Thanks for everyone showing up so early in the morning for this day of education. My name is Sarah Spencer. I'm an addiction medicine and family medicine specialist. I've been working in rural Alaska for 15 years. I work on the southern Kenai Peninsula now for tribal health, and I provide teaching and consulting services also for non-profits related to addiction treatment. I also volunteer with our local syringe access program down in Homer. So just to get a sense of kind of who's in the room today here learning, how many folks in the room here are medical providers? Most people. Do we have any nurses in here? Any behavioral health providers? Okay. Other people like administrators or other interested people? Okay, great. Who in here does primary care? Okay. How about hospitalist care? Okay. Emergency room care? Okay, good. Who works with pregnant people? Okay. And youth, adolescents? Okay, great. So that's great because all of those are, you know, it's great that we have a broad audience of folks here today to learn. So this first talk, we're going to talk about the management of chronic opioid prescribing, and we're going to review the updated CDC guidelines, and we're going to talk a little bit about kind of what the evidence is behind using chronic opioids and kind of delve into some of the challenges that we face and strategies when it comes to considering stopping or tapering opioids. I don't have any financial disclosures. Some abbreviations that you might see me or hear me use during this lecture, MOUD, medication for opioid use disorder, so that's going to generally refer to buprenorphine in this, but it also includes the FDA-approved medications of methadone from an OTP or a methadone clinic or naltrexone, which would be Vivitrol. Buprenorphine, there's two major forms we're going to be talking about when it comes to treating opioid use disorder, which is sublingual buprenorphine as well as long-acting injectable buprenorphine. So you might see those abbreviations, also abbreviations for overdose withdrawal and precipitated withdrawal. So we all know that we're here because we're in an overdose crisis, and we have been for over a decade, and it continues to get worse every year, despite what we're trying to do, and we know that one of the key, one of the multiple factors that led to this was the overprescribing of opioids, that along with many other factors that kind of started this wildfire of the opioid epidemic, and we've done quite a good job at reducing opioid prescribing. We've cut back a lot on opioid prescribing, but that hasn't stopped the increase in overdose deaths. So you know, I think it's one important piece, and we're not wanting to kind of continue to fuel the fire, but we also need to help put the fire out, right, with treatment and addressing all the other issues that surround opioid use, misuse, and opioid use disorder. So in 2016, the CDC guidelines for opioid, chronic opioid management came out, and people really were really excited about this, and they really took them up rapidly, but they, in a lot of ways, they were misinterpreted and misapplied, which led to some unintended consequences. So 90 morphine equivalents sort of became the de facto daily dose limit, like you can't prescribe more than that, you got to get everyone down to 90 no matter what. It actually led to like some states actually imposed laws upon like people couldn't prescribe more than that, insurers imposed specific restrictions that you couldn't prescribe more than that, or patients were forced to taper down, and when this really is not what the guidelines said, the guidelines had said to, you know, if you're going to go above 90, that should be justified, and there was no, they did not support abruptly discontinuing or rapidly tapering people off of their opioids. So the 2022 guidelines have made an attempt to try to clarify some of that, and to kind of bring people more to a middle ground when we're thinking about chronic opioid therapy. So we need, some of the guiding principles behind this, we need to make sure we're assessing and treating people's pain, whether that involves opioids or doesn't involve opioids, it's important to assess and treat pain. These are guidelines, they are not regulations, they are intended to support, not supplant individual patient-centered care. They support a multimodal, multidisciplinary approach to pain management, and really caution against misapplying these guidelines beyond its intended use, and also for healthcare systems to be vigilant about health inequities in vulnerable populations. So again, not intended to be inflexible standards, they are intended to provide us information that can help to improve communication between clinicians and patients about the risks and benefits of various pain treatments. So what do the guidelines address? First of all, whether or not you should use opioids for pain. If so, what kind of dosages and formulations should be used? How long should they be prescribed, and how should patients be monitored and follow up in ongoing assessments of the risks and potential harms of opioid use? So we're going to go through not every single recommendation, and not all in order, but most of them, just a general review. So recommendation number one is that we, the evidence shows that non-opioid therapies are at least as effective of opioids for many and most kinds of acute pain. So even in the setting of acute pain, we need to discuss with patients the realistic benefits and known risks of opioid therapy. So there have been a couple of studies that have looked at this, of this is acute pain in the emergency room, and a number of these are looking at fractures and things, significantly painful injuries. These are double-blinded studies, and what we find is that a combination of ibuprofen and acetaminophen is actually twice to three times more effective than 15 milligrams of oxycodone. So we have this, you know, this sense in our mind that opioids are going to work better than anything else for pain, and they are an important tool in acute pain. There's no doubt that they aren't, but we can't underestimate that, you know, many of other non-opioid may actually be more effective than the opioids are for acute pain. There are, I think even when you're prescribing opioids for a short period of time, it is important to educate people about what the risks are with those, and it can be good to have on hand some, like a handout that you give to all patients to kind of prompt you to have this discussion with patients on discharge about the risks associated with opioid use, and this is one of the national ones from the CDC that there's a link that you can go to. And then, if we're going to decide to use opioids, we want to use