Hi, I'm Dr. Steve Wyatt, and I'm an addiction psychiatrist practicing in Charlotte, North Carolina. I'm a University of North Carolina adjunct faculty member. I'm going to talk to you today about pain and addiction, and we're going to be focusing on considerations on safer prescribing and pain management in patients that have a diagnosed opiate use disorder. This is part of the American Osteopathic Academy of Addiction Medicine Essentials in Addiction Medicine course, and I welcome you all. I have no disclosures. I don't talk for any pharmaceutical companies or have any major or any pharmaceutical investments. I am a co-director of the Provider Clinical Support System for Medication-Assisted Treatment, which is a SAMHSA grant, and do receive some compensation for that. So today, we're going to talk about consideration of opioid safe prescribing and alternatives to pain management with chronic long-term opioid therapies. We're going to look at assessing risks and addressing harms of opioid use, and then talk through and hopefully, at the end, you'll understand the options for treating the opioid-dependent patient that has co-occurring pain. So I thought I'd start off with this rather dramatic case patient that I took care of a few years ago. He was a 57-year-old male with a past history of an alcohol use disorder and had a injury that resulted in a hip replacement at 25 years old. It was a motor vehicle accident. And then at 32 years old, he was pulling a canoe out of a lake and had a back injury, and that was the onset of his chronic use of opioids. He had had them during the hip replacement, but it had been off him for a few years prior to this accident. Since that time, he had remained on disability. He had been hospitalized in November, about three years prior to my having taken care of him with a clonazepam overdose. And when I saw him a number of years later, he was taking acetaminophen, 500 milligrams, and hydrocodone, 5 milligrams, vicodin. He was taking seven, six times a day. So a lot of short-acting opioid. And I suggested to his psychiatrist that was taking care of him at the time and prescribing these medications that he possibly at least would be converted to a long-acting opioid and suggested to her at the time that I'd be willing to see him and see if we could do, manage it in a different way that could potentially be more safe. Because he also was still taking clonazepam. So a few months later, he came back and saw me, and this was for consultation because now he was on oxycodone long-acting, the brand name was OxyContin, 60 milligrams, 5 of those, so 300 milligrams, four times a day, really a tremendous amount of opioid. And so now I'm going to go into what things we could be thinking about with a patient like this, and then we'll talk about him a little bit at the end. So pain is hugely prevalent in our population in the US, really throughout the world. There's an estimate that 11% to 40% of people will have some form of chronic pain. And about 1 in 10 Americans report having persistent pain of at least a one-year duration in their lifetimes. And 1 in 5 individuals 65 years and older report pain persisting more than 24 hours in any given month. So 6 to 10 report persistent pain over a year, and they have some area of discomfort, not necessarily severe enough to need an opioid. High-risk groups are those that are living in poverty, have less than a high school education, and with public health insurance. The cost to the US economy, and this was a few years ago, is approximately $100 billion a year in pain management alone. So there have been a variety of things that have happened, and many of you have probably heard these, and I'm not going to spend a lot of time on this, but I think it's important to put it in perspective. Reasons why opioids became sort of the mainstay for the treatment of pain, and that's quite obvious, but why it rose to the prevalence that it did in the 90s and continued into the early 2000s and created the problems that we're faced with today. Chronic pain was one of the most common reasons, again, for seeking medical care, and about 20% of the population have been significantly affected by chronic nonmalignant pain, so that's non-cancer pain. And a successful initiative to address cancer pain had inspired the efforts to say, wait, we've been able to manage chronic cancer pain or cancer pain quite effectively with opioids, why not non-cancer pains? And based on the belief that non-cancer pain deserved pain relief as much as those with cancer, and sustained pain relief is possible with stable doses of opioids. There was also some publications during the time that indicated that people with pain and were prescribed opioids had less of a potential for developing addiction. So in 2001, the Joint Commission put out a dictum that all hospital and hospital-related settings, so clinics that were related to a hospital, needed to install quality standards on pain identification. So everyone had to have a pain assessment, and if it reached a 4 on a 1 through 10 scale, then there had to be something in the assessment or the treatment plan of the patient that would discuss treatment of that pain. And the easiest thing was to go ahead and prescribe an opioid. So consequently, we had a huge increase in the number of opioids being prescribed over those years, those early years. And this then contributed significantly to the overdose problems that we then were confronted with and the increase in opioid use problems. This has not necessarily improved dramatically, but it's definitely stabilized, and there's been certainly some reduction in the number of opioids that are being prescribed in a variety of settings now. But this is information that was made available through the Substance Abuse and Mental Health Service Administration in 2019, and it's indicating that we still have 9.7 million people that are prescribed pain medications and are using it in patterns that are misuse. And essentially, the definition of misuse is to use it for anything other than a bona fide, excuse me, anything other than how it was prescribed. So if you sprained your ankle and you had been given a prescription for oxycodone and then took three or four of them, got you through that, didn't throw them away, put them in your medicine cabinet, and then took them again for a headache two months later, that's misuse of the medication. Controlled substances are prescribed for a particular problem, and if they're used for anything else, it's misuse of the medication. The other would obviously be taking them in larger amounts than were prescribed, giving them away, those sorts of things. Now giving them away, giving them even to a family member, is actually illegal. So that's actually giving a narcotic to someone, and it's not legal to do that. And heroin use didn't dramatically increase during this period of time, but the combination of prescription medications and heroin use did increase. What we also know is that the majority of the misuse, and this is information up until 2014, and it hasn't changed significantly, is that people were getting these opioids. So this was non-medical use of opioids, was being given by a friend or relative for free, typically just prescribed by one doctor. So one doctor is giving a patient medications and they're misusing