So, welcome to Rethinking DSM-5 Opioid Use Disorder, Is it Time for a New Definition? I'm gonna go ahead and start. I assume that there'll be people kind of trickling in, but we're gonna go ahead and get started. I'm gonna introduce my esteemed colleagues here. Dr. Will Becker is professor in the Department of Internal Medicine at Yale School of Medicine. He's a primary care and addiction medicine trained physician whose research and clinical efforts broadly aim to improve the quality of chronic pain treatment in general medical settings, especially in the complex overlap of chronic pain and opioid use disorder. He's the author of close to 200 papers based on what I looked at this morning related to this topic. He's co-director of the Chronic Pain Management Clinic Opioid Safety at VA Connecticut, formerly known as the Opioid Reassessment Clinic. That's how we know each other because we've been co-directors of this clinic since 2012. And it is a clinic that's been disseminated throughout the VA. He's PI on many grants through the VA, NIH, PCORI, and FDA. Then there's Dr. Wilson Compton. He is a psychiatrist, you can wave. He is deputy director of the National Institute of Drug Abuse, NIDA. And in this role, his responsibilities include working with the director to provide scientific leadership in the development, implementation, and management of NIDA's research portfolio in order to improve the prevention and treatment of drug use and addiction. Relevant to this topic, he served as a member of the DSM-5 Revision Task Force and vice chair for the DSM-5 Text Revision. He's author of more than 250 publications, including widely cited papers drawing attention to the opioid crisis in the United States. And then Karen Drexler is known to many of us. She is an addiction psychiatrist. She served as medical director of the AAAP for several years until stepping down last year. She's a military veteran and is associate professor in the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine, where she served for many years as addiction psychiatry residency training director. She has also served as national mental health program director for addictive disorders in the central office of the Veterans Health Administration. And it was at one of the VA state of the art or SOTA conferences in 2019 that the four of us kind of first met and really started thinking about this issue and thinking about how to study it, how to frame it and how to talk about it. So in some ways, this is the culmination of five years of a relationship. I'm Ellen Edens, I'm an addiction psychiatrist. I'm also at VA Connecticut and I work with Dr. Becker in the chronic pain management clinic opioid safety. We've just changed our name, so. All right. Here is our disclosure slides. It looks slightly different than what I had put in, but our disclosures have been reviewed. They were very minor and I'm assuming this is sufficient. You'll have had a chance to look at it. So the objectives for this workshop is we hope that by the end you will recognize that there is an ongoing debate and some research needs for a new diagnostic category for people who have been prescribed long-term opioid therapy. So they're on opioid prescriptions for chronic pain who now are struggling with tapering. What is this? We hope that you will appreciate some of the historical contexts of DSM-5 criteria. Expect especially the exclusion of tolerance and withdrawal under medical supervision and evaluate the need for revisiting the 2013 criteria and decide for yourself whether a review of DSM-5 substance use disorder diagnosis is actually needed. In order to really highlight what we're talking about, we thought it would be helpful to use a case. So this is a case of Ms. Morris. She has chronic chest, neck and back pain. She's a 59-year-old. She's on 180 milligrams oxycodone daily. You translate that into morphine equivalent daily dose and that's 270 milligrams, I think, if I've done my math right. Her pain really stems from breast cancer that she had. She's in remission for many years, but she's status post bilateral mastectomy, continues to have muscle spasms in her chest, and this is when her opioids got started, was in the context of cancer treatment. From a psychiatric standpoint, she does have depression, anxiety and PTSD, and she's never had any mental health treatment. Just context for what it's worth. This is a patient similar to a patient that we saw in our chronic pain management clinic at the VA. From an opioid safety standpoint, which we do assess whenever we see people initially, she had no evidence of loss of control over her prescription opioids, no misuse on her state prescription monitoring program or per her report, there was no history of substance use, no current alcohol, nicotine, or cannabis use. From a functional standpoint, she reports that she's quite active. She gardens, she socializes, she practices yoga, and she feels like she's doing quite well on this opioid regimen. As far as non-medication treatments, she is open to multimodal care, but has never really obtained any. She's open to CBT for chronic pain, which we provide, but she's also open to any skills-based or psychotherapy, which might include MBSR, or might include ACT for chronic pain as well. She's open to referral to mental health treatments. As far as medication treatments, she notes that she's very, very sensitive, exquisitely sensitive is the term she used, to any medications. She can tolerate only venlafaxine up to 75 milligrams. Anything higher than that is gonna cause too many side effects, and she cannot tolerate. She cannot tolerate any gabapentinoids. She's been on those, they cause too many side effects. Nor is she open to, or can she tolerate NSAIDs. So she does have a lot of side effects to medications. She is not on any muscle relaxant, but does note that diazepam has been effective in the past, which is often used as a muscle relaxant. From an opioid standpoint, she has a strong preference to maintain her current opioid dose. She's highly anxious about tapering. She has experienced withdrawal before, but not because she ran out early, not because of overtaking her meds, but because the refill arrived late. So we do know that she has tolerance given her dose, and we do know that she would have withdrawal, but again, this is in the context of a refill arriving late. She's very opposed to switching to buprenorphine, quite adamant against it. So, given what you know about Ms. Morris, would anyone in this room diagnose her with an opioid use disorder? Anyone confident of that diagnosis? If anyone was listening, no, I think I'm not getting any hands raised. I know that was kind of a long and involved case. We didn't either. We didn't think she had opioid use disorder. So when we, in our clinic, whenever we see somebody, this is the framework we use. And the first thing is, do they have an opioid use disorder? And often when people come in, it's not clear. Sometimes it is. And if it is clear, then this audience knows, guess what we do? We get them on medications for opioid use disorder. It's kind of a slam dunk, easy thing. Not easy, but it's easy for us from a treatment