Welcome to the Buprenorphine Update. I'm very pleased to see we've got a robust crowd today. Dr. Lavounos is not going to be able to join us today because of his other obligations at the meeting, but I'm John Renner from Boston University. I'll be joined by D.C. Park, also from BU, and Dr. Andy Saxon from the University of Washington. I'm going to start out by just giving some general information about where we are in terms of the epidemiology and the problems that are going on with addictions right now. Let's see. I wanted to start with this slide because I think it really captures a good sense of what's been happening over the last 20 years or so. You can see those are opioid-related overdose deaths in the United States, and the black line at the top is obviously the total number. In this slide, there's one thing that this slide has at the bottom, which is the stimulant deaths, the red line. So it isn't, even though it's labeled as opioids, it's a combination of opioids and stimulants, mainly methamphetamine. And what you can see in the beginning is the beginnings of the opiate problem were driven primarily by Oxycontin. And then around 1910, or rather, 2010, we begin to see an increase, which is probably related to the increase in heroin, which is going up. And then we get to the end there in 2015, and we begin to see that purplish line, which is fentanyl, and you can see that gradual increase where that sort of takes over. And at the very end there, the increases are marked, but they're driven by fentanyl and methamphetamine. And it's interesting to know that the line for heroin, the blue line, and the lighter blue line, which are prescription opioids, is beginning to drop. So I think we're having some improvement in terms of how clinicians are handling medications and are prescribing practices, and that's beginning to show. But that's being masked by what's happened with fentanyl and methamphetamine, and that's what's driving the problem that we have right now. And this is, you guys have all probably seen this slide. It just gives you some idea of how some formulations of methadone. This is the amount of a medication that would be fatal, and you can see that with some derivatives of fentanyl, particularly carfentanil, it takes just a speck to produce a fatal overdose compared to what it would take with heroin and with other variants of fentanyl. And one of the problems that you're running to all over the country is you have no idea, not only do you not know that fentanyl may be in the substance someone is taking, but you don't know what derivative of fentanyl it is. It could be a somewhat safer, weaker form, or it could be a potentially lethal form. And we have no control of that and really no way to identify that. This slide really just shows the peak of overdose problems, how they've gone on, and what this doesn't show very clearly is that the overdose tendency through the COVID epidemic has continued and continued to go up. That's shown better in the next two slides. These are national drug-involved overdose deaths. These are all drugs combined from the CDC data in 2023, and you can see, and this is divide both of men and women. And you look at the next slide, which is just opioid deaths, which is driving most of the numbers in that first slide, and you'll see that this is data that goes to 2023. It was released in 2023, and you can see the numbers are just continuing to go up. I think one of the more encouraging parts of this, if you can find something in such deadly information, is that the work we're doing to get people on treatment with buprenorphine is working, and this report suggests that the people on buprenorphine are not driving this overdose thing, that this is actually protective. And there's no, even though the numbers are going up for buprenorphine, there's no indication that that's really related to the overdose, that that seems to be independent. So I think our efforts to get people in treatment are paying off, and there's no reason to not continue to push very hard to make sure that happens. And this slide is just a review slide. It looks at 10-year changes, where the states have had the hardest problems with opioid overdeaths. And you can see the Rust Belt, the Northeast, this area for the last 10 years has gotten worse and worse and worse in terms of the overdose problem, the fentanyl problem. Just talk a little bit about regulatory changes. I wish I could be a little bit more specific about what government is going to do, what's happening, but if any of you have been following that information, I think you're aware that it's vague at best. They have made the decision to eliminate the buprenorphine waiver. And along with that, they eliminated the limits on patients, so any physician with a DEA license can prescribe buprenorphine, and they can prescribe to as many patients as they want to prescribe. But I think the data in the background suggests that that has not really dramatically increased the number of people on buprenorphine. And I've been concerned all along that even though people complained about the waiver, that it was really stigma towards patients that was holding the numbers down. And it was just more convenient to blame the bureaucratic process of having to get the waiver. But since that's no longer required, I've yet to see that there's going to be a jump in the terms of the number of people who are placed on buprenorphine. But what's going on is that the DEA eliminated the requirement for the waiver, but now they attached a requirement for training that will be with every DEA license. If you're getting your license renewed or if you're getting a brand new DEA license, after the end of June, you're going to have to show that you've had eight hours of training. Now, they haven't defined what they mean by that eight hours. And what they have said is pretty vague. It has to be training about addiction treatment. It has to be training that includes information about medications for addiction treatment. But it doesn't have to be coordinated. It doesn't have to be very specific. You can get an hour here and an hour there, and you can put together your eight hours without any problem. And I think it's really unfortunate because I'm afraid that people will be able to meet that requirement easily, though I think they're concerned about it. But I'm afraid that they're not going to get really good coordinated teaching. So I think they will probably be able to match the numbers that are needed. But I'm not sure that that's really going to improve the quality of care that we're delivering. The law originally for the waiver, you may recall, originally there were only four organizations that could provide the training. ABA, APA, AAAP, and ASAM, rather, and the osteopathic group were the only ones who could do it. It's really being opened up now to practically any medical organization. So I think we're going to see a wide variety of options for training, and we'll have to see how that works out. Now, there are some exceptions to this requirement. People who will not be required to meet that eight-hour requirement are anyone who's addiction-certified in medicine or addiction psychiatry. Anyone who's taken the eight-hour course anywhere along the way will have met the requirement. Anyone who's been in medical school or dental school or a number of other professional schools in the last four or five years, they've had eight hours of courses in many schools, and they will also meet the requirement. So there are going to be a number of people who are exempt from meeting that requirement. The telehealth situation is very unclear at this point. The DEA wanted to basically terminate the liberalization that occurred and go back to something that looked like the Ryan-Height Act that would make it more difficult to promote care. Their suggestions that they were going to do that were met with a rounding critical response from the country. They got something like 38,000 comments, which is the largest number, I think, that they have ever seen for any changes like that. And it's going to take them months, they say, to analyze it. But what the outcome is going to be, I suspect that we'll be left with some liberalization, because I think the medical community has just made it very clear to them that we like doing telemedicine. We like the ability to start people on buprenorphine, not having to make sure everybody comes in and is seen for every visit and things like that. So I think some of those liberalizations will continue, but we don't know. We'll have to wait and see. But I think they extended everything for about six months, and then we'll see what happens. I just want to talk very briefly about buprenorphine formulations. Let's see a show of hands, just to know, and who are my audiences, how many people here are currently prescribing buprenorphine? Can you see? Okay, so most of you. We're talking to the choir here. Good. Well, I won't spend much time on this. The newer formulation of the DEPA formulations, the sublocate has been approved, and people are using that. We're learning how to use it effectively. We're still waiting for final approval on the weekly shot, and that was supposed to have been approved two years ago, and the DEA and the FDA sort of got nervous about it, and we hear rumors they are about to give final approval, but that hasn't happened yet. But we will have another tool when that is approved, and we'll make it easier when we want to give a one-week shot to patients. I also want to talk to... Let's see. Okay. Andy, do you want to get in here with an ultrasound? Do you want to do that? Yeah. A couple of people can go to slide 37, or do you want me to go... Well, no, no, you want me to see you? You want to get into that? Okay. We're going to go back and forth with some of the presentation today, so we will be flipping speakers. D.C., do you want to take off from here? So, yeah, I just