them for the shortest period of time possible, especially when we're dealing with acute pain, and one of the main reasons for this is that we know that the longer that duration is of the first opioid prescription, the more likelihood that people are going to go on to use opioids chronically. And so, and that risk increases dramatically during, across that first 10 days to two weeks. So we see here at five days, you're looking at, you know, about 10% of people still taking opioids at a year versus 10 days, it goes all the way up to 20%. So those additional days in the initial prescribing really add significant additional risk of, you know, chronic opioid dependence. There's a lot of debate about how many days and how much opioids is enough for post-surgery. There's no consensus on this. This is from John Hopkins. Their expert panel recommendations for the range of oxycodone, the number of oxycodone tablets to consider prescribing for opioid-naive patients after discharge. So it's looking at common surgeries, you know, laparoscopies, orthopedic surgeries, gynecological surgeries, and essentially saying, you know, probably shouldn't be prescribing more than like 20 pills of oxycodone for that initial. You would always do a refill of these medications. But it's, so that's their opinion on what they feel is a reasonable quantity. Next recommendation is before we start an opioid for subacute or chronic pain, again, really sitting down with the patient and having a good discussion about what those risks and benefits are and establishing what the goal is. And the goal should really be focused on the patient's function. So we should identify with the patient, what is it that you're not able to do right now in your life that you want to be able to do if we can improve your symptoms that would improve your quality of life? We're never going to get rid of the patient's pain. We might improve it. It might, it's going to, you're going to have good days and bad days, but the goal is actually not to eliminate their pain. The goal is to improve their function. So we want to identify what their functional goals are and really outline with the patients, these are your functional goals. And so that we can monitor that during the treatment to see, is this medication actually helping you to meet your goals or not? Because if it's not, then it's probably not worth the risk of the medication. And I also really encourage you to check out the VA 2022 guidelines. The VA has a lot of excellent guidelines and resources. They've made huge turnarounds in the way they recommend managing opioids and chronic pain. But they really dig into some stuff that the CDC doesn't to really identifying some of these other really important underlying risk factors for developing opioid use disorder. So starting at an early age, if you start chronic opioid use, the earlier you start it, the more likely someone is to develop an opioid use disorder. People who have a history of substance use disorder, maybe that's a no brainer, but people who have underlying behavioral health conditions. So traumatic brain injury, depression and anxiety, issues, pain catastrophizing. If you want to learn more about that, you can check out the VA guidelines and they have more information about that. But these underlying conditions significantly increase the risk of negative outcomes from opioid prescribing. So that's important to assess that and have a conversation with the patient about that before making that decision to start chronic opioid therapy. And the VA specifically recommends against the initiation of chronic opioid therapy for the management of chronic non-cancer pain. So the CDC doesn't. The CDC says, it's your decision, you know, figure out what's best for that patient. The VA says, we recommend not doing it. So we all know there are many non-narcotic medications for chronic pain. And so depending on the kind of pain, you may choose one or more of these non-narcotic medications to help with management. And essentially all of these medications, none of them work great, but they all work at least as good or better than opioids do to manage chronic pain. And I'm always surprised when I have patients, you know, coming to see me who are wanting to get off their chronic opioid therapy. And when we really dig into a conversation of things that they tried, they actually haven't had an adequate trial of one or more of these, you know, evidence-based treatments for chronic pain. And what works better than medications is non-pharmacological treatments. These work much better than medications do for chronic pain. And this is, it's difficult, of course. The most difficult thing about this is, you know, access to this and availability, affordability of these interventions, especially in Alaskan and rural areas. But we know that these interventions have better outcomes. So this is some, just some consolidated evidence from some review studies, meta-analysis. So looking at the opioids versus placebo, looking at pain and function, long-term and short-term. When we look at opioids versus placebo, in the short-term, we see a small improvement in pain and a small improvement in function. However, there is no evidence that opioids are any better than non-opioids for pain or function, either in the short or long-term. And also, there is no, yeah, even, yeah, anyway, that's all, this is a busy slide. But this is the effectiveness of the non-pharmacological. So we see all the green boxes here, right? The non-pharmacological treatments actually have significantly more evidence that they are effective against pain. And this, a lot of this is about, you know, retraining your neurological symptom, system that the way that we sense pain has been altered and the dysfunction in the neurological system and trying to retrain that through some of these other practices in a way that medicine just can't do. Also, side effects. Opioid treatments have significantly more side effects than non-opioid treatments. So if you look, again, very busy slide, but if you look in the middle, the relative risk, so we're seeing that opioids have, for a lot of these symptoms have like two to three times the rate of side effects from the opioids as you do from the non-opioids. So I think a couple of really important, it's important before you start chronic opioid therapy to talk about what are these side effects and these long-term side effects in particular that people, you know, may not be aware of. So some of the ones I bring up, especially in men, but it happens in women too, endocrine dysfunction. So we're going to get suppression of gonadal suppression. Over half of men who are on chronic opioid therapy will develop hypogonadism. And so you can get sexual dysfunction and