disorder, utilizing buprenorphine for the treatment of opioid use disorder. So things we're going to talk about in this, we're going to talk about some of the epidemiology and assessments and kind of what the standards of care are for helping people who have opioid use disorder, touch again on the pharmacology of buprenorphine. We're going to explore some of the regulatory issues around prescribing and talk about some different strategies that we can use to initiate this medication and kind of troubleshooting some of the problems that can come up in early treatment. So we had the unfortunate statistic in Alaska in 2021 that we had the greatest increase nationwide in our rate of overdose deaths. So in one year, our overdose deaths went up by 75%. They have gone up slightly since then. Luckily, it seems to have sort of leveled off, which is good. And it's really important to note that Alaska Native people have tripled the overdose rate that white Alaskans do, and I think in 2022 and 2023, the gap increased even a bit more. So a vulnerable population that is wildly overrepresented in mortality. And I think it's also really important to understand that most people in Alaska are using fentanyl right now nationwide, not heroin or other prescription opioids, and almost everyone is using methamphetamine with fentanyl along with it. So both methamphetamine and fentanyl overdose deaths went up by 150% that year. Another really key thing to understand is that detox is not a treatment for opioid use disorder. You hear over and over again, we need more detox beds, we need more detox beds. Yes, we do need withdrawal management facilities for certain conditions and comorbid conditions and complex social situations, but strictly for the treatment of opioid use disorder, detox is not a treatment and actually causes more harm than good. So this article just came out a couple months ago. So we know that medication improves mortality rates, however, non-medication-based treatments, so you just go through detox and then just try not to use, right, you go to counseling, you go to AA, NA, whatever, actually increases the rate of death by 77%. So it is worse to detox someone and then just have them go to counseling than to just have them continue using drugs. It's better for them to just continue using drugs than to put them through detox and not start them on medication. So we never want to recommend doing that. Some patients may choose to do this, but it's our job as providers to counsel them on the evidence and that that is a dangerous approach and a 95% chance that it's going to fail and could result in death if they do that. We know that medication for opioid use disorder is the number one most effective intervention we have to reduce mortality in opioid use disorder. It reduces mortality by between 60 to 80% in most studies that you look at. There are very few interventions, can you think of, in medicine that reduce mortality by 60 to 80%? Very, very few. It's an incredibly effective medication to reduce mortality. The issue is, though, too, is that this is a chronic disease. Just like with diabetes or hypertension or anything else, the medication only works when you were taking it. When you stop taking it, you go right back to where you were before. And actually, you go through a period of like that first month when you're off medication where your overdose risk can even be a little bit higher because you lost that tolerance that you used to have before. It's a very dangerous time. The time of trying not to use and being abstinent and then return to use is the most risky time for people for overdose. So we really need to reframe the way that we think about buprenorphine. So when buprenorphine was first approved for the treatment of opiate use disorder back a little over 20 years ago now, we didn't really know what to expect. We didn't have any experience. So they've been doing it in Europe, but we don't really trust any of those studies from Europe on how effective it was there. And so the only contacts we had was methadone in an OTP in a methadone clinic, which is incredibly tightly regulated. People have to go in every single day. They're observed dosing. They have to do counseling. It takes a couple hours out of every single day of them for them. It's incredibly tight, and the providers have no leeway. They can't make any decisions on how to change things. They have to follow the federal regulations. So that was the only thing we had to reference as far as treating opiate use disorder. So we weren't really sure what to do with this medication when it's out in the outpatient field, you know, and with prescribers. So we had all these regulations. You had to take an eight-hour course to learn how to prescribe it. You had to be able to refer to counseling. You had limits on the number of patients that you could do, all of these regulations. And we think this is a very specialized medication. You have to have integrated behavioral health, and there's all these risks around it. We learned after 20 years of using it that almost all of that was wrong. And so that's why the government has changed regulations and removed almost all the restrictions. We realized this is a very safe medication. It's the gold standard for treating a deadly disease, and all prescribers should be comfortable prescribing for it. And the government removed these restrictions because they want everyone to prescribe it in any situation in which it is appropriate. So the waiver is gone. If you can prescribe a Schedule III controlled substance, then you can prescribe buprenorphine. You don't have to take any special classes to be able to do that. There's no specific limits on like how much or what formulations of buprenorphine you can prescribe. There's no limit on how many patients you can prescribe to. You don't have to be able to refer for counseling. And a separate thing, the MATE Act, which came up when we were talking about the CME, a separate act that was passed with the omnibus bill last year was saying that the DEA wants all licensed, DEA licensed medical providers to get addiction medicine education. So that is to renew your DEA. If you didn't do it in the last year, in the next two years when your DEA renewal coming up, you will be asked, you'll have to attest, you'll have to check a box to attest that I have had eight hours of addiction medicine training. If you ever took a buprenorphine waiver in the course in the past, that counts for that. If you recently graduated from a school that provided that education, that counts for that. So but that is not, that's completely separate from being able to prescribe buprenorphine now. That's only to renew your DEA. And I think it's also very important to understand that every day a patient takes buprenorphine is a day when they're less likely to die from overdose. They're less likely to use other drugs. And sometimes we don't know what's going to happen, especially in the hospital. We don't know where a patient's going to go after that. We lose track of them. We don't know for sure if they're going to get connected to care. And so sometimes we think, well, I'm not going to prescribe this to a person because I'm not really sure where to refer them to. Like that's really not an excuse because every single day a medication takes is going to be helpful for them. Even if they don't end up staying on it for forever, that time, if they have a positive experience and they realize that this is helpful for them, that just increases the chance that they are going to get into treatment in the future. Even if they don't get into treatment that time, it makes it more likely that they are going to get into treatment for the future. And every dose that they take is a day that they're going to be safer. So we want all specialists to be comfortable in prescribing buprenorphine. Depending on kind of what specialty you are, there's different ways in which you might be utilizing this. But again, we can use it not just for chronic pain, not just for opioid use disorder, but also in patients with chronic pain. All pregnant and postpartum women should be on either buprenorphine or methadone. That's the standard of care in pregnancy and postpartum. The postpartum time is, we'll have a pregnancy talk here at the end of the day that will discuss those risks associated with pregnancy. In the emergency room, anyone that comes in with OUD, whether they're in withdrawal, whether they just had an overdose, whether they have another infection-related complaint that they're coming in, it doesn't matter why they're coming in, you can use buprenorphine in almost all of those circumstances. In our hospitalists, we're going to manage withdrawal in patients who have... And then also, even if they're not really sure that they want to continue on outpatient, we still need to manage the withdrawal when they're in the hospital. And we'll talk about that in the next talk. Surgeons can prescribe it for post-op pain in patients who have OUD. And we can use it in adolescents. We encourage the use in adolescents. Adolescents are dramatically less likely to be offered evidence-based treatment for opioid use disorder, which is really tragic because those are the people that we really want to get them the best treatment possible as quickly as possible. We see it also increasing use in palliative care, either with patients who are coming into palliative care because they have a history... They might have a history of substance use disorders and have some fear of or inability to manage their opioids, or they're just having a lot of side effects from their other opioids that you're seeing a lot more of it in palliative care. So just to review again, the pharmacology of buprenorphine. So it is a partial opioid agonist. So when we think of a full opioid agonist, like methadone, morphine, oxycodone, the more you take, in a pretty linear fashion, the more you take, the more effect that you get. And if you take too much, then you stop breathing. So what you have is kind of the pain relief and the side