wanted to tell you guys about the Neewer, one of the Neewers, not entirely new, which is a long-injectable subcutaneous injection of buprenorphine. The brand name is sublocatus. And we've been utilizing this for about the last 2.5 years in my hospital, and it's really been the game-changer for some of our sickest and most challenging patients. How it is you're supposed to start is that you're supposed to get them stabilized on buprenorphine for at least 7 days, although there are some data where the 7 days is not really necessary, and we'll talk more about that later on. The purpose of making sure that it's going to be 7 days of stable buprenorphine is to make sure that they're not going into a precipitate withdrawal. And once they're on the 7 days, then you can, as long as there's no liver function enzyme deficiency and EKG is okay, then you can go ahead with the initial dose of a 300-milligram injection. It is designed to achieve this stable level after 3 series. The most conventional dosing is the 300-milligram the first month, and on the first day of injection, you can actually stop the sublingual buprenorphine. And the second month, you proceed with the 300 milligrams, and you kind of top it off. The third injection at 100-milligram, you'll top it off every month on 100-milligram maintenance. This will be equivalent to about 16 to 20 milligrams of buprenorphine sublingual a day. Now, alternatively, for patients who are more used to in line with the buprenorphine sublingual 8 to 12 milligrams a day, you can then go ahead with the 300-milligram on the first month. On the second month, 100-milligram, and then go ahead with the continue with the 100-milligrams on the monthly kind of topping up the level injection. Now, please keep in mind that this is the, just kind of like a guideline. You know, this is one of the, you know, obviously you guys all know, this is one of the situations you have to follow the patient and not the number. I do have a patient who's on 300 milligrams continuously, and I imagine that their buprenorphine serum level is equivalent to someone who's on sublingual buprenorphine 28 to 32 milligrams. I have one patient who's on 8 milligrams daily on top of the 300-milligrams injection, and that was required to stabilize him. The, I will say that some open label, there was one open label study that showed that the, this of course was an ED study, where a patient, you know, the ED, what they did was they made sure that there were, you know, patients was in mild to moderate withdrawal, and they give the four milligrams of first dose, and when they tolerated it, after 90 minutes to two hours, they went ahead with the 300-milligram injection right then and there. They, you know, from the open label, obviously, you know, you cannot design really like, you know, double blind, you know, studies in that kind of protocol. About 21 patients, I think they saw about two patients with a precipitated withdrawal, but otherwise, 19 patients tolerated fine, and the, really is, like I said, as I mentioned, the, it's been really the game changer for some of my sicker patients, and just the idea of being able to get the buprenorphine injection delivered on the day of presentation really is appealing. And the, I can go into the center. So, just brief review of a standard, you know, induction or initiation, what have you. So, just, it's gonna be a brief overview. You know, we've seen that I'm speaking, you know, we are speaking to the choir, so I'd rather keep this brief. You do want to keep the patient in mild to moderate withdrawal because the idea is that the patient's mu-opioid receptors are, you know, are developed, have developed tolerance for full agonist opioids, and if you give, if you introduce partial agonist of buprenorphine too quickly, the displacement of buprenorphine at the mu-opioid receptor levels of the full agonist, and the rate at which this takes place will make them susceptible for what we call precipitated withdrawal. You know, I think the, before the fentanyl era, I think the cows number that we waited for was, you know, eight to 12 range. With the fentanyl, I think all of you have seen that it's been more difficult to start or initiate buprenorphine. These days, we wait until, you know, cows are 13. Before, when it was only heroin, you had to wait for eight to 12 hours since the last injection. With the fentanyl, I find that it's been increasingly longer before they can get to cows of 13 or higher. You start with the 2.5 milligrams of buprenorphine or 4.1 milligrams of buprenorphine naloxone. Buprenorphine sublingual, their peak level will be reached in one to three hours. You know, re-examine them in two hours if their cows are relatively stable or even lower, which is what we like to see. Then we repeat the dose and try to stabilize them as much as possible on the first day. The conventional way of starting buprenorphine, I think it was to aim for eight to 12 milligrams on the first day. Many people, many colleagues and I, myself included, are finding that a lot of my patients will need 16 milligrams on the first day of injection just to make sure they're not going into withdrawal by the nighttime. The ideally, return to clinic the following day or in two days, or you at least give them a call to evaluate their dosing, whether they need more, whether they need less, whether they've slept okay. One of the first things that I learned from Dr. Renner was that try not to do this on a Friday morning because you're not gonna be available on a Saturday or Sunday. So we try to keep patients in on the early of the week as much as possible. But these days, because we don't know if they're ever coming back, we wanna get them. I think a lot of providers are getting more familiar with just get them in, get them started, and let's see if they can come back. Most stabilize on 12 milligrams to 16 milligrams when it was not fentanyl. But if it was, they're used to fentanyl, I would aim for 16 to 24 milligrams of a sublingual buprenorphine. And the others have to approve those ranges up to 24, six milligram. It is perfectly okay and advisable to go over that. I just wanted to make sure that maybe some insurance company may not pay for more than 24, six milligrams a day. That's one thing that you should keep in mind. So, again, this is gonna be a review for everyone. 12 to 16 hours since the last short-acting opioids. 24 hours for system-release opioid medications. 36 hours of, you have to wait for them to get into moderate to withdrawal from someone on methadone maintenance. However, if they have been maintained on, say, like 80 milligrams of methadone, 36 hours is not gonna be enough since their last use. The conventional method, and we'll talk about other ways to transition people from methadone to buprenorphine, it should be tapering down their methadone dose by 10 milligram per week, and then until they get to 30 milligrams a day. Continue that dose for Friday. Saturday, they can get 15 milligram, and then Sunday, they skip the dose. By Monday, they should be able to start buprenorphine without risk for perspective withdrawal. Cal score of eight to 10. That was before the fentanyl era. I think most providers are finding that they have to, we have to wait for 13 or even higher to avoid any unnecessary risk for perspective withdrawal. Consider use of a high-dose or low-dose protocols, and we're gonna talk about that next. I think it's coming. Home induction or home initiation is increasingly popular. I think a lot of providers have experienced, and got familiar and got comfortable with using the home initiation because of the COVID pandemic. I started buprenorphine over a phone call, never saw them, never saw their faces, didn't have their urine screen results on my hand. I just kind of took down their history and mailed out buprenorphine. I guided them how to start it, and they've been fine. So home initiation, obviously, the process that they can do this at the comfort of their home, and they can wait. Now, if you're talking about in-office induction, and especially with the fentanyl, you are having to wait for up to 24 to 36 hours in CASA 13. What if they never get to that level in the office? Your office is closed at a certain time of the day, unless you work in the ED. Now, with the home initiation, they can wait for that mild to moderate withdrawal until that threshold is there, and they can start it at the comfort of their home. You do want to send them home with a comfort medication, which is not really comfortable, but I'm talking about like clonidine, ibuprofen, bentonamide, diphenhydramine, and loperamide for other opioid withdrawal symptoms. The one thing is that because, especially for some patients, they can be overwhelmed with the prospect of having to start medication without any guidance, without any phone call available to physician's office. There is an app for that. So you can download, you can, I don't have any conflict of interest with that, with a particular company. I don't get any loyalty from that. But you can easily search for buprenorphine in the app store, and they can give you an app. And that's gonna kind of guide the patients on, okay, this is what symptoms I'm having, and overall score is that. I should wait for a little bit more. I should wait for a little bit more. Okay, I'm okay to start two milligram. And then it's gonna continue to count down, count the number of total medications they have taken, and the patient can take easily, show the result after a day or two to their physician or provider, and talk about the dose evaluation. Can you raise your hand if you are doing home initiation, home induction? No. How many of you are doing in-office induction? How many of you are doing both? Okay, great. And if you have any comment about, you know, if something happened where there's more risk, you know, on one way or other, or there's more, you know, benefit one way or other, I'd