other symptoms of low testosterone related to that. That's something, you know, for a lot of men that can be an important side effect that they don't, it's not worth it for them. Hyperalgesia. A significant portion of patients who are on chronic opioid will develop opioid-induced hyperalgesia. We don't know exactly how much. We don't totally understand how that happens, but we know that even single doses of opioids make you more sensitive to pain. Your body is constantly trying to regulate the homeostasis. And so opioids make you more sensitive to pain. So that's important for people to understand before they go into chronic opioid therapy. And there's a significant risk, especially high-dose long-term chronic opioids have a significant risk of developing opioid use disorder. The longer you are on them and the higher the dose, the higher the risk. So when we are choosing a dose, we want to choose the smallest effective dose that is possible. And we want to start with short-acting opioids. And then we're going to continue to monitor during that therapy to see, are they benefiting from this? Is their function improving or not? Are they having side effects or other safety issues that we're concerned about? And if we see that the benefits are not outweighing the risk, then we're going to work with patients to develop a plan to gradually taper them off. Unless there is an eminent life-threatening situation, we are not going to rapidly taper or stop opioids, because that results in worse outcomes than continuing them at the same dose. So rapid discontinuation. So there's been a number of studies. There's more and more the last couple of years looking at bad things that can happen when we stop or taper opioids. So if you rapidly taper someone who's on a high dose. So this study was looking at patients who were on over 120 MME. Rapidly tapering meant less than three weeks of tapering. And half of those people ended up in the hospital because of that. And although up to half of those people ended up with a diagnosis of an SUD, so that could have been why they were stopped or tapered, right? I think you have opioid use disorder. I'm not going to prescribe this to you anymore. Less than 1% of them were then put on the appropriate treatment for OUD. So other inadvertent dangerous things that can happen. There's an increased risk of people then turning to illicit opioids. There is a significant increase in the rate of mental health crises. There's an increase in the risk of overdose. And there is an increase in the risk of suicide. So all of these are dangerous things, bad things that can happen if we rapidly taper or rapidly stop opioids. So even though we can feel really uncomfortable with writing a prescription for these really high doses of opioids, it's also important to remember that not doing so could be significantly more dangerous than writing that prescription. And so we're we're dealing with a patient population in the last five years or so that we didn't didn't see so much before which is opioid refugees. So these are our patients who they've lost their prescriber for whatever reason. They they just moved up from the lower 48, their provider retired, their provider died, their provider lost their DEA maybe, you know whatever happened often of no fault of the patients they have lost their prescriber and they're left with no person to prescribe. And more and more there's a number of studies that look at you know there are many practices that just flat-out say patients call say I need to get a new doctor I'm on this opioid prescription and say no we're not taking patients for that we don't do that here. And patients get turned away over and over and over again. So patients are left abandoned with no place to go which again is a much more dangerous situation than being it finding someone to take over their care and continue it in a safe manner. So when we think of what are the options when we have someone on chronic opioids we have basically five options. First is when we have the feeling you know the patient this is you know this is helping the patient to improve their quality of life and function. They appear to be tolerating it well enough. They're not having intolerable side effects. They're not having kind of untenable levels of safety concerns with this. Then we can just continue the dose that they're on even when it's a high number of MMEs with close monitoring. When patients are particularly complicated we could consider referring them to pain management. But I think it's really important too that we we don't want to overly burden our pain management folks. There are very few of them left now. I think we have like one left on the Kenai Peninsula that that they should you know they're there to help manage the more complex patients. So when you have someone kind of who is not particularly complicated just because they're on a high MME doesn't mean they should automatically go to pain management. You know you should really consider like can I actually manage this person or is it actually too complicated for me to manage and I need the help of a specialist to do that. Second option is a slow taper of the opioid which we're going to do over months to years. A rapid taper is only when there is really eminent danger to that patient. Sometimes the patient that will be patient directed, sometimes the patient wants to do a rapid taper. Generally this is safest when done in an inpatient withdrawal management setting which those are very limited in Alaska of course. They potentially could be done at home with some some selected low risk patients but generally we're not going to recommend rapid papers for most patients. Alternatively if we have a patient who they don't want to or cannot for safety reasons continue their current opioid therapy but they also are not are not tolerating a taper or really aren't on board with stopping or tapering their medications an alternative is switching to buprenorphine for the treatment of chronic pain and we'll talk more a little bit about that at the end. Also buprenorphine can be used for withdrawal management. It's a very excellent drug for withdrawal management. So in the case in those rare cases when for some reason we do need to do a rapid taper typically would recommend using buprenorphine as a withdrawal management medication to taper those patients quickly more comfortably. We really should be reviewing all of these all the appropriate choices with every patient. You know not just saying this is what you're going to do we need to have the patient on board and helping to develop this plan. The VA has some really nice resources about how to communicate with patients and have these conversations and how to kind of guide this process of the