perspective. It's when it's not or unclear that we have to go to the bottom half of this framework, and then we move to a benefits harms ratio assessment. So for Ms. Morris, do the benefits outweigh the harm? No, the benefits do not outweigh the harm, or the harms actually outweigh the benefits. If we think that's the case, then we would offer Ms. Morris patient-centered tapering, including an optional rotation of buprenorphine. If the benefit we think is outweighing the harm, but the dose is high, anything above 50 milligrams morphine equivalents, then we also would offer Ms. Morris patient-centered tapering including an optional rotation of buprenorphine. And the reason for that is, even though there is potential benefit from the opioids, could there be equal benefit and less harm from a lower dose? And so we offer the same strategy. If the dose is low, and there does seem to be some benefit from the opioid regimen, then it's fair to monitor that person, to reassess, but we almost always also offer an optional rotation of buprenorphine as well. For Ms. Morris, this is where we put her. We decided that Ms. Morris, the harms outweighed the benefit. If you decided that there was some benefit, and maybe just the benefit is outweighing the harm, you wouldn't have been wrong. We would have gotten to the same point. It's really that she had untreated mental health needs, and we felt like the dose was really quite high, and we thought that she could get more benefit, and obviously less harm from a different approach. So that was our determination. All right, so with Ms. Morris, we explained this to her after our initial assessment, and we said we'd like to initiate a taper. She was not interested in switching to buprenorphine. So we gave her a choice. Wherever we see patients, we offer choices whenever possible. That's, humans like to be given choices about what they have to do, or what they are going to do. She wanted a slow taper, but she wanted to decrease her immediate release first, rather than the long acting. We decreased it by a little over 10%, from 180 milligrams of oxycodone to 160. Between visits, she was upset with that. Between the visit and the follow-up, we saw her four weeks later, we had frequent calls. She was very tearful, angry, I cannot function, I can't go out with my friends like I used to. She said, I need some diazepam if this is gonna be successful. We really kind of helped her through that, mostly by reassurance, calling her, talking to her, and got her through that month. Week four, or follow-up day 28, she was very angry, she was tearful, she felt like we were really applying a cookie-cutter approach to her case, and we decided to stall the taper. And this is often what we do. We don't give up on a taper, we just simply say, you know, it takes a while for the body to adjust, we'll be here, we might add other things, we're gonna offer support, but let's press forward. So that's what we did. We kept her on that 160 milligrams of oxycodone. 28 days later, or four weeks later, she came back, she said, I'm still in a lot of pain, I'm not socializing, I'm not functioning, I can't participate in yoga. She was really quite frustrated, planned to complain about our care, and we decided, once again, that we would not proceed with any taper, but we would stay at 160 milligrams for month three as well. Prior to the third month that we were gonna follow up with her, about three days prior, she called, she said, I dropped my meds in the sink. She was extremely tearful, very anxious. We did not provide early refills, which is our protocol, or at least just normally what we do, but we did offer her buprenorphine. If she was gonna go into withdrawal, we certainly wanted to avoid that, and so we were gonna offer buprenorphine to help with her withdrawal symptoms. She declined, she said, I can get through three days, and I'll see you back in three days. So that's what we did. We saw her at follow-up three. We gave her another month, so this would have been four months at this 10% reduction of oxycodone-160, but we did prime her, and we said, at month four, the next time we see you, we're gonna reinitiate a taper. It's gonna be small, but just to kind of prime her to let her know that that's what was coming. At that point, about less than three weeks later, she called, did I get that right? Yeah, so then she comes back, sorry. She comes back at follow-up at four months. We do decrease the oxycodone by 7.5% at this point to 150 milligrams, and she was pretty upset despite our priming her. It's so anxiety-producing for patients. And then about 20 days later or so, she called, and she said, I've thrown away my medications. I'm so frustrated. I don't like y'all controlling me. I hate this stuff. I wanna be done with it. I threw it away, but now I'm panicked. What am I gonna do, right? I'm out of my medications. And so at that point, we offered buprenorphine as Ms. Morris' only option. So now, what's the diagnosis? Is this long-term opioid therapy, and Ms. Morris is having difficulty cutting down, or is this opioid use disorder? Now, if we look at the DSM-5 criteria for opioid use disorder, as everybody in this room knows, when somebody is prescribed a medication under a provider's supervision, you cannot count withdrawal intolerance. Ms. Morris has both of these symptoms for sure, right? She meets those criteria, but we can't count them. So if we look at the other nine, use of larger amounts or over longer periods of time than intended, you know, we're gonna say no. Did she overtake her meds and just tell us she lost them or threw them away? Maybe, but we're gonna take her word for it. But she's never had any evidence of that before. She has had unsuccessful efforts to cut down. As far as a great deal of time spent, you know, she's calling a lot. We're spending a lot of time on the phone with her. There's definitely a lot going on now. There's definitely a lot going on now in the context of this tapering. I don't know that we had seen that prior to the taper. So maybe, as far as cravings, that's not entirely clear to me either. She certainly would take her opioids every, you know, right on schedule as prescribed. She was denying any of the major negative consequences of opioid, associated with an opioid use disorder. And then this one, maybe, you know, at this point, she's been told that high-dose opioids are harmful or potentially harmful or risky. And I think in a lot of these patients, the salience and the importance of opioids kind of might shift their perception of the harms compared to ours. And sometimes that can be some of the disconnect, I think. She does have psychological, you know, untreated PTSD, depression, and anxiety. So maybe. And so you look at this list, and here we are as psychiatrists or whoever, using these medications to treat chronic pain, and we're trying to diagnose an opioid use disorder. And we're still left, even after going through the DSM-5 criteria, we're left with maybe? Yes? Can you go back to that slide? What did you answer, yeah, to the second question? You didn't decide to cut it down, right? Yeah, we were having a hard time cutting down, right? This was an