them. And then, so that's the opaque tan color there, is friends or family. One doctor is 22%, and that makes up nearly three quarters of this population. The rest are bought, taken, so bought or stolen, and or going to doctor shopping, which we think about as being a big deal, but as you see, it's a pretty small group. And in the other is actually some of the internet buying of these medications. So also not the huge part. The huge part is potentially having some extra and giving them away, a kid getting a hold of them and giving them away, those sorts of things. So let's talk about pain again for just a moment. We have sort of a progression of pain from the transducer in the peripheral parts of our body. And this is stimulated by either noxious thermal, mechanical, or chemical stimuli. So it's something happens, we have an exposure to something toxic, and we have a stimulation of the receptor. And this is nososeptic neurons. Then there's transmission of the nerve impulse. So after that stimulation, transmission via axons of afferent neurons from the periphery to the spinal cord, to the medial and ventral basal thalamus, sort of the operator of the brain, you know, sending, getting a signal and then routing it to the right areas. And the cerebral cortex, you know, it includes the cerebral cortex in that we're able to actually consciously be aware of the pain. And then that is, again, partly cortical, but it's partly limbic in that particularly how long it's there. We begin to interpret the pain differently. We begin to either understand it as a noxious stimuli or just disruptive to our lives. So it starts to affect our mood and anxiety. And we begin to talk about, you know, even painful emotions. It's how we begin to view pain. And the other important thing to understand is that we can modulate the pain. Modulation really starts in perception, that is, how we are interpreting the pain or dealing with the pain. And I'm going to show you a little bit more of this on the next slide. But then there's modulation that has to do with as the pain is there, as we continue to experience it, we begin to be able to interpret it differently. And we can actually downregulate the pain over time. So that's something that then we, you know, we've all heard, living with the pain. I can live with it. It's there. Whereas if, and typically at the time of initiation of the pain, it was overwhelming. And that's really the difference of it. So we can have this huge reaction to pain initially and then kind of shake it off. Or even if it's rather severe, we can begin to alter our behavior in a way that we can live with it more successfully. So once the pain feedback system identifies the pain's no longer indicating a worsening problem, and in some ways this is the difference between cancer pain and non-cancer pain. Now that's solid tumor cancer pain, where a tumor continues to grow and it's putting pressure on more and more tissues. So new tissues are being stimulated. And that pain is overwhelming because we just, you can't get a handle on it. You can't modulate that pain well. So as the problem, the feedback mechanism modulates the response. If it's now stabilized, the pain's not getting worse necessarily. Pain is isolated and suffering's reduced. That's a natural way in which our brains effectively interpret and are able to live with pain. This can also occur through perception of pain by cognition and conditioning. So a famous one, and it's been written about extensively, this quote is from 1816, but there's been a variety of things written about it since then. The war surgeon explained the absence of pain is due to the men's great excitement. That is agitation, elation, enthusiasm, ideologic fervor, states of mind, diminished suffering. In quotes, the drumming of the dervish dance, the whirling dervisher, this hypnotic state of the deafening sounds of battle. So rather poetic. But if you think about it, look at the pain that NFL football players experience every Sunday. And they get up and they run right on and do something more. Most of us. If it happened just, we're walking down the street and someone hit us like that, it would be overwhelming and we would take the next week off from being hit so hard. So it has to do in many ways with our preparation, our excitement, our understanding that, yeah, there's going to be some pain involved in this, but it's what I want to do, it's fun. And medications, however, can either augment these adaptations or disrupt them. So they can actually make it worse and they can disrupt this modulation by not allowing for normal sort of modulation to take place because we put an opioid in its place or we haven't allowed for that normal ability to begin to adapt to the pain. And it is normal, obviously, I'm going to talk about how we can overdo this too. So there's clearly a value to pain and that's why we have this allosteric response to pain that if there's no pain, if we've numbed ourselves to pain, eventually, and this is hyperalgesia, there will be an augmenting, a greater sensitivity through cytokine initiation changes in the periphery. So we become more stimulated and consequently, the more opioid we add, the potentially worse that hyperalgesia can become. But because we need to experience pain, we need to be able to get our hand off the hot plate if we put it on there or correct our stance immediately if we step off a curb wrong. And then if we have a problem like a bad back or a sprained ankle, then we're going to know what we can do and what we can't do that's going to aggravate that pain and allow whatever the problem was to heal. At the same time, pain is an overwhelming problem, pain, chronic pain. It results in us avoiding certain behaviors. We have then, because of decreased mobility, altered function, we're not doing things that we used to enjoy doing or that we really want to do, which then begins to diminish our self-efficacy and limit social interactions resulting in social limitations. That sort of mood and that sort of stance can then make pain even worse. When we get into this vicious cycle, a lot of anxiety can be associated with it. And that's where benzodiazepines often get added to this regimen. And that also can make the problem much worse because now we're adding a benzodiazepine to an opioid medication, which I'll also talk about in a few minutes. So those patients that have the least ability to actually be able to modulate the pain well and consequently put them at risk of misusing their opioids or potentially even becoming opioid dependent are people that have already attempted to control their environment through a drug. And that can be alcohol, it can be marijuana, it can be any drug, even nicotine or particularly tobacco use. So they're already at risk of, let's control it with a chemical. I don't want to sit with this adversity. And that can be, you know, it's not, it can be people that have had emotional trauma that led to their initial substance use. It can be children that have had multiple adverse childhood experiences, you know, physical, emotional, sexual abuse, or neglect. Certainly young people that are from families that have been, that are dysfunctional or there's heavy alcohol or drug use going on. Those are children that often have had ACEs and again, have not developed coping skills, haven't been