the same thing was true in terms of dose with methadone. At lower doses of methadone, you get zero to 40, which is really the lower range of methadone. You get only 8% retention. If you went to higher doses, you got much better retention. The takeaway from this in terms of methadone dosing is you really want to get higher than 60 milligrams. Methadone, I don't know if anyone here has ever tried to manage methadone, but you have to raise the dose slowly because it builds up in the body, and you really can't just go straight to 60 milligrams. But again, if you're ever doing it, you should just keep people in treatment, even if they're using at the beginning, and just keep raising the dose until you get to at least 60 milligrams, and then some people will go much higher. So that's the second takeaway from this trial. Very important point that we learned on secondary analysis. All right, so that's the methadone versus buprenorphine trial. So we have another CTM, Clinical Trials Network, trial, which is another randomized trial between these medicines. This time, it was a randomized trial between people, randomizing people coming for treatment either to buprenorphine or to XR naltrexone, the long-acting injectable naltrexone we mentioned earlier. So again, the question was, how do people do if you take people who are coming for treatment? You want to decide, okay, they're not going to be able to go to a methadone program every day. They don't live near a methadone program. Methadone's out. It's not an option. So now I have a choice. Should I put them on buprenorphine or should I put them on XR naltrexone? That was the goal of the trial, and the primary outcome was time to relapse, which was defined as either you have to stay in the treatment, you have to stay, and you also had to not use opioids two weeks in a row or go back to using every day. So that was the outcome. So what was the results of this trial? So the first point is that people had a hard time getting onto long-acting injectable naltrexone. So naltrexone blocks the opioid receptor. So there's a problem in terms of how to start it. Because it's blocking the receptor, if someone's actively using, say, heroin or fentanyl, if they get an XR naltrexone injection, they're going to get extremely sick. We call it precipitated withdrawal. They can even get to the point where they get delirious and they really end up in even the medical hospital, which very rarely happens with people in opioid withdrawal. Opioid withdrawal is generally very unpleasant, but doesn't cause significant medical problems. But if you give someone a medication that pushes the opioids off the receptor all at once, that does cause serious problems. So you can't just give the medication. You have to wait. You have to manage their withdrawal some other way, and you have to usually wait about at least a week, maybe two weeks, according to the package insert. And so it took quite a bit of time to get people onto XR naltrexone. Only about 70% of the trial, of the people in the trial, were able to actually start XR naltrexone. So three out of ten just didn't make it onto the treatment, which is a pretty significant drawback for that treatment. If someone's already, say, on an inpatient unit and they haven't used for the last two weeks, so then it doesn't matter, right? They can get on. But if someone's coming actively using, that's a drawback of only acting injectable naltrexone. With buprenorphine, almost everyone was able to get on. More than 90%, 94% were able to start buprenorphine. So that was the first takeaway from the trial. Second takeaway from the trial, if you look at, so that's sort of, the graph on the left shows you that the XR naltrexone, right off the bat, you get this huge drop in terms of how many people were able to start treatment. So they already weren't doing well. And that sort of played out throughout the trial. So overall, the primary outcome of the trial showed buprenorphine wins. Buprenorphine is a better treatment if you just look straight up randomization. The second takeaway from the trial was that once people were on medication, they did about as well on both medications. You can see here, that's the graph on the right. This is just basically time to relapse. And the percent of the people that were in the trial that were relapse-free. So that goes down in both groups as people start to relapse over time. But you can see they're basically the same graph. So both XR naltrexone, long-acting injectable naltrexone, and buprenorphine, they both work about as well when a person starts the medication. So that was the big takeaways from that trial. So those are, I'd say, two of the big randomized trials in opioid use disorder. I'll just say them again. If anyone's interested in looking up the primary trial, the first one was called CTN27. If you type it into Google, CTN0027, you'll get it on the Clinical Trials Network repository. You can get all the papers from that trial free. And the same thing with the second trial, it's CTN0051, the XBOT trial. That's what people call it. So those are those two trials, good trials to know about. Okay, so let's talk about recovery in a little bit of time. Excellent. So let's talk about recovery. Question for everyone. And this is sort of has to do with the cynicism people feel