effects like suppression of breathing that go hand-in-hand in a linear effect. However, with buprenorphine, when we think of the effects of euphoria, suppression of respiratory, those kinds of things, initially we'll see some increasing effects with dose, but by the time you get to about eight milligrams or so and above, it doesn't matter how much more that you take, you're not going to suppress the respirations or generally cause euphoria in an opioid-tolerant, an opioid-dependent person. So the thing to remember about this, because this is a full agonist and this is a partial agonist, where we can sometimes run into trouble when we give someone that very first dose of buprenorphine, is if they still have a ton of, let's say methadone or fentanyl in their system, and they're not really in withdrawal yet, and we give them a certain dose of buprenorphine, what can happen is that they suddenly, within an hour, go from a full agonist effect all the way down to a partial agonist effect, and that's called precipitated withdrawal. So instead of that happening, you know, if you stop your medication or you get there two to three days, you would get to that level of withdrawal, it happens like instantaneously within a matter of an hour. Has anyone seen someone get Narcan before who is dependent on opioids? So if you've seen that, you know, it's very unpleasant, they're writhing, they're sweating, they're puking, they're having diarrhea, they want to tear their skin off, it's absolutely horrible, and it hits you hard and fast. So the main little trick with prescribing buprenorphine is we want to make sure that we get the timing right and the dose right so that we don't cause precipitated withdrawal, because if you cause that to happen, the patient obviously is not going to be too keen on continuing to take that medication. Making yourself continue to take a medication that just made you violently ill is not what most people want to be doing. Buprenorphine is an incredibly safe medication. So this is looking at opioid-naive patients, and single doses of up to 32 milligrams still does not cause any dangerous suppression of respiration or oxygen saturation, so that we know that it's a very safe medication. So we really don't need to worry about overdose risk in patients, especially when we're monitoring in the hospital and they might be needing very high doses of buprenorphine to control their pain, that's okay. So to review some of the formulations of buprenorphine that are available, probably the one you're the most familiar or have heard about is the sublingual film here, which the brand name is Suboxone, but there's many generics now, there's many different formulations. So this is a film that goes under your tongue and it has a combination of buprenorphine and naloxone in it. They also make tablets that go under your tongue that also have the same doses, the same combination of buprenorphine and naloxone. They also make plain buprenorphine tablets that only have buprenorphine and don't have naloxone in them. Traditionally, this has been used for pregnant people or people that are intolerant of side effects from the naloxone, but more often now we're seeing a lot of use of the combination product as well in pregnancy. For the last about six years, we have had a long-acting injectable form of buprenorphine, which is this one. It was the first one, Sublocade, comes in two doses, a low and a high dose. We generally use the high dose in our patient population. And then just in last September, we had this other new one that's been used for a while in Europe. It just recently got approved here, Brixadi, and that comes in a little more variety. It has both weekly and monthly doses and more variety of different doses. Also, buprenorphine comes in an IV form, which most hospitals don't use, but can be useful in patients who are struggling with sublingual or it can be useful to have that and to really kind of carefully titrate the dose. One of the most common misconceptions about combination sublingual products, so the combination of the products that have buprenorphine and naloxone in it, is people think, okay, naloxone, that blocks opioids, that reverses opioids. So by giving this patient naloxone, I'm making it so it's going to block other opioids that they might take. It's going to block them from being able to misuse. There's a misunderstanding about it's going to make the medication less... Patients think it's going to make the medication less effective because the naloxone is somehow blocking some of the relief effect that they're getting from the buprenorphine, but none of that is true. So the reason that naloxone is in this is purely as an abuse deterrent, a misuse deterrent. So it's to deter people from wanting to inject the product. So if you inject, I think we all know if you inject naloxone and you're dependent on opioids, what happens? You go into precipitated withdrawal, that's pretty awful. So it makes people unlikely to want to inject the product, and it'll either cause precipitated withdrawal or it will actually just block some of the effect of buprenorphine, so it's really no better than if you just took it by mouth. But when you put naloxone under your tongue sublingually, very little of it is absorbed. Very, very little. Essentially so little that it has no clinical effect. Anything that is absorbed, we know it's a very short-acting medication, it's excreted within an hour for the most part. So sometimes, occasionally, we'll see... So it has no clinical effect. It's not blocking opioids. It's not doing anything, and it's only there as a misuse deterrent. And there are some limited data that say that this product may be like three times less likely to be misused than the plain buprenorphine monoproduct, however, that's very, very limited data. And we're hearing more and more talk and discussion about the fact that some people may really have side effects from the naloxone. They may be absorbing. If you do a confirmatory urine testing, you can see that there is naloxone in the person's urine. There's some that they are absorbing. And so especially when you're seeing those patients that in that hour or two after taking their buprenorphine, they're consistently... Even after they're used to the medication, they've been taking it for weeks, they're consistently complaining of having a period of nausea and headache for that hour or so after taking it. Some of those people seem to respond better to the plain buprenorphine product. So the general recommendation is that we should probably use the combination product for most people because it is inherently an abuse deterrent. However, it doesn't mean that for other patients that you can't consider the plain product in certain situations when it's not tolerated. Unlike when we were talking about the treatment for chronic pain, so when you're treating pain in someone who does not have opioid use disorder, you can use any formulation of buprenorphine that you want. However, when you're treating opioid use disorder, you cannot use the pain formulations, Butrans or Belbaca, you cannot use those to treat opioid use disorder. That is illegal. You can't do that. And it doesn't work anyway because there's such a low dose. It's not going to be effective in any way. So now those medications, that's in the outpatient setting. When you're in the inpatient setting, you can do anything you want. You can give them these, because you'll see if you look up when we talk about the low dose overlapping starts or the microdosing, some of those protocols involve using the transdermal patches to get people used to it. That is totally fine in the inpatient setting, in the emergency room. You can give people fentanyl. You can give people hydromorphone. You can give them whatever you want to manage withdrawal symptoms when they're in the hospital. In the outpatient setting, you can only use the preferred, the sublingual formulations or the monthly, you know, the long-acting injectable formulations to treat opioid use disorder. So let's talk about how we're going to assess the patient and how we're going to get them started on therapy. So when we're getting the history, it's just like any other history we're going to get from a patient on what's going on with them, but we're going to focus a little bit more on their social history than we might in some other situations. We want to find out a little bit more about, you know, what substances are they using? How do they use them? How long have they used them? How much do they use? What have they tried before for treatment? What worked? What didn't work? What kind of, what is their social situation? Do they have supportive family around them? Are they living with other people who are using drugs? Are they unhoused? Do they have children? Are they, do they have work? Do they have transportation? Can they get to the clinic? Can they get to the hospital? Do they have legal issues? Are they on probation? Are they at risk for re-incarceration? These are all things that you might not talk about so much at a first visit with a patient who doesn't have OUD, but that can really affect your treatment plan for patients who have opioid use disorder. Of course, the state requires that we're going to be checking the PDMP, and that can be helpful to see if they're being prescribed other CNS depressants so we can counsel patients on what some of those interactions might be. We're not going to withhold buprenorphine for patients who are taking other CNS depressants, but it's always important to have the full picture on what's going on with the patient to have that educated discussion with them. A physical examination, the initial physical examination sometimes is really brief. Sometimes we're doing this over telemedicine, and we can't lay our hands on patients, but especially to focus on some of the physical findings that might be related to addiction. Are they having skin infections? Do they have dental issues going on? Do they have a heart murmur? Are they malnourished? Those sorts of things. Laboratory