able to have that nurturing that says they fall down and they cry, they get on, you know, mom or dad's lap, guardian's lap, they're soothed, they talk them through it and they begin to recognize it's going to be okay. I can have adverse events take place in my life and I can persevere. More dependent traits in individuals can result in these problems and changes in hedonic tone, that is, which can come from alcohol and drug use, chronic use, where the ability to find joy in things has been reduced. So they're in sort of a, not necessarily dependent, excuse me, depressed state, but just not enjoying life and then some adversity happens and it just makes it much worse. So the evidence of efficacy of opioids has been, has been challenged in some way. So most, mostly literature surveys is the literature that we have on this. Most of it is literature surveys and uncontrolled case studies, randomized control trials of short duration, typically eight months or less with small samples, fewer than 300 patients, mostly pharmaceutical companies sponsored and pain relief is often modest, better analgesia with opioids versus control in all those studies. And that's statistically significant, but again, not large groups and not typically randomized control and not for longer than eight months. So there's mixed reports on function and that is one of the things that's come out of some of the chronic trials where there's been some reduction, some inability to actually get people back to work or actually get them back to the level of functioning prior to starting the opioids. And this is often in people that it's not, there's not a clear disability in terms of their, of their function secondary to the injury. And most of these studies, addiction was not assessed. A Cochran review of this looked at 26 different studies longer than six months and 25 studies were case studies or uncontrolled long-term trial continuations. And many patients discontinued due to adverse effects and or insufficient pain relief. But some evidence suggested that patients who continued opioids experienced long-term pain relief. They did have improvement in their pain, but it was very unclear as to how, how, how much increase in function there was, particularly in that there was a, you know, essentially a 33% dropout rate. The other that I mentioned earlier that the other complication that has really caused a significant part of the overdose rate of the use of opioids in, in this country and, and other parts of the world has been this, the problems that result from, from chronic pain and from opioid use just put people in an anxious, uncomfortable state and, and consequently are often prescribed or have, there's a fairly significant percentage that would have be co-prescribed a benzodiazepine. And this really has put a significant cost, a significant toll in the number of people that have, have overdosed on, on these drugs over time. The other thing that I'll just point out is that, you know, we, we have a complicated problem here that is healthcare has a complicated problem here and that's, that's very clear. But the automobile industry, and again, there we're dealing with a, you know, with a structure that we can take parts out and put them in, and we can't do that with a human being. But the automobile industry did a pretty darn good job of inventing, establishing certain criteria in an automobile that increased its safety, seatbelts, airbags, engines that drop to the ground on a head-on collision, as opposed to going into the, to the driver's seat or area of the car. There have been things that we have done to reduce the lethality of the motor vehicle accidents. But we haven't done such a good job of establishing in healthcare ways in which we can more safely take care of pain while keeping the general public safe. And certainly that was a big problem in the last 25 years. And we're starting to get a handle on it, but we've got a lot of work to do to actually get there. So prevention and problematic opioid use of prescribing and treatment should involve a good assessment of the patient. So we have a better idea whether we need to be keeping track of whatever of a particular patient because of some of the risks that they may have. Alternative treatments to opioids certainly should be considered. Trials of opioids instead of put them on it and leave them on it, have some way to assess is there improvement and they should stay on it. Develop real treatment plans and be monitoring again, both subjective monitoring, objective monitoring, which may include urine drug testing, and then overall monitoring them in terms of other outside sources that can give us information. So the treatment would include a good treatment plan, potentially tapering opioids over time, paying attention to the morphine equivalents that a patient's receiving, and then looking at other both pharmacologic and psychotherapeutic interventions that could help the patient. Keeping in mind that only a small percentage really are gonna develop a opioid use disorder. So these are abuse and dependence were from the DSM-IV. We're now using the DSM-V, and that would be an opioid use disorder, mild, moderate, or severe. Abuse is typically over overlapped with mild to some of the moderate, and then what was dependence is more moderate to severe. But those people that would then, or just misusing their medications, they'll keep them around and use them when they might be going to, I don't know, a party, and they decide to take a couple Percocets and drink on them, and that's real misuse. That's moving into definitely the abuse state more so than kind of overusing their medications. Using their medications differently than they were prescribed. Aberrant medication use behaviors, a spectrum of patient behaviors that may reflect misuse, that you're concerned about it, and then a huge number of patients that take them as prescribed. So again, keeping in mind that this is a lethal disorder. It hasn't gone down. In fact, during COVID, we saw an increase in the number of individuals that died of an opioid use disorder. So people with opioid use disorders, it's remained stable, it's not gone up. The problem of overdoses has been impacted significantly with the advent and the availability of various fentanyl products. The dose thresholds associated with overdose were established by the CDC, and these are what many of us became very aware of as they put out sort of, not sort of, they put out dictums looking at, watching very closely if a patient is being prescribed greater than 50 morphine equivalents a day, avoid going above 90 morphine equivalents daily. The average dose in overdoses was 98 morphine equivalents per day, and 50% of those overdoses in patients on less than 60 morphine equivalents. If higher doses are used, then you need to be more frequently and or intensively monitoring the patient and looking at risk mitigation strategies. So ways in which you could maybe control it and help them so that they don't overdose. So these were the guidelines, and I'm not gonna spend a whole lot of time on this, but just to, we're gonna talk about a little bit about the non-pharmacologic therapies, treatment goals, to just know the risks and the realistic benefits of opioid therapy, the idea of starting with immediate release opioids and then with