Good morning, everybody. We're delighted to see you here. I hope we're going to have a very interesting and interactive event. I want to introduce you to the rest of our panelists. I'm John Renner from Boston University. There's Steve Wyatt from the University of North Carolina, and DC Park from Boston University. We're going to flip back and forth as we go through the slides, so you'll see us moving from the podium and back and things like that, but we're all in one set. Before we started, I wanted to ask the audience some questions. I'd like to know, how many people already have their buprenorphine waiver? Great, great. And how many of you are physicians or psychiatrists? Any nurse practitioners or one nurse practitioner? So we're primarily a group of physicians, and I presume you all are practicing buprenorphine, or you have had experience with it. Great. So please feel comfortable making comments, asking us questions. We'd like to really get into as much discussions as we can. We don't have any relevant disclosures, really. Our goals are really, I'm going to show you a little bit of slides on epidemiology, but I think you know most of that, so I'm going to skip some of that stuff. And then we're going to talk about regulatory changes, describe how COVID has affected things, and then look particularly at standards of care and what's happened in terms of our practice in the last two or three years. This is the overall outline of the topics that we're going to cover. I'm just going to go through these slides to get to this. Just briefly, we're now in the third, if not the fourth, wave of an opioid epidemic. Some people are describing the events that have happened during the pandemic as the fourth wave. I think that everyone here is probably familiar with this graph. There's been a steady increase in opioid use, a steady increase in overdose deaths. That's primarily driven by fentanyl. This slide also shows the rate of overdose deaths, what's happened with the pandemic, and how that's going higher. The last numbers I have seen suggested there have been over 100,000 deaths in the last year. So things are certainly getting worse, not getting any better. Just to give you a visual picture of what we're talking about, this is the potency of heroin equivalent doses, heroin compared to fentanyl compared to carfentanil. You can see that just a tiny amount of carfentanil, and you can get an Adderall, which you think is Adderall, which really has got a little carfentanil in it, and you can be in serious trouble very quickly. Where we practice in Boston, we almost never see a urine positive for heroin anymore. Practically everything is positive for fentanyl. I presume that's what's going on around the country. This data is from 2015, and that just shows you fentanyl data earlier and how it's changed in 2015. The darker numbers are obviously higher. This is 2016. This is looking at methamphetamine, and you see how those numbers clustered in the West Coast in the middle of the country, but again, 2016. But this is 2017, and this gives you some idea of death rates. And methamphetamine death rates compared to fentanyl death rates, and you see how the country is sort of split right in the middle. But I think from our point of view, what this suggests is that fentanyl is moving. Fentanyl is well-entrenched in the East, but methamphetamine is moving towards the East, and we're seeing more and more methamphetamine in our area. Now, I'd like to just make a few comments about, I think, the more significant regulatory changes that have happened in the last two years. We now have the possibility of getting a buprenorphine waiver without having to take a course, and what that means is you're not required to have specific training. You have to file a notice of intent that you'd like to treat 30 patients, which is the maximum number of patients you can treat. You still have to apply for a data waiver, so you have to go through that process, which is done online and is fairly simple. But if you want to treat more than 30 patients, then the standard requirements still apply, everything that was in place before. There are current regulations from SAMHSA that buprenorphine treatment programs can use. I'm sorry, the opiate treatment programs or methadone clinics can use buprenorphine, but if their doctors are wavered, they can dispense buprenorphine and prescribe it pretty much as they would in any private practice setting. They're not bound by any other regulations. But it's important for everybody to know that one item that is part of the DEA ability to regulate things is the diversion prevention plan. DEA still has the authority to visit your practice. The main thing that they're going to look for is how many patients are you treating and how many patients are you allowed to treat, and are you staying within the numbers. As far as we can tell, the number of inspections has been very, very slim. There's so many people wavered now that DEA can't really keep up with things. But the other thing they can look for and they have the authority to look for is a diversion control plan. And I'll show you a slide later, give you a little bit more details on that. They basically have to know that you are thinking about the risks of diversion and you practice in a way that your practice cannot be abusive, that you're careful about what you're doing. And then finally, they've asked us to change the content of the eight-hour waiver courses. We're now providing more information on extended release naltrexone, more information on methadone, and generally pain management in every course. But some states require a higher agenda covering pain management. These are somewhat more recent changes. As I mentioned before, that you still need the notice of intents for your practice. The practice limits are either 30, 100, or 275. They're very special requirements if you're going to treat 100 or 275 patients. The applicant must be board certified as addiction specialist. That means either addiction medicine or addiction psychiatry. Or you have to work in a qualified practice setting. And what does that mean? That means that you are able to provide case management and related services. One of the requirements for the non-waivered prescribers, people who have that 30-patient limit but without taking the course, is that they don't have to promise to provide counseling services or referral. That's not a requirement for people who haven't taken a waiver course. But if you're in a qualified practice setting, you have to provide those. You have to be registered with the state PDMP. You have to provide 24 hours emergency coverage. You have to follow practice guidelines. And I think the ones I would recommend are primarily the ones done by the VA and the Department of Defense. And those were published in 2015. And I think it's the most comprehensive set of practice guidelines. You have to make sure that you're using electronic health record. And you have to make sure that you accept third party payments. And basically, I think what they want to avoid with these large practices is you're not a pill mill. And you're not a cash-only operation. You're just cranking out prescriptions and collecting money. You really have to meet a higher standard of care. Telehealth, as I'm sure everyone is aware, is now approved. And we're still in the middle of a declared public health emergency that permits these regulations. We can use telehealth for drugs in schedules two through five. So that covers buprenorphine. The rollback has affected the constraints of the Ryan-Heith Act. And that basically mandated that you had to have at least one face-to-face visit with a patient before you instituted telehealth. Well, that is no longer required. You can start with telehealth. But you have to be doing what is considered legitimate standard practice. You use telemedicine that has to be an audio-visual content. So you just can't do telephone calls. You have to have the visual content or the capacity to see the patient for them to see you. And basically, you have to comply with any applicable federal or state licenses and rules. And now I will switch to Dr. Wyatt. And he'll talk to you a little bit about buprenorphine formulations. Hello. And so how many people are actually using Sublocade now? So about maybe a third of the group. And so there's been some changes over the last 10 years, which probably most of you know about. Some of you never used some of the older products. But there has been the advent of the strip. There now are Suboxone-type combination product strips available. And they come in two, four. The Suboxone product comes in two, four, eight, and two, four, and eights. The generic product only comes in twos and eights. There is a product most people hardly use. Does anybody use a product called Casipa? It's a 16-milligram strip. So that has been approved by the FDA. But again, I've never used it. And I've actually never seen anyone that's used it. So I'm not sure how long it's going to stick around. So Sublocade has, well, the other thing that happened was years ago, 2010, Reckitt Benckiser at the time took Subutex off the market. So that was the monoproduct. And they did that because of liability issues. And it was at the same time that they started the