love to hear your thoughts, but we'll have, you know, dedicated time for those comments later on. Okay? Okay. Any questions so far? And I will ask you to please come up to the mic because we are being recorded, and if you don't feel comfortable, I'll just have to repeat your question to the mic. Sir. Hello. So one place where I struggle a bit with the induction recommendations is that its moderately complicated nature scares away some prescribers, I find. Yes. And I found myself, as dumb as it sounds, giving 4-1 milligram twice a day, call me in a few days if you need more, the patients usually do pretty well. That simple. And when I tell other providers the more simple method, then they're more willing to try it, which then saves lives, because, well, I don't want my patients in precipitated withdrawal. I want to save as many lives in the community as possible, which means also having my colleagues not be afraid to prescribe buprenorphine. Yes. So do you have any comments? Is it how important it is to stick to the best practice protocol as opposed to trying to get as many prescribers to do it as possible in our community? I really appreciate your comment, and there's definitely a value in simplifying the protocol as to let's get more providers in. Maybe we're overcomplicating things. I'm going to ask Dr. Renner and Dr. Saxon if they can comment first, but can I ask you what region you're practicing? I'm in the Midwest, in South Bend, Indiana. Thank you. I think those parts of the country where fentanyl has not arrived yet are probably able to stick with something that you're describing. I think in the areas where we're seeing a lot of fentanyl, I think we really have to individualize our dosing, which means probably go higher, both with induction and with maintenance. And I'm curious. I wanted to ask the people in the audience, how many people feel like they're using higher doses of buprenorphine now for long-term treatment, not talking about induction, but just your patients in general? Do you think you're using higher doses or just the same, lower? How many higher? Can we see a hand? Okay. How many think there's been no change? Because nobody's collected this data yet, and I think we're certainly getting reports from some parts of the country that if there's a lot of fentanyl around, that in general the feeling is that the doses for buprenorphine are going up. I really feel like while there are a lot of prescribers in this room, in my community, that's not the case, and people are having trouble getting access to people willing to prescribe buprenorphine, even amongst psychiatrists, thus primary care providers. So I worry that saying, okay, we have to start at 2 milligrams, call them in an hour, tell them to wait, that it creates people then back off and say, I'm just not going to do it. I think it's a legitimate concern. I think we're caught between do we get more patients in treatment, do we get more docs or nurses or what have you prescribing, because ultimately I think to individualize the dosing is going to be better. The other part of it I work on too is people are afraid of the substance use disorder patient, irregardless of the medicine, and that can be a barrier to overcome. Thank you. Yes. Hi, I'm Smitha Patel from Massachusetts, and my understanding is that the 16 milligram, when Suboxone came out, 16 milligram is the threshold dose, and by increasing the more than 16, it did not give, or it does not give the better effect. And I hear that people on fentanyl requires more than 16 milligrams, so it's kind of confusing. So I think you're referring to the flexible dosing and really the buprenorphine when it comes to flexible dosing, it really didn't make much of a difference in that particular study. I think, you know, this is one of those classic scenarios where you do have to follow the patient. The patient's not going to read those studies, they're not going to read the textbook. If they're telling you that I'm still having cravings on 16 milligrams, and here I am, and telling him, like, look, 16 milligrams should be enough to cover that craving, it's not going to matter. The patient is going to go out and relapse. And we know that, especially when we know that there's no long-term serious side effects associated with the buprenorphine, and we actually encourage them for long-term maintenance therapy, I'm going as high as they say is controlling their cravings, up to a reason. And when we know the data is that up to 24 milligrams is entirely approved by FDA and some insurance companies, and some people need more, then treat those patients. So where does then the threshold come in the picture? The threshold comes... which threshold? The 24 milligram are you talking about? 16 milligram threshold comes in the picture. Does anyone have, you know, like a set limit of 16 milligram in your practice? Can you show... raise your hand if you are doing that? Yeah. Thank you. Good, thank you. There are some states that have regulations, I know, at least in the past, Ohio. Is there anyone here from Ohio? Oh, so I know, because I was working with the program there, and I understood it was very hard to get a dose over 16 milligrams for people on Medicaid there. So if any of you want to comment on that. Okay, that may have changed. That was a couple of years ago. Great, thank you. Can I take a question from the back end first, because she was here, and then first. Yes, sir. You had mentioned that long-acting subcutaneous buprenorphine was a game-changer for your most difficult patients. Could you please elaborate on how it was a game-changer, which meant by most difficult, you mean most severe withdrawal? Sure, sure. So some of my patients who still struggled on 24 milligrams or even higher dose of buprenorphine sublingual were struggling because they were still in the mindset of I'm taking more depending on how I feel, or I'm taking less depending on how I feel. And they can still have the decision in their hand not to take it. If I want to get high, if I want to relapse, they have kind of figured it out. Because of this amount of fentanyl, I can stop it for about 12 hours, 18 hours, or 24 hours, and they can still use. What the patients have told me about being on buprenorphine injectable was that it's kind of like having the best of both worlds from sublingual buprenorphine and the long injectable naltrexone. With the, obviously, long injectable naltrexone, they know consciously, I mean, physiologically, they know that there's a blockade of a mucoporeceptor level, but also consciously they know that if I do use, I'm just going to be wasting my money, so why should I bother? And that can be an additional tool to continue their recovery. Now with the buprenorphine long injectable, what the patients are telling me is that it's the same thing. I have the medication. I cannot dig it out. I mean, there was a concern for a patient digging it out and trying to abuse it by IV. I think that was largely kind of like overblown. I certainly haven't had any patients attempting to do that or being suspected of doing that. And the patient is saying that there's buprenorphine controlling their cravings, their withdrawal symptoms, and if they're having mild to moderate pain, it's also helping with that. And the elements of decision is taken away from them. They know that they got the medication. If they use, probably they're going to be wasting their money. May I have a follow-up to that? And I assume the answer is they tell you this, but my question is how do you identify those patients? Patients tell me. And their urine screen also shows. One last question before we proceed. Just two points. Anecdotally, I find that those patients that need escalations and dosages from time to time tend to be those that decline to access psychosocial treatments concurrently. But I hope that we'll get to talking about how to get people off of buprenorphine. I have a number of patients that have been on it for 10 years or more on very low dose. They can't tolerate coming down, and they're getting dental complications. And I have one patient that has lichen planus under the tongue, and he's very afraid of getting further oral issues. Yes. Yeah, so I think your experience is very constant with what probably everyone in the room has experienced, that it's, for stable patients, very easy to get down to 2 or 4 milligrams with a slow taper and then very, very hard to go from there off. And we were going to talk about this later, but we can talk about it now. I think everyone knows that the FDA put a warning in the package insert about dental problems. We're really unclear if sublingual buprenorphine actually is causing those dental problems or if people have preexisting dental problems or just the fact that many of our patients... I mean, I work at the VA, so my patients can get all the general medical care they need and specialty care. They can't get dental care unless they have 100% VA connection, and it's not available in the community. So it's just poor dental care, perhaps. But in terms of taking them all the way off, I don't think anyone... I don't have any more knowledge, and I doubt my colleagues do. Maybe someone in the room has some knowledge. What I usually do is encourage those patients to be happy with the situation they're in and continue on their medication. It might be that sublucade is an alternative that would work for you. If they're on a low dose, you could give them 100 milligrams of sublucade. That would obviate the dental concerns because they're not taking a sublingual medication. And we're starting to explore, since it is a long-acting injection, if you build it up for a few months and then you stop, could that be essentially a spontaneous taper down that might work for people? So I think... I'm not saying that works because I haven't really tried it. It's just in theory. But that might be something you would consider for your