stabilization, move to longer term, long acting opioids, and certainly prescribing the most, the lowest effective dose, keeping the quantity just that which you think the patient needs, evaluate the benefits and harms of patients within a week to four weeks of starting an opioid, periodically evaluating the risks, use the state drug monitoring program to just see that patient's not getting medications from someone else, doing urine and drug testing at the start of treatment, and then periodically throughout the treatment of the patient, avoid prescribing opioid medications with benzodiazepines, which I've mentioned, and offer or arrange evidence-based treatment for patients that have developed an opioid use disorder. So non-pharmacologic management could include non-opioid medications, medications, adjunctive medications for that whatever particular problem the patient's experiencing, interventional approaches, neurostimulation, injections, psychological support through psychotherapy, group therapies, lifestyle changes, talking to them about exercise, weight loss, diet, complementary or alternative medications, osteopathic manipulative therapies, massage, potentially supplements, and physical therapy, as I just mentioned. So there's a variety of things that people can be doing, and it's sometimes an indication as to the patient's state and their use of opioids as to whether they'll be somewhat receptive to looking at other things that they could be doing that might reduce their pain. And so much of this has to do with how we're addressing the patient, so using motivational interviewing techniques to help them think about the fact that moving up on the opioids could be causing some problems and could be kind of reducing their ability to be able to move forward in their lives, which they're typically looking forward to. And if they're not, that would be something else to address. Have they just gotten so dismayed by their chronic pain that they've just kind of given up, and that needs to be addressed. So we establish goals. That's what function are they looking forward to, identify or eliminate positive reinforcers and things that would be holding them back, increase physical activity, and avoid opioid misuse. The goal is not necessarily pain eradication, and I think that's another thing I hear from pain specialists frequently is talking to patients about the fact that this is probably not gonna go away entirely, but let's try to get you to the best function we can. Let's look at some baby step goals. You wanna be able to walk to the mailbox and back. You wanna be able to get on the floor and play with your grandchild, those sorts of things. So that, how do we get there? And then we can, once we get there, we can look at what's the next goal. But it's not take the pain away entirely because that's what I was talking about before. The pain is important to us to live in our environments. What are the risks and realistic benefits of opioid therapy? These are risk assessment tools. So we wanna be monitoring the patient before and during their assessment. And the opioid risk tool is probably the one that is used most frequently. There is a tool called the SOAPP, which includes cigarette smoking, which I think is interesting. We know that particularly with back pain, cigarette smoking can actually make it worse. And it also is often associated with other substance use or mental health problems. The COM is one that's used to monitor people while they're getting opioids or they're being administered opioids. And then the STAR is a screening tool for risk reduction. And the SISAP is a screening instrument for the potential, similar to the opioid risk tool or the SOAPP. This is the Dyer, which is also very interesting because it does look at some of the, some of the history of the patient in a way that helps us assess the risk. And at the same time, looks at the intractability, which is a very interesting piece. And that is whether the patient really feels it's helping at all, the opioid. And are they following through on some of those alternative things that they could be doing that could help mitigate the pain. The PEG is a tool that's used to look at the amount of pain that a patient may be having in a particular week, the amount of enjoyment they're finding in their lives, and what is their general activity. And these are done in recent history. So it can be used, just three questions, can be used to just monitor the patient. Are we moving in the right direction? And if there's no enjoyment in their life, should we be looking at other things that either could help them enjoy their life more or reduce maybe their depression or their anxiousness over their lives now that's impeding their enjoyment of life. The prescription monitoring tool can be very helpful. I find that as you really engage with patients and you begin to really look and monitor some of the things that I just talked about, that you don't find too much going on in the monitoring program that you don't know about. You know what doctors are saying, you know how they're doing and that sort of thing. It's typically those patients that it just doesn't seem to be to fit that all that you've been doing isn't working out. And it could be that you need to be looking at psychiatric problems that they may be experiencing or just other problems in the household. But it could also be that they're not being totally open with you about other ways they may be getting controlled substances. And that's where certainly on initial visit, they should all have their PDMP reviewed, but sometimes obviously subsequently. So is it misuse or is it an opioid use disorder? Misuse is often defined as running out early, calling for early refills, repeated or lost prescriptions, multiple prescribers, selling or trading medications and tampering with the formulation, crushing and snorting and potentially crushing, dissolving and injecting. That's certainly misuse. And some like the last one can be, now we're really getting into an opioid use disorder. But opioid use disorder, keeping in mind, it is an alteration in the frequency of use and how they're using and inability often to the inability to cut back. So cutting back larger amounts and for longer periods of time than they expected to use, obviously then more time is used in that. And they can't cut back because they have continued cravings. But then it starts to affect their social functioning and they're not meeting certain expectations, both of their own expectations and others around them, family and work and those sorts of things. And they continue to use. Now they're potentially using in risky situations or really having consequences to their use. And they still don't quit. Those are the categories of, the primary categories of opioid use disorder. Tolerance and withdrawal are physiologic effects that take place. And they certainly happen with patients that are just being prescribed opioids for a pain problem. So we don't, if it's just those two alone, they don't have an opioid use disorder. But if it includes some of these others, then we start to get a higher index of suspicion that they're really developing an opiate use disorder and something more needs to be done. Adverent drug related behaviors can include aggressively complaining about the need for more drug, drug