strip. Some of that had to do with the strip actually had to do with the advent or the real concerns over children getting ahold of buprenorphine, buprenorphine combination product. And we did have, that's the only group, and it was actually three and four-year-olds, that actually died of overdoses of buprenorphine. So we've never had a clearly identified overdose from buprenorphine alone. But we do know that infants or toddlers have died from buprenorphine alone. And it's thought that there's just some poor regulation of the medullary respiratory center that resulted in that. Most of you probably know it's really the idea that buprenorphine does still lower respirations, but it maintains a certain level of identification or response to rising levels of CO2, whereas full opiate agonists at a point of overdose actually results in the brain no longer really responding to those rising levels of CO2 in the way that it normally would and people just suffocate. So buprenorphine has the potential for maintaining some normal response. And so that's the reason why people don't overdose from buprenorphine. So when the monoproduct was taken off the market, there was only and still is only the generic product that's still available. Of course, there is the subsolve. Subsolve, which has a greater bioavailability. So that's the only reason that it actually is lower doses than suboxone products or the generic products. And yet, the amount of buprenorphine that's actually in the system is the same. So it's not like you're getting less in some ways. And there has been some controversy around that in terms of using subsolve, the 1.4 strip, or excuse me, tablet. So it's a tablet. It's rather effervescent. So it dissolves more quickly than the generic tablet, which is the only type of tablet that's still available. But that 1.4, so people have been using that. We're going to talk about microdosing in a bit. People have been using the subsolve microdosing thinking that people are actually getting less than 0.5, which would be a quarter of the suboxone or a quarter of the generic tablet. But it's not actually any less amount of medication that the patient would actually be getting. Then there was the advent of sublocade, which has been a bit of a boom. It's been really, I think, slow in coming, partly because of regulations and the difficulties that people have had with being able to hang on to the medication in their office, the way in which now specialty pharmacies are involved to actually deliver the medicine. I do a fair amount of work with the provider clinical support system. We're actually putting together a group of people to talk to the FDA and DIVIR to talk about ways in which people can deal with medication that has been paid for by a patient's insurance, typically, but then the patient doesn't show up. Now what do you do with the medication? It's a shame to actually just waste it, which is what DIVIR right now typically has said, although apparently there is some way in which you can send it back to the company. And yet, that's difficult because it's been paid for by the insurance company. So there's a lot of difficulties around how that's going to be handled. One way in which some states have started to look at this is actually having injections done at a pharmacy, where not until the patient shows up does the insurance actually get charged, which I think is going to be interesting. And it also means that if it does come into the private office prior to the injection, then they're able to have the private office, and those of you that are using it know this, that you have to have it in a regulated refrigerator. You have to be able to have double locks. And so it's more hoops for people to be using this medication. And again, I think it has tremendous potential for helping our patients, just as depots in general have been helpful in psychiatry. But at the same time, these regulations have really slowed the utility of the medication. There's also been some interesting things, and I think we're going to be seeing a lot more around using it as taper medication. So when people are actually coming off buprenorphine after an extended period of time, an injection might be helpful. I will tell you that the injection being a monoproduct, so it's buprenorphine alone, it's of interest in that large studies that have been done looking at the incidence of overdose after coming off the monoproduct compared to the combination product, there's actually less overdose in that first month. And this was reported by a study, a review really, in Australia, and was identifying the potential that the low dose of naloxone that the patient gets over an extended period of time, so I'm not saying they use it for a week, but we're talking greater than six months, that there is greater sensitivity of the brain to opioids, just as we see with naltrexone. And so consequently, that may have something to do with this idea that the patient was then more sensitive to opioids if they relapse after coming off the combination product. So it's not huge. I don't think that it's something that we all have to worry about. Hopefully, at the point people are coming off, they've been on it an extended period of time, they've made significant changes in their lives, and they're not going to have the craving and desire to fall back into opioids until the system is able to re-climatize to not having the medicine on board any longer. But it is of interest, and it's one more reason why supplicate, which comes out of this system extremely slow, may be something that in the future we do. There's also been reports of being able to start people in the hospital without having been on the oral medication for at least a week, which is the standard way in which we do it as an outpatient. There are people that are considering using the 300 milligram injection for a longer period of time because of the problems that we're having with fentanyl. I mean, I'd be interested to hear if there's people here that have been using it regularly that have had anecdotal things, because that's all we're dealing with right now, particularly with fentanyl. We're all looking at problems associated with fentanyl, but in many ways, it's what analog are we dealing with, what area in the country are we living in, so what's the prevalence of it. There have been some fairly large groups together, and they identify that they're still doing standard inductions, and they're doing fine. They're doing OK. They're very rarely having some big problem, but then there's other areas of the country where they have switched to alternative ways, none of which have been fully approved as an outpatient way to actually initiate. But we're going to go through microdosing in a little bit. We're still looking forward to Brixida to be approved by the FDA. Ran into some more problems late last year, and that might give us even more opportunity to have some variability in how we're using injectables. And I've pretty well covered the injectable and things. So it's been pretty straightforward. And again, I think that we are going to be learning more and more about that as time goes on. So questions, comments? Yeah, if people can use their mics for making comments, I think then it'll help everyone to hear each other, and it'll also get recorded. So I think it's going to benefit more audience. But yeah, we've been using cell blockade in our hospital. And just to note that there has not been a head-to-head trial between cell blockade versus Suboxone. We've mainly been limiting the use of suboxone in the hospital, and we've been using it in the hospital for a while. And we've been using it in the hospital versus Suboxone. We've mainly been limiting cell blockade use for patients who failed on Suboxone. And anecdotally, it's been a game changer. And with Suboxone, it's a very good medication. It's one of my favorite medications. But as with the other weaknesses of other medications, such as oral naltrexone or oral disulfiram, you have to take it for it to be effective. If patients are still like, oh, I want to be able to get high on the weekend, they have figured out to skip a day or two to relapse. With cell blockade, it's been a combination of best of both worlds of Vivitrol and Suboxone is it takes away the occasional cravings and consciously knowing that they got the medication no matter what takes away that behavior part of wanting to use and knowing that they're going to be just wasting their money and while providing the similar level of buprenorphine throughout their body. Has anyone experienced a similar thing with a sublocate? You might have to repeat everything so I don't have to get up over there. Okay. We've definitely used it quite frequently in our patient population. Found it even potentially effective for an induction because of its slow onset. Also found after three months of steady injections we can detect the buprenorphine in their systems up to six to nine months which sometimes gets parole and probation to give us a call wondering why it's still there. But it's been a great tool for those who choose to want to come off of buprenorphine altogether and experience a very, very slow take. We think it's a great tool in a lot of patients' lives. I think a lot of people have experienced