patients, at least to relieve your concerns about the dental issues. I would just add to that anecdotal reports of patients who have completed tapers with sublucade at the very end, and it's just self-tapered. But there's no research on it. There's absolutely no data, you know, that we can recommend something like that. But people are talking about using the shot at the end. So, yeah, the buprenorphine, the long injectable subcutaneous have shown that as long as you complete the first three series, the residual buprenorphine level can be around if you end with 300, 300 milligrams and 100 milligrams maintenance, their buprenorphine, the serum level, can be detected up to 12 months after the last injection. And I think, again, coming to the also anecdotal reports from the patients that when they're stopping the medication for one reason or other, they stop the buprenorphine sublucate injection abruptly and they don't feel the withdrawal symptoms at all. The level dissipates quicker if someone was only 300 milligrams loading those once and 100 milligrams maintenance, but that's still been the case. I just wanted to add one comment that a lot of patients who are on the tail end of buprenorphine, and obviously I'm assuming that you guys have talked to the patients about the benefit of remaining on the buprenorphine and that you have determined it is safe to do so. I found that a lot of our patients have that mini-PTSD symptoms from opioid withdrawal. And when they're on the tail end of buprenorphine, when they consciously know that they're taking less of those than before, their brain will interpret every symptom of anxiety, irritability, insomnia, fatigue, as an impending opioid withdrawal. And all the PTSD-like symptoms kick in and their brain is saying, warning, warning, warning. You're about to get dope sick. What are you doing? What are you doing? Take more of those. And when I counsel patients about that, there's that tendency when they're coming from 4 to 3, 3 to 2, 2 to 1. They have a, you know, it's my just small, limited sample. They tend to do that a little bit better. But yeah, you can add to that, to the counseling. We're going to continue with the slides and just ask you to keep your comments. You know, don't forget them. We'll try to get to them as much as possible. High-dose and low-dose initiation. So I'm going to talk about the low-dose first, which is micro-dosing or Burnist method. It's called the Burnist method because it was developed in the Switzerland burn in 2010. And the idea was that the, okay, what the perspective withdrawal happens because the abrupt introduction of partial agonist is displacing the full agonist opioids from the mu opioid receptors. What if we just make them so gradually, you know, that the majority of the opioid receptors are still occupied full agonist opioids, and then you're just slowly introducing the partial agonist of buprenorphine to the mu opioid receptors and continue to build that up and continue to build that up and stop the full agonist. And they never had to go into mild-to-mild withdrawal or they never were at risk for perspective withdrawal risk. Usually a lot of, you know, there are different protocols from Europe and from America. Usually it's seven days of gradually increasing the buprenorphine introduction and then abrupt cessation of the illicit opioids or full agonist opioids. Simple protocol. So 0.2-milligram formula is not available in the U.S. So that's the smallest dose that we have available for sublingual buprenorphine. With the suboxone, it's 2-milligram. I think with the Zopzol, this can be slightly lower, but the bioavailability is still about the same. Now in Europe, 0.2-milligram or 200-macrogram rescue formula is available, and that's the lowest sublingual dose. What they have done is that the patients are still using heroin continuously, and you're using while they're using and not waiting for any mild to moderate withdrawal, you give them 0.2-milligrams of buprenorphine sublingually and repeat that, and then increase that a little bit, increase that a little bit, increase that a little bit. By day nine, by I think day six, you know, the patient was on 6.5-milligram. Patient stopped the illicit heroin, and he, you know, the patient never went into withdrawal. And then you just kind of titrate up the buprenorphine dose. Okay. Other sample protocol. So again, the smallest U.S. buprenorphine sublingual formula is 2-milligram. This particular protocol is from the U.S., 0.5-milligrams, and then continue to go up on the buprenorphine, thus the micro-dosing initiation. And by day eight, this particular patient, it went all the way up to like day 27 until the patient stopped using the illicit fentanyl. Now, one ethical consideration to, you know, to take is that, you know, SAMHSA or we do not recommend or condone ongoing fentanyl or heroin use. We do counsel them that while they're continuing to increase their buprenorphine dosing in a micro-dosing induction, they're less likely to go into personal withdrawal, but we're not obviously telling them to continue to use, you know, heroin or fentanyl. Does anyone, is anyone doing micro-dosing induction? Okay. Hey. Okay. And, you know, has there been any adverse events, notable adverse events with the micro-dosing induction? You have. Actually, can you actually, can we hear from you, please? Yeah. Yes, please. Yes, I'm from Australia, so we've just started doing micro-dosing in our clinics there. More with high-dose methadone, had a lot of people go into precipitated withdrawal, even following the protocol. This is as outpatients, so coming to the clinic every day. And when you say high-dose methadone, how much dose are we talking about? Well, I think the limit was 150 milligrams. 150 milligrams. I didn't do any more than 100, but they really struggled. Yes. My opinion would be it's more comfortable in an inpatient setting. Yes. At least for methadone. Yeah. Thank you. Thank you. No, I think that makes sense. Most published protocols on the micro-dosing induction is actually, you know, someone on meth maintenance and they get transitioned to buprenorphine, had been done on patients on 80 milligrams methadone or lower. I've had colleagues doing this micro-dosing induction in an inpatient setting. I work in clinic, and in our residential program, we've done micro-dosing transition to buprenorphine from methadone on someone who is taking 60 milligrams of methadone. But obviously, 150 milligrams of methadone is a different game. Now, I'm going to talk about the high-dose macro-dosing initiation of buprenorphine. This is mostly done in an emergency department setting, which makes sense because they know that if they don't get the patients then and there, then they're probably not going to come back. You know, this is, you know, get them while you have them. And, you know, of course, they have more support, you know, as opposed to like a, you know, clinic or in office. So what they do is that they'll wait for mild to moderate withdrawal and they'll wait for, you know, eight hours, 16 hours, since their last use, and they give the four milligram. If they tolerate it, then give them eight milligrams and eight milligrams, four to eight milligrams, continuously up to 32 milligrams on the first day. And following their protocol, obviously you're going to discharge them, you know, maybe bridge a script for three days, depending on their resource and the capability of your community. Maybe, you know, they have a bridge clinic or they have a rapid intake, you know, substance use clinic, and you arrange for follow-ups. And that has been really the key when they compared just SBIRT treatment as usual versus SBIRT plus high-dose initiation of buprenorphine. This group did far better. And they reported minimal perspective withdrawal risk. And, you know, but I will say that they please avoid doing this in someone who has been on methadone maintenance. Because methadone, again, it doesn't matter if it's been 36 hours, if it's since their last dose. Methadone's half-life is such that it's going to take a lot longer before they're ready for buprenorphine initiation. This is a sample algorithm for ED, for macrodosing initiation. It's a little bit too small of the font. But it's in the PowerPoint that you can download. And obviously you can look up the article yourself. And Dr. Herring has published the algorithm that their ED is doing. Do the 4-milligram and repeat 4- to 8-milligram dose continuously up to 32 milligrams on the first day. Okay. And it just shows that... There's 1,200 patients with the opioid disorder and cost over $4 were seen in 28 EDs. And, you know, 70% of them was screened for fentanyl. And when they did the macrodosing initiation in the ED, it just was a very low risk for first-degree withdrawal. And that is... I would emphasize this study. I mean, this is a report from a group of seasoned investigators. They did all of the macrodosing in the setting of an emergency room. So this isn't something that we're recommending that you would be trying in your office. But what was surprising in this study, over 1,200 people, they had 800 of the people in the study they know were using fentanyl. And the number of precipitated withdrawals that they got was less than 1%. And that was the striking finding because I think there's been this general sense that we're going to see lots of precipitated withdrawal, particularly in people who are using fentanyl. But they didn't see that. And this is pretty well-respected, at least initial published data. So it certainly would suggest that the incidence of precipitated withdrawal is less than we thought it was. I mean, out of, you know, 1,200 patients that they had, they observed a nine precipitate withdrawal, which is less than 1%, .76%. All positive fentanyl, all were stabilized and discharged from the ED within the 24 hours. I think it says about as good as it gets. Again, for those