taper. So most important is this has to be shared decision-making. We need to if you haven't taken a motivational interviewing course before I highly recommend that you take that it's useful in every part of your job in medicine. You know motivational interviewing is asking the right questions to help the person identify within themselves their own motivations for change. Because when that motivation comes within yourself that is when you're going to be more successful and more more on board with that. So trying to help the patient identify you know what are the benefits that you're experiencing from this? What are your fears? What are the risks or dangers that you're worried about? And you know engaging them and that conversation not just telling them about you know what your concerns are. And we want to make sure that we are validating their experiencing that we're not we're not judging them. We need to be be flexible and understand this is a highly emotional and highly anxiety-provoking discussion for patients. And it's something that we do not want to be rushing into. We want to take the time to really develop a plan that is right for this patient and that they're that they're on board with. We're gonna get their buy-in. It could take months to develop this plan of you know what what do you feel is the best taper that you want to do of gradually preparing patients for what this is going to be like and all the support that you're going to provide for them. What other issues do they have in their life that they may need extra outside support for and allowing the patient to help you choose how quickly we're going to taper off of them. And ideally we should be we should be tapering opioids slowly enough the patients are not experiencing withdrawal symptoms. But occasionally you know we think you know we've chosen a good reduction a small reduction maybe 10% but the patient still may experience some withdrawal symptoms in the first few days that we that we change those. So making sure that people have comfort medications on hand unless there are contraindications so that just in case you do get these symptoms they're probably only going to be for a few days and these medications can help you to manage those symptoms. Clonidine is one I give to pretty much everyone. So a taper typically a taper is going to involve like about a 5 to 10 percent reduction per month. You may be the very first month you could maybe get away with a 20% reduction but the farther into the taper you go the smaller the reduction is going to be and it slows down till you gradually can gradually stop. And it can take a long time that I think the the last time I did this with a patient who was on oxycodone I think it took 18 months for him to taper off. And at the end of it when he got on the other side it was it was not fun for him despite it being slow but when he got on the other side he was very grateful for it and his pain was no worse than it had been before. We really want to avoid any tapers that are making dose reductions of greater than 20%. And also being able to pause the taper is important. So if you make a step down and the patient is struggling with that, pausing and just waiting until they feel comfortable before you make the next step. So even though your initial plan with might have been with the patient is every month we're going to go down by 10%. If you hit a particularly difficult month maybe the person has something very stressful happen in their life and I say okay let's just pause here we'll stay at this dose for another month and then we'll then we'll you know restart the taper again next month. We don't ideally we don't ever want to go backwards but we want to keep moving forwards but we can we can have some pauses in there and that that is you know a patient-centered way to approach that. We want to continually reassess chronic opioid therapy while we are prescribing it especially in those first couple of months because this is the time where we're really going to assess like is this improving your function or not the risks and the and if there if we find that there are issues coming up early in treatment it's the sooner the the less time you're on the opioids the easier it is to stop them. So we want to have really frequent follow-up you know we're gonna write short prescriptions for a week at a time two weeks at a time we're not just gonna just we said okay yes we're gonna put you on chronic opioid therapy here's a month prescription see you later and you know call me for a refill. Definitely don't want to do that we want to really closely monitor these people to make sure that the medication is actually helping them to meet their goals in a safe manner. So when we're reassessing the patient we want to specifically address their functional goals. Sometimes we need to reassess those goals sometimes maybe they weren't realistic expectations or their life has changed in some way that we need to set new goals. We're gonna look for issues with breakthrough pain and how to address that when it happens and address the known side effects like constipation, screening for endocrine dysfunction, and if people are are developing tolerance considering rotating the opioid to reduce that. Our understanding of the way that opioids act in the body has been changing over time so initially our understanding is you know this hey this this opioid it binds to the mu receptor and it gives us pain relief and that that was good enough but then what we realize is that you know the there's a reason we have these endogenous opioid receptors right it's not because someday someday we were gonna you know create heroin and oxycodone for these to bind to it's because we have endogenous opioids endogenous chemicals that bind to these sites that help us in our survival. So the what we realize is that you know when humans experience stress and that can be pain or it can be emotional stress that triggers their body to release some of these natural endorphins that bind to the opioid receptors and provide that relief from that stress they provide analgesia and they provide emotional stress relief and that's critical in our survival and that helps us to do difficult things it helps us to to survive and that's why we have this endogenous opioids and so it's important to understand that that the system is part of our innate survival system that's really deeply ingrained in our brain and that the opioids are not just physical painkillers they're also psychological pain relievers and stress modulators. Also it's important to understand that our body is constantly trying to achieve homeostasis so if you dump tons of opioids or alcohol or whatever is into the system especially with chronic use your body is constantly trying