how it can be difficult for patients to come off of suboxone although we don't recommend taper, right, of suboxone maintenance. But if the patients want to come off, we help them come off of the suboxone and if they've been on it for a year or two, it can be exceedingly difficult especially the last four milligrams or two milligrams per day. And sublocate, the anecdotal reports have been that the patients really it's a very, very gentle, slow taper that they don't even know that they're coming off of a suboxone and they can do very well. I would just add the additional comment. In that sense, I think it's really a good drug for people who are doing well in treatment and unfortunately in some sense is being marketed as something for problem patients which certainly helps, but I think it also works well for people who've done well. It can definitely be considered for convenience purpose or for someone who wants to come off of a suboxone. Dr. Renner and I had this conversation because our VA, I mainly work out of VA hospital, our VA pharmacy limited the criteria for use for patients who fail suboxone maintenance. So we couldn't offer it to patients who wanted the convenience and wanted to utilize this as a tapering tool, but we couldn't approve that. Just to add that the interviewer updated their dosing guidelines. So it's the first three series. After you get the third series, it's 300 milligrams, 300 milligrams, 100 milligrams that achieves equivalent to 16 to 20 milligrams of suboxone a day. Thereafter, you're just getting 100 milligrams every month to just kind of top it off. Alternatively, if you use 300 milligrams, 100 milligrams, and 100 milligrams, that's equivalent to 8 to 12 milligrams a day, and you just continue to use 100 milligrams to top off. We've had a couple of patients who we have continued to give 300 milligrams, 300 milligrams, 300 milligrams because, as Dr. Renner and as Dr. Wyatt mentioned, the potency of the fentanyl in the region and the cravings just continued. I will say that it didn't make too much difference, and I think you'll agree with that. When patients are struggling on 24 milligrams a day of suboxone or 32 milligrams a day of suboxone, it's usually not the dose of suboxone that's the problem with achieving their recovery. Then you can have to ask the questions about what else are you doing for your recovery. So we have done the 300 milligrams continuously. The pharmacy have told us that it's going to be equivalent to about more than 24 milligrams a day. We haven't seen any adverse events, but we haven't seen too much of game-changing outcomes either. For a lot of my patients, I actually counsel them until they get the third series. They may feel that the effects wear off towards the fourth week between the injection. So I usually take an 8-milligram suboxone in addition to your sublockade. I do have one patient who happens to be a little bit larger, has a lot more back pain than other patients. He's been on sublockade for the last 15, 18 months, and he still utilizes about 5 days worth of supplemental suboxone on top of that. I wouldn't know how it would work out if their insurance were paying for sublockade, and if they would approve suboxone in addition to sublockade. But clinically, we follow the adage of you follow the patient, you don't follow the numbers. So if they're complaining of cravings or wearing off of medications, then yeah. I've had two patients that we've done that with. One of them, it didn't make a whole lot of difference, and I think, again, it's partly changes that they're making in lifestyle and how they're really working their program of sorts and staying away from environments that are going to trigger their use. But the other patient did. He did do well, but there have been reports, many reports of that around the country. So that will be something else that we'll learn over time as to how to handle it and what the recommendations might be. Okay. If a patient is 100 milligrams and he missed a subsequent dose, do you need to start him on 200, or do you have to start him over for seven days and then put him back to the other medication? So the question was if a patient missed the injection, then how do you go about resuming the medication? So I don't think there have been any guidance of that so far. What we do is if they missed the injection, we offer them to continue with us. We offer them to continue with an oral sublingual suboxone until we can arrange for them to get the next injection. We had an incident where a patient got the first 300 milligrams and then dropped out of treatment for three months and came back into treatment, and we said, you know what, we're going to just start anew. We're going to start with the 300 milligram, 200 milligram, and then 100 milligram. But I don't think anyone knows yet. You mentioned the phenomenon of patients requesting to taper against sort of physician advice. You know, everything's going fine, but they just, for the sake of not being on medication, they want to taper off. In terms of, like, research that's been done on relapse rates in that setting, could you apprise me of what, if anything, is out there? Like, I'm vaguely aware of some short-term data from a long time ago showing that when you first put people on, when they're actively using, if you take one group randomized and take it away, almost all of them will relapse, but those are people who are, you know, three months out of their drug-using lifestyle. These are people who are maybe five years out, you know. I'm going to talk a little bit about that at the end. I think there isn't any good data on sublucate. There is some data on methadone and buprenorphine. It just shows a higher increase in mortality rates when anybody comes off, just in general. That's data from Europe and the U.S. Is that specifically on people who've been stable on suboxone for years and years? It's ranged for how long they've been on. It's a large data sample. It's all sorts of pooled predictions. Very good. Okay, so we're going to go on to some of the induction protocols that are being used. So as you all know that are using the medication, that patients need to show some signs of withdrawal before we would initiate buprenorphine, if that's withdrawal from a full agonist. And typically we've started, you know, it's mild to moderate withdrawal. It's cows eight or above. I typically look at 11 just to see some evidence of objective signs of withdrawal, and then begin with two to four milligrams. It's been the standard, and no longer are we necessarily recommending the monoproduct, that you can go right ahead and start the combination product. And then within, you know, the first couple of hours, patients typically is going to have some relief of whatever withdrawal that they were experiencing, and we can go ahead and re-dose them. After that initial re-dosing, we can typically have patients go home, if we're doing it in the office, and just tell them that depending on what you're giving them, whether you gave them eight milligrams, you know, had them buy eight milligram strips or tablets and brought into the office, or two milligram products that it would depend on what your recommendations are as they go home. But typically we're looking at somewhere between eight and 16 milligrams on day one. And then typically patients would continue the same dose of day one and day two, and then we start looking at, one, getting them to a steady state. So we don't typically make too much of a change unless there's real problems in the first four to five days, but then we're really increasing the dose for cravings. So that's our goal, as opposed to necessarily any further withdrawal symptoms. People are going to stabilize on really eight milligrams or above. More people are going up to 16, or excuse me, well, definitely going to 16, and many are going up to 24 milligrams. So it's becoming more of a standard to be stabilizing people on between 16 and 24 milligrams with the advent of fentanyl. So when we start looking at fentanyl, and as we've already stated, many parts of the country, that's all that is on the street any longer. So pretty much that's all the patients that you're taking care of. We do want to try to see that they're in a higher state of withdrawal at the point that we start that. That obviously also makes it more difficult because the patient's more uncomfortable at the time waiting to get started, which has been certainly one of the big issues of trying to use naltrexone. But the recommendation is that people be at least 13 to 15 on the clinical opioid withdrawal scale and then start to escalate the dose fairly rapidly. So home induction, as I say, I would imagine, is anyone only doing office inductions? Yes? Okay. So I think that's great. Like when we teach the waiver training, I was a group that started using this back when it was first released, and we all did in-office inductions, and I think it's of tremendous value because if you do it at least long enough that you have seen this very clearly, so at the point that people do start doing home inductions, you have ideas about what might have happened, how they maybe had not been using it appropriately, or there was something that was going on. You're able to talk to them from a more knowledgeable