of you who have been consulted or who are working in the ED, this is something that you could consider. The other thing that I would add is that I think one of the things to think about this is the general concern to get patients on to buprenorphine as fast as possible. And this is one way, particularly for the patients who are being seen in emergency rooms, that they can be initiated and discharged within 24 hours on buprenorphine. You need to have a system that is gonna be able to pick them up and continue the care. But I think that it is a good example of what can be done to get more patients in treatment quickly instead of struggling and ignoring it and delaying the care. So I think we need to look at this and we need to look at other ways that will initiate patients very quickly on to buprenorphine so that we don't lose them because we're in a very dangerous era where a patient walks out the door and they may die. And I think when we've got them in the potential care and the entry of care, I think we have to do everything possible to proceed with that opportunity. This is a slide just comparing different strategies to start the buprenorphine. With the low dose, you, and we're not condoning, again, continue the fentanyl use, but with the low dose, they may be continuing to use fentanyl or they have stopped it and introduced the buprenorphine ever so slowly and touch it up over seven days. And with the high dose, you get them in and you start the dose and you get them to 32 milligrams a day on the first day. This is the, you know, this is the crossovers, the microdosing induction while they're still using fentanyl or being on methadone maintenance, you can gradually introduce the buprenorphine ever so slowly. I alluded to how microdosing can be done on patients on methadone maintenance. And so the conventional technique before the microdosing induction was that if someone wanted to switch from methadone to buprenorphine, they had to taper, to do this safely, they had to taper their methadone dosing 10 milligrams per day per week for all the way until 30 milligrams per day. Now, mind you that the other patients are gonna be at increased risk for relapse. They're gonna have increased cravings. They may be uncomfortable. They may be showing some mutual symptoms. And in my experience, only a limited number of patients can go through the entire protocol. You give them the last dose, 30 milligrams on the Friday, 15 milligrams on Saturday. Again, by Monday morning, they should be able to start on buprenorphine safely. Now, with the low-dose transition technique, and this has been very much, it just was very much comfortable for the patients and for us as well. And what they do is that you continue, you maintain the patient's original dose of methadone. Again, most published protocols focus on patients on methadone 80 milligrams or lower. You'll continue them, and then you'll introduce buprenorphine ever so slowly. Now, some protocols that were published, and certainly something that actually we use in the residential program, actually utilized buprenorphine transdermal patch. And please keep in mind that the buprenorphine transdermal patch in the U.S. is not FDA-approved to treat opioid use disorder. They're only approved to treat chronic pain. I also want to add that the transdermal patch is produced by Purdue Pharma, and I try not to use their products as much as possible. But in Europe, there's no limitation about what can you use or what can you not use to treat opioid use disorder. Keep in mind that the transdermal buprenorphine patch is only approved for chronic pain. But the idea is the same. When you're using transdermal buprenorphine patch, the highest formula that we have in the U.S. is 20 microgram per hour, and that'll deliver about 0.5 milligrams of buprenorphine in the next 48 to 72 hours. Their peak is reached 24 to 48 hours after the patch was applied, as opposed to sublingual buprenorphine, one to three hours. So just kind of like taking the advantage of the slow onset, ever so slowly, while they're still continuing the methadone, apply the transdermal patch, introduce buprenorphine slowly for the first 48 hours, and then introduce sublingual. Patients not subjected to tapered dose of methadone at any point. There's no waiting for them to go into mild to moderate opioid withdrawal. And there's no consensus on the protocol, but my conversation with my colleagues and my experience has been that this has been pretty safe to do, as long as the methadone is 80 milligrams or lower. So day one, transdermal buprenorphine patch, 20 microgram per hour, you apply it, you continue 100 milligrams of 100% of methadone dosing, and this particular protocol that Gosh et al talked about, decreased the methadone dosing. I think a lot of programs just continue the methadone dosing up until day six, day seven, when the buprenorphine dose is attached up to eight milligrams, and they just stop. And before I go into, I just wanted to share just one story. This was done so well in our residential program. A patient felt so thankful, and he said that I don't need the program anymore, so he left the program earlier. So I said, thanks guys, you guys done too good of a job. I think it'd be good to see if we have any more questions or comments at this point. I mean, I think the dialogue we can all have together is probably much more important than listening to us, pontificate from up here. I just wanted, my name is Jacqueline Posada. I work on a CL service in Texas, and I don't know if this is that common, but we initiate Suboxone for people who come in with injuries, infections associated with opioid use, and we start them on Suboxone while they're on pain medications, and then we discharge them to a bridge clinic. And I would say our biggest stigma is honestly the staff who think that we're kind of crazy, and we're gonna precipitate withdrawal, and staff who are worried about giving too many opioids, but we've had very good success. So I'm curious if other people do this. It was not my idea. I have a much smarter colleague who's not here, and I just joined her. So are you saying you start it without stopping the opioid medication? Exactly. Are you starting sublingual buprenorphine? Okay. And we do like micro-dosing, but basically we don't want the patients to leave because they need to be treated. So you're giving less than two milligrams on the first dose? Yes. Oh, okay. So it's a micro-dosing or low dose. Yes, but even we do go up sometimes to eight or so before they leave the hospital. Yeah, so it's good to hear that's working. So with the different options available as far as we have micro-dosing, we have this, there's ways where we can treat pain and, for example, I'm thinking of like the practice, at least at BMC, where they will take a pregnant patient who's on buprenorphine and use buprenorphine and treat additionally if necessary. And it seems, basically my question is, it sounds like we don't really know what does or doesn't precipitate withdrawal because it clearly doesn't necessarily have to do with- Yes. Are there any other out there thoughts about what might be, because it seems to be pretty random. Yeah, I think it's a good point. I mean, we know, there are some not very good predictors like having very high tolerance, less time between full agonist opioid and the partial agonist, but it's absolutely true. Some of this is idiosyncratic and we don't understand it. So, what Dr. Renner said, every patient's different. We have to handle each patient on an as-needed basis and just, that's about all we can say because we don't fully understand exactly why precipitated withdrawal occurs with some patients and not others. In the back. Yeah, hi, my name's Jen Bransetter. I do consoles at university hospitals in Cleveland. And there's actually a lot of microinduction protocols, especially in cancer patients, whether it's a patient that has a history of abuse or just a patient that's not getting the pain control and needing high doses or coming into the hospital for pain. We also have a MedTOX service who's taken over a lot of the buprenorphine induction and they're all ED trained physicians who've done MedTOX and they actually will give people eight milligrams three times in rapid succession in the ED and stabilize it that way. And it's basically the idea is if you precipitate withdrawal just give more buprenorphine until you overcome that. So, and they have a bridge clinic themselves so that's how we get that done. So, it's kind of split how we do it but then when we come in and we're saying like, oh, we're gonna do this induction with four milligrams and every four hours we give you two more, it's not as tolerated by patients as by doing it. So, I think it could be done better especially in the hospital. Yeah, so that's very similar to the ED high dose protocol that DC was describing. Okay, two more and then we'll move on. First of all, thank you so much for the talk. So, I'm a general adult outpatient psychiatrist up in Alaska. I just had a question, is there currently any consensus on how to handle patients who are stable on buprenorphine who need to have surgery? I've heard, you know. Yeah, yeah, so we actually have a section that we're gonna talk about that. Okay, nevermind. So, you anticipated us and we'll make sure we, that's really important, we'll make sure we get to that. Okay, last question for now. I was wondering about, I'm a community psychiatrist, so I'm usually prescribing Suboxone that somebody else has started and I'm, you know, continuing the person on it, but I'm wondering about using, I guess, especially sublucate in people who are past the point of withdrawal, especially wondering about just people who are like discharged from jail, if people are doing sublucate injections before they return to the community, since that's such a high risk. That would be a great idea. I don't know if anyone's doing that, but