testing, if you're able to get laboratory testing before treatment or early in treatment, that's great. It's nice to have a urine drug screen just to see what their baseline is. It's not necessarily going to change what you're going to do. Remember that fentanyl does not show up on a rapid urine drug screening. I'm not sure if you have it in your hospital, if your rapid test has a fentanyl on it yet. There's one that was just CLIA approved for the outpatient setting. We didn't have any way to do a rapid test for fentanyl before that happened. Generally, we might want to send out for confirmation to get a better sense of what patients are taking and what their baseline is. It's nice to have a pregnancy test because sometimes people don't realize that they're pregnant, especially when you're using drugs. A lot of times people will experience amenorrhea and they can get pregnant without realizing it. We have a very large overlap, certainly in the state of Alaska and nationwide, with people who have opioid use disorder and have hepatitis C. I would say most of my patients who inject opioids have hepatitis C, which is probably over half of my patients. Because it's so common, we keep a rapid test in the office so that we can just test everyone with a finger poke to screen them to see if they've been exposed to hepatitis. If they test positive for exposure, we're going to draw blood for a full hepatitis panel. It's going to give us a quantitative level of their viral load. We're going to see CMP to see what their liver function test is like. These are all optional tests. None of these tests are absolutely required to start buprenorphine treatment. I can tell you most of my initial encounters with patients are done via telemedicine. That very first visit, much lower no-show rate with patients. I'm not able to get labs on that first. I'm not able to put my hands on patients, but I don't really need to to safely start buprenorphine. In the long term, I would like to get all those things. I would like them to get a full physical. I would like to get these labs, but it doesn't have to be right then before the first prescription. Some important points that you want to review with the patient for counseling on important things they need to do when they're taking this medication. We need them to understand that this medication only works when they are taking it. If they stop taking it, they almost certainly will go back to using and it dramatically reduces their risk of overdose. We need them to understand. I can tell you probably more than half the patients when they come to see me, they're like, okay, I just want to take this to detox. I just want to be off of it within a couple weeks or a couple months. I'm going to do this on my own and to really talk with it because there's so much stigma around taking this medication. They hear things from their family and friends like it's just replacing one drug with another. You shouldn't be on it. You should get off that medication. They have all these outside pressures that are all based on myths and stigma. None of them are based on evidence. It's really important to give the patient the education and support to understand that it's critically important for them to stay on their medication. If they stop taking their medication, they almost certainly will go back to using. Not always. There's like five percent of people that can do it without it. They make the ultimate decision whether they're going to take the medication or not, but we really need to make sure that that's an informed decision that they're making. Let us know if they get pregnant. We're going to offer everyone contraception if they have the ability to become pregnant if they want that. To really make sure that they'll let us know if they're going to have surgery or they have a trauma, they have some painful event because we can really help as their primary buprenorphine prescriber. I can be very helpful to the surgeons, the anesthesiologists, the hospitalists who may not be as comfortable with managing the buprenorphine and helping manage that patient's pain both in the hospital and after they discharge from the hospital and planning so that they don't fall through the cracks with that, which we'll talk more about next lecture. You don't need to reinvent the wheel with any of this stuff as far as protocols, patient education. This is an excellent patient educational handout from the California Bridge Program, which is kind of the number one resource that I recommend. It's called Bridge to Treatment now, I think, but it has all kinds of wonderful free handouts, protocols, algorithms that you can use for managing buprenorphine and methadone. This kind of gives all of this. It's a one-pager. It's meant to be easy for the patient to read and understand, and it kind of explains all of the basics about buprenorphine because these people, like that first visit, they're probably not feeling well. They might be intoxicated. They might be going through withdrawal. It's so much information. They're not going to remember what you told them after they left, so giving them some kind of resource that they can go back and look to later to read is a nice thing to do. Another common misunderstanding about buprenorphine, we think with a lot of medications, we want to start at a low dose and then gradually work our way up until we get to a dose that works. That's a lot of medications we're thinking of that, but there are certain medications that a low dose is not better, like with antibiotics, right? It's not a good idea to take 100 milligrams of amoxicillin a day, right? That is not doing any good and can cause more harm than good, okay? Same thing with buprenorphine. Too low of a dose of buprenorphine can cause more, you know, it's not going to be a therapeutic dose, so what we have found is that, especially in early treatment, the minimum recommended dose, kind of target dose, is at least 16 milligrams a day of buprenorphine. Not all patients will agree to take that much, but we need to counsel them that those are the current recommendations, and over time, as they're stable for many years, sure, they can go down to a lower dose gradually and slowly, but for those in early treatment, higher dose is better. There have been a few studies that come out lately in the last couple years that have demonstrated that doses of 24 to 32 milligrams a day have superior retention and treatment and absence than doses of 16 milligrams a day. It's also really important that the fentanyl, the ability for buprenorphine to block fentanyl is dose dependent. It's also dependent on how much fentanyl they're using, so the higher serum drug level of buprenorphine that you have, the more protection you have against the fentanyl-induced respiratory depression, so higher is better when it comes to blocking fentanyl. This is just a few of the articles, if you want to go back and read them, about improved retention and treatment for higher doses. Blocking the liking effects of opiates, so this is a very subjective, right, so we would like buprenorphine if a person does have a slip up and they do use opioids, we would like the euphoric effect of that to be blocked, so they're not getting that positive reinforcing effect of when they do use opioids. This is incredibly subjective and it's widely varying between patients, so we say that there are some patients who have a liking effect, so this is down here, the people that are down here at zero have no liking effect from the drug, so we see that there are some patients at very, you know, low serum drug levels below two nanograms per milliliter that have good blockade of the liking effect. This is a liking effect of 18 milligrams of hydromorphone IM, so that's a pretty hefty dose. I think if you gave that to me, you'd have to resuscitate me pretty quickly, but so that, so and hydromorphone is kind of similar in the fact that it's very high potency, similar to fentanyl, but we see there's certain patients that really, in order to get like really good suppression of the drug liking effect, there are some patients that actually need to have, you know, three nanograms per milliliter or above serum concentration in order to get a good blocking of the liking effect of the potent opioid. So again, that to achieve serum drug levels of three nanograms per milliliter could potentially take up to 32 milligrams a day or more, or stabilizing on monthly high dose, monthly long-acting injectables, so the 300 milligram supplicate once it's stable. Medicaid only pays for 24 milligrams, almost all insurances only pay for 24 milligrams a day. So if you're running into a patient that, and I mean, I'm trying to kind of battle with the pharmacy, Medicaid pharmacy folks about this, about how important it is in early treatment to be able to get a symptom, symptoms and cravings and withdrawal and everything under control those first couple weeks, but essentially if you, if you feel like a patient does need more than 24 milligrams a day, you have to put in prior authorization, and it's not just one you can do over the phone, you have to send it in, they send them a result, you have to send in the records, it can take weeks to get the prior authorization approved, which is very frustrating. There are sometimes, you know, patients have the resources and they have, you know, 20 or 30 dollars to buy some extra buprenorphine, they might, might need that for the first week just to manage the withdrawal symptoms. So I have been able to get it approved, but it's not an easy process, which is, which is too bad. This, this is a really excellent article that talks about kind of what the evidence is on buprenorphine dose limits, really, really arguing that in this day and age of high potency synthetic opioids like fentanyl, that they recommend changing the labeling on the, on sublingual buprenorphine to allow for recommended doses of up to 32 milligrams a day. So there's a lot of push towards this, but we haven't seen the insurance companies agree to this yet, unfortunately. High doses, the, and