state because you've seen it in the office. But certainly the majority, just as we just saw here, the majority of people are doing home inductions primarily now. And it's giving people the instructions. We typically send the cows home with them, and it's done pretty much the same way. We always do call them on day two just to talk to them about how it went and how comfortable they are and if there's questions and things that we need to review with them. Microdosing. So we're going to talk about microdosing induction. Actually, I'm going to see if I can turn the computer around and I can be closer to you guys. Hopefully I'm not going to break it. So microdosing induction is an idea where you will continue to – because, okay, so for us to initiate the suboxone, you have to wait for 12 hours of washout period for them to be in moderate withdrawal. And compared to, you know, like Naltrexone or Vivitrol where they need to be free of opioids for 7 to 10 days, for the most part that was not a big problem. That was not a big problem. The microdosing induction was first developed in Switzerland in 2010. The idea is that we're going to start very, very small dose of buprenorphine gradually and slowly while continuing the full against opioids so that they don't have to go through any withdrawal period at all. And they're going to avoid – they'll be also avoiding the precipitate withdrawal because the starting dose is so small. And you're going to gradually increase it and increase it and increase it. And when you get to the 16 milligrams, which should take about the majority of the opioid receptors in your body, you stop the full agonist abruptly and patients don't experience any discomfort or withdrawal at all. Now, there have been more increased attention lately because you've just heard that the fentanyl, especially with the fentanyl analog these days, and they're disturbed like half-life. Some of my patients, I'm detecting fentanyl up to three weeks later of their last use. Sometimes even after waiting for 36 hours, 48 hours, sometimes precipitate withdrawal is still a concern. So there has been more attention being paid to the microdosing in light of the fentanyl. The hope is that the patients, because now 12 hours between the dose and you are in moderate withdrawal and you start the suboxones, then that's usually not an issue. But if you have to wait for 48 hours, 72 hours between the dose, can they really do that as an outpatient setting instead of coming to the hospital? So the microdosing induction has been more utilized. Thank you. Thank you. So this is the sample protocol that was used in Europe. Please note that the – one more, one more. Okay. So this was used in Europe. Please note that the other than is absolved. We don't have a small dose of a micro, you know, suboxone available. You just have to then manually cut off the strips and films, which is usually – pharmacy would usually hate that kind of instruction. And try to convince the inpatient pharmacy to do that. You know, you're not going to get anywhere. But in Europe, they have, you know, 200 nanograms or 0.2 milligrams of rescue pills for suboxone. And they utilize this. And patients were continuing to use heroin. And they start with the 0.2 milligrams instead of 2 milligrams. And then, you know, you continue that and continue that. And by day seven, by day six, they stopped using it. And they didn't have to go into any withdrawal whatsoever before getting started on suboxone. Next slide, please. This is other sample protocol from Europe. And there were, you know, patients were using fentanyl and heroin from the streets. Please note that the SAMHSA and our official guideline is we cannot endorse continued heroin use or fentanyl use while being started on suboxone. But when you counsel patients who have difficulty waiting for moderate withdrawal from fentanyl, you can tell them, starting suboxone at this dose is not going to cause precipitated withdrawal. My recommendation, my instruction is that you stop using fentanyl and heroin as soon as possible. But taking starting suboxone micro-dosing is not going to cause precipitated withdrawal. So I just wanted to kind of get that on the record. And 0.5 milligrams, 0.5 milligrams, 1 milligram twice a day. So compared to our conventional suboxone initiation protocol, it's really, really a quarter or even eighth of the dose. And then by day seven, they are able to, even if they stop using fentanyl, they're not going to go through withdrawal. So I'm going to talk about how this is applied to methadone transition. So there are many patients who benefit from being on methadone maintenance, right? And we don't recommend to taper them off, anything like that. But for their convenience, for logistic purpose, or for them, some of the patients experience side effects or adverse events from being on methadone, and they want to consider suboxone. And usually the transition from methadone to suboxone is the biggest barrier, right? Because conventional technique is that you have to come off of methadone slowly, 10 milligrams per week, if they're on 80 milligrams, until they get to 30 milligrams a day, which is going to take about, what, six weeks, right? While they're going through some mild withdrawal, increased cravings, increased pain. And they stop the dose on Friday. Alternatively, you can add a 15 milligram on Saturday morning. But usually they have to wait for 48 hours to 72 hours of no methadone, and then we start the suboxone on Monday morning. And for a lot of patients, that's the biggest barrier. The microdosing technique for transition from methadone to suboxone works in a way that you continue to dose them with the methadone up to 80 milligrams. They continue to take 80 milligrams, and you start suboxone in a very, very small dose, and you continue to titrate up. And by day seven, you stop the methadone cold turkey. And just hearing the words, stopping the methadone cold turkey, you know, gets me nervous. But they're fine. They don't experience any withdrawal, and they don't experience any cravings. So actually, the pilot case that we did in our residential program, it worked so well, the patient left the day after. It was like, I feel good. I don't need a residential program anymore. Thank you, thank you, and he just left. So next slide, please. Now, this is just a disclosure. ButransPatch is not approved for opioid use disorder in the United States. In Europe, where there's no, you know, Harrison Narcotics Act or anything like that, you know, they've been using buprenorphine pain formula or opioid use disorder interchangeably. That's not a problem. In the U.S., the Ex-Waiver only covers the buprenorphine products that are only approved for opioid use disorder treatment, and Butrans is not approved for opioid use disorder treatment. I've heard of, you know, providers using transdermal buprenorphine patch for using to use with the transition from methadone to suboxone protocol. Technically, that's not allowed. Well, unless the patient has a pain. If the patient has a pain diagnosis, you can use the ButransPatch. And actually, a fair number of our patients have got pain, serious pain problems, as well as addiction problems. So in that particular patient, it's perfectly legal to use that. Or in the hospital. Or in the hospital. So if you're dispensing Butrans instead of giving them a prescription, so you kind of take the advantage of the general slow onset of a patch of Butrans. So 20 micrograms per hour, that's about 2 milligrams. That's kind of like 1 milligram, which you will have. How much is it? So it's a 0.5 milligram, but it has a little bit more bioavailability. So it's about equivalent to 1 milligram of suboxone a day, sublingual suboxone. And so that is microdosing to begin with. And you also take advantage of the slow onset release of the patch formulation so that you make the first dose of suboxone just kind of like slipping in there, just slowly taking on more and more MUP receptors. And then you continue to increase it. And by day 7, you abruptly stop the methadone. It still gets me nervous. But patients are entirely fine. And more and more methadone clinics are offering this. And so far, the feedback has been very, very positive and very good. Patients love it. A lot of patients, especially if they've been on methadone, stable on methadone for now decades, but they now want to consider coming off of methadone for various reasons. And when they're on Suboxone, the quality of life, their perceived quality of life is better. So just want to briefly touch base on Vivitrol, which is an extent-release naltrexone. It comes in intramuscular. You push in the upper gluteus muscles, 280 milligrams of intramuscular over 20 days. It is FDA-approved for opioid use disorder. There was a head-to-head trial between Suboxone and Vivitrol. And once they get on Vivitrol, the efficacy is about comparable and similar. But they lose quarter of the patients while waiting for, you know, we talked about how they have to wait for 7 to 10 days of opioid-free period. And I think a lot of you will recall that the patients just couldn't tolerate that unless they were in an inpatient hospital, you know. So if you use the intent-to-treat analysis and you get them, then it is inferior compared