unsuccessful attempt to cut down. I think that's a very good point. I can't answer that, but your point is well taken. Why does this matter though, right? I mean, I think what we're raising here is maybe we could have more diagnostic certainty if we got more collaterals or if we thought about it a different way or the bottom line is it's tricky. I've just gone through all of that. Most people don't go through all these criteria, but I've gone through all of them and we're kind of like maybe she does, maybe she doesn't. Maybe if we had more information and so it's just hard. It's hard to kind of figure this out and why it matters ultimately, it might not, I mean that's part of what we're talking about here. I don't want to say it doesn't matter, but I think one of the things that forces this is that we have regulations, we have codes, we have clinical practice that require that we differentiate between chronic pain when somebody is prescribed opioids and somebody who has an opioid use disorder. We even have different formulations. So all of us are very familiar with the OUD formulations of buprenorphine, but many psychiatrists aren't necessarily familiar with transdermal buprenorphine or buccal buprenorphine, right? We're trained differently even though it's the same medication. Different practice settings are required, some not required, but often chronic pain clinics will say we don't treat opioid use disorder and settings that treat opioid use disorder say we don't do chronic pain and so we're kind of forcing this dichotomy when perhaps we shouldn't be. And so there's also fear of punitive oversight and I think we'll get to this also later. Patients are often very vocal about their own diagnoses and treatment preferences. Overlying all of this, I believe, is stigma as well. And so is this indeed a clinically distinct entity? Is what Ms. Morris is experiencing opioid use disorder or is it something different? If it's opioid use disorder, is it mild opioid use disorder? Would it better have been characterized by DSM-IV dependence before tolerance and withdrawal were excluded? And then as Dr. Becker is about to come and talk to us, if it is a distinct clinical entity, what are the defining characteristics? And we all know the importance of reliability. If you don't have defining characteristics, you can't actually study something to find out if it is indeed a valid disorder. So with that. Thank you, Dr. Edens. For folks who missed the intro, I'm Will Becker. I'm a general internist with addiction medicine and pain management training. So bring a little bit of a different perspective. It's also my first AAAP meeting. And gosh, it's awesome. Woo! Yeah, I was hoping for a star or a lollipop, but I will just settle for y'all's warm feedback. So I'm here to present the case for a new diagnostic entity for clinical scenarios such as Ms. Morris's. And I'll start by summarizing the key features of her case from my perspective. First of all, she has longstanding chronic pain. And that's important. We'll come back to that. And for that pain, she has been treated by the medical system, who, whether they've explicitly acknowledged it or not, but every time they fill the prescription are saying, I believe that this prescription is benefiting you more than it is harming. High-dose, long-term opioid therapy, to which she has experienced neuroadaptation and what I would define as physiologic dependence. She's had downregulation of her mu receptors. She's had upregulation of counterregulatory hormones, such as the sympathetics. And therefore, she has experienced tolerance. And if we were to abruptly stop her opioids, she would experience withdrawal. She's been adherent to her LTOT treatment agreement, and she's had no evidence of loss of control, as Dr. Edens noted. But now, as we've ascertained her, the harm of continued LTOT is outweighing benefit. She's experiencing fear of, resistance to, and difficulty with the taper. And I would argue these two are expected and normal responses in physiologic dependence. What is 100% clear to me is that she needs a new pain treatment plan. And I believe that the evidence would support that that would be built around switch to high-dose buprenorphine formulation. I say high-dose because she's on a high-dose full opioid agonist. So to make this transition and address the neuroadaptation, she needs a high-dose buprenorphine formulation. This would potentially offer three benefits, addressing the physiologic dependence, potentially improve pain control because of its long-acting nature, and reduction in opioid burden. Now this is sort of a nonspecific term. She's actually not experiencing these to a great degree, as many of our patients are. But it sort of can often be somnolence, it can be loss of sex drive, it can be actually depressed mood, all of which are associated with high-dose full agonist opioids. But she also needs to be plugged in with what we consider standard of care chronic pain treatment, and that is at its core both physical and behavioral therapies, evidence-based for pain, and while improving her self-efficacy and her pain self-management skills. So let's talk a bit more about high-dose buprenorphine, which as we all know is FDA-approved for OUD. So if we want to use it for Ms. Morris, we would need to do it off-label for pain. And this brings in, as Dr. Edens noted, potential legal reimbursement and insurance coverage issues, which I frankly don't think are fair to burden the patient with. We could also be what I call OUD-forward, and take an OUD lens towards the DSM-5 criteria, and basically wherever there's a maybe, we kind of just shade it towards the OUD diagnosis. And in some ways that does give her access to a medication which I think she would benefit from, but on the other hand, it, I think, to me, sort of violates what I think is first principle of medicine, which is we give people diagnoses that we are confident in and not that we want to give them. So the third option I would advocate for is to recognize this as a gray area, under-defined clinical scenario for which a new set of criteria could make a new indication for high-dose buprenorphine therapy. Kind of going to repeat some of the things Dr. Edens mentioned, the difficulties in applying the DSM-5 in scenarios such as this. One that our, one of our audience members brought up, with this persistent desire to cut down according to whom becomes a challenging question. The great deal of time spent, this may depend on prescriber practices, increasing number of prescribers aren't going to prescribe opiates. So patients are calling around, prescriptions are not being filled, and so on. Craving is sort of a murky, you know, I need my next dose or else I go into withdrawal. Is that craving? It's sort of unclear. But this one, I think, this chunk, which I think of as the sort of consequences bundle of the DSM-5, pain often confounds these criteria. So patients have moderate to severe pain, which can have marked impact on their functioning. Then you layer in high-dose opioids, teasing apart to what degree the opioids are responsible and to what degree the pain is responsible, I think is challenging, if