long-acting injectable, high doses also have superior retention and treatment. So this is looking in patients who inject drugs. So the first, the first couple weeks here, they're both getting, the dosing for this medication is you give two of the loading doses of the big dose of 300 milligrams, and then you can switch to the lower dose of 100 milligrams. What we see is that a significant number of people drop, are dropping out of treatment more when they're on the lower dose and the higher dose. And also, you get about twice the serum drug levels. You're going to get about three nanograms per milliliter when you stabilize on 100 milligrams versus six nanograms per milliliter when you stabilize on 300 milligrams. So I can tell you in my situation, I just keep almost everyone on 300 milligrams, unless the patient's having side effects or the patient themselves prefers to go down to the lower dose. How, how often should people take their medication during the day? So if you look at the prescribing information for sublingual buprenorphine, it says that it can be given once a day, which it can because it's a very long-acting medication. So when we're talking about simply the control of cravings and withdrawal symptoms, it can in theory be taken once a day. There are good things about that. There are, you know, there, you know, part of the, part of addiction for many people is kind of the ritual of use. And so that kind of the, the behavior of taking something multiple times a day throughout the day to help yourself feel better. And for some people that can be, for some people that can be a therapeutic thing. Like they, they like that this medication helps them to feel better. They like being able to take it multiple times a day that they feel a little bit better each time they take the medication. For other people, they have difficulty that that's just, it just perpetuates, you know, some of, some of the issues going on with their addiction. And so it really, it's whatever makes the patient feel the best. So if they feel their best when they take it twice a day or three times a day, then great. But it's important to tell them, like, you have to be able to do it the same way every day. You have to take the same dose the same way every single day, because we all know that taking any medication three times a day is incredibly difficult. You know, adherence to that is very poor. People are going to say they're going to take one too many. They're going to take one too less. They're going to, you know, they're going to forget their dose that they normally take at noon. They're going to forget it at home or on their way at work. So for simplicity's sake and possibly for, you know, kind of the psychological benefit for some patients, once daily dosing might be better. But it's whatever dose, whatever way that they can take it, that they do the same way every single day and it helps them to feel their best. That is the right way for them to take it. It is important to understand that the analgesic action, although it's a very long-acting medication on the receptors, the analgesic action of this is more like six to eight hours. So most patients who have chronic pain are actually going to prefer to take this medication three times a day. I even have a few patients that do it four times a day, but because they get better pain relief when they split the dose up throughout the day. This is a sublingual medication that's really important, especially if you're prescribing the tablet formulation. That's very important to let patients know that this medication is not absorbed in your stomach, like less than five percent GI absorption. It gets destroyed by first pass metabolism. So it needs to be absorbed in the blood vessels that are under your tongue. Also option is putting it buccally, kind of between your gum and your cheek is another option, and to leave it there for a good 15 or 20 minutes. Don't eat, drink, talk, smoke during that time, and then afterwards you can spit out any excess. You don't need to swallow this stuff. Some people, if they swallow a lot of it, they feel like it makes them more nauseous. It's also good to encourage people to rinse out and spit afterwards. There have been some reports that it could cause some enamel damage of softening of the enamel of the teeth, possibly in long-term use. It's a little up in the air. How much that still, you know, how much of that, how often, you know, we don't know how much that happens, but it's better to encourage people. Just like we would tell people to rinse their mouth out after they use a steroid inhaler, right? Same kind of thing. We're going to tell them to rinse their mouth out after you take about 15 or 20 minutes after you take your medication. You don't need to swallow this medication. The most common side effects that we're going to run into, especially in early treatment, very common in the first few weeks to experience nausea and headache. You know, if we, if the person has a low tolerance, maybe they feel a little over-medicated at first, sweating with any opioids, sweating is a possible side effect. These side effects almost always go away once people are used to the medication. After the first couple weeks of a stable dose, generally side effects go away. Nausea is such a common side effect that I give every single patient prescription for Ondansetron when I prescribe this medication. Edema, I've seen there's rare cases of that with the high-dose extended-release injectable buprenorphine. It usually is self-resolving. Then constipation is just the number one thing. I ask every patient, every single visit, how they're managing their constipation because it can be quite severe, just like with any other opioids. It can be dose-related. The higher the dose you're on, sometimes we see more severe constipation, so making sure that we have a bowel regimen for people, and also understanding the frustration of Medicaid not covering the most effective treatments for constipation. Medicaid doesn't cover SENA. Medicaid doesn't cover Miralax. These are the ones, things that we want them to be using. I'm lucky that a lot of my patients are Alaska Native, so I can get those medications from A&MC. We actually carry a lot of samples of laxatives. We get bulk SENA off Amazon. That's like $5 a bottle. The 90 tablets, and we just hand it out to patients because, gosh, what a tragedy if someone ends up going to the emergency room for a patient in constipation when it could have been prevented with a bowel regimen. So precipitated withdrawal, this is kind of the main trick. If there's anything tricky around prescribing buprenorphine, this is kind of the main trick that we want to make sure we understand how to avoid. So again, we talked about precipitated withdrawal happens. It's only when the very first dose of buprenorphine that you take that this happens, and it is when you still have a lot of full agonist in your system. So we see this most commonly in methadone because we know methadone takes weeks to eliminate for your system, but also chronic fentanyl use, which we'll talk more about. So if you give that dose of buprenorphine too soon and it's the wrong dose of buprenorphine, the wrong dose being anything between two to eight milligrams typically, then very rapidly, in an hour or less, people have this sudden onset of very severe opioid withdrawal symptoms. And so the best way we can avoid this is to generally is we're going to wait until they have stopped taking their opioid of choice and they are experiencing a moderate amount of withdrawal. Fentanyl has complicated this, the situation of starting buprenorphine has made it more difficult. So fentanyl is in every single opioid that people are going to buy on the streets right now. There is really no, there's no such thing as pure heroin anymore. All of it has fentanyl in it. These blue fentanyl pills, and people will call them blues or M30s. They're originally meant to look like oxycodone 30 milligrams, but everyone knows that they're fentanyl. You can't buy oxycodone on the street. It's all fentanyl. They're very cheap. The other pressed pills, so we also have see pressed fake Xanax, pressed fake Adderall, that are all just pressed fentanyl. You have no idea how much fentanyl is in any of these. They're made in some garage somewhere with people cutting all kinds of things together with them. But if an opioid naive person took one of these, they could easily die by taking one of these pills, very easily. If you don't have an opioid tolerance, more than about half of these pills contain a lethal dose with a single pill if you lost your opiate tolerance. Again, the danger behind people when they lose their tolerance, it only takes two weeks to lose your opiate tolerance. So two weeks after someone tries their stopping, they're trying not to use, maybe they got released from incarceration, so they went through kind of involuntary withdrawal. They get out, the first thing they're gonna do is wanna go back to using again and one pill and smoking. So this last year, if you might've seen in the news, was the very first year that more people died from smoking opioids than they did injecting opioids. So traditionally, we think of smoking as a safer means of use, which generally it is, because it hits you kind of fast, but you can titrate, take a little bit at a time. But the fentanyl is just so incredibly potent that even like one or two hits smoking inhalations, smoking fentanyl can potentially be deadly in someone that has lower levels of tolerance. So fentanyl, we think about fentanyl as being a short-acting medication. Like that's why we love to use it in the ambulance and for conscious sedation in the emergency room, because it's short-acting, but it is very lipophilic. So like THC or benzodiazepines, it stores in your fat. And so when you've been using it chronically, you develop very high, you build up very high levels of fentanyl in your fat. And that when you stop using fentanyl, it can actually take weeks even to a month or longer to completely eliminate