to Suboxone. But if you count the patients who were able to get on Vivitrol successfully, the effect is comparable. I will say that the, anecdotally, because of the potency of the fentanyl, we've been using every 21 days of Vivitrol. I've heard of, you know, my colleagues using it every two weeks up to because their insurance will not pay for more frequent than Q20 days. So their patients are paying out-of-pocket every other, every month, but they alternate in every two weeks. And for many patients in early, early recovery, like also the first three months of the recovery, every 21 days seems to be helpful for them. I do not have any data and I do not know of any clinical trials that have examined that. Okay, I'll move on then. We're going to skip the next slide and we're going to go directly to talking about counseling. And I want to expand on some of the research that's been going on recently. Some of you may be aware that there's been some data showing that people do not need counseling groups or external counseling. And I wanted to look at this data in more detail and give you some idea of what I think is the real situation. You know, it's been standard as long as we've been using buprenorphine and methadone, frankly, to show that ancillary counseling was really very important for patient success and that you just could not use medication and expect to see good recovery, that people needed something more than medication. And this was documented very well, particularly in methadone. But there have been four recent studies that suggested that brief frequent physician contact or medication monitoring visits was equal to if not more effective than intensive counseling. So that's been shown in studies and I want to walk you through these studies in the hope that you can understand what I think has been going on. First of all, what are we talking about? Patient management has really been described in greater detail in the VA DOD guidelines, so you can look that up if you want to see it. It basically describes what I think would probably just be a good standard visit between the patient and the prescriber. You check how the patient's doing, you look at their urine results, you describe how their behavior has been, what's going on in their life. You encourage them to keep doing well, encourage them not to use other drugs, encourage them to get involved in community resources. So not very different from what you would do with most patients, except you do it in a more careful way. And it is certainly significantly more than just sitting them down, writing a prescription and pushing them out the door. I think you're giving a message to them that you're concerned about how they're doing, that you're encouraging them that they can do well, and you're assisting them to do that. So that's what medical management is. It was originally designed to be used in research studies, and that's where most of this data comes from. There have been four studies that suggested that this type of brief, frequent prescriber visit was equal to, if not more effective than required groups or participation in more intensive counseling. So what does that mean? There have been four studies, one by David Filene, one by Roger Weiss of the Clinical Trials Network, one by Walter Ling, and another one in primary care by David Filene. So these are all very respected people with a very solid background in research on addictions and on buprenorphine. So I looked at those studies, and I tried to analyze what was going on. If you look at this chart, you see that two of them occurred in primary care settings. One of them was in a psychiatry clinic, and Walter Ling's study was in a psychiatry research clinic. So there were at least three different settings. The length of time of the studies went from 18 weeks to 36 weeks. The inclusion criteria are listed there. Usually these were people with significant histories of drug abuse. In two of the studies, people were included who used IV use, but they all included people who were using prescription drugs and were in pretty good health. Because if you look at the exclusion criteria, what you can see is that these were patients with no serious problems. They were not duly addicted. They were not addicted to alcohol or cocaine or other drugs. They were not using benzodiazepine. They were really very good patients. If you look at your practice, these are the kind of people that you might see and think that prognosis is pretty good with them. They don't have a lot of comorbidity, and they're not going to take a lot of ancillary services to keep them going. What did these studies show? First of all, extended counseling in the original Phylene study was no better. It was basically equal to medication management. They just didn't see any difference by adding extra counseling. In Roger Weiss's study, there was no difference between the medical management and adding opioid counseling. Both groups of patients did equally well. In Walter Ling's study, they added CBT and contingency management, and that didn't improve the outcome at all. The patients who just got the good prescriber management did just as well. And then David Phylene's other study adding contingency management was no better than just the straight medical management. So what can we take away from this? I think, first of all, that this suggests that contingency management can be a very powerful intervention. It works well, but number one, it's done in the context of research studies. What that means most of the time is that these patients are being seen weekly for urine toxicologies, and that someone is checking in with them fairly regularly. So they're not someone that they're handed prescriptions to and said, we'll come back in four weeks and we'll see you. These were people who were checked regularly. I think just that process of monitoring urines really can be a very powerful intervention for patients. There are no severe medical or psychiatric comorbidity. Anyone with those problems were excluded. And the positive outcomes favored patients with no IV drug use. So these were patients who did well, basically, who had histories of prescription drug abuse and not IV heroin use, and minimal use of alcohol and other substances. So what does that tell you? Not that this isn't a good way to manage patients, and not that some patients will do extremely well, but these are not typical patients in my office. And I would suspect for many of you that these are probably not the typical patients in your office. But I think it does tell you very clearly that you should tailor the treatment plan to the patient. And that healthier, less-compromised patients can probably do pretty well with simply seeing you. You know, being checked regularly for their meds, getting urine checks, looking on what's going on. You're encouraging them. Hopefully, you're getting them engaged in AA or NA or something in the community. But you don't need to force them to come to counseling. You don't need to set up a group that they have to attend, whether they like it or not. That doesn't have to be built into the program that way. But that isn't going to work for everybody. So you just need to understand who this kind of treatment will work well for. Any questions? I have a question. Yeah. How long can patients keep themselves off of buprenorphine? Well, I think our standard answer is as long as they need it and it works and they're doing well. You know, this is a long-term treatment. And there's not a lot of data to suggest that taking them off at some point is going to work well. And I'll comment on that towards the end. But we don't have a lot of data for long-term studies. NIDA, I think, is looking at some things now. In another two or three years, we may have more data than we have now. But we don't have any data to suggest that that's a good idea. I mentioned before the diversion control plan. Let's see. This is an example of what we're talking about. This is a very standard approach. The thing is that the DEA wants to see that you have a plan. In your individual practice, the plan may be different from what I'm showing you. But you've got it. And you've fine-tuned it to what the environment is in your clinic. That you're using buprenorphine naltrexone for patients where everyone except pregnant women. That is, you're using a combination product for pregnant women. That may change. There's research going on that may show that they do perfectly well on the combination product as well as the monoproduct. But right now, the monoproduct is the standard. You try to keep the dose at 16 milligrams or lower. But you may be in a part of the country where fentanyl is rampant. And you may need higher doses. So that may be different in your plan. If you go through this list, weekly physician visits until stable, that may be okay in your program. It may be a little different in your program. How often you do your toxicology may be different. You are required to check the PDNP. Every time, at least in our state, every time you write a prescription for buprenorphine, you have to check the PDNP. You should have patients call back for pill counts. You may add clonidine to minimize stress in certain situations. And you may try to reduce the dose for patients who are