not impossible. So we're left with the Rorschach test of different observers can make a different adjudication of a diagnosis, and that leads to a lot of inefficiency. Patients are not getting the treatment they need to get better. And inertia, prescribers are not sure, they dither, they continue opioids that are probably not helping and are almost certainly harming, and patient care is compromised. I don't love the proposals, prescribers need better education. That is true, but I think it sort of says you need to apply the OUD lens, and it's hard to convince people to use a lens that they may not see. The other proposal, ascribe or use mild OUD. Some of these patients are profoundly functionally impaired because of this hard-to-disentangle pain and opioid mix, so automatically ascribing it a mild adjective seems problematic. I want to be 100% clear, no one in my camp is suggesting OUD is not possible among patients prescribed LTOT. Put it another way, it is definitely possible to develop OUD in the course of prescription opioids. However, for it to be clear and therefore diagnosable, there needs to be, in my view, a pattern of loss of control and recurrent episodes of compulsive use marked by unauthorized dose escalations, increasing drug delivery via altering formulations like crushing to inject or snort, or accessing additional source of opioids like multiple prescribers or friends and family or non-pharmaceutical opioids. So we've been thinking about this for a long time, as Dr. Edens mentioned. We finally got to studying it five years ago with a recommended Delphi study, and I'm going to spend a few minutes telling you about this. Delphi methodology was developed by Rand in the 50s, I think, and it seeks to explore and generate consensus by convening subject matter experts, providing anonymous input on a topic, going through iterative rounds of voting, and hopefully molding consensus. So we sought to build consensus on the need for, definition of, and potential criteria of a new diagnostic entity, which I will call Condition X. For now, we invited the invitees to the SOTA conference to participate in the Delphi, including multidisciplinary experts in all the fields you would hope, non-VA and VA experts, and then conducted a three-round online survey. This was the depths of COVID. So the first round was open-ended questions to generate ideas for criteria. Round two was having folks vote on these and make revisions to the items that they saw fit, then a re-rating of items. And then, since we ended up with 18 criteria, we convened a post hoc expert panel that included psychometricians to pare down to the most efficient items. So a lot of interesting data came out of this. First to the initial question, should there be a diagnostic entity distinct from but not replacing OUD that pertains to patients on LTOT for chronic pain? Three-quarters said yes, but a significant minority said no. And I'll show you the reasons for the yes and no. So the arguments for included recognizing a distinct clinical pathway and set of experiences for patients on opioids for pain would be useful, it would address problems created by exclusions in the DSM-5 criteria, would facilitate treatment and additional research, and it would reduce stigma and mitigating unique social consequences. I won't read the quotes in the interest of time, but take a look. And then the arguments against, I would say, equally firmly held, that actually the biology of long-term opioid therapy is really indistinct from what occurs in OUD, that we can capture the experience of patients on LTOT with DSM-5 criteria as they stand, or instead of coming up with something new, we should modify the DSM-5 OUD diagnosis. And then, interestingly, stigma came up here as well, that creating a separate entity could worsen stigma for patients with OUD. So the panelists came up with 31 criteria, 18, as I mentioned, met the a priori cutoff for consensus, and those included benefits of the therapy were no longer outweighing harm, patient was experiencing difficulty tapering, and they were exhibiting withdrawal symptoms. The workgroup agreed that does-not-meet criteria for moderate to severe OUD and physical dependence on opioids were useful criteria to include. There was no consensus on whether this potential new condition and mild OUD could co-occur. The topic of what name might be best was posed to the panelists. Several were highly rated, and the one that was most highly rated was prescription opioid dependence syndrome. Under the smaller ad hoc workgroup convened that included psychometricians, the final most parsimonious items were harms outweighing benefits of LTOT, difficulty tapering, but absence of a pattern of loss of control. Regarding tolerance, it was thought that because this was so pervasive in this population that it was neither sensitive nor specific, or it's not specific enough. And then regarding withdrawal, that was thought to be neither sensitive nor specific. Last slide. The HEAL Initiative actually took an interest in this topic and released an RFA called the Multilevel Interventions to Reduce Harm and Improve Quality of Life for Patients on LTOT or MIRACLE, and they funded our center to be part of this effort. And essentially, to put this slide into one summary, it's kind of take a broader set of partners to help weigh in on what criteria might be useful, including persons with lived experience and a broader array of non-VA specialists, perform a systematic review for the known harms and benefits of opioids so that we can inform this decisional point of our harms outweighing benefit, create a clinical definition using our prior Delphi as a starting point, but including important modifications as proffered by the new Delphi panelists, and then ultimately perform a longitudinal cohort study to validate the clinical definition. And with that, I hope I didn't go too far over and be happy to take any questions. Sure. Yeah, it's a great question. And for the back, were there... I have one more question. Oh, sure, go ahead. Did she also, and that might be more for Alan, did she have any overdose incidences? Yeah, so was she referred for any particular harm or was it the pendulum swinging where it was more of a system approach to get people reduced on their opioids? And then did she experience overdose? She had not experienced an overdose in her life. Regarding why she was referred, I think increasingly there's a recognition that high-dose opioids, whether or not there's apparent harm that's obvious, that there's probably harm accruing in the background. And it's as wise to help people consider a change while things are going relatively well as it is, it's perhaps even wiser to be more preventative about it than to wait till things have gotten much worse. So I don't think there were all that many harms identified by the prescriber, but more along the lines of let's be proactive and try to help this person while there's a lot more of her life to live. Thank you. I want to be mindful of time. Are we good? Yeah, I'm going to pass the mic, but. Well, I guess the question that I have, sorry, I had two questions, but I'll try and pick one. Well, I