I'm a big fan of sublucate. I think it does remove a lot of the complications and anxieties that we have with self-administered sublingual and gets to higher plasma levels that are probably gonna work better, but if someone were being released from incarceration, you give them the injection, you know they're protected, or somewhat protected for 30 days, and the time when people leave incarceration is very, very high risk for overdose, lethal overdose, so it's a good idea. So we'll move. Sorry, would you need to put them on oral first? Well, so the package insert says someone must be stabilized for seven days on sublingual, and the reason it says that is just because that's the way they did the pivotal study, and we're studying now, and several people, can you just give one test dose, and the person doesn't have an anaphylactic reaction, so go ahead and give the injection. The newer injection that was mentioned, which is a weekly or monthly injection, the way they studied that was to just give one dose and give the injection, so when that comes along, it'll actually be on label to give one dose and start the injection right away, but plenty of people are now not waiting the seven days, but to do it on label, you have to wait seven days. Okay, so how many people are using extended release naltrexone to treat opioid use disorder? Okay, a few people, and so we'll talk about that. We certainly have it available at our place, and we use a ton of it for alcohol use disorder, but we don't have too many patients who want to go through the necessary withdrawal to get on an extended release or even oral naltrexone, but if they can get on it, it's a very good treatment. The one 380 milligram dose, here's something that's simple. It's always one dose. It's always every four weeks, not complicated. The XBOT study, which some of you may be familiar with, so that patients were recruited in withdrawal centers, and they were randomized to either sublingual buprenorphine or injectable naltrexone, and what happened is, because you needed seven to 10 days free of opioids to get on naltrexone, many patients did not make it onto naltrexone fewer than made it onto buprenorphine, so the intention to treat analysis showed that buprenorphine prevented relapse better than naltrexone. However, among the group of patients who got on their medications over six months, the relapse rates were equivalent, so it's just a matter of whether we can get them on the medication. The slide says, and I don't think there have really been head-to-head studies on this, so it's more observational, that retention might be a little better on methadone than buprenorphine, and a little better on buprenorphine than extended release naltrexone, but again, I think it's a reasonable treatment for patients who want it and are willing to go through the withdrawal. Let's see. Trying to... Okay. So, the two phases of treatment, withdrawal treatment and naltrexone induction. We talked about the seven to 10 days, so we're gonna go over three potential methods of doing the withdrawal. The first one is taking someone who's using illicit opioids, first stabilizing them briefly on buprenorphine, tapering the buprenorphine, and then you're waiting seven to 10 days to start the naltrexone. A second method is to not give them an opioid, I think this is what people are very familiar with, use essentially the main treatment is alpha-2 adrenergic agonists, it says quantity on the slide, it could be lofexidine or others in that class, and then other comfort medications to treat all the other withdrawal symptoms. It says benzodiazepines, which we could use for sleep, and muscle cramping, and something for, as Dr. Park said, diarrhea, and nausea, and vomiting, that sort of thing. And then when they have seven to 10 days, you can start the naltrexone. And then we have this more experimental method that looks promising. The most promising study hasn't been published yet, but it was done in an inpatient setting, and it's actually sort of akin to the buprenorphine, low-dose initiation, so it's giving buprenorphine for one or two days, just to kind of keep them there, and then moving into the clonidine, benzodiazepine, something for sleep, something for nausea, et cetera, and then starting naltrexone at very low doses, like three milligrams, and gradually building it up. So that means you would have to pretty much have a compounding pharmacy that's gonna make those low doses of naltrexone. But we're gonna, this is gonna be studied further, and if it looks really good, and so far in this one inpatient study, it did do better than just waiting to start the naltrexone in terms of getting people on that first injection, we'll see this may be something new coming down the road. And so, are people familiar with nalmethine? So, nalmethine is another mu-opioid antagonist, it's somewhat similar to naltrexone, it has some other properties, and it was studied for alcohol use disorder, and actually the oral form is approved in Europe for alcohol use disorder. There was a study done in the US that didn't look that promising for alcohol use disorder, so the company never pursued FDA approval, but it actually has been approved as a parenteral overdose reversal agent for many years, and it went off the market because it wasn't being utilized, but what happened in 2022 is the company just said, we're gonna put it back on the market, and we're not trying to make a profit, we just wanna make it available to be good citizens. So, what's the advantage of nalmethine over naloxone? It's got a much longer half-life. So, we do know what we've seen with some of these fentanyl overdoses is that because fentanyl is stored in adipose tissue and may leach out slowly into the bloodstream, we can give a dose of naloxone, partially reverse the overdose, and then when the naloxone wears off, because it has a short half-life of 90 minutes, we're back into an overdose again. So, I'm not suggesting that any of you are gonna be rushing out to use nalmethine to reverse overdoses. You know, most psychiatrists aren't doing that on a daily basis, but it's good to be aware that this medication is out there. So, if you hear about it, you're aware of it. So, we're gonna talk about some of the clinical management and counseling here. And so, we as psychiatrists think that the behavioral interventions combined with the medication can be very important. We do know for opioid use disorder, the medications are the treatment and the behavioral interventions are ancillary. Someone already mentioned, you know, some of the patients refuse the behavioral interventions and then if we think they need it, it's just incumbent on us to use motivational techniques to move them towards accepting what might benefit them. But we certainly don't wanna require behavioral interventions if the patients decline and take them off medication because they won't do that. But I think the good news is these four studies we're gonna talk about where they compared high quality medical management, which is probably what most of you are doing in your practices, because I know as a psychiatrist, I don't just have the patient come in and say, how are you doing with your buprenorphine? I'm doing fine, here's your prescription, goodbye. I mean, I spend 15 or 20 minutes asking about all aspects of their life and other things that could be contributing to their risk for return to use if they're stable or if they're still using illicit opioids, what can we put in place besides medication to help you get more stable? And so these studies compared just physician medical management to, and I'll go over them in just a second, to some type of added behavioral intervention. And so this basically goes over what you would do in medical management. I also do like to ask about how they're doing with their psychiatric disorders and their general health disorders. Not that I might necessarily treat their general health disorders, but I might encourage them to see primary care if they need to or at least make sure they're taking their medications that their primary care provider has prescribed. And so here are the studies. These are the references. And this table goes over them, so we have more time for discussion. And particularly, I wanna make sure we have time to cover the pain topic that was brought up. I'm not gonna go over this table in detail, but suffice it to say, in every one of these studies, they added on counseling or they added on even cognitive behavioral therapy or contingency management. And as long as the patient, so there was no benefit in terms of treatment retention or illicit opioid use if the patient was getting this high-quality medical management. So I think the message to all of you is, as good psychiatrists, you can, in 20 minutes or whatever time you have with your patients, give them most of the behavioral interventions they need along with their prescriptions for medication. If they want to do more, that's absolutely great, but you shouldn't feel that you're giving them somehow substandard care because they're not going to a group or they're not going to a weekly therapy with a psychologist or whatever it might be. So it is important to recognize that the table indicates that they were somewhat selected group of patients. They didn't take very, very unstable patients into these studies. And so we don't actually know if just medical management alone is going to be enough for the more unstable patients. That's something we need to learn. Contingency management. How many people are familiar with contingency management? OK, about a third or almost half of you. So contingency management is based on the operant conditioning theories of B.F. Skinner. So the idea is all organisms will work to receive rewards, and all organisms will work to avoid punishments. So in contingency management for humans with substance use disorders, if they are engaging in the behavior that we