very stable and doing well long-term. And you should encourage mutual support programs. None of this is unusual or different, but the DEA is going to want to see that you have some version of this that you say, this is what I practice in my clinic. They want to know. And the hope is that this will minimize diversion. You're just being careful about what you're doing. And now I'm going to turn this back to Steve at DC, and we're going to talk about side effects. So buprenorphine, like other opioids, has certain problems, particularly constipation is seen, though we typically see that there's a reduction in constipation as the patient moves from being on full opioid agonist to buprenorphine, and really just stabilization of their opioid use. We can treat it symptomatically, and I often will talk to patients just about diet and staying well hydrated, and those sorts of things can often be very helpful to them. There's no particular evidence of there being cognitive or psychomotor disruption with buprenorphine. Ellie McCants probably has done the biggest study on this, and there was identification through very tightly controlled psychometric studies that there was some reduction in cognition, but it was really negligible. So there has been no particular recommendations that people shouldn't do certain things while taking buprenorphine. Obviously airplane pilots is the big one that we always think about, but there's physicians in the country now that are on buprenorphine, which would make sense because there were always physicians that might be taking an opioid for pain, and they're still working, so why not buprenorphine? There's no particular evidence of hepatotoxicity or organ damage with chronic dosing. I'm going to go through one study on that in just a moment. There was a FDA warning that came out earlier this year around dental problems that can take place. There was quite a controversy about this when it first came out, because certainly we don't want to be telling people that somehow their teeth are going to fall out if they start taking buprenorphine. But at the same time, those of you that have been doing this for a while, one of the most common problems, pain problems, or problems that patients have after having been opioid dependent is dental problems, and it's largely because of very poor dental care for years prior to them starting to work with us. So this is something that we talk to patients about, but we also just want to be very clear, and I think it is important that they brought this up, that we do talk about oral hygiene and again, staying well hydrated. But the idea that it was actually the film in particular that it had greater potential for, and it was the maliate, it's believed, that maybe was causing this incident more, but it has not been entirely clear. But I do think, again, the idea that we do talk to people about good oral hygiene is just a good practice of medicine. So in terms of hepatotoxicity, the START study was done in 2012, and this was a study that the FDA was interested in seeing take place. And it was after the identification that high doses of buprenorphine could be associated with increased liver enzymes and potential hepatotoxicity. So they really wanted to just document for us what is the incidence, what should we be concerned about. So again, there were four cases that were reported. All four of those cases were people that were positive for hepatitis C, and the idea that buprenorphine inhibits hepatic mitochondrial function at high doses, and so how is that playing into it? And so, again, the Food and Drug Administration wanted to see this study done, comparing buprenorphine to methadone. It compared changes in liver enzymes related to the treatment of the combination product to changes in liver enzymes when treated with methadone, and to identify risk factors at baseline and during treatment that could contribute to us identifying it early and making adjustments in the patient's care. And what it found was that if a person had liver enzymes that were less than the upper limit of normal, less than two times the upper limit of normal, they typically remained less than two times the upper limit of normal. So that's the majority of patients that we're going to see, and there's no clear recommendation that we should make changes. If there were a few patients that there was a change, so some did after a period of time, there was an increase in their liver enzymes, then there were patients that were above that, and actually, with stabilization of their opioid use disorder, there was actually a reduction in their transaminase liver enzymes. And then there were a few people that if they, that there was no change, and then there were a few that had fairly dramatic increases. So the recommendations out of this were that, well, I guess, the recommendations are that we definitely should be getting liver enzymes at the initiation of treatment. That doesn't necessarily mean, and I want to be clear, it doesn't mean that these labs have to be drawn before we start people on buprenorphine. But sometime in that first couple of weeks of treating patients that we should get lab values. And certainly, many of us would be getting HIV, hep C, and for women, pregnancy tests, potentially sexually transmitted infections, you know, just treating people. So you get the original, if it's normal, we typically will then go ahead and get a follow-up within a month or two. We're typically in that second month before we get a reevaluation. And then, if that's the case, there can be follow-up. There's not necessarily a recommendation that you check it six months later, but it's not a bad idea. But there's not a clear recommendation that we need to continue to get buprenorphine levels if there hasn't been a significant change. If, however, there's a problem when we first get it, so it's above that two times the upper limit of normal, then we need to be following it more closely. The primary problem has been in patients that are hep C positive with the advent of medications to essentially cure hepatitis C. I think a referral to a hepatologist is, you know, what we should be doing if you're not treating it yourself. And then, obviously, we would continue to follow their liver enzymes. So that is the study. I don't know if there's any questions about that. Yes? I have a question about hepatitis C. In my residency, we contracted our transplant center to treat people with opioid use disorder. And this is something I looked at. I've never seen this study, but there's lawsuits out there. So that's relatively safe in liver failure cases. Yes. Have you seen, have you treated people with Spox or with liver failure? And have you seen any recommendations from them personally? Yeah. So I have also worked with a transplant team and a couple different hepatologists in my career. And I've never had one of them tell me, no matter what the level of their enzymes are, to take them off buprenorphine. They all see it as a way to stabilize the patient's disease. And then if it is severe enough, they're going to be following it. So again, early on, I would be alarmed with what I'd see. And sometimes we were, you know, early on, it wasn't that low-threshold initiation that we're concerned about now. So we would actually get labs before starting buprenorphine. And if it was really high, I'd be real concerned. Talk to the hepatologists. They were all, you know, Steve, don't delay. You know, get them on and send them over to me. You mentioned earlier some of the common side effects, one of which is loss of libido. Could you just say a little bit more about loss of libido and low testosterone in general as side effects of agonist medications, and specifically whether buprenorphine has a relative advantage in that department compared to methadone? Yeah. It has a relative advantage. So it's definitely better. Often patients come in using opioids and they've had libido problems for a while. There can be even some stabilization. The only study that I know of that was done, and it was done like 2008, it was quite a while ago, did not show appreciable reduction in testosterone with buprenorphine. Now, yesterday, Dr. Livonis, who works quite a bit with a male homosexual population, really brought it up as a real concern. So I do think it's something we should be asking patients about and whether maybe they'd be a better candidate for naltrexone if there is a problem. But for the most part, we haven't seen, we certainly don't see as great a change as we do with methadone. My question was along those lines. These patients have abused opioids chronically, and they do tend to have hypogonads in any way coming in. So their testosterone levels are probably low to begin with. So just a question, we're treating this replacement population. Over the years, I have been paying more attention to their testosterone levels. And I think it's important, as a matter of general men's health, to attend to those issues. So I'm glad that people are looking into this. Thank you. I've certainly had. But you have patients that are taking testosterone supplements. And it's always somewhat questionable what they're doing anyway. But they're certainly quite, yes. But it's been quite popular. So yes, they are. We're going to be going