guess in terms of the buprenorphine for pain, is that going to be later and one of the later parts of the talk? Clarify. No, not really. Oh yeah, I guess, how do you, I guess you mentioned that like the buprenorphine could potentially be better for the pain. And I guess like when I'm explaining like that, how it works and being like, maybe not as, I guess, powerfully activating patients are like, oh, well, that doesn't sound like it's going to be helpful or be as helpful. And so how do you kind of approach that discussion? Great question. So how do you know it's a partial agonist? Does that mean partial analgesia? The short answer is no. If you look at the dose response curve for analgesia, buprenorphine is very potent analgesic at very low doses. In an opioid naive person, you can give them five micrograms per hour. So 120 micrograms per day and have a pretty robust analgesic response. Of course, we like it because of its ceiling dose for respiratory depression, but it's analgesic effect is pound for pound more potent than full agonists at therapeutic doses. All right. Thank you. Well, we're going to step back and continue this discussion from a little broader perspective, but we'll have a chance to come back to the case towards the end and think through some of the issues. And I certainly already have questions for Will and Ellen, but we'll try to hold back on those a little bit as I go through some additional background here related to the overall diagnosis and how we think about, in this case study, the importance of overlap with other psychiatric conditions. So a little bit of a reminder that substance use and mental health are linked. You all are well aware of that. Addiction psychiatry as a specialty is born out of that knowledge, understanding that persons that use whichever substance you pick have an increased rate of almost every other psychiatric condition, not all of them, but almost every other. So a couple of examples of that just from the National Survey on Drug Use and Health and thinking very broadly about the overall classification of any substance use disorder or any mental illness, you see graphically displayed the important overlap. So more overlap than expected, not universal. Some people have one, some have the other, and more than expected have the combination of these. So that's sort of the background here that I think is important to keep in mind in evaluating and coming up with a careful treatment plan. And that's in some ways why the multimodal pain treatment at least resonates very nicely for me in this case study, because that patient has many things going on and the treatment of her back, neck, and other pains is only one part of it. Okay, so one way to think about this is why are opioids, what's going on with opioids in this space? I just want to remind you that opioids have an impact on all forms of pain, whether that is the sensory aspects or the affective aspects. In fact, there's an old literature on use of high-dose opioids as a treatment for major depressive disorder that doesn't respond to anything else. I'm not saying that any of you all will be going down that road because we have many other treatments now, but that's a reminder that in our single brains here, we have overlap in these conditions. And so we're left trying to disentangle in a diagnostic system or a diagnostic approach when our brains put these together in important and meaningful ways. Now, just to remind us of the changes from DSM-IV to V, and we've heard a little bit about this, so I'll go over this quickly. A reminder that in DSM-IV, you had any, you started out by do they have the dependence syndrome? Not physiological dependence as Dr. Becker was describing, but substance dependence as defined by the DSM system. Part of the reason that label was eliminated in DSM-V was because of the confusion that other parts of medicine have with our use of the term dependence in psychiatry that's different from what every other pharmacologist uses it for, which is purely tolerance and withdrawal. So in any of those seven symptoms, if you don't have that, then you can consider whether abuse might be present. It turned out that we did a lot of work that suggested that there's really no distinction in the symptoms of abuse and dependence. They don't cluster nicely into two separate groups. And as a matter of fact, several of the abuse symptoms only show up in people who have quite a severe underlying condition, particularly the legal problems. By the time you have multiple legal problems related to use of substances, you have a whole host of other symptoms on average. And that was also true in terms of failure to fulfill important obligations. By the time you're not able to function as a parent, not able to function at work, not able to function in school, that's not mild. That's not sort of that conceptual idea of abuse as an early milder condition. So that was the argument against DSM-IV and the committee because the symptoms really do cluster nicely together. Organize it by putting them all together and finding that any, any, we chose a threshold of two, which as we were discussing before this session was a bit arbitrary. And if you look in this month's American Journal of Psychiatry, we have a paper on how there is a big difference between DSM-IV and DSM-V in the diagnostic rates, at least as far as the National Survey on Drug Use and Health are concerned. When we developed DSM-V, what, 14 years ago? The data we had at that time suggested that a threshold of two symptoms produced approximately the same overall rates as abuse and dependence put together. So the committee didn't have a real reason to select one, two, three, four, or five as the threshold because there is no natural threshold. These are continuous in terms of their association with poor functioning. And so that's how we came up with two. We used the data that we had at the time. But when you look now, there really was, it really does create a big difference and DSM-V identifies a larger number of persons who tend to have more mild conditions. If you add new ones, they tend to be at the mild end. Mild is sort of a misnomer. I would just say two or three symptoms because the label mild suggests, as Dr. Brecker pointed out, that it's not really clinically significant or a major problem. And that's not always the case. It just means that there aren't very many symptoms involved. Okay, so that's a little bit of the background. I always want to point out, and I don't do this for this group, but when I do this lecture for non-psychiatrists and non-experts in this space, I remind people of the distinction between what I think of as addiction or severe substance use disorder and physiological dependence. Physiological dependence develops very rapidly. That can occur as quickly as just a week or two. So you see patients in the CL services in the hospital that have been on opioids because of their horrific orthopedic procedures or dreadful burn situations. They can have significant development of tolerance and may have significant withdrawal symptoms when it's abruptly discontinued. A lot of our colleagues don't know that. They think that you only