all of the fentanyl metabolites in your body. So the trouble that people get into is, and this is just kind of an example of that, it can take a few weeks to eliminate the metabolites. And I've seen reports of it taking up to a month. So fentanyl withdrawal is reported to kind of, it hits people sooner, it lasts longer, it's more severe than withdrawal with less potent opioids. More likely to lead to precipitated withdrawal with buprenorphine. And the withdrawal can be more difficult to treat and you can need higher doses of buprenorphine and other medications to relieve it. And it is not uncommon at all to need more than 24 milligrams a day of buprenorphine those first couple of days to relieve these symptoms. And I've seen people need 60 milligrams or more to relieve their symptoms in the first couple of days if they experience precipitated withdrawal. The other flip side of this is that there's some arguments that really precipitated withdrawal is not that common. It definitely happens to some people, but it's not as common as we think it is. So this is looking at in the emergency room where they had a population where over half of the people were using fentanyl and they were started on buprenorphine in the emergency room and less than 3% of people developed precipitated withdrawal symptoms after their dose of buprenorphine in the emergency room. So it happens, but we don't wanna scare patients to say, you know, we wanna talk to patients to find out. You know, we wanna ask them when they're coming in and they're seeking treatment, we wanna ask them, you know, what's your experience with buprenorphine in the past? Because I think almost everyone, not everyone, but almost everyone that you're gonna run into who has opioid use disorder, especially if they're seeking treatment, will report that they have tried buprenorphine in the past. Commonly, it's because a friend has given it to them to help them manage their withdrawal symptoms when they're going through withdrawal. 90, 95% of non-prescribed buprenorphine use is used for the medically indicated purposes. So people aren't, you know, you'll hear sometimes law enforcement have to say that like, oh, we got all, you know, we, hey, we just confiscated a bunch of, you know, buprenorphine that someone is selling on the street. And you think that, you know, buprenorphine is being sold on the street, it must mean that people are using it to get high. They're not using it to get high, they're using it to get well. So they, for whatever reason, they can't access, right? They don't have, they're not seeing a doctor, they don't have a prescription for buprenorphine. 95% of the time, people are using it to relieve withdrawal symptoms, cravings, to help, you know, detox themselves at home, to try not to use. That's the reason people are using non-prescribed buprenorphine. So it's very rare that I have a patient that walks through my door that hasn't at least once or twice tried buprenorphine before, even if they've never been prescribed it. So it's important to ask the patient, like, what was your experience with it when you took it before? Did you feel sick? Did it make you feel better? How long did you wait? How much did you take? We want to get the feeling of what happened. And if they did say, you know, say, oh gosh, like every time I try to take it, I get so violently ill. I just, I don't think I can take that medication. I'm scared to take that medication. That's when we really want to spend a lot more time with patients. I'm really trying to create a good plan for them to start taking the medication that will not result in precipitated withdrawal. Patients are much more likely to experience precipitated withdrawal when they're using non-prescribed buprenorphine than we're using prescribed, because they're not getting that education and instruction on how to properly take it. So usually we're able to reassure people that like, that's, I'm sorry that it happened to you. That's really common, but we're going to make a plan so that that hopefully doesn't happen to you again. And if it does happen to you, we're going to help you to manage those symptoms and to get through it. So we really want to go into kind of what worked in the past, what didn't work. If they took it before and say, oh yeah, every time I take it, it helps me. I feel great. Okay, great. Just do however you did before. Most patients, I can tell you, most patients that come through the door are going to tell you exactly how much buprenorphine they need to feel well. And they know exactly how to take it already. I mean, we always provide the education, but patients might know a lot more about this medication than you do. So we want people to be in enough withdrawal. What is enough withdrawal? So it's, so CalScore, any, you know, MD Calc or any of your calculators, you know, you can pull up apps on your phone. You can, you know, calculate the score in less than a minute. We're looking at, you know, all the symptoms, the rhinorrhea, the pupil size, the achiness, the anxiety, the runny nose, and scoring that. We want to get at least a 13 on this to be considered to be in moderate withdrawal. Some people say, you know, hey, if you're, you know, withdrawing from fentanyl, maybe you should get up higher. Maybe you should get up to like 20 or so. But patients aren't going to calculate their CalScore at home. And this medication almost always is going to be started by a patient in their home. So what do we tell patients when they're doing it at home? Essentially, we tell them, you know, wait about 12 to 24 hours from the last time you used opioids. Wait until you have at least three to four withdrawal symptoms. So, you know, give them a list of these withdrawal symptoms, nausea, vomiting, diarrhea, all these kinds of things. And basically just wait until you feel like you can't possibly wait anymore. When you feel you can't possibly wait anymore, that's probably the right time to start taking a buprenorphine. So what would I write for prescriptions after that first intake visit when I see a patient? So I'm going to write for them for a week of buprenorphine. The Alaska Opioid Prescribing Law says that we shouldn't prescribe more than a week of opioids. But you can, you know, I do have some patients who are in the bush, right? And it's really hard for them to get their medication. So in my note, I might write, like I'm going to prescribe two weeks because I don't want this patient to run out of, you know, lose access to their medication in between visits. So generally a week of buprenorphine, it's better to err on guessing the higher dose. Because you don't, especially in patients who don't have a lot of experience with buprenorphine, and you don't know exactly how much they need, it's much better to have too much than to have too little. Because if you have too little, and the patient, you know, they're either going to overtake their medication and they're going to run out early and then you can't get an early refill, right? Because of insurance, they can't afford to pay cash for it, or they're just going to say, hey, this isn't working, and they're just going to continue using. So it's much better to err on the side of giving them extra. So most commonly, unless I know a person has done very well on lower doses, most commonly that first prescription, I will just write for 21 tablets for a seven day supply just to be on the safe side. But you know, I'll instruct them to take what you need. You don't need to take three a day, but two a day is kind of our goal for a dose to start with. I give everyone Zofran. I give everyone Clonidine. So that can be really helpful with that restlessness, sweating, creepy crawly, like you want to crawl out of your skin feeling can be really helpful for that. And as long as people stay well hydrated, they tend not to get any hypotension on this, unless they're quite dehydrated or quite a small person. And make sure that everyone has Narcan. We keep some in our office to hand out to people. I'm not sure if you guys have it in the hospital to hand out to people, but if you work for a clinic, you can partner with the State of Alaska Project HOPE and they will give you boxes of Naloxone that you can hand out free to people. So it's a very easy thing to do. Because otherwise, you know, we worry that people won't pick up the prescription if we send it into the pharmacy. And then, you know, there's lots of other medications that we can use to augment treatment of withdrawal symptoms. We can use Transodone for insomnia. Tizanidine is also an alpha agonist like Clonidine. So it also provides not just muscle relaxant, but provides some withdrawal symptom management as well. Ibuprofen, Imodium, Hydroxyzine for anxiety. There's a bunch of other, sometimes people use Seroquel, sometimes people use Gabapentin. It's really just asking like, you know, what is, if people are really scared about their withdrawal because it's been very traumatizing for them before saying, what is your worst withdrawal symptoms? They're like, oh, it's insomnia, I can't sleep. That's what makes me go back to using every time is I can't sleep. Okay, well, let's talk about a non-narcotic medications. So we don't prescribe benzodiazepines, they don't prescribe Ambien. It's just, you know, with people who already have a history of substance use disorder, it's too easy to kind of latch onto those things and then it's hard to give them up after that. And if you are going to, if you are gonna start the patient, if the patient wants to start on long-acting injectable buprenorphine at that first visit is when I'm gonna order that medication. That medication is not carried at local pharmacies. It's only carried at like a couple dozen, you know, specialty pharmacies nationwide. So you actually have to order it, fax the prescriptions to specialty pharmacy and they ship it to your clinic. So that first visit, I'm also sending that prescription for the long-acting injectable and having the patient plan to follow up the week after to get that injection. Standard instructions