want, in this case, coming in for their long-acting injectable medication, or it could also be maintaining abstinence from a substance, we are giving them a reward which is typically a monetary reward. And so that is a way to make sure people are coming in for their injections. And it looks very promising to improve adherence. And if people have questions, we can talk more about that. I'm probably the wrong person to talk about diversion control. So I'll probably irritate John a little bit. But we can have the discussion. So how many people are concerned about diversion? OK, I mean, I'm a little concerned about it. I'm more concerned about people dying from overdose than I am about diversion. But I guess one important point here is we used to teach that for pregnant patients, they should be on buprenorphine mono. And there's been enough experience now using the combination of buprenorphine naloxone to have the prevalent belief that it's safe to use in pregnancy and not dangerous to the developing fetus. So certainly nothing wrong with using the mono product if that's what you decide to do. But if everything else being equal, you can stick with the combination product. Eddie, I would just add to that the certainly we ought to be concerned about diversion. But the reason this is here is because the FDA was required, and the DEA was required. And in the days when DEAs were doing inspections of your office, they had the right to ask whether you had a diversion control plan. So it's more to keep the DEA happy. Nobody knows whether that's still going to continue. But they legally had the right to do it. And it would be helpful to have something resembling this tucked into your office somewhere that you could use. OK, thanks, John. Thanks for the clarification. So yes, if people are stabilized on 24 or below, that's fine. We've already had this discussion about whether we need higher doses for fentanyl. And some may. Given the half-life of buprenorphine in general, once you've got an initial stabilization in the first few days, it does make sense to give it a week or so at a given dose before you just jump ahead to another dose. Using behavioral interventions when needed. I don't know about the weekly visits now. I don't know how many people are doing weekly visits in person at the outset. So some of you have become more liberal. As we've gotten more experience, we're realizing, let's figure out an algorithm that makes it easy for the patients to stay in treatment and not put too many demands on them. So they go, this isn't worth it. It's too busy. But that's something you can do. Obviously, if we're getting urine drug screens, we can look for buprenorphine and norbuprenorphine in the urine. Checking the PDMP is easy and goes without saying to see if they're getting controlled substances elsewhere. Callbacks, where you call someone and say, come back in 24 hours with all your outstanding medication, that's something you can consider telling them that they might do. We did a little quality improvement project at our place. They were patients on methadone, not on buprenorphine. But we found that the yield from random callbacks, let's just call people back to see if they've got their outstanding methadone doses, that was like zero yield. But when we were concerned about a patient, because there was some evidence that they might be unstable or there might be diversion, and we did the callback, we had a very high yield. So that's something you could use in patients you're concerned about. So they bring in their film strips of the pills, and you count them up, and they're not the right number. Then you know you shouldn't be giving them that many every month, or maybe you should switch them to sublucate at that point. Clonidine does help with craving. And if people are very stable, yes, as we've already talked about, you can start. If they're willing, you can start to lower their dose and encourage self-help groups. You know, I think we should skip ahead to the pain part. We've got 15 minutes left. And that's something people really want to hear about. And so we skipped over some side effects and xylosing, so people can ask questions about that if they need to. I'm going to be talking about managing chronic pain and also acute pain and or perioperative pain management on patients on buprenorphine. So acute pain in buprenorphine patients, you know, obviously buprenorphine blocks the, and it provides the partial agonist effects of the mucopore receptors. It may depend on the dose. So, you know, for most patients, stress have shown that the eight milligrams of sublingual buprenorphine will occupy about 50%, and at 60 milligrams, it's going to be subsequently higher. It may be a challenge to provide adequate analgesia. And I've kind of repeated this phrase about five times in yesterday's course, but it's a given that for patients who are experiencing pain, maximize the NSAIDs and acetaminophens, try to stir them, and so that should be a given. And I'm sure you're already doing that. The moderate to severe pain, consider using buprenorphine as an analgesic effect. So now it's perfectly legal and okay to use buprenorphine off-label to treat pain. Now, the other way is a lot more complicated, and, you know, I'm sure you guys know it already, but especially for patients on buprenorphine and their PCPs are telling you, like, I don't know what to do, and their surgery team is, I don't know what to do, then as their, you know, psychiatric provider, feel free to utilize buprenorphine as the analgesia to manage moderate to severe pain. You can, first of all, you know, try to keep the dose the same, but provide them with a divided dosing. It has been shown, and many providers and patients have reported that the patients report better analgesic effect when it's divided in TID or QID dosing. Same thing is seen with the methadone. So when methadone is given to people for craving purpose, they're usually dosed once a day. Unless they have proved to be a fast metabolizer, then they'll be eating the dose twice a day. But when they're prescribed for pain management, you've seen the methadone being prescribed as a TID or QID dosing. So, for example, if a patient is on 60 milligrams, maybe they're on 60 milligrams once a day or eight milligrams twice a day, try to offer them four milligrams four times a day to see if that makes any difference. Then we can then kind of go up to 20 milligrams, maybe they can do eight milligrams, four milligrams, eight milligrams, or go up to 24 milligrams total divided in TID dosing. If you're talking about, you know, obviously you're not gonna be, I think most of you are not gonna be prescribing full agonist opioids on top of that. And most insurance companies will not pay for combining prescription of a full agonist opioids and buprenorphine products. But if you're managing, I think there's a slide coming in for perioperative pain management, and it is still possible to supplement buprenorphine maintenance with a full agonist. Severe acute pain in perioperative setting. I did list, so I'm hoping that my notes section of the slides will show up on your PowerPoints. I've listed, you know, several references there. There's no consensus on how to manage patients on buprenorphine perioperatively. However, at the same time, there has been increasing, you know, publications on case reports and the, you know, gathering of the various hospital's protocols. There's no, you know, recommendation from the American Society of Anesthesiology about how to manage patients on buprenorphine at this time. Now, there was a time, old times, where it was recommended to taper everyone off of buprenorphine three days before the surgery, subject them to unnecessary risk and pain and relapse risk. That is no longer the case. We do wanna keep the buprenorphine as long as possible. And some protocols will call for, increase those maintenance buprenorphine. If they think that the surgery is gonna be, you know, not so complicated, you're talking about, you know, hernia repair, laparoscopic, you know, like a cholecystectomy, or even, you know, bunion removal, then you actually can, you know, kind of do away without any full agonist opioids and just increase the buprenorphine temporarily to treat that post-operative pain. Now, some protocols will call for, especially if it's gonna be a more complicated surgery, a more invasive surgery, then try to decrease the maintenance dose to eight to 12 milligrams. If you are decreasing the buprenorphine, for someone who's on 24 milligram to eight to 12 milligrams a day, that's gonna prevent them from going to the worst withdrawal, you know? They'll feel the decreased dose of buprenorphine, but they're not gonna be at imminent risk for relapse or, you know, withdrawal, hopefully. And by doing that, you are leaving some rooms for some new opioid receptors to be occupied for agonist opioids. Some hospitals will say, you know, get it down to eight milligrams and just give it once a day. And throughout the day, you treat the breakthrough pain with the full agonist opioids. Some protocols will say four milligrams three times a day and just supplemental with the, you know, maybe patient-controlled analgesia or, you know, some other, you know, PR and dilaudid or PR and other full agonist opioids. Again, maximize the NSAIDs and the acetaminophen. You know, so for people on, you know, especially if their surgery site is gonna be, you know, on the limb area. Anesthesiologists have, you know, said that they have utilized very much regional block, epidural, and other, you know, analgesic techniques to control the pain. Now, so actually, that's the slide coming on. And it is especially helpful. Obviously, it's gonna be very dependent on where the patients are. The hospital that's doing the surgery has a multidisciplinary pain team. They can, you know, that includes, you know, addiction medicine, psychiatry, and anesthesiology. But