develop withdrawal when you've been on these products for years at a time. Not true. And it's a little bit unpredictable. Some patients do quite well with an abrupt discontinuation. Others have really significant impairment and distress. So this is something that we all can do to help guide our colleagues to understand the differences between, you know, what we're thinking of as the classic substance use disorder, severe case of addiction, and what can occur quite rapidly in use of opioids and many other substances. You've heard a little bit about how DSM-5 distinct separated out prescription use disorder from other substance use disorder by suggesting that you shouldn't count tolerance and withdrawal when the medications are completely taken as prescribed. And this was really to make sure that we weren't ascribing to a psychiatric condition, significant symptoms, tolerance and withdrawal can be significant symptoms, but they don't carry the weight of having a behavioral condition of a full psychiatric illness when that occurs as in some ways expected part of regular administration of a medication. That was sort of the background here. I will say that Dr. O'Brien, our chair of our committee, was particular avid about this. And so like every other group, there's both data to help drive it and then there's also champions that help change a system in some ways as well. I wanted to highlight for you some work that we did now a number of years ago. Just remind you that when you do a crosswalk of DSM-4 to DSM-5, you see dependence, which is DSM-4 dependence most reflected in at least moderate or moderate to severe opioid use disorder or alcohol. It was very similar for cocaine. For cannabis, it was a little different. It actually required even more symptoms to be the equivalent of DSM-4 dependence. But it's a reminder that if you have somebody with an opioid use disorder with fewer than four symptoms, with two or three symptoms, we're not sure that they have met the threshold for an FDA approved medication. Because buprenorphine and methadone, while we think of it as anybody with an OUD can qualify for it, that actually isn't technically true. The FDA approval was based on a DSM-4 dependence diagnosis or more likely at least moderate to severe DSM-5 disorder. So even as Dr. Becker was describing in this case, well, we might stretch to give her a diagnosis. I don't think we were stretching to give her a moderate or severe OUD diagnosis under almost any circumstances. So we're still left with the difficulty of, are you just going to take the plunge and use buprenorphine off label for her pain condition and potentially be at some risk? Or do we need a new diagnosis that can then be coupled to the appropriate treatment? The appropriate treatment seems like you've figured out what you think is the best treatment. But the question is, can we map our system of care and our diagnostic system onto what our patients need? And that is always a goal here, which is we want our diagnoses and our treatment systems to map onto patient needs. I just have a couple of general comments to wrap up here. One, we did some recent work looking at the National Survey on Drug Use and Health. And for the first time, starting in 2021, maybe in 2020, but we started using the data in 2021 to look at the new way that the National Survey ascertains prescription use disorder. Up through 2019, the screening question was basically, do you misuse an opioid medication? So it asked people about taking it other than under a doctor's order or in any way that a doctor didn't recommend. It's a pretty well-crafted, thoughtful question, but it's extra medical use was sort of the screening question. If you said, no, I've never taken it other than as prescribed, we didn't ask you anything else in that survey. Didn't ask you about tolerance, withdrawal, didn't ask you about hazardous use, didn't ask you about organizing your life around it, spending too much time trying to control it. We didn't ask any of those symptoms. Starting in 2021, they changed the survey to ask about any use of prescription opioids. So with a prescription or extra medically, they were all included. And then the symptoms were now asked of everyone who was classified as having reported that they used an opioid. That made a huge difference in the number of cases found. About 60% of the cases of a prescription opioid use disorder are in people that don't report any misuse. Now that's not contradicting the case we heard, because she didn't really meet any of those criteria. But I bet she would have said no if I'd asked her all those symptom questions. But it means that when we go out and ask our patients who are prescribed opioids about their development of continued use despite those medications causing them harm, maybe they've fallen down a number of times because of their medications, or they're getting real sleepy while they drive and crash their car. Those are typical harms that might have happened, and people will say yes to that. They'll say yes to organizing their life, spending too much time. We don't include tolerance and withdrawal, because if you didn't misuse, you're not supposed to include that. And even excluding those, a large number of people meet criteria who use these medications under medical supervision but still report some symptoms. So we do have room for understanding that clinicians caring for patients on long-term opioid therapy need to be aware and paying attention to not just typical misuse, but also some of the symptoms that can develop at some point. I think that's really what I wanted to highlight for you. I do think that you all are, this is the audience where paying attention to comorbidity is not something I have to explain or highlight. For general addiction medicine folks, sometimes that does need to be emphasized a little more. But for an addiction psychiatry group, that's what we were all trained to do for many years of development. I do think that there's a real question about do we need a separate diagnosis, or this more, a matching treatment to an already described situation of somebody who has complex, at least withdrawal, because that's really what you're addressing. Somebody who every time you reduce it, they're miserable and they have significant problems. That's a withdrawal syndrome. It's a, the case described was very difficult to manage, but that's at least what occurs to me. Do we need another diagnosis? Well, you might in order to justify high dose buprenorphine, but maybe we can use other ways to have buprenorphine tested and examined for patients who had been on immediate or short-acting opioids for an extended period and so you're transitioning them to what appears to me and to many of us to be a safer medication. With that, thank you very much. I'll turn it over to Dr. Drexler. We're gonna have time for some questions and discussion when we've all wrapped up, so thanks. Okay, thank you very much. So I'm going to give my perspective as well. And as Dr. Eden said in the beginning, really my perspective started when I started in VA central office as the Deputy National Director for Substance Use Disorders and one of my first