for buprenorphine. This has changed from what standard instructions were 10 years ago because of fentanyl. So we used to tell patients, start with like four milligrams of buprenorphine and then take another four milligrams, you know, every couple hours or so. Maybe don't take more than eight milligrams in the first day. Well, that is all out the window now. I tell everyone to start with a minimum of eight milligrams for their first dose. If they have a pretty high tolerance and they're using all the fentanyl, I actually encourage them to start with a high dose, start with 16 milligrams, which means that you have to put like one tablet or strip under each side of your tongue. It's a little bit cumbersome, but giving the higher doses reduces that risk of precipitated withdrawal. And then they're going to repeat, take another four to eight milligrams, kind of as needed up to 16 to 24 milligrams what they need to control their symptoms. And again, some patients those first couple of days might need significantly higher doses than that. So it's important to have them, you know, reach out to you if that's occurring because we're worried that they're going to run out of medications early. These instructions, what I just described is what is written here on another great handout from the Bridge to Treatment Program that in very simple language describes how to take the medication. And it kind of describes the variation of, okay, if you have a really, you know, you're using very little, you have a very low tolerance, you might be able to start with four milligrams. When I have patients who are opioid naive, so those would be patients who, common situation is incarceration. Okay, like they've been incarcerated, they haven't been given buprenorphine while incarcerated, which should be changing in the next couple of years here in Alaska. We're a little behind the times with that, but let's see, whatever situation, they have gone through withdrawal, they've been abstinent for a couple of weeks, they no longer have a tolerance to opioids. If we tell them to take 16 milligrams of buprenorphine, they are going to just feel awful, most likely. They're going to have a lot of, it's not, again, it's not a safety issue, it's a tolerance of side effect issue. And we want the patient to feel well when we take this medication. If they feel badly when they take this medication, they're not going to want to keep taking it. So in those patients who do have really low levels of tolerance, then yes, you might want to take, just take a quarter of a strip to start with. And you might, it might take even a couple of weeks to build up the tolerance as tolerated by side effects to get to that kind of goal of 16 milligrams a day of buprenorphine. And you folks can all have access to these slides too later in case you want to do so. Now, if someone does experience, and we do our best to try to educate people and try to guess what the right dose is and everything, so they don't experience precipitatory withdrawal, but sometimes it happens even when we're not very good at predicting when it's going to happen. So sometimes it just happens. So it's important for patients to understand if this does happen to you, what should you do? We used to counsel patients, okay, why don't you just stop? Just stop what you're doing. Let's just try again tomorrow or try again in two days. Well, that didn't work because people were like, I don't want to try again tomorrow, that made me sick. I'm just going to go right back to using, right? And you lose patients, they get lost to follow up. So what we have discovered is that the treatment, the only way to make people feel better is they need to have more opioid agonist effect. That's the only thing that's going to truly relieve their symptoms, more opioid agonist effect. And once you start a precipitatory withdrawal, really the only way to do that is to push through it and to go to very, very high doses sometimes of buprenorphine. Some patients also will self-treat with fentanyl, their opioid withdrawal symptoms. We don't recommend that, but they do do that sometimes just to get through this. So these are the instructions we give to patients on how to treat precipitatory withdrawal if you get it. If you get it, immediately take 16 milligrams of buprenorphine, and then you can kind of repeat that. We usually tell people they can do up to 40 milligrams of their experience. I have had a couple of patients that did up to 60 milligrams before. That's kind of the highest reported in the literature. On dancetron, and I'll actually have people, if they've had a history of precipitatory withdrawal, I'll often have them premedicate with on dancetron and clonidine, like the half an hour or so before they take their first dose to kind of get that on board to help a little bit. And again, any comfort medications. We'll talk more in the hospital thing about treating this in the emergency room when we have very severe precipitatory withdrawal that is not responding to sublingual buprenorphine. We're gonna use things like IV ketamine, benzodiazepines, and IV filaginous, like IV hydromorphone or fentanyl. But those things, obviously, we're not gonna use in the outpatient setting. There is off-label use of ultra low dose sublingual ketamine for buprenorphine precipitatory withdrawal that's starting to be used, but that's a compounded medication. The patient's gotta pay cash for it. So it's not something you're gonna see very often. I'm gonna talk briefly specifically about long-acting injectable buprenorphine. So some advantages to this medication, long-acting injectable buprenorphine. It's simpler for us as the providers, it's simpler to use because one of the barriers to prescribing this medication is probably our worry, we spend too much time worrying about diversion of this medication. Divertive buprenorphine probably causes more good than harm and when you look at the studies about it, but we have to do our due diligence to try to prevent diversion, especially we don't want it to get into the hands of an opioid naive person like a young person. We clearly wanna avoid that. So we don't have to worry about that with this medication. So it takes all that extra case management and work, ancillary work about doing urine drug tests to see if you're taking your medication, counting medication, all these things, we don't have to worry about. So it takes all of that work from our end of things, which is nice from our end of things. And there's remote locations where they just don't have the facilities. The patient can't get to the clinic to do a urine drug screen. They don't have a video on their phone where we can watch them count their medications over the phone. It's just not accessible to some patients, it's more remote areas. And when patients do live in remote areas, they're constantly at risk for medication interruption. So when you live in a rural area, if you're off the road system, what if the plane doesn't fly and you only get your mail two or three days a week and then you run out of your medications? What if you can't get to your follow-up appointment because of weather or your car's broken down? What if you can't afford the gas, you don't have your license? There's so many things, either getting to your appointment or getting to the pharmacy or the medication coming to you in the mail. There's so many points at which we could, patients could run out of their sublingual buprenorphine. When that happens, within 24 to 48 hours, they're going to go into withdrawal. That withdrawal is going to trigger cravings for many people and then many people are at risk for return to use and then of course overdose when you return to use. So the nice thing about this medication is that if you miss your appointment for your scheduled injection, you do not immediately go into withdrawal. It wears off very, very slowly. It will wear off eventually, but it wears off very slowly and gently so you don't have that abrupt onset of withdrawal symptoms. So it gives you more flexibility and time to reschedule that person and get them into treatment without that. And it provides a really long lasting protection. You can get a much higher dose of buprenorphine. So it can be really great for people who we know are going to lose access to medication because they're going to go out fishing or they might become incarcerated. They have a warrant out for their arrest maybe. So this medication, because potentially you can achieve very high levels of buprenorphine and serum drug levels on long acting injectable buprenorphine. So this is a clinical study where they're looking at a patient who, this is a patient on this side who does not have any buprenorphine on board and they're being given increasingly higher doses of fentanyl up to about 800 micrograms of fentanyl in a single dose. And not surprisingly, they tend to stop breathing. But when you have patients with high levels of buprenorphine, so this is patients with five nanograms per milliliter, which those are doses that, levels that you're going to see in patients who are stabilized on like 300 milligrams of supplicate, which it takes a number of months to get there. It's not the first month that you get there, but once they're stable. So with those folks, even 800 micrograms of fentanyl does not suppress their respiratory drive. So this, so it is dose dependent though. And this study, there's a couple of studies that did the same thing, but when they see is that when you get down to lower levels, when you drop down below two nanograms per milliliter, you start to lose that protective effect. It's very dose dependent. So the higher dose, the more protective it is. And it's important to understand if someone is taking 16 milligrams of buprenorphine a day, especially if they miss a dose, they may very well have times in the day where they drop down below that 2 nanograms per milliliter. So especially we have patients who are at risk of exposure to fentanyl. They might be using methamphetamine that can be contaminated with fentanyl. Maybe they're