obviously, you know, not everyone's gonna have that kind of resource. For patients on buprenorphine injectable, there is, you know, again, there is no consensus at this time. Buprenorphine injectable can be removed surgically, especially within the first two weeks of the injection. After the two weeks of injection, it is no longer possible or recommended to be able to remove that surgically. Now, but we talked about buprenorphine's, injectable buprenorphine can last a long time. You know, even after you stop the medication, they got the first three series, the serum will have detectable level buprenorphine up to 12 months since the last injection. So you have to think about, even if, you know, they're going into surgery within the first two weeks of injection, is it really worth it to go in to remove that surgically? It really is not, unless you, there was some, by a lot of coincidence, the patient got their first injection of buprenorphine, and five days later, there was a, you know, it was gonna be very, you know, very invasive surgery. Then maybe, you know, you can, you know, talk to their surgery team about removing that surgically to optimize the perioperative analgesia for that patient. But I really, that would require a lot of, you know, it's like stars lining up. The, if it's elective surgery, try to convert that to buprenorphine sublingual, you know, you know, a month before to see if that makes a difference and see if, you know, because buprenorphine sublingually obviously can be reduced. We will still have the buprenorphine detectable from the buprenorphine injectable medication, but hopefully, they can make the, they can make the manipulation of the mucoperceptors a little bit easier. For elective, so that's for the elective surgery. For non-elective surgery, again, maximizing the regional block acetaminophen, and then it says, and, you know, as a psychiatric provider, what you can tell, how you can counsel the patient's team is that the, just informing that the patients may, will probably likely require higher than normal opioids. You know, if you're used to just giving them, giving your patients two milligrams of morphine every four hours and just call it a day, my patients who've been on buprenorphine sublingual, 60 milligrams a day for the last five years, it's gonna require a lot more because you're not even covering their opioid debts. Don't call, don't accuse my patients of drug seeking or faking their pain. I'm sure you guys have been all in that situation and you have to fight for your patients and advocate for your patients. I will say that the, my patient, I had a patient on a stable buprenorphine injectable, 100 milligrams monthly. He had a very bad flare up of rheumatoid arthritis for going on months and he requested to try 300 milligrams of buprenorphine injection. So we gave him the injection to see if that makes a difference. Five days later, he calls me and say, hey doc, my doc, my surgeon wanted to talk to you. I finally am getting my elective cholecystectomy tomorrow. And I said, and you couldn't have told me this like last time, last month, before you got the 300 milligrams injection. But what that patient told me was that so he got the laparoscopic cholecystectomy. There was no complication. It went very well. But he did say that they gave him hydromorphone, parenteral hydromorphone after the surgery. It didn't touch him, it didn't touch his pain. But he said total shot, catarolic. He got the maximum dose of six shots. It made a world of difference for him. So I cannot share if patients on buprenorphine injection with a lot more invasive surgery. We're talking about maybe open heart, like an aortic valve replacement will kind of fare the same. But we are still looking and as soon as we know more, we'll share with you at next year's APA. Opioid use disorder and chronic pain. There's a, so five minutes, I'm gonna just go through this. The limited evidence of usefulness of long-term opioid therapy for chronic non-malignant pain. But obviously we have to deal with patients on chronic opioid therapy who are now being cut off or are being recommended to taper their opioids because of the opioid epidemic. And you try to get a treatment agreement with the patient, keep the treatment team, one team, one physician, one pharmacy. They, ask them for urine drug screens and again, diversion risk, just being able to do the pill counts. Now, maybe you don't really have to do pill counts, just informing them that you can do the pill counts will be enough for the patients to say, oh, really, I should not take more pills. You know, really, I should not take more than I'm prescribed for, maybe sufficient. Really, discharging patients from chronic opioid therapy for any other reason, it's gonna require very careful documentation and very careful reasoning. You don't wanna be accused of medical abandonment of those patients. You wanna make sure you're gonna be thoughtful about being able to refer patients to different pain specialties or other, maybe patients should be referred to methadone clinic for methadone maintenance. You wanna document all that. So, we got five minutes and I'm gonna stop and take questions. Thank you. My name is Azim Shasabar. I'm working as a psychiatrist in Baltimore, Maryland. What's the maximum dose of naltrexone for alcohol use disorder? I have a patient I prescribed 50 milligram, but she insisted on having 100 milligram. She also have chronic fatigue. I don't know if this is something to do with that. So, you're talking about alcohol use disorder? Yes, alcohol use disorder. Yeah, so people have used 100. There's some studies reporting that. The combined study, which is the largest study ever done for alcohol use disorder used 100. I don't know about her chronic fatigue, but and we sometimes gone up to 150. Okay, that's fine. Yeah, so yeah. So, I think it's what you're doing is perfectly fine. I hope Solarnik, Philadelphia VA psychiatrist. We treat a very complex population of veterans with opioid use disorder. We have about 300 plus maintained on buprenorphine. And what we find is that we have difficulty retaining folks in treatment. We're piloting a chronic care management model where we have a licensed social worker reach out as soon as the person falls out of treatment. And I'm wondering if you can comment on strategies to retain folks, especially in the Northeast where we're now seeing fentanyl with xylosine known as Tranquil Dope, Tranquilizer. And very, very much a very ill population. And, you know, and just you're doing, just I want to say you're doing God's work. We see the documentaries on YouTube from the patients on the 10th Street. And we, you know, we kind of skip the slides on xylosine. That's a very powerful tranquilizer alpha-2 agonist. And that's, you know, causing the more like a, you know, just skin ulcers and just a lot of vasculitis. I will say that the, for what we've done is that the, so we've implemented a nurse care manager model. And what we've done is that the, instead of physicians, you know, kind of checking up on every patient who's at risk, it's gotta be a nurse, you know, and it's gonna be a brief visit. And I think a lot of us got confident and more comfortable with the less urine drug screen during the pandemic. And it really is not, if they don't want to come in or they cannot come in every week, then we'll still see them. We'll still, you know, try to work with them. If we are worried about their use or diversion, then we'll consider a buprenorphine injection for those patients. But being able to just, you know, have the personal relationship with their nurse care managers who are trained and qualified to deliver brief counseling, being able to order, you know, urine screens and have access to physicians if there's any questions about the urine drug screen results and make it convenient for the patients have helped somewhat. And it also helped with the providers part too, because our hospital had a lot of departures of psychiatrists through the pandemic. They either, you know, like some of them retired, some of them went to, you know, went to telepsychiatry positions. And having the nurse care manager model that has a very robust evidence, you know, originally from Boston Medical Center has been helpful to manage the patient loads and patient engagement. Hi, I just had a couple other comments on the management in the hospital, whether it's post-surgery or for other patients. So there is a short acting subcue as well as an IV formulation of buprenorphine. And so we've had some success using that, especially if patients are already on buprenorphine when they come into the hospital. So then you can continue their dose, but you could give them that on top of it, or if they're not able to take sublingual, you're able to give it that way. We also use that sometimes for micro-induction. I work particularly with sickle cell patients and the sickle cell team, and we've had a lot of success managing acute pain crises for patients with sickle cell, knowing that they have chronic pain on top of acute pain. And so using that multimodal approach has been really successful with us, but I just wanna make sure everyone can, if it's on your formulary, that might be another way of trying to manage people and not getting them off their buprenorphine, because when they come in the hospital, if you have to take them off, then it's so much harder to get them back on it, or it's gonna prolong their hospital stay. Thank you so much for sharing your comment. It is now three o'clock. Dr. Winter, I will stay around for a little bit, but at this time, we're gonna turn off the mic, and really, thank you for coming, and thank you for your attention. Thank you.

Buprenorphine

Opioid addiction

Fentanyl

Methamphetamines

Overdose deaths

Buprenorphine treatment

Regulatory changes

Sublocade

Induction protocols

Chronic pain management

Opioid dependence

Care access