tasks was being part of the VA DOD working group that was establishing new guidelines on opioids for chronic pain. And I learned a lot about the harms related to long-term opioid therapy and after reviewing the literature, we recommended against initiating opioids for chronic pain and the updated CDC guidelines also recommend and maybe even go a step further, they say most acute pain can be managed without opioids and opioids for acute pain is often the gateway into long-term opioid therapy. So I'm coming from both a frontline clinician perspective but also as a policy person who thought about what can we do to improve the healthcare of nine million veterans under our care. Oops, I'm not sure I know which way. Okay, thank you. Oh, no, that's my, sorry if I blinded someone. Okay, this one, the other green button, okay. So for this perspective, I'm thinking about societal pressures and issues, things outside of our clinics that also influence how we think about these illnesses and I'd like to step back all the way 150 years ago to the first epidemic in this country and then review a little bit the process of the DSM diagnostic changes over the years prior to what Dr. Compton just talked about and then bring it back to Ms. Morris. Ms. Morris is a typical patient that would have fit right into Dr. Herbert Cain's clinic in the 1870s. At that time, there was an explosion in the science of chemistry. We were able to isolate the morphine molecule from the opium poppy and concentrate it and we had also developed aseptic technique and a brand new tool, the hypodermic needle so that we could administer morphine intramuscularly and it was amazing. It really advanced the field of surgery. We could do surgery humanely and successfully and out of that enthusiasm for how well it worked in surgery, physicians, pharmacists, and lay people because there really wasn't a need for a prescription at that time except to get the hypodermic needle to administer it but started enthusiastically trying opioids for any and all kinds of pain and the typical patient at that time was an affluent housewife, middle-aged like Ms. Morris with rheumatism and what Dr. Cain described in his book, Drugs That Enslave, the opium, morphine, chloral, and hashish habits is that physicians would see their patients suffering feel compassion, want to relieve the pain immediately to give them time to find the underlying cause and what they found though was once the patient experienced morphine, they didn't want anything else and it was really hard to stop the morphine once you started it. So at that time, they called this a morphia habit and lots of things were tried. These ingredients and cocaine were often included in patent medicine so Congress passed the Pure Food and Drug Act to require us to label when we had an addicting substance in a patent medicine. That didn't really help. So in 1914, they passed the Harrison Narcotic Tax Act and that law and subsequent case law and interpretation and statute led to the current state that it's really illegal to prescribe narcotics to a narcotic addict and the law has lots of older terms in it that we keep updating our terms. So that was actually quite effective in that the number of new iatrogenic cases really just went away but it also created a new business for the criminal elements meeting the demand of the drug hunger that had been created and so there were still folks on the margins of society but the typical patient instead of being affluent and female was now poor and young and male and was using heroin which by the way was the brand name for diacetylmorphine as created by the Bayer Pharmaceutical Company. They got out of the business because of its bad reputation. They stopped making it but their brand name stuck. Oh, and before I moved on, this graph is just showing how the sales skyrocketed over 25 years and that's from Dr. Kane's book. Okay, so by the time the first DSM came out, heroin addiction was the primary. It was again, folks on the margins of society and so the first panel of experts at the APA classified drug addiction under sociopathic personality disorders. 10 years later, another decade later, we took it out of personality disorders and sociopathy and classified it as a non-psychotic mental disorder but again, this was largely just consensus of experts, not nearly as rigorous as what Dr. Becker described. By 1980 though, biological psychiatry was on the ascendancy, the research diagnostic criteria out of Washington University in St. Louis was used as the basis for DSM-3 and so these diagnostic criteria have the list of signs and symptoms that we're used to seeing. Some first version of that had already been researched to some degree and they said there was an umbrella substance use disorders, its own category and abuse which had the behavioral changes and dependence as we've already talked about had tolerance and withdrawal. Then something happened after 1980. It was the cocaine epidemic and that turned the idea that tolerance and withdrawal is what really drives the more severe end of the substance use disorder spectrum on its head because once someone uses opioids or alcohol long enough, they build up a tolerance, they try to stop, they experience withdrawal and then the pain of that withdrawal is what keeps them going. That's what we had thought for 100 years and then cocaine happened and people's lives were turned upside down but when it came to the withdrawal, managing the withdrawal was really pretty easy. You just need to give folks a safe place to sleep, let them sleep it off and the symptoms resolve and yet their lives were turned upside down. Families were destroyed, communities were destroyed and we were scratching our heads about what to do about it. A lot of research went into trying to understand what if it's not negative reinforcement, what's driving it and a lot of the pendulum swung to say, well, it must be the euphoria. Folks are chasing the euphoria and some patients would say that but I know when I was practicing in the early 90s at the Atlanta VA, my patients would come in and say, doc, it's not even fun anymore and I can't stop. So Terry Robinson and Kent Barrage did this massive review that was very influential to me. If you haven't read it, I recommend it to you, 1993 Brain Research Reviews and they said looking, they're basic science researchers and they said looking at all of this animal model research which I often have a hard time understanding, the negative reinforcement model and the positive reinforcement model, both are inadequate. They don't explain what we see in patients and they don't explain what we see in animal models. Why does drug craving persist after prolonged abstinence? If it's all due to withdrawal that drives craving, why do we see it after abstinence? Secondly, is wanting drugs the same as liking drugs? Does the euphoria, like in a dose response way, is the most amazing, compelling euphoria, does that accompany the most difficult addictions to treat? Half a million people die of tobacco dependence, nicotine intoxication. Meh. So putting all this together, what they came up with is that what all addicting substances have in common