for people with substance use disorders in general, maybe opioid use disorder in specific. Individuals with substance use disorder who receive a rehabilitation or treatment will just use substances or overdose again. And you don't really have to put your answer, your votes in the chat. It's just something to think about. Maybe think to yourself, have you heard people talk about this in a cynical way? Like, oh, there's that person again, they're never going to get better. You know, a frequent flyer in our ED, a frequent flyer in the unit that keeps coming back again and again. Unfortunately, I'd say in my, at least in my medical training, it came up a lot. And there is sort of a feeling that people just don't get better. But that's not true. The reality is, is that people who start treatment and we can get them into treatment, obviously, we can't talk about everything about substance use disorders today, but there are ways to help people get into treatment. But once people start treatment, if people stay on their medications, many of the people actually do remain in good, full recovery, and they're able to really change their lives and go back to living lives, which are almost free of this chronic condition. They almost have no evidence of that except for the fact they're on medication. So this was a follow-up trial, just to show you that. This is a follow-up trial for the first trial I mentioned, the methadone versus buprenorphine trial, the start trial. So this is a trial that was done five years after that trial. And they just asked people, so how are you doing? How many days are you using opioids in the last month? So people that weren't on any medication, a lot of them were using, a lot of them were using about half the time. So quite a number of them were still using many months later, so 60 months later. But if you look at the people that remained in treatment, the number is much lower, and it keeps going down. So you can actually see that over time, if people stay on methadone or buprenorphine, there's a good portion of people that are nearly zero average days of use. Many of these people were not using at all. So if you look over here on the right, this is sort of a summary of the trial. 65% of people were not using opioids to follow. And the people on medication had a much higher chance of being in that 65% group. So if you follow someone who's coming in with active opioid use, they're in a trial, maybe they're trying to put on medication, more than half over the years will probably not be using opioids many years later. So that's something to think about. I mean, I think hopefully encouraging and reassuring that if we can get people started on treatment, it can do really well. Okay, so here's, we're going to come to the answer to this question that was asked in the chat. When is the right time to consider stopping medication? How long are we talking about? So there's a myth that says that people will often tell you, I feel better, I'm doing okay, it's time for me to stop. I've actually seen clinicians say that to people, which really bothers me. I once had someone that I was, when I was a trainee, they were talking to someone who was about to leave an inpatient unit, a residential unit. They said, well, now you should come off your medicine, you're doing well. I said to them, well, don't you think that when they go out to the real world, that's exactly the time they should be on the medicine? They didn't listen to me. But I think you should, you know, always think about where the person's up to when you think about these questions. So the answer is, the question is, how long should people be on medication? So I'll tell you that in the field, there's a controversy about this. Some clinicians are very conservative. They say, well, we don't really know when it's safe to stop. So let's keep people on forever. Let's keep people on for their whole lives and help them. You know, it's a chronic condition, just like diabetes. People with type one diabetes have to stay on insulin their whole lives. So someone with opioid use disorder should stay on medications for opioid use disorder their whole lives. Other people say, well, it has to be a shared decision making with the patient. And there are people that maybe can come off safely. And we have to allow that option. And being on medication forever has its drawbacks. You know, these medications have side effects, cause constipation. You have to go get them. You have to keep going to the doctor. There's lots of things that are really a headache about these medications. So even among the people that are saying, well, let's talk about coming off medication at some point. If you do a survey, most clinicians say minimum of one year for someone who's coming for opioid use disorder. So that's what I tell my patients. If they come in, they ask me how long I have to be on this. I say, let's talk about it in a year and then we'll decide. We'll see how you're doing in a year. There's someone who I work with, his name's actually Arthur Robin Williams. He did a observational trial looking at claims data and he seemed to show that even after 18 months, people still are pretty high risk for having problems if they come off their medication. So longer is probably better. People often stop too early and put themselves at