hoarding during periods of time of reduced pain and requesting specific drugs. Now there are genetic predispositions to why one drug works for someone and not as well for another. And there's reasons why people that have chronic pain will hoard medication because they are looking towards having worsening pain in the future. So these are not absolutes, but they're things that we need to be looking closely at if they're openly acquiring similar drugs from other medical sources, that's problematic where they would be better off saying, this isn't helping, you're not helping me doctor. Is there someone else that you could refer me to or are you recognizing that they'd be better off referred to another source. On station, but just going to another physician or healthcare provider is clearly outside the boundaries of whatever relationship that you've set up with them. On sanctioned dose escalation or other non-compliance on one or two occasions where they use a lot extra over a weekend and now they're calling in for more drug and you're not seeing a significant change in their pain. Those that really predict addiction include obtaining prescription drugs from non-medical sources. So buying them on the street, concurrent abuse of alcohol or other illicit drugs, multiple dose escalations or other non-compliance with therapy, multiple episodes of prescription loss, prescriptions from other clinicians, emergency departments without seeking primary help from the primary prescriber and determination that the function appears to be related to drug use. They come in intoxicated into your office and resistance to change in therapy despite significant side effects from the drug. So you're really able to help them understand that the opioids are really causing some impairment but they're steadfast on their need to be just taking opioids and the importance of the opioid. So that is leading to their development of a opioid use disorder which is interpreted like the rest of our environment by the prefrontal cortex. And it's really an impaired response in their inhibition their ability to reduce their risk around using opioids and salience to the attribution of getting and using opioids. So it becomes the most important thing in their life and the risk that they take is down-regulated significantly in the risk to get these drugs or while using. So the response to the drug related cues has gone up significantly response to non-drug related cues also goes up. So just the environment in which they find themselves in impaired inhibitory control and impaired awareness of the illness. They are seeing their life through this drug overlay. And it's very hard to constantly say, I'm only seeing this, I'm only doing this because I have a drug use disorder. No, it's I need to do this and I'm gonna go do it. They said this and that doesn't make sense. In my reality, I need drug. I don't need to hear this other stuff. They can't hear it. They cannot hear it. And so their awareness, this is denial and it's not necessarily lying. It's literally not seeing it, not experiencing life the way they once did or certainly the way others might interpret what's going on. So drug testing can be very helpful. When to test certainly on initiation of treatment and then randomly throughout their treatment. It can be to the point of annually if it's a very stable patient that you had no indication of misuse and certainly as needed. There's point of care testing, which is immunoassay testing, a cup that changes and the color is not there if they have drug on board. And then there's both liquid chromatography and gas chromatography and mass spec, which is much more, it's confirmatory testing. It's more clearly if you get a positive opioid and you're prescribing opioids, you may still send for confirmatory testing that could show up than other opioids in the system. If you're prescribing something that doesn't typically show up on a drug screen like oxycodone, most of the time doesn't even show up but can have a light pinkish color and you're uncertain, that's when on the cup, that's when you might do a confirmatory testing. You might do it periodically if you're prescribing a benzodiazepine just to see, are they taking the one that I'm prescribing? If they come back with a positive stimulant or amphetamine, you might do it just because there's so many false positives with that drug screen. So how do you interpret it? You think about the metabolism of opioids, that is only those that result in, as it's broken down or as a morphine derivative are gonna show up on point of care testing. So all the synthetics, unless specifically indicated on the cup, aren't gonna show up. And false positive or false negative results are reasons why, again, you would send for confirmatory testing. If the results are, you know, you're unclear about the results, then certainly to get a consult, talk to the lab, refer the patient out, change the therapy or potentially discharge them. Although I typically encourage people to always be thinking about moving them to, or referring them to a higher level of care. Drug use disorders include these things, okay? Include having problems with drugs, that's what drug use disorder is. So if that's the problem, then let's get them to the right treatment source. So if, even if you're prescribing something for their opioid use disorder, like buprenorphine, you would, but you're not a specialist necessarily, and you're having problems controlling what's going on, then you would refer them to someone that could help them. They may not take that up because they, because of the situation that they're in, but that's what we would do as opposed to necessarily just discharging the patient. So if you do determine the patient has an opioid use disorder, and you are, you know, you know that they're still experiencing pain, what do you do? And how do we control this? Well, again, to think about the two different areas of the brain that are most dramatically affected by opioid use disorders, and that is the limbic system, where we're interpreting pain. It has an emotional aspect. It has, we now have developed withdrawal. If we abruptly stop it through the amygdala, we're interpreting pain differently through the dorsal striatum, and then there's the conscious aspects of it that have to do with the prefrontal cortex, how they're thinking about what their consciousness is, what now their perception of pain is, and their potential opioid use disorder. The first, the limbic system, we can have a significant effect by treating with medications. That will help definitely the consciousness of not having the cravings and stabilization, but some of the discomfort that they may still be experiencing from some of the predispositions to the development of an opioid use disorder in the first place will be impaired, and that's where psychotherapeutic interventions can be very helpful. So, if the patient you have decided, if you're in that quandary of whether they have an opioid use disorder or not, you decide that they do, then you would be looking at moving them to a medication for their opioid use disorder, and that would include methadone, buprenorphine, or naltrexone. And I'm gonna talk about how you can use these medications for the treatment of patients with opioid use disorder if they don't have an opioid