just struggling. They're living with other people who are drugs. It's constantly around them. And they're going to be having kind of intermittent use, even though they're trying really hard not to use, those higher serum drug levels are going to help to protect them against overdose. And this is one of my favorite things about this medication is how incredibly long lasting it is. So if you're able to attain steady state and steady state in this medication for the highest dose of 300 milligrams, not surprisingly is five doses, four to five doses, which we think of with any medication, and then the medication is stopped, the levels go down so slowly that each one of these bars here is two months. So they could potentially maintain protective serum drug levels for up to five months after their last injection. So they have to get to steady state for it to last. The higher serum drug levels you get, the longer lasting protection you're going to get if that is interrupted. But this can be really great for people who are at risk for losing access to care. Maybe they're at risk for losing their insurance. They're going to be going out commercial fishing for three months and we're not going to see them. They might become incarcerated. This is going to give people that extended protection. This medication in multiple reports has a very high patient satisfaction rating. Patients really love this medication. They love that they wake up feeling normal every day. They don't have to deal with the hassle of taking an everyday medication. They love that if they are late or miss their injection that they don't experience withdrawal symptoms. It has a very high patient satisfaction rate. And I tell you, I don't have to convince any of my patients to take this medication. They come to me asking for this medication because their friends took it and they say, you know, all my friends told me I have to get on this medication because it works so well. And that means way more than anything I could tell a patient. That word of mouth and that personal experience from other people with lived experience is much more valuable to them than anything that I can tell them about how this medication works. It's important to understand that it takes time to build up stable and therapeutic serum drug levels and that is not achieved for many patients in the first month. So if we see in the first month, if we compare the 24 milligrams of sublingual buprenorphine, we're going to get lower levels with the 300 milligram, both the average, the peak and the trough. And then we see here the trough is going to drop significantly down below two nanograms per milliliter. So that is not protective in theory against fentanyl-induced respiratory depression. For some people, that is enough to control their cravings. Some people feel great the whole first month, but it is very, very normal. And we counsel patients. We want them to have realistic expectations around what this is going to feel like. Because if they feel like it's wearing off, oh, this isn't working. Oh my gosh, I can use fentanyl. I can still feel it. This is just crap. I don't like this. We need to prepare people and tell them realistically what that first month is going to be like. And we're going to allow them to take sublingual buprenorphine on top of the monthly injectable, at least like the last two weeks of the first month. And there's no magic as to how much that is, but it's better to err on the side of giving people more than you think they might need than underestimating what they think might need. And then after a number of months, we see that we get these very high, steady states that, regardless of the dose, that don't drop down below two nanograms per milliliter. So that it will get better. They don't generally have to continue taking sublingual buprenorphine for forever, but it's really important to remember that that first month may not be therapeutic for many patients. So counseling patients on what to expect, you know, call us if your symptoms aren't controlled. Call us if you're still having cravings to use. It's going to take a number of months for you to stabilize. Every month that you get a shot, you're going to feel better and better and better. It's very common, especially if people have lower levels of tolerance. It's very common that the first couple days after that first shot, you really get a peak level, a very high level of medication the first couple of days. And for some people, that can cause a lot of nausea. They can feel dizzy. They can feel sweaty. Sometimes they actually confuse that with going into withdrawal. They think they're having withdrawal because some of those symptoms sound like withdrawal, but it's actually they're having side effects from because of the very high medication levels. So counseling patients, you know, give them nausea medication and counsel them that, you know, your body's going to get used to this medication and you should not have that. It shouldn't happen again the next time you get it. It's generally only the first injection. And it's also very important. The thing that people love about this medication is also the thing that inherently can be dangerous about the medication is that you don't feel it wearing off, especially once you stabilize and get a couple of shots. People feel so well, they don't feel it wearing off. They love that. They miss their appointment and they're like, oh, I'm going to reschedule. Maybe they do. Oh, I missed that appointment again. And they just kind of forget. They just, I just feel great. I'm doing fine. I don't even need another shot. I feel so good. And then, but what happens is it is wearing off. They just can't feel it wearing off because it's happening so slowly. And so two, three, four months down the road, when it has worn off and they don't realize it, something happens like something stressful happens. Someone offers them, someone offers them drugs they end up using. And then that's when they realize that they don't have that blockade anymore or God forbid they've lost their opioid tolerance and then they have an overdose because they don't have a tolerance anymore. So it's really important for people to understand that it's going to wear off even if you don't feel it wearing off. And most people will return to use. It takes longer than when sublingual. So it might take a few months for people to return to use, but most people are going to return to use if you don't stay on this medication. So it's critically important to stay on it and get that medication every month. And we also make sure that patients know that they can always get their injection, no matter what's going on in their life. It does not matter what drugs they're using. We don't require them to do urine drug testing. The only thing we require them to do is to show up. If they show up, we're going to give them this injection of medication. So very, very low barrier access to treatment. This is just a great article if you want to learn more about buprenorphine use in patients who are using fentanyl. This is excellent guidelines that just came out from the American Society of Addiction Medicine. It's worth reading if you want to learn more about that. And then when patients are stable, how are we monitoring them? So we're going to initially, initially a lot of times I see people every week until their dose is stable and their use and cravings have stabilized and we've managed any side effects and all that kind of thing. Once they're stable, we'll go to every two weeks for a while and then eventually we'll see them once a month. And when I see them, we're of course by law, we're going to check the PDMP when we're refilling medications. Drug testing can be considered, you know, drug testing is actually it's not an evidence-based practice. And there's an excellent talk at ASAM annual conference I just went to a few weeks ago talking about that, you know, a lot of times drug testing causes more harm than good. Most physicians actually do not, are not good at interpreting drug testing. We misinterpret it and we misapply it. And so it can be a tool that can be useful to guide a conversation with patients, but we never want to stop prescribing buprenorphine because the person is using other substances. So I'm not really, we're not using it to police. We are not the police. We're not doing that, right? We need to trust in what patients are telling us and how they're feeling and put much more emphasis on that than we are on these tests that are, especially the screening tests are horrible tests. They're wrong a huge percentage of the time. So a lot of times you don't even know what's in it until a week later when it comes back from confirmation testing. And so, you know, yes, we want to make sure that people are taking their medications, but you know, do we test, you know, diabetics to see if they're taking their metformin or whatever, right? Like we trust that the patient is telling us you're either taking it or not taking it. So there's a lot of argument right now about your drug testing and its utility. And in many cases, it's really important to understand it is not an evidence-based intervention. It's not shown to reduce diversion. It's not shown to improve outcomes. And we didn't even do it during COVID and people did great. And actually more people got into treatment. Overdose, you know, for people who use telemedicine went down. So there's a big argument. So I just really be cautious when you use drug testing and really utilize experts in interpreting those results because often they are misinterpreted with consequences that can be dire for patients. We want to talk with people, how are you taking your medications? I don't assume that they're taking the drug. Tell me about how much buprenorphine you're taking and how you're taking it. Well, what's prescribed for me? Well, tell me because I don't remember how much I prescribed you. So, you know, getting to, because some people can't, well, I take a little piece here and I take a little piece there and then maybe I'd later