to compensate by down regulating or up regulating receptors dumping other kinds of neurochemicals in there that are going to counterbalance that effect. So there's the initial process when you take an opioid of having the positive response the improved mood that the pain relief and initially when you first start taking opioids this is kind of the predominant state the patients are experiencing but then as the medication wears off we shift into a hedonically negative state which is worsening pain, worsening anxiety, worsening mood. And as this this changes over time so this is kind of the the when you give someone a dose of opioids we get this initial analgesia boost in mood and or euphoria that then wears off but you have this underlying opponent process of your body working to try to counterbalance the effect of the opioids which ends up that you end up with this biphasic response where you feel good and then you feel worse after it wears off and the longer you were on that the less good you feel and the less good effect you get from the opioids and the stronger and more prolonged the negative effect is. So this it's not just pain relief that when people are wanting to continue taking their opioids it's not just because they're getting some pain relief it's because they're getting relief of this negative state the state where you have increased pain you have increased anxiety just anhedonia. Hyperkatifeia is the term you'll see in addiction medicine just just general negative yucky affect that you just feel like crap. So the longer you're on it the more that that that you know we have this negative reinforcement and that you're taking the opioids to relieve the the bad feelings that you have that are actually triggered by the the inter dose withdrawal between doses of the opioids. So opioid induced hyperalgesia kind of ties in with this and we don't completely understand why this happens but it's a significant portion especially especially at people who are high MMEs for a longer period of time and essentially this is folks that their pain seems to worsen over time when they're on the opioids it seems when you increase the dose it doesn't really help to reduce the pain they continue to have severe pain and then the pain starts to change in character it starts to become more diffuse they just kind of hurt all over they become more and more sensitive to pain from non-noxious stimuli and you know that this is really a dysfunction of the neurological system that has happened because of the because of the presence of opioids. So again what works for chronic pain is non-pharmacological interventions work better than anything else. The if you're interested in this I encourage you to check out pain reprocessing therapy so that you know it's it's basically training the brain to learn to live around the pain to it's you know that rather than trying to shrink the pain down and get rid of the pain we're trying to expand our lives to learn to live and work around the pain and despite the pain and to train our brain to think differently about the way we think about pain and this really addresses some of that pain catastrophizing the anxiety and depression that comes around pain helping people to learn how to live their lives despite the fact that they are experiencing chronic pain and these are a couple of very good kind of evidence-based self-help and workbooks that patients can access that can that can help them with this. And when we reduce opioids in general we see a significant improvement in pain for most people. And lastly the CDC guidelines really which they didn't address in 2016 is that if you do identify a patient that does have an opioid use disorder then what we should be doing is getting them on treatment for that opioid use disorder. We should not just be stopping their opioids and discharging from care that's just causing more harm than good. So we need to make sure that we're getting people on evidence-based medications and generally that's going to be buprenorphine or if you live in a city in Alaska perhaps methadone. But the other thing this guidelines make clear is that even without a diagnosis of opioid use disorder transitioning to buprenorphine for pain can also be considered because it reduces the risks associated with full opioid agonist. So the CDC guidelines both in guideline 5 and in guideline 12 say that in patients you know who are at high risk and they need to taper but they can't for whatever reason that we should consider switching those people over to buprenorphine because it's a safer medication. And the VA guidelines specifically say again they said don't use chronic opioids but they said if you do decide to use chronic opioids you should use buprenorphine as your opioid of choice. It's a partial opioid it's not a full opioid because it is safer and in less risk of developing misuse with that medication. So we can really think of buprenorphine for pain as a form of risk reduction or harm reduction. I don't advocate starting patients on chronic opioids for chronic pain but when you have someone who's already on high doses of opioids and they have a lot of risk factors maybe they have a lot of comorbidities like cardiac or pulmonary comorbidities, their age for whatever reason, their other mental health issues that they have going on. If we can switch these folks to buprenorphine we can reduce many of the opioid related risks to their health. So what kind of patients would you consider switching from chronic full opioid agonists to buprenorphine? So folks that when they're trying to do a taper but they just can't stand it. Even when they're making small reductions they're just miserable, they're experiencing withdrawal symptoms or intractable pain and they just can't manage to tolerate an opioid taper or they don't want to. They don't want to taper, they have no interest in tapering. You can't get them on board. The folks who have significant high risk of morbidity or mortality and this can be also due to polypharmacy, right? Maybe they're on benzodiazepines, maybe they're on gabapenoids, and maybe they drink alcohol and they have all these other issues going on. So we can reduce those risks from the comorbidities. Perhaps patients with opioid induced hyperalgesia. There's evidence that switching to buprenorphine can improve pain control for these folks. Also people who may be having other side effects from their chronic opioid therapy, the buprenorphine may cause less side effects. And of course patients with opioid use disorder, which we'll talk about in the next presentation. So buprenorphine, it's a really unique and unusual medication. So it works differently than other opioids at numerous different receptors. So at the mu receptor, it's a partial