risk for relapse, overdose, and death. So you should warn people if they are thinking of coming off. You know, this is pretty risky. You have to be really careful, you know, make sure to go back on if you are having problems. And you probably have, and it's very important to have a discussion with people so they understand what's happening. I will say in my practice, you know, I've occasionally taken people off of medications. There are other patients I have that, you know, I've been on for 10 years and they're struggling with other psychiatric issues, they're struggling with other issues, and it's just not the right time to put them at an at-risk situation to start taking them off their medication for opioid use disorder. So it really should be a shared decision-making kind of discussion. And actually we went pretty, I went pretty fast. So we have a lot of time for questions. Anyone want to discuss anything? Well, I'm just going to make a comment first. Thank you for this presentation. It was really informative and really relevant to the work that we do and the stigma that we face both with patients that they have and also just I think within the medical community oftentimes there's stigma about these types of patients and how we approach them and engage them. There is a question here, so I'm going to actually withhold. I just wanted to make that comment. Thank you for this talk. It's really important and I don't know if you can read the comment if you want me to read it out. Yeah, I see. I see that you can read it if you want to. Go ahead. What does it say? Okay. Do you find that the efficacy of MOUD varies based on the opiate preferred by the patients? Yeah. Good question. So could you explain it? Is your question, is it whether it's prescription opioids versus fentanyl versus, is that the question or is it heroin versus fentanyl, that kind of thing, is that what you're asking? I can tell you a little bit about that. I would say that we do, I would say with fentanyl being in the drug supply, we found that people might need higher doses of medication. There are people that maybe try to override the blockade with Vivitrol, with Exxon-Naltrexone. So some people are arguing that we should maybe give those shots more frequently. It's easier to start people from, to help people transition from prescription opioids to medication for opioid use disorder in comparison to people that are actively using via IV or using heroin or fentanyl. So it's people that are actively using heroin or fentanyl generally are harder to start on medications for opioid use disorder, it's a little bit more tricky. But I would say that in the literature, there's no clear signal that we should use, we should match, treatment match. I think my approach is to just tell people, well, these are the three options, which one works best for you. You know, methadone is a little bit inconvenient, you have to go every day to treatment. Buprenorphine is, you know, you can just get the prescription, but it's an agonist, so you're still going to be on an opioid. If you don't want to be on opioids anymore, you're against that, then you have to go with the third option, which is Exxon-Naltrexone. So that's how I approach it. I see here, yeah, right, so I think I answered that question. Hello, Dr. Shulman. Hello. My name is Dr. Gray, I'm one of the residents at Inspira Psych. I was just curious, your clinical experience with patients on methadone, what kind of advice do you give them for protecting, like, dentation, or am I, is it, I've talked with some patients and honestly loved ones that have been on methadone and said that their teeth fell out, and is that more of, like, a myth going on versus, like, the higher substances they were using? And then if that is, in fact, true, what recommendation do you give to your patients on methadone to help with that? Thank you. Good question. Yeah, so it's not a myth, most likely. So the FDA actually just came out about a year or two ago, maybe a year and a half ago, two years ago, with a warning about dental caries with buprenorphine, and it's probably the same with methadone. Buprenorphine has to be taken sublingually, so it needs to stay in the mouth. Methadone, in theory, should be swallowed straight down, and you could even take it in a pill form, which wouldn't have this problem. But in most methadone programs, they give it in a liquid form to prevent diversion. So the, I don't know, clinically, an evidence-based approach to the methadone, but I do know that with buprenorphine, there is guidance on how to approach it. I believe it's to wait 20, rinse out the mouth 20 minutes later with water, and not to brush your teeth or eat anything, I believe. I'm trying to remember the exact guidance, but there's guidance from the FDA in terms of how to approach cleaning the mouth after the medication. It probably does increase the caries due to the acidity of the medication, that seems to be the reason for that. So patients, I mean, you should tell them, yeah, we believe you, you should take, I mean, obviously tell people to take care of their teeth, go to the dentist, you know, but that's how I would say it. So rinse out your mouth after, make sure to rinse it out, you know. Don't brush your teeth right after you take methadone, that kind of thing. Thank you. All