take a little piece like, okay, that's not good. We got to get you on a pattern so you're taking the same way every day. We're going to talk about are you having uncontrolled cravings? So what's triggering them? I feel anxious. I have pain. I can't sleep. Okay, now we need to address those underlying comorbidities. So a lot of the ongoing care we're seeing with people is really the chronic medical care to address those chronic underlying comorbidities, which were the issues that were triggering their substance use to begin with. You know, getting them treatment for their depression, their anxiety, their chronic pain, their insomnia, all these really common comorbidities. And how long should people stay on treatment? The longer, the better. So this is looking at patients who, this is comparing patients who are not taking any medication for opiate use disorder. They're just getting counseling to patients down here who are taking either methanol and buprenorphine. And this is the number of relapses that they're experiencing. So we see this first month we have about 10, first couple, first couple months we have about a tenfold higher incidence of return to use when people are not taking medications. At three years out, we still have a third the rate of relapses in patients who stay on their medications that don't. And there's also looking at five years out, people still have half the return to use rate if they stay on their medication than if they go off it. So there is no time when we can tell patients that it's 100% safe to stop taking their medications. There is always the risk when people stop taking their medication that they might return to use. And so we need to take that conversation very seriously when people say, I want to stop taking my medication. We really need to talk about why that is. So when patients, when is the right time to consider tapering medication? First, it should always be patient directed. We as a providers should never be telling people, hey, you've been sober for a year now. How about we try coming off your buprenorphine? How about we try tapering down to a lower dose? No, it should always be patient directed. It should be the patient wanting to do it and for the right reasons. And when you ask the patient, why do you want to come off it? Well, I just feel like I'm trading one drug for another. Well, my girlfriend says I shouldn't be on this medication. More often than not, it's issues related to stigma and pressure that they're getting from outside sources that are the wrong reason to stop taking the medication. The right reasons is that they've been stable for ideally a number of years, not using other drugs. Their housing is stable. They got a job. Their family life is good. Their financial life is good. Their mental health is good. They have a strong recovery network around them. Those are people that when they're ready and they bring up like, yeah, it sounds like you might be ready. Let's give it a try. And we're going to do it very slowly and gently, just like we would for other chronic opioids over the course of many months to years. And any reduction of more than four milligrams in a month has poor outcomes. We're really going to work strongly to counsel patients against discontinuation during the really high risk time. So when they're going through a lot of stress in their lives, things are changing during pregnancy and postpartum times, when they have a surgery or hospitalization, or really just from these outside pressures that are related to stigma that are encouraging them to do it when it's not a good idea medically. These are some helpful resources to consider. So again, the Bridge to Treatment is one of the best ones because it has just tons of handouts and algorithms and protocols that you can use that have already been vetted and created by the experts. They're actually meant to be used mainly in the hospital and emergency room. So they're meant to be very easy and straightforward. The SAMHSA has a quick start guide as well. And again, the ASAM has the considerations for people who are using fentanyl that are kind of different than what we might see in other patients. All right. Well, I'm going to stop there for that and take some time to answer questions for folks who might have questions. You guys are so quiet. You didn't interrupt the whole time. I'm not used to that at all. Usually people are asking questions in between. Yeah, perfect. Is that something that somebody administers at home or is it always administered in the office? Yes. So all of the long-acting injectables have the same, they have a REMS criteria around them. And the REMS states that these medications can never be in possession of the patient. They must be kept either at the specialty pharmacy or at the clinic locked up. And they can only be administered by a healthcare professional. It doesn't have to be a doctor, it can be a nurse or someone else that's authorized to give subcutaneous injections. But they can only be administered in the office or medical setting. They can never, and the reason behind that is because once they're injected under the skin, they change from a liquid to a solid kind of instantly. So you can imagine if you injected that into your vein, you'd cause a massive embolus. So that is the reason why they can never be in possession of the patient at any time and they can only be administered in the hospital. Is there the same site reaction with Celicaid? So the injection site reactions, you know, about one in four people get mild injection site reactions, meaning they get a little sore, they get a little itchy, they get a little red. There is a very, you know, there's been some reports of like allergy to the depot where people get like really itchy and swollen and red. There is this very, very rare complication. I've seen it twice in patients, it wasn't injections I did where it's probably was injected too superficially, like injected intradermally instead of subcutaneously. And it was putting kind of pressure on the skin and caused like a pressure necrosis of the overlying skin. And actually, you know, you get a necrosis and actually the depot is actually extruded because of that. It's super, super rare. And it's probably related to technique in that it was accidentally injected intradermally. You know, the needle, it comes with a subcutaneous needle. And so you're supposed to put it in the full depth. It's meant to be, it's a five inch needle or a half inch if you're doing the bruxade. So yeah, I haven't ever seen any severe injection related with like proper technique before. And I've done like well over a thousand of these myself, but yeah. What do you, without telling a client what to do, do you ever discuss, especially living in Alaska, to maybe delay their coming off the meds to spring, summertime, or you believe in just start whenever? I mean, obviously when you're in your client relationship. So like if a patient wanted to taper, decided that they had been stable for a long time and they were ready to taper off their medications. Yeah, absolutely. You want to make sure that it's a time when they don't, when life is good and they don't have a lot of other pressures, right? So if winter is hard for them and they're feeling depressed in the winter, or if maybe like summer is a super busy time for them, right? Because they're going to be out fishing and they're like crazy busy all the time and they have a lot of pressures on them. You want to make sure that it's a time when life is good for them, their stress level is low, and they have time to deal with it. And again, the taper process generally is going to take many months. And so you want to plan for like how are you going to be doing over the next six months or so if this is a good time. An alternative taper strategy is actually administering, switching from sublingual to long-acting injectable, doing a couple of those injections and then stopping because it naturally comes out of your system very slowly. So that's kind of an alternative, like no-brainer, easy way to taper someone off of buprenorphine. But yeah, you definitely want to make sure people are in a place in their lives where their stress level is low and they don't have a lot of other stressors. In whatever form, stressors are like the number one thing that's going to trigger people to return to use. So we want the stress level to be stable and as low as possible before we, you know, are encouraging people that it's like sounds like it's a good idea for you to try coming off your medications right now. I've seen the pills, the sublingual pills used before. Is that because of reimbursement or is that a patient experience thing? I think, you know, they, so it's more recent. The generic sublingual, like the sublingual strips have been out for like more than 10 years. I think the sublingual combination tablets, the plain buprenorphine tablets, which used to be called Subutex have been out for forever too. The combination tablets are most commonly used tablets are like more just in the last five years or so that those are widely available. So it's just not, I think it's just not as familiar. People don't necessarily know that it's an option and so they don't necessarily go to it as prescribing. But some patients have strong opinions about whether, like some, I do have some patients that say like the tablets taste way better. I like them way better. It's usually, it's a matter of generally how they dissolve in your mouth and how they taste. Some people have a very strong preference for one over the other based on that. So sometimes too, people say, you know, I'm getting nauseous or I hate the taste or it's making my mouth burn. So, okay, well, let's try switching to the different formulation, a different generic, whatever, to see if that's better tolerated. Any other questions? So let's take like a good 15 minute break or so.

buprenorphine

opioid use disorder

detox

mortality rates

pharmacology

side effects

treatment initiation

withdrawal

fentanyl

patient-centered care

long-acting injectable