through these slides a little bit quicker, on a quicker pace. And we'll try to get all the questions at the end of the sessions. So managing acute and or chronic pain on patients on Suboxone is always a challenge. Because the buprenorphine binds to the immune receptors affinity of 1,000 times more than the adenomorphin. And really, getting them to get any pain relief from other full agonist opioids will be a challenge. It is the first thing that we always say with patients on chronic pain or acute pain or any patients on opioid therapy is to utilize non-opioid, non-pharmacological alternatives as a first line. It's easier said than done. But you're going to utilize all the maximized on the end says they're getting the PT and OT. They're getting pull therapy, exercise, tense unit. And if it's a moderate pain, then for some reason, I don't think I've talked to anyone who exactly figured out why that is so. But the methadone and buprenorphine, their analgesia effects are actually shorter lasting than that of the craving control effect. So for patients with chronic pain or acute pain, we actually ask them to divide up their existing dose first. For example, if they're on 60 milligrams a day or 8 milligrams twice a day, we'll ask them to try taking 4 milligrams four times a day. And see if that makes a difference. We can then temporarily increase the suboxone dose further up to 32 milligrams, which will be 8 milligrams four times a day, so 32 milligrams a day total. If that is inadequate, you can consider adding short-acting opioid analgesia. I don't prescribe a full opioid agonist. And that means I have to work with the PCPs or other pain teams. And it's going to be my experience is that it's going to be a hard sell. Also, their insurance company may not pay for full agonist opioids on top of their suboxone. You can consider adding supplemental low-dose buprenorphine for their pain. We certainly don't recommend PRN dosage of suboxone for their cravings. If you recall from your initial ex-waiver training, there was a case of a lawyer who just wanted to take suboxone as needed on the weekends. And we didn't think that was a good idea. So we don't recommend the PRN dosing of suboxone for opioid craving control property. But for analgesia, we can consider giving them PRN dosing of opioids and suboxone. For severe acute pain, right now, we're looking at we're thinking of all these catastrophic injuries and falls and motorcycle accidents. I'm going to go to the next slide. There has not been any consensus of how to manage these patients. Certainly, there are different protocols that have worked fairly well. The patients with the moderate intensity of post-operative pain, you can actually consider continuing the buprenorphine. So there was a protocol before about stopping the suboxone three days before the surgery. And that was not a good situation for patients in early recovery. They're subjected to withdrawal, increased pain. And if they relapse with the opioids, then they'll put them at risk for perioperative infection as well. Now, that's a different story. If you can keep them inpatient in the hospital and the surgery is going to be coming up in two to three days, then you can, if you're working in a hospital and you're a consultant, then you can advise the pain team to replace their suboxone dose with a full agonist opioids and maintain them through the surgery and then manage the post-operative pain just as they would. The patients may need a little bit higher dosing or significantly higher opioid dosing than other patients because of their developed tolerance to opioids. For patients who need full general anesthesia and severe post-operative pain, you can consider giving reduced buprenorphine to 8 milligrams to 12 milligrams a day. And that'll leave about 50% of the mu opioid receptors to be occupied with the full agonist opioids. And different hospitals have different protocols. The Stanford protocol gives 12 milligrams of suboxone once a day in the morning. And they sprinkle the full agonist opioids for PRM pain throughout the day. For MGH, they give the 8 milligrams in divided doses. And they add full agonist as needed. OK, I have to go on. I have to move on. So opioid use disorder and chronic pain, it's a huge comorbidity. And this is more for, right, we've known from the CDC guideline in 2016, they really recommended against starting opioids for chronic pain no matter how severe it is, unless it's a cancer pain or their life expectancy is less than six months. They have limited evidence for usefulness of a long-term opioid therapy. However, for patients who are coming off of long-term opioid therapy, buprenorphine has been used as a replacement therapy. And I think a lot of us and a lot of you probably have seen benefits of such a therapy. If patients have opioid disorder and they have chronic pain, and if they're getting full opioid therapy from their PCPs or their pain doctors, you want to make sure that the PBMP is checked accordingly, their urine drug testing is conducted appropriately. And keep it with one physician and one covering clinic and use the one pharmacy. Consider obtaining the GC-MS testing, which will obtain the quantitative levels of certain opioids. And before you start the opioid therapy, you want to talk to them about what constitutes as a misuse or abuse and our reason to discontinue those opioid therapy. I imagine from our quick survey, almost all of us were in the mental health field, so we'll be advising more of a role for PCPs or other pain clinics. Sometimes patients with chronic pain, they may do better with the full agonist, such as methadone. And I spoke about how suboxone in divided dosing, smaller divided dosing, can be helpful for pain, so that's just the last line. Sorry, we had to hurry up, but yeah. Any questions? The one thing I would underline from what DC said is that clearly, if we've got protocols for keeping people on at least a partial dose of buprenorphine through most surgery, they're going to do better. I think the real risk is taking them off buprenorphine completely during surgery. And if we can avoid doing that, so they don't have to be re-induced, then I think you're probably going to have lower dropouts and lower risks with the patients. I wanted to spend a little bit of time. I don't think, I presume all of you are familiar with the CACO study, which showed very clearly that they had a somewhat smaller group of patients, but they did the study very well. Everybody got buprenorphine for the first week, but half the group, it was a tapering blinded dose, and then they got placebo for the rest of the year. The data shows dropout was dramatic during that first week or two. The important thing in this study was that everybody got counseling, everybody got a lot of referral services and supports, but that didn't work unless you stayed on the buprenorphine. And if you stayed on the buprenorphine, you continued on the study, and you did well. The most surprising or the shocking finding in this study is that among the people who were on the detox, not only did they drop out of treatment, but there were four deaths in the course of the year. There were no deaths in the group that maintained on buprenorphine for the year. So that was a really dramatic demonstration of the effectiveness, at least preventing that type of death. David Filene's study is one study that looks at the differences between maintenance and detox. In this study, people were treated on, you can see the lines there. People were on medication for the first six weeks or so, and then they began to taper for three weeks. You can see that. And then the buprenorphine was stopped. And you can see that there was just a dramatic drop out of treatment for patients who did not get the drug. So it was demonstrated pretty clearly in that primary care setting that the patients needed to stay on maintenance treatment. The next couple studies just look at the question of retention. I think one of the unanswered and unsolved problems in our field is that once people get on to methadone or buprenorphine, how do you keep them on it? Because the people who stay on it generally tend to do well, but they don't always stay. And in the general parts of the country, in some settings, the length of time on buprenorphine is three months or six months. I think we all know that that's probably inadequate. So we have to learn more that we can about these things. This was a study done in the VA by Manhapra and Petrakis. They looked at all the people in the VA nationally who were started on buprenorphine during 2012, and they had over 3,000 subjects. The mean duration was a year and six months, so that was pretty good. 61% were retained for more than a year. 32% were retained for more than three years, which again, these numbers are better than the numbers from the rest of the country. And these patients were all getting more supportive services. I think one of the things that we should be concerned with, though, is the higher odds of discontinuation or dropout was with people who were black and people who had a lot of emergency room visits. So whether that translates just into stigma or there are other issues, we don't know. But it clearly identifies that it is a population problem. What's interesting in this group is that there was no difference in psychiatric comorbidity. That is, if you had a lot of psychiatric comorbidity, you were just as likely to be retained. If you didn't have any, it was equal. And I think you can assume for most of the people in this study, they were in the VA, so they had lots of access to psychiatric services. So the psychiatric conditions were being treated. And if that was done, they continued in the study. This study was done by Zoe Weinstein at Boston Medical Center and the clinics associated with them. It was a 12-year retrospective study over 1,200 patients. 