right, so we have a question here. Should I read this out? I can read it out. Have you ever encountered female patients who reported that the efficacy of medications vary across the menstrual cycle when taken alongside contraceptives, et cetera? There's debate in the preclinical field right now about whether fluctuations in ovarian hormones affect the potency or efficacy of OUD medications. Have you heard any anecdotal evidence of this in any patients? So I actually have not, and I've read, and I work with actually a woman who does some of the research in terms of the changes in cravings and substance use across the menstrual cycle, but I haven't heard about any issues in terms of more problems with relapse or craving in terms of people that are on buprenorphine or on methadone or on Vivitrol in terms of hormonal fluctuations. So no, I haven't seen that. I think there probably are, there probably is some effect, but you know, I haven't seen any evidence on it and I haven't seen it clinically. Perhaps the medications are over, maybe overpowering that effect or that fluctuation and they're effective enough that it doesn't make that big a difference. I think that's what I would, I would guess, but I'm not sure. I have a question, I guess I'm wondering your thoughts on sort of, I guess your thoughts on what providers or specialties, you know, obviously most of us here are from psychiatry but not everybody, but other specialties as well, should sort of maybe be regularly trained in either, you know, with buprenorphine use or other, you know, sort of opiate kind of management. Because, you know, there's of course a course that you have to take, you know, for certification with, you know, certain things. So I'm just kind of curious your thoughts on that generally of who should be that, should it be everybody, should be familiar with this, you know, and, you know, from a training standpoint, we have residents who are interested in addiction medicine, some who may not be, but certainly something that we're going to see, you know, regardless, just kind of your thoughts on that generally. I'm really glad you brought that up. I'll tell you, I'm really glad you brought that up for two reasons. First of all, I want to give everyone an update. So there was this law, which I mentioned, the Data 2000 law, which required in order to prescribe buprenorphine, you need to get an X waiver, which was you had to do eight hours of training, and it was a barrier to treatment. And it was in our field, a long advocacy, and there was a lot of sort of grumbling in terms of the logic of saying, well, people can prescribe fentanyl patches without doing an extra training. We can't, why can't we prescribe buprenorphine, which is a much safer medication than fentanyl. And so recently, the legislation was actually changed, and they got rid of the need to do an X waiver. So everyone who has a DEA license is allowed to prescribe buprenorphine. All of you, anyone who has a DEA license is obligated, I would say, if you see a patient with opioid use disorder, to prescribe buprenorphine. I guess there isn't that barrier of saying, well, I don't have an X waiver. You could say, you could argue, well, I'm not trained well enough, that's a separate discussion, but the X waiver is no longer a barrier, I would say. So that was the first piece. So in terms of that, they actually, they changed the requirement that anyone with a DEA license has to do some training in substance use disorders, and I think it's less stringent. So I think do different things to get that training, but that's just, people should be aware of that, that you need to get some training. I would say that everyone should learn how to use these medicines. They aren't hard, buprenorphine isn't that hard to use. It isn't as easy as writing, let's say, a prescription for an SSRI, because you have to time it right. But a lot of patients know how to start buprenorphine themselves. A lot of them have used it before. Some of them may have even started it on the street. So there may be situations where you could just tell someone, well, have you ever used buprenorphine before? Did you ever start it yourself? We didn't talk about starting buprenorphine. I could just give you very quickly, but the idea is you wait till the person's been off of opioids for 24 to 48 hours. I would say maybe even a little longer now with fentanyl, because fentanyl stays in the body for a little longer. You can try to tell them to just, you know, white knuckle it for those 24 to 48 hours. I usually prescribe some medicines to just treat their withdrawal, to comfort medication, like clonidine. I actually use clonazepam just for the two days. And after they're in some withdrawal, or it's been, you think that it's been quite a long time since they last used, that's when you can start the buprenorphine. You can't start buprenorphine right away because buprenorphine, again, will, since it's a partial agonist, it will push the opioids off the receptor. If a person is 100%, the receptors are 100% occupied. But beyond that, I mean, I think everyone should be able to do it. I mean, I'm an advocate, and this is my area, but I do think that you'll come across patients with opioid use disorder in any field of medicine. It's a pretty common problem. And I will say many of them