use disorder, then you need to determine what's the benefit versus the harms of continuing opioids. If the benefit is less than harm, then you may send them to a patient-centered tapering situation and consider buprenorphine. The same would be true if they're on doses greater than 50 morphine equivalents. Again, consideration that maybe one of these medications could be helpful, tapering them down, and then possibly considering buprenorphine. If the harm is less than the benefit significantly, and they're on 50 milligrams of morphine equivalents, then you would maintain the same dose and continue to monitor them. If the decision is to discontinue opioids, then you need to educate the patient about the need to do so. Try to engage them through motivational interviewing, helping them understand why this may be the best option, discuss the process involved in tapering, and or moving them on to a different medication. That would be reducing the dose through a slow taper, typically less than 10% or less every two weeks. And it could also be titrating up on buprenorphine while maintaining a full agonist dose. So that is, we can start them on a low dose of buprenorphine, half a milligram, twice a day, while they're taking the full agonist dose, then slowly taper off over a five to six day period to typically we talk about 12 milligrams, so eight to 16 milligrams, and then just taper down, just slow pretty rapidly, take them off the full agonist, and they'll have very little in the way of any kind of withdrawal symptoms, or which is probably much more frequently done, and that is have them stop, if they're on a short acting, have them stop that for 14 to 16 hours, and then start a full agonist, or excuse me, start the buprenorphine. So three different ways in which we would typically change things. One would be slow taper off an opioid, or to a level of risk that you and the patient would be comfortable with, start a titration up on buprenorphine, and then stop the agonist, or do as we would normally do with patients that are initiating buprenorphine, and that is put them into mild to moderate withdrawal, and then start buprenorphine, and for the most part, people will tolerate that very well, because even patients that are on chronic opioid therapies have gone, have missed a med, have had some level of withdrawal, they've experienced some level of withdrawal in the past, and that's all we're asking them to do, if they're on oxycodone or hydromorphone, and none of these are necessarily superior over the other, then explain alternative therapies that you could be using along with reducing their dose, show continued commitment to caring, that you're gonna stick with them, and you recognize they have pain, and that maybe start talking to them a little bit more about how to manage the pain, and focus on the patient's strengths, what are the things that they used to enjoy doing, how can we get you back to that level of enjoyment, and encourage therapies for coping with pain, schedule close follow-ups during and after the therapy, the taper, that is stay in contact with them, these are difficult things that they potentially are gonna negotiate, and the more that they can feel that you're there, the greater their chances of being able to do it effectively, so it's important that the correct diagnosis be made, the goals are established, pharmacologic therapy, treatment is considered, non-narcotic medications, such as acetaminophen or non-steroidals, can be tried first, and can be very helpful, this is patients that are already on buprenorphine, excuse me, it's recommended that opiate agonist, methadone or buprenorphine be considered for patients with active opioid use disorder, who are not in treatment, so getting them, if they come in, they've got pain, let's definitely start with buprenorphine, if it's an outpatient basis, or send them to methadone, pharmacologic therapy in conjunction with psychosocial treatments should also be considered, when patients have an opiate use disorder and have pain, so we always wanna include the, kind of talking them through it, helping them understand ways in which they can manage pain more effectively, if they're on buprenorphine, or methadone, they should understand that it's been shown consistently to be effective in the treatment of opiate dependence and pain, these medications are most effective when used in conjunction with psychosocial treatments, and naltrexone is also a very effective medication, wouldn't necessarily be something you would start with someone with pain, but I am gonna talk a little bit about if they have had an opiate use disorder, are on naltrexone, then what do we do? So it was identified, or Melanoff published this back in 2005, quite a while ago, that buprenorphine is a very effective medication for chronic pain, and 86% of moderate to substantial pain relief was obtained and 8% discontinuation due to side effects or increased pain, so very little. I've done this with many patients, worked closely with a couple different chronic pain groups, including the sickle cell community here in Charlotte, and all the patients weren't referred to me to get started on buprenorphine, but many were, and we had tremendous efficacy to the point where now, more frequently, it's even patients that were not misusing, using other drugs, there was some concern about also prescribing an opioid, those were the ones that were first sent to me. Now, just stabilization in many ways is taking place with a number of those patients with buprenorphine. It's been shown to be very effective in reducing even the dependency on the drug, and that's beyond the medication, that's beyond physical dependency. The one aspect of buprenorphine that's clear and I think is having a significant effect, both in the patients with opioid use disorder and these patients that were prescribing buprenorphine for pain, is that it's a kappa antagonist instead of a kappa agonist, so it sort of reduces some of the dysmorphic aspects of opioids, so very frequently, I would hear people say, you know, my pain is just as stable as it was, but I feel brighter, I have more of an interest in trying to do some of the things that I used to do, that within reason, depending on the area of pain, but they're just brighter cognitively. Individuals treated with buprenorphine and comorbid chronic pain, we address the patient's fears or concerns that their pain is not gonna be treated effectively because of the healthcare community and stigmas associated with them, that we will treat their pain effectively and address the addiction and pain facilitators, both, you know, that we're gonna keep an eye on not getting into trouble with opioids, but at the same time, thinking about what's facilitating your pain and how can we take care of it more effectively. Unrelieved pain can contribute to reoccurrences of their opioid use disorder, and so it is very important that we actually be addressing it, and opioid tolerance impacts analgesic requirements, so they may need more opioid than you would think for this particular problem, and certainly a safety plan should be put in place. If you're continuing buprenorphine, they're already on buprenorphine, you would consider splitting the dose or increase it as indicated. I typically have only needed for many, many patients to just split the