53% had more than one year of treatment. 45% were, the treatment periods were greater than a year. There was greater retention associated with women, people with psychiatric diagnosis, and older people. Not too surprising there, but again, interestingly enough, if you had a psychiatric disorder, you actually did better. That was not a cause for early dropout or failure in treatment. Lower retention, again, is issues that we need to understand better. Obviously, unemployment was a problem. Hep C was a problem, but race was a problem. Being black or Hispanic was associated with higher dropouts. So I think that just demonstrates in some way that stigma is an unresolved issue and that we don't totally understand how that's affecting treatment, but it is causing problems. This was a study done by Maria Sullivan in Anabasaga, Columbia. They were looking at naltrexone and they were looking at different ways of getting people on naltrexone. I think we demonstrated to you earlier that once you're on naltrexone, you do just as well as people do on buprenorphine. But a third of the people assigned to naltrexone just don't make it. They never get onto it. And so the research question is, how can you do inductions in a more successful way? And they compared the standard induction, which has been present in the beginning, which was sort of seven days bup taper and then seven days with no medication and then start the naltrexone. Obviously problems. I mean, if people could go a week without any medication, they were unusual and certainly not very likely to stick with treatment. They compared them to a group where they got one day buprenorphine and then escalating doses of naltrexone for another seven days. And it's clearly, if you see the numbers at the bottom there, that that group who got one day of bup and then escalating naltrexone almost did twice as well as the people who got the standard induction protocols. So I think we're still working on that area. I'm sure that microdosing techniques are gonna be very effective in helping us get people on naltrexone quickly. And I think that'll make a tremendous difference in the utility of the drug. And lastly, this is a sort of study. This is data that was collected from both the US and Europe and South America. A very large sample over 120,000 patients on methadone, almost 16,000 patients on buprenorphine. The minimum treatment was 1.3 years. Their significant reduction in all cause and overdose mortality. What they're specifically looking at is were people staying alive? And what was the severe mortality occurring in the group? And if they stayed on treatment, clearly those numbers dropped. They were doing well. But what they saw in the study was that there was an increase in mortality during the first month people were on methadone and also an increase in mortality in either group in the first month or two after they tapered off. So why that first month in methadone? I think if you work in a methadone clinic, you know you can't reach a blocking dose right away and it may take several weeks to get to an effective dose of methadone. So during that period, patients are still vulnerable to overdose and mortality. And it just says what it says in terms of what happens when you taper off either drug. What goes up are mortality and morbidity. And I think I will stop there and see if we have any questions. Thank you. Yes? I just have a simple question. Is there anybody who just wants? This will be posted probably in 48 hours on the website. I think they're gonna post the tape and the slides from today. Sir, so my patient population, more so alcohol use disorder than opioid use disorder. So he's a lot of naltrexone. I've had some struggles with Vivitrol with patients that end up getting elective surgery. They're high risk for surgery. I've seen some guidelines, of course, for the oral formulation. But how do you manage the LAI? You stop it. You know, if it's elective, then you talk to the surgeon or the anesthesiologist and you stop it. The surgery would be one month or more after the last injection. Sometimes people have to be on a oral for a few days, but they still should stop at 72 hours prior to the procedure. And if they present acute and they've been on Vivitrol? Yeah. If they present acute, then there's ways in which they, you know, conscious sedation, you know. You can override it with fentanyl. With fentanyl, so typically, it has not been the problem that we thought it was gonna be. Okay. And there's a good literature in the anesthesia literature around working with patients that have been getting naltrexone. Thank you, appreciate it. Just a quick question. My biggest challenge for me is co-occurring substance use disorders, particularly methamphetamine and cocaine. And again, with the MAT, it's harm reduction. I've moved past the idea of complete abstinence. You know, going to med school in the 90. And so, to my colleagues and to the panel, how are you addressing and working with co-occurring? Because I'm still getting marijuana in two-thirds of my regulars. And cocaine, maybe 25%. Methamphetamine, about 10%. And I'm not sending people back to inpatient rehab programs. And we're still continuing to work in peer support specialists. But I wanted to hear what other people are doing in this. Or are people putting them out? Am I being too lenient? I would say no. I mean, if someone is abusing marijuana in the sense that it is affecting their function and they're not doing well, I think it needs treatment. But if people just occasionally use it, it's legal in our state. It's no more problem that I can see than people have two drinks of alcohol a week. I mean, I don't necessarily endorse it or like it, but I don't think that's any reason to discharge someone from treatment that does work. I'm usually adding my note, like that I have evaluated the patient for a need for approved higher care. And I might put something like still able to, well, actually most of my inpatient patients, their functional roles are improved compared to before. So I can deal with marijuana. That doesn't scare me at all. I just want to make sure that I'm covered in my clinic. No, well, I agree with you. I mean, I think- Yeah, and so the idea that you're doing what you need to do, documenting it. But I have found over the years that if you continue to bring it up with people, you start to see these functional improvements in their lives. And then I've had people then start to back down on how much marijuana they're using. And one waitress told me, yeah, Dr. Wyatt, I remember my orders so much better. I mean, people begin to recognize that there's improvement. And so I think you're doing a nice job. Yeah, if you get quantitative labs, you can try to trend the THC over cranium ratio as well. And sometimes that can get patients to kind of, if they have a baseline number when they first come in, that, oh, their number is 30 or something. Then as they come down, you can see, oh, now you're around the 10 or something. Sometimes that objective data is a little bit helpful. Yes, it can be. But then if you have somebody who's like using wax or gabbing, right? They might have levels that are like 120 or something compared to people who are just smoking. And so that can give you a sense of scale sometimes to how much they have in their system. Last question. Okay, so I'm having two major problems. I got people, when buprenorphine first came out, they said 32 milligrams was the maximum recommended dose. Now they lowered it to 24. And a lot of insurance companies will not pay for 32 milligrams anymore. I've had to reduce doses for people. I've appealed, they refuse, they refuse, and there's nothing I can do. The other issue is generic buprenorphine, generic strips. All my patients are saying, put brand name only on the prescription because their pharmacy tried to switch me to generics and the generics don't work, or I got nausea and I can't tolerate it. Almost all of these guys say, I can't take generics because generics don't work. I'm just asking if you have the same experience with that. I've had some experience with generics where I've had to increase the dose, maybe like two milligrams or something for some patients who presented those problems, but most patients don't say anything. I mean, at least in my experience, most of them do fine on it. We'll have to end, but you can come up to ask us, but yeah.

opioid use disorder

treatment options

panel of experts

regulatory changes

Suboxone

Vivitrol

individualized treatment

sublocade

microdosing induction

differences in effectiveness

counseling in substance use disorder treatment

patient retention challenges

long-term maintenance