agonist with a very high binding affinity. So it binds to that mu receptor and it binds very very tightly. And it binds so tightly that at high, it's dose dependent, but at high doses of it, it blocks other opioids from binding to those receptor sites because it binds so tightly to those receptor sites. And it has a very long half-life, so it stays there for a very long time blocking those receptor sites. But it only partially activates. It's only a partial agonist, so it only turns the receptor on a little bit. It doesn't turn it on the whole way. And that's what really makes it much safer in that it doesn't activate the receptor enough to cause dangerous issues like respiratory depression. Also it has very different effects than some of the other opioid receptors that we don't really know or think that much about. So there are delta and kappa receptors. It's actually an antagonist at these receptors, so it's blocking and stopping these receptors from being activated. That reduces side effects. It also reduces abuse risk and it also has a mild antidepressant effect because of the blocking the Kappa receptor. Opioids tend to have a depressive effect. They can cause depression versus buprenorphine tends to have a mild antidepressant effect because it works opposite way on the Kappa receptor. Also, there's another receptor called the NOP receptor and it just has very low affinity to this receptor which also tends to reduce the development of tolerance against this medication and misuse. And although buprenorphine has a sealing effect in that you can give lots and lots of it and people won't stop breathing, there is actually no documented sealing effect for buprenorphine for analgesia. So we can give high doses of it to get the pain under control without having to worry about suppressing respirations. And that's in adults. Very tiny children because of their blood-brain barrier and other issues, that's not necessarily true, but in adults that is true. So this is just a study kind of looking at this. So when we look at the effect on respiration, we see that there's no change between the doses versus the pain control. We get twice as much pain control on the double, the dose that's twice as high. Is buprenorphine effective for chronic pain? Essentially, there's not a ton of studies on this, but the studies that are looking at it say that it's at least as effective or more effective than other chronic opioids are for chronic pain. So that's something that can be helpful to share with patients. It's very anxiety-provoking, the thought of switching to a new medication, especially when patients consult Dr. Google and they find out that, oh, this is a medication used for addiction. So you're saying that I'm an addict, right? Things, you know, very stigmatizing. There's stigma, a lot of stigma around this medication. So really talking to patients about this patient was originally in this medication was invented as a pain medication. When we, this medication was invented in the 70s, I think it was, it was invented as a pain medication. It was used IV in the hospital as a pain medication. It was not until later in the 80s and 90s that we started to realize that it has this usefulness to treat addiction, but it's a very effective and potent, you know, pain medication as well, especially for, you know, short-term. So a number of studies kind of look at this. This is a study looking at very low-dose buprenorphine, which is transdermal buprenorphine or the patch butrans. That shows, you know, roughly equivalent, maybe a little bit less reduction in pain intensity compared to our other typical forms of buprenorphine. And we see that the buccal, which is slightly higher dose, seems to not surprisingly work better than the transdermal, which is the lower dose. A higher dose of buprenorphine can be achieved with sublingual buprenorphine. So this is a really interesting study that looked at patients on very high doses. So the average was 550 mMe for these patients. Switched to sublingual buprenorphine, dose average of 8 milligrams of sublingual buprenorphine followed for six months. And what we saw is that patients, on average, they had dramatic reduction in their level of pain, you know, by up to half of the pain that they had been experiencing before. And that was true of regardless of how much, how high their mMe was. It also was true regardless of how severe their pain was before they started it, whether they were at a 0 to 7 or an 8 out of 10 pain. Kind of across the board, people had improvement in their pain when they switched from their high dose full agonist to their buprenorphine. Also, less side effects. This is looking at buccal buprenorphine, which is the medium-low dose of buprenorphine, has significantly less side effects than your typical opioid agonist that you're going to be seeing. I think constipation is much more common. It's a very low—buccal buprenorphine is a very low dose of buprenorphine, so it would make sense that it has significantly less side effects. There are two formulations of buprenorphine that are approved, FDA approved, for the treatment of chronic pain. So, the one that you'll probably see the most often is the transdermal, which is Butrans. These are both currently only available still in the brand name formulations. So, the transdermal, the Butrans, is intended to use—they have these tables and the prescribing information to calculate the dose switchover, essentially meant for patients who are on 80 MMEs or less. But although it says that in the prescribing information, it also says that you should taper patients down to below 40 for the week before you start this, which is obviously can be very difficult for patients. So, I kind of tend to think about this as people, you know, maybe in the in-between of like 50 to 80 MMEs, maybe. It might be strong, it might not be. So, you could consider that for patients who want to make that switchover who are on—or you're going to be starting patients who are on less than 80 MME. The Belbucca, which is the buccal film, has significantly higher doses, but it's still a low dose of buprenorphine. That could be considered in patients up to 160 MMEs. This formulation—I haven't personally seen an insurance that covered this medication, but it could potentially, especially with private insurance with some prior authorizations, could potentially be covered for some patients. So, it's worth looking into and checking out. These are very—both of these formulations are much more expensive than sublingual buprenorphine, but if you have patients who have lower levels of tolerance and lower MME requirements, then these are a good kind of first go-to because they are the FDA-approved formulations to treat chronic pain. And when we