dose, tell them to take whatever, you know, 12 milligrams, take four milligrams three times a day, or 16 milligrams, four milligrams four times a day, or if their pain is worse in the morning or worse at night, then take four, four, and eight, or eight, four, and four. Try, on occasion, however, you would go up on the dose. I will say, 10 years ago, I used to always go up on the dose, but I found that I didn't really need to always do that, and it left some opportunity to go up on the dose if there was a problem. Try non-opioid analgesics. Consider non-pharmacologic therapies as we talked about before. Consider a multidisciplinary team. I wish they were more available. Consider consulting a pain specialist. I wish they were more available, and interested and capable. I think they are, many times, interested and capable of taking care of these problems, but they just are often just overwhelmed with other problems. But they certainly can help with those alternative ways of dealing with pain. Add short-acting opioids in addition to buprenorphine, and that's one of the things that is relatively new in this. Typically, it's done only in controlled settings. That is, in the emergency department. So, sometimes, my sickle cell patients would have crisis. They go in the emergency department. Let's say they've been splitting the dose of their buprenorphine, 16 milligrams a day split, but the pain is worsening. They're really starting into crisis. They go in the emergency department. Some work is done to determine why they're having crisis, because it's often associated with some other insult, some other problem, an infection, or something else. Then, hydration often can be helpful. And they would often get an injection of hydromorphone or Dilaudid, some powerful, high-affinity opioid. And many times, it would just take that. They would settle down, get rehydrated, and be able to go home. So, it not only reduced the number of people being able to control their pain at home and not go to the emergency department, but it also has been helpful in reducing hospital readmissions. But again, those problems that would mean the addition of a full opiate agonist is typically in the hospital, the emergency department, or on hospitalization. I have managed a couple patients, outpatient, with full agonists, and it hasn't necessarily gone very well. It's very difficult to get them to a place where they wanna stop it. And I haven't typically been prescribing the full agonist, so it becomes even more complicated. The features of buprenorphine that make it so effective are that there's little in the way of respiratory suppression that is, it doesn't continue to go down with the increasing doses, and it doesn't have the effect on the respiratory center, that's the medullary respiratory center that monitors our CO2 levels. So, as respirations go down, saturation goes down, for full agonists, continues to go down, CO2 levels get misinterpreted, and people just don't have the stimulus to take a breath, and that's why people overdose on full agonists. Buprenorphine, it doesn't do that. They still have that CO2 response. With rising levels of CO2, they are stimulated to take a breath. It is a Schedule III drug, so we can prescribe it for opioid use disorders in the office. It has a 30 to one morphine equivalence. It's a very powerful analgesic, and it's long-acting. Again, the analgesic effects of the medication are not 24 hours, so typically we wanna split the dose. It has a high affinity, so it's going to reduce the euphoric effect of other opioids, but not necessarily all the analgesic effect, particularly maybe some of the peripheral effects of full agonists. So again, you can add a full agonist to buprenorphine and have some pain relief. It has a slow dissociation from the receptor. You can also use the combination products. So don't shy away from that. Don't think that because there's naloxone in it that we can't use it. In fact, there's very little bioavailability of the naloxone if it's taken sublingually as prescribed. And it will reduce the potential that they're going to use it other than prescribed because it is not as rewarding as the monoproduct, that is the buprenorphine alone product. The combination is not as rewarding as the monoproduct. It's not so much that they are going to go into immediate withdrawal, which is often talked about, like you inject it, you're going to get sick. Not really. You're going to, if you got opioid on board, you're going to have some withdrawal from both of them because they're both going to kind of drop the intrinsic activity of an opioid because if it's affinity, it's going to take over those receptors, but it's not going to drop to zero because it's buprenorphine and it's going to still have some intrinsic activity. But with the naloxone on board, which has a competing affinity to the receptor, there's going to be an immediate little discomfort, but it's not going to last long at all. And then there's going to be a slow onset of the buprenorphine. So the graph that you see below here, the yellow line, you can barely see it, has an immediate sort of drop, uncomfortable feeling, but then a slow, the yellow line, a slow increase, and that's the combination medicine compared to the blue line, which does monoproduct. And people inject drug to get the effect now. They don't inject drug to get the effect 45 minutes or an hour later. And so that's the deterrent effect of the combination of buprenorphine and naloxone. There's not a difference in terms of the analgesic properties, okay? So don't think I can only prescribe the monoproduct for pain. Pain and buprenorphine for opioid use disorder temporarily increase the buprenorphine dosing, may be effective for mild acute pain, for severe pain in a controlled setting, discontinue buprenorphine and add a high-potency full agonist, something that's going to potentially compete with the buprenorphine like a fentanyl product, and discontinue, or you can discontinue the fentanyl, commencing with a high-potency opioid. That might happen if they come into the emergency department and they're, you know, major trauma, then people know how to use the full agonist more effectively, and that's what will happen. Hopefully, there'll be someone in the hospital that understands buprenorphine, if the patient had been on it, and will be able to either do a titration of buprenorphine and a slow discontinuation of the full agonist to stabilize the patient over time. It is certainly important to recognize that their tolerance will be higher, and the ability to titrate back down to a level of agonist treatment is one of the advantages of just leaving them on their buprenorphine. It also maintains a baseline opioid mu-activation, so you're not gonna run into them kind of experiencing withdrawal pain, which is a very real thing, and no need to go through re-initiation of buprenorphine, so you don't either need to titrate up slowly on the buprenorphine and discontinue the full agonist, or have them hold all their opioid overnight. You know, you've just got it on board, and you just taper off the full agonist, and they're still on buprenorphine. Perioperatively, we used to always discontinue buprenorphine. For most procedures now, both surgery surgeons and anesthesiologists understand that you can maintain buprenorphine. They