are very nice people that just, you know, got hooked because of surgery or, you know, it's, I think there's a, I shouldn't say, use judgmental language. I'm trying to reassure everyone that there's, I think, a feeling that people with substance use disorders have maybe some antisocial tendencies, or they're breaking the law, they're doing things that are illegal. I don't want to treat that kind of patient. I would say, in my experience, that's not the case. Most people really just want to get better, may have got caught up with this, maybe they're ambivalent about treatment, they're ambivalent about getting better. But it's very rare that I'll come across a patient and I say, this person I can't even talk to, I can't even discuss with them recovery. So yeah, I want to encourage everyone to learn how to prescribe these medicines and use them. I mean, that's my take, that's, I'm a big, I'd be a big proponent of doing that. There are a lot of resources to help people who are, just need a little coaching. I would say that in order to learn how to do these things the first time, you really just need someone to coach you like once or twice, and then you know how to do the rest of your career. So there's a website called PCSSMAT, which is free. It's also SAMHSA funded, and it actually allows providers to get coaching. Lots of expert coaches that work with me at New York State's Adjunct Institute at Columbia that are available if you just want to talk through a case, and I have a case of someone who I want to put on buprenorphine, you could have them as a coach. And then once you've done it once or twice, and it's actually pretty, actually quite easy to do. And, okay. Another question on that, we're going to start into one more time. Okay. Next question is, I wonder if a patient's interested in participating in 12-step programs, do you get pushback from patients regarding remaining on MAT? Yes. My understanding is that this may conflict with the idea of entire absence required by 12-step programs. Thank you. Great question, and really good point. This is a controversy. So, historically, the 12-steps had made a statement that they didn't consider someone fully, you know, in abstinence, and there was sort of almost a spiritual, and if you go to, if you ever go to a 12-step meeting, there's almost a spiritual element to being abstinent and living life on life's terms. So there was a time when there was sort of open animosity towards medications for opioid use disorder. That is no longer the case. The official policy of 12-steps is that if it's a medicine that's prescribed by, you know, a prescriber, and it's taken appropriately, then you can still be considered abstinent. You can count your days. But the reality is, is that if someone actually is going to meetings, there may be people at those meetings that are saying otherwise. 12-step meetings are unregulated. They're just really, the people, it's a, in some ways, it's a religious aspect to it. It's very grassroots. Each group is really its own, you know, unique unit, and whoever happens to be there will be saying what they believe without anyone telling them what to, you know, there's no regulatory body that regulates 12-step groups. So you may run into that. I mean, I think the reality is, is that this is actually a real barrier to treatment in the field, and we are, and we are, we're trying to sort of push against this. But it's better for people to be on medication for opioid use disorder than 12-step groups. I mean, the reality is, is that the risk of overdose is so high that we really just have to try to get everyone to medication. You know, we talk to people about how this is considered abstinence. I want, maybe I'll talk to people, I'll say to people something like, you know, I actually absolutely agree with you. I'd like this person, I'd like you to be off all medicine, and that would be great if you'd be, but you're just not early, you're still too early in recovery for that. The risks are too high. I want you to be alive. And so a lot of times people can understand that, and, you know, if they stay on for a year and a half, two years, and then they're willing to taper off, you've probably, you may have saved their life. So I think that's sort of the way I talk about it to people that are bringing that up. But it is a huge challenge in the field, and we're certainly trying to deal with it. And now we're running out of time, so I'll just say, yes, that is the, that is exactly the right link if anyone wants to link. This was great. Thank you all so much for coming and listening. If anyone wants to provide feedback to the ORN, here's the link. Scan me. And then. Yeah, thanks so much. This was really great, really helpful, informative, and even having this resource that I didn't realize we had, and even actually I didn't realize about the waiver now no longer being a requirement. Yeah, now people don't know about it. It should be, we should, it should be publicized, right? Yeah, sure. And, and here's the, if anyone wants the CME, this is the instructions on how to get the CME. Thanks so much again. We really appreciate it. All right. Thank you. Take care. Good luck, everyone.

opioid use disorder

clinical trials

technology

medication

methadone

buprenorphine

naltrexone

legislation

12-step programs