look at the serum drug levels, comparing some different formulations and the serum drug levels, this is looking at the 10 mg butrans patch. So, that's kind of the medium dose of the butrans patch. And we see that we're having a peak serum drug level of about 0.2 nmg per mL. The average is probably more around 0.1, 0.15 from that medication. And that is in comparison to, if we look at 8 mg sublingual, we're looking at a 1.2, so from 0.2 to 1.2 serum drug level. And then with 24 mg, we're getting about 3 nmg per mL. There's also monthly injectable formulations that are used mainly to treat addiction, and that can get you up to 6 nmg per mL. So, it's important to understand that these formulations are going to result in very different serum drug levels. So, when we think about comparing these formulations—so, this is kind of the maximum dose that you can get with each of these medications here. And the price is dramatically different, you know, especially if you have a patient who, for some reason, has to pay cash for the medication, or they have very expensive co-pays, you know, maybe they have Medicare and they have a big co-pay. You can get generic buprenorphine for as little as $100 a month. I mean, it's dose-dependent. It depends how many tablets people are needing in a month, but that is significantly cheaper than, you know, the $1,000-plus that we're looking at for these brand-name, FDA-approved formulations of buprenorphine. I particularly like the sublingual films because, in general, they kind of dissolve faster in the mouth. You can cut them into little pieces very easily with scissors versus the tablets. They're dissolvable tablets, so they can kind of crumble a little bit when you try to cut them. They have naloxone in them, which is an abuse deterrent, and we'll talk more about that in the next lecture. So, they have an inherent abuse deterrent formulation, which is nice. They are the most widely available and generic. They come in many different dose sizes, and they're really easy to count and transport. They're like individually-wrapped films, so it's easy to kind of keep one in your purse. It's easy to count them, just all that kinds of things, rather than dealing with loose tablets. So, it's important to understand that it is completely legal to prescribe sublingual buprenorphine to manage pain. We prescribe medications off-label all of the time, right? We prescribe trazodone for insomnia. That's off-label, right? There's so many medications, you know, gabapentin for different forms of pain that's off-label. So, yes, it's off-label. That's 100% legal to do. The issue comes up with insurance coverage. That is where we hit a bump sometimes. It's getting better and better, but still we have a bump. So, it's important to look in to see what is covered by the patient's insurance first before we're writing any prescription and rushing into a plan. Butrans, for example, is covered by Alaska Medicaid. I haven't run in very few. Medicare tends not to cover either of these, but, you know, you never know. It doesn't hurt to ask. So, looking in to see, you know, what is covered by the patient's insurance because if these formulations are not covered, a patient is not going to be able to afford to take these clearly. And especially also, too, if you do have someone who's over, you know, 100 MMEs, then they may not get adequate relief. These lower doses with the FDA-approved formulations may not be adequate to treat their level of opioid tolerance that they have. So, I can tell you from my experience is that I've had very good success with getting prior authorizations approved when they are initially denied, you know, prescribing sublingual buprenorphine for pain. So, essentially, you know, writing out a brief letter that states that this person is on this high MME, they're having these side effects, they have these comorbidities, they are unable or unwilling to tolerate a taper of their opioids and switching to buprenorphine is going to clearly reduce their overdose risk. And then you can cite in there the VA and the CDC guidelines and even quote them that specifically say that we are supposed to do this. And I, in like the last five years, I don't think I've had one denied, actually, because of that. I think they've all been approved. So, we all hate doing PAs, but it can get approved. Very last-ditch effort is for certain formulations, especially if patients are looking for long-acting injectable formulations of buprenorphine. Sometimes, no matter what you say with the insurance, they will not cover buprenorphine for chronic pain. They only cover it for opioid dependence or opioid use disorder. So, I've had a very few select patients in which I prescribed to them under the diagnosis of opioid dependence with withdrawal and specifically changed the wording in our EMR to cite that they are physiologic only and they do not have opioid use disorder. And then, you know, all insurances cover buprenorphine for opioid use disorder. That's 100%. There's no insurances that don't cover buprenorphine for opioid use disorder. So, but the danger in this is that even though, yes, that person is physically dependent on opioids, they have a physical opioid dependence, we're trying to taper them. They're experiencing withdrawal. They're not tolerating that. So, that opioid dependence with withdrawal, that is an accurate description of what's going on. Unfortunately, when that information leaves your office, right, it goes to the health information exchange. The emergency room sees it. It goes to records someplace else. That can be misinterpreted as the patient has opioid use disorder, and that is very stigmatizing to that patient. And they could be treated in ways that are very inappropriate because of the ongoing stigma around opioid use disorder. So, I would never put this diagnosis in a patient's chart without their explicit approval of what the ramifications might be with their records get transferred or accessed by an outside provider for this. Now, calculating the dose, this is the trickiest part. Calculating the dose of sublingual buprenorphine when you're transitioning from someone from their full opioid agonist. So, first of all, there is no MME conversion for buprenorphine. It does not exist because similar to methadone, worse than methadone actually, it's not a linear metabolism. It's like kind of logarithmic or exponential. And so, there is no calculator in which you can put in, okay, this person's on this MME. How much buprenorphine should I give them? There are those tables in the two in the Butrans and the Bellbacca. They do have those tables. So, if you're going to prescribe, if your insurance covers one of those medications, if they're within that appropriate dosing