just use a high-potency full agonist perioperatively for relief of pain, and maintain their regular dose of buprenorphine, or potentially methadone. Research has demonstrated that addition of a full agonist can be effective in treating pain. That's adding to the buprenorphine. Decisions related to discontinuing or adjusting the dose of buprenorphine prior to planned surgery should be made on an individual basis with the surgeon or anesthesiology team. So you talk to them, and if they say, oh, I'm uncomfortable with that, I don't wanna do that, well, then you talk to the patient about the day before they're gonna go into to their elective procedure to discontinue. Don't take it the following morning. Go in. They'll still be covered. They're not gonna go into withdrawal, and then let the surgeon or anesthesiologist certainly know that you've stopped your buprenorphine, and you're gonna need to be, they're gonna need to manage not just the pain, but the withdrawal. If it's naltrexone the patient's taking, patients will not respond to opiate analgesics. If it's a mild pain, you would start a non-steroidal. If it's moderate to severe pain, then they can be treated with more high-potency opioids. And certainly many times ketorolac, trazodone, can be used quite effectively, and is actually a good medication to be used for moderate pain. If it's high dose, excuse me, it's a severe pain, then potentially they would also be given a high-potency fentanyl product, typically, and be able to manage their pain quite well. Oral naltrexone, if it's the medication patient's taking preoperatively, you'd need to stop at 72 hours prior to the procedure. And if it's the injectable naltrexone, then it would need to stop 30 days prior to, you know, their last dose would be 30 days prior to the procedure. Usually you're down to about two nanograms of the naltrexone and might wait a little bit longer, but not too long. And if it's gonna be too much longer, then I typically have patients take oral naltrexone just so that they're covered and they don't get into trouble. So this is a graph showing some of what I just talked about, mild pain, non-steroidal, selective surgery, stop the oral 72 hours ahead of time, extended release four weeks after the last injection. If it's major pain or emergency, then regional anesthetic, conscious sedation, general anesthetic with high-potency fentanyl analogs to override the naloxone, naltrexone affinity. Always think about some psychotherapeutic interventions, the determination of a level of intensity of clinical services should be derived from the severity of the patient's condition as determined through a multidiscipline and multidimensional assessment. So really looking into the psychosocial aspects of their lives that can definitely be affecting their ability to deal with pain effectively and their opiate use disorder. So the level of psychosocial treatment care should be determined through the use of appropriate utilization of a management algorithm. This could be the American Society of Addiction Medicine Standards of Care of addiction specialists and ASAM criteria. It's a six dimension assessment, really looking at are they gonna have withdrawal symptoms, do we need to be managing that? Do they have motivation to, what is their motivation to their keeping their or treating their opiate use disorder as they're dealing with pain and what other medical or psychiatric problems do we need to be aware of? And then what setting should this be done? Do they need inpatient care or can they manage it at home and all the sources of treatment in between? Psychosocial treatment is recommended in conjunction with other pharmacologic treatment. We should look at psychosocial needs, supportive counseling, links to existing family supports and referrals to other community services. So certainly peer supports can often, for these folks be very helpful because many people that have like the vast majority that people that have significant substance use problems have had trauma, one kind or another. And that's where peers can be very helpful. Naloxone should always be offered to these patients. The Guideline Committee of the American Society of Addiction Medicine office-based treatment recommends that patients and their family members be given prescription naloxone. They should have it at home and really, it should be thoroughly reviewed with them that the importance of understanding, knowing where it is and some of the guidelines of safe prescribing, keeping their medication safe in the household. You never know when a child's gonna be in your home even if you don't have children. So just keeping the medication safe can go a long ways towards reducing the potential for overdose and having naloxone available can be helpful. Availability of these kits have gone up significantly as we've talked about it more and it has saved lives. So back to my patient, what were our treatment options? How would you approach his pain? How would you attempt to initiate treatment? So just to cut to the quick, at the time he was overwhelmed with the idea that he would taper down and have a period of withdrawal, particularly in that he had been taking OxyContin, as you remember. So it was determined that he would be better off treated at a, or initiating his buprenorphine in a residential treatment center, which I had access to. Not everyone would and so, but we did. And he actually was able to taper off all that OxyContin to 32 milligrams daily. And he took, he was still taking one milligram of clonazepam at bedtime, 50 milligrams of amitriptyline, taking an NSAID and using lidoderm patches. We were able to taper down eventually to 16 milligrams. He was off the clonazepam entirely. He did continue 50 milligrams of amitriptyline at bedtime and took a nonsteroidal three times a day, though really his pain had subsided significantly and his wife indicated that he was no longer really asking for the nonsteroidal as frequently as he had been. He did continue the lidoderm patches. But at the time that I last was in touch with him, he described mowing the lawn, whereas prior to that, he had actually been using a electronic wheelchair in the house and not going out hardly at all. So he was actually out walking. He was walking this lawnmower and going grocery shopping and had been out to dinner with his wife. So there was a significant improvement in his life with tapering off that huge dose of opioids and stabilizing on buprenorphine. And with that, I'll suggest that you take a look at the Provider Clinical Support System that has a lot more information on pain and treatment of pain and might have scenarios that would be more appropriate to your practice. There's the Prescribe to Prevent site that is associated with getting naloxone made more available and then a variety of other sites that could be helpful in giving you more information. And with that, I'm sorry, we can't take questions, but maybe we'll see each other at some point in time and you can ask me a question. Otherwise, good luck to you.

pain and addiction

safer prescribing

pain management

opioid use disorder

opioid crisis

alternative treatments

non-pharmacologic interventions

buprenorphine and naloxone

initiating opioid therapy

tapering opioid therapy

multidisciplinary approach

psychosocial treatments