range, then great. Start there and just follow the directions in the package of, you know, what dose that you should put them on. However, if their insurance doesn't cover it or they're too high of an MME to be able to take those FDA approved ones, then you're just going to have to make your best guess. And there is no way to know exactly how much the patient is going to need. It's very patient specific. So, this comes into the planning portion that we're not going to rush into this. We're going to plan this very specifically for a time when both the provider and the patient are able to closely monitor this over the course of, you know, the three to five days that you're getting onto this medication and figuring out what the right dose is and not just, you know, give them a week's supply and say, here, try this, you know. So, we're going to, when we first start out, we're going to start with the low dose, the small films. So, they come in two milligrams. We're going to start with that and they can cut those into little pieces. They can take a little bit at a time, but only give them one to two days and you're going to plan to have a follow-up. That can be by telemedicine. It doesn't need to be in person, but then to follow up with them the next day or two days, you know, maybe two or three times that week, scheduling ahead of time so that you can troubleshoot and say, okay, this is, you know, this clearly, this dose isn't high enough. We need to switch to the eight milligram films or, you know, you don't want someone to be stuck with a medication that's not working and then they're experiencing withdrawal and then they're stuck with it for a whole week because you can't do an early refill, right, because you underestimated the dose. So, this is where the planning ahead comes in so that you and the patient are both going to be available. We start this on a Monday. We're never going to start this on a Friday to make sure that they aren't having any uncontrolled symptoms during this time. We want to make the switchover gentle and comfortable as possible. And when we're switching people over for pain, there's two main options for starting buprenorphine and we're going to go into these in the next two lectures. The traditional way to start buprenorphine is that you stop taking your fallopioid agonists and then you wait about 12 to 24 hours, longer if it's something like methadone, until the person starts to feel withdrawal symptoms. We want a moderate amount of withdrawal symptoms and then you start taking your buprenorphine. So, that's the traditional way to do that. That can be very scary for some people. Some people have never experienced withdrawal before. They've been taking their medications as prescribed. Some people have and it was very traumatizing for them and they don't want to experience that again. So, an alternative to this, which we'll talk about in the hospital lecture, is a low dose overlapping start, where the patient actually continues to take their fallopioid agonists as you start taking the buprenorphine but at a very low tiny baby dose starting at a half a milligram and titrate the buprenorphine up and then once you get to your goal in the buprenorphine, then you stop taking the other fallopioid agonists. So, and we'll go into the details of that in a little bit. All right. So, that's the end of the first show. So, I'll stop there and see if people want to ask some questions or have any discussions about that. I just want to remind everyone that we are recording this. I believe it becomes available on your guys' Opioid Response Network site. So, your questions will be recorded. Yeah. Mom, do you ever use a combination of the patch and the film? Well, generally, no. I mean, I've seen that happen in a few patients before from other prescribers, but just remember, like, the patch at the very highest dose is going to be, like, less than a half a milligram a day of buprenorphine, of sublingual buprenorphine, if you do the 20-microgram patch. And so, and a half a milligram of buprenorphine is a quarter of a two-milligram strip. So, they're very different doses. So, it's not impossible, but, like, if you're going to have someone say, okay, this is your baseline, is you have one 20-microgram patch on for the week, and then you're going to give, like, breakthrough sublingual, that breakthrough dose is going to be equal to your entire daily dose in one breakthrough dose. So, it's not, it's not dangerous. There's nothing dangerous or unsafe about that. It's fine, but it's just, you just have to be aware of how very different those doses are, you know, when you're, when you're, and the risk of side effects when you give someone a much higher dose of medication than they're used to taking. You know, so, let's say they took a whole film. They took two milligrams. So, that's four times their daily dose from that they would get from the patch. It's not unsafe, but it can cause unpleasant side effects. So, it can cause the person to feel over-medicated. They feel drowsy. They feel dizzy. They feel intoxicated. And nausea is a big one. Like, it can cause a lot of nausea. So, really just understanding what the equivalency is with those medications so that you don't inadvertently cause, like, adverse medication side effects because they don't have the tolerance to the higher doses of medication. Has there been any studies on, especially for clients that are off the road system and they can't get physical therapy, they can't do acupuncture and massage, that anyone has offered to give them a massage chair to mail out to their house in the village or something for the benefit, you know, of not even needing the medicine? Yeah. You know, I don't know very much about the, like, current approaches to try to increase access to kind of the non-pharmacological treatments in rural areas, but that's, it's very important because that's the issue that we deal with in a lot of these, the remote areas, is that there just isn't access to any of these, you know, even the behavioral health support, you know, even via telemedicine. We have so few behavioral health specialists that are actually trained in therapy for chronic pain that even when you have telemedicine, it's hard to access those. So, I'm not aware of any particular efforts that are ongoing at the moment or previously to try to do that, but that's very important because that's one of the hugest barriers that people face is that we know that these work, but they're not available to people or accessible to people. So, yeah. Any other questions? Okay.

Dr. Sarah Spencer

addiction medicine

family medicine

chronic opioid prescribing

CDC guidelines

multimodal approach

buprenorphine

patient-centered care

non-pharmacological interventions