is they activate what they call the mesotelencephalic pathway. We would call it the mesolimbic dopamine pathway and what this pathway does for us normally, physiologically, is to help attribute incentive salience. What's the most important for survival? We have thousands of sensory inputs every day. Which ones do we pay attention to and which ones can we ignore? And the mesolimbic dopamine pathway helps us recognize what's important for survival, whether that's food or whether that's sex or whether that's escaping from danger. It's activated by all of those natural stimulants. On the other hand, it's also activated much more powerfully by addicting drugs. So this happens, as Dr. Compton pointed out, in the deep part of our brain where a lot of unconscious processes happen. So it really happens a lot outside of our conscious awareness. It doesn't matter why we take the drugs, whether it's to get high or to relieve pain. As long as we expose our brain to enough of the drugs, we can sensitize it so that our brain, our primitive brain, pays more attention to cues that the drug is available. That brings up this wanting, even if we don't like it anymore. So, we come back to the DSM and its iterations. Dr. Compton's already given us a bunch of details about this. So I will just say, 3R, you could still give someone a diagnosis of substance dependence just based on physiologic tolerance and withdrawal. If they had tolerance, if they had withdrawal, plus taking the substance to avoid withdrawal. And that was problematic for the reasons we've already talked about. By DSM-IV, the committee had eliminated that problem by putting withdrawal and using the substance to avoid withdrawal together. So you had tolerance, withdrawal, and then you needed at least one more sign of a behavioral problem, continued use, despite some kind of problem created by the drug. And if you had that more severe end of the spectrum, then abstinence was recommended. Then, while all this is going on with the cocaine epidemic amongst the addiction treatment community, there's this other movement that's happening, and that's the palliative care movement. So, the compassionate response to patients with pain, we were often withholding opioids for fear of patients becoming addicted. And many experts rightfully said, this isn't an issue at the end of life. We really should be more compassionate and be more willing to prescribe opioids. So we did, and it seemed to work well, and that led to an enthusiasm about prescribing opioids, once again, for other things besides end of life care. And into that came Purdue Pharma. They had already developed MS content, they had already made a lot of money selling Valium as mother's little helper, and then they created Oxycontin, a slow-release oxycodone, high-potent preparation. And they applied to the FDA for treatment of cancer pain, but in the very first year, when they obtained approval, in 1996, they were not able to get approval. In 1996, their very first marketing plan said, the cancer pain market is seven million patients, and it's pretty much saturated. If we really want to meet our sales goal of $1.4 billion in sales by 2001, we need to expand to a broader market, and there's 35 million back pain patients. So that's what we're gonna go after. And in 1997, the next marketing plan says, the major barrier to this is most physicians and most patients are worried about getting addicted. We need to allay those fears. So they put $250,000 for an educational grant, for a consensus panel to develop guidelines for opioids for non-malignant pain. Two years later, they created a terminology visual, $90,000 for addiction, physical dependence, and tolerance, which wouldn't have caught my attention, except that at this SOTA, I became aware of this document. In 2001, the American Pain Society, the American Academy of Pain Medicine, and ASAM, issued the statement, it appeared on their websites, saying physical dependence, which they really meant withdrawal, and tolerance and addiction are discrete and different phenomena that are often confused. I just said for 100 years, tolerance and withdrawal were thought to be really central to this phenomenon, whether we call it an opioid habit, or we call it narcotic addiction, or we call it narcotic dependence or opioid dependence, but now they're saying these are completely separate and different. Most specialists agree that patients treated with prolonged opioid therapy usually do develop physical dependence and sometimes develop tolerance, but usually do not develop addictive disorders. There were no references, there was no data, there was no peer review, and there was no disclosure of financial conflicts of interest. But this was highly influential, and it may have made its way into some of our other thinking about how to manage chronic pain. So Dr. Compton has already spoken to this. What I wanted to show was one of the graphs that the DSM committee used to make the decision to go from separate abuse versus dependence. And what I'll point out is this graph is for alcohol use disorder, but it's color-coded, and all the other ones from the papers that you shared with me, Dr. Compton, were not color-coded, so I'm going to stick with this one. They all look about the same. If DSM-IV was right, and abuse was separate from dependence, and abuse was milder and dependence was more severe, then this graph would have looked different. So let me explain the color-coding and what this shows, I think. So for factor analysis, what you want is a steep curve on each of these lines. Each line represents one of the DSM criteria. If it's color-coded black, it's a former DSM-IV dependence criteria. If it's color-coded red, it's abuse. And then the bright blue one is the new one that was proposed of strong urges to use or craving. And the steepness of the curve illustrates that it does distinguish disease from non-disease. And where it's placed, left to right, has something to do with severity of disease. So the ones on the left side of the curve, and I guess I do have a pointer here, like this one, that's the more common or mild end of the spectrum, whereas on this side, this is the more rare or severe, if you think of a progressive disease. So what I see when I look at this graph is this is like a ponytail, with lots of strands of hair that are overlapping and crossing. And they're all clustered together in one entity. So I think this illustrates nicely what Dr. Compton said earlier. Really all of these signs and symptoms travel together. I want to point out that there's this symptom of use longer in larger amounts than intended, is relatively mild for alcohol use disorder. But these others, and that's a former dependence criteria, but there's another dependence criteria on the other end. This bright black line is tolerance, and the one in the middle with the black squares is withdrawal. What you can see is these are right in the mix, in the middle of all these other symptoms. They overlap, and they're not out on the mild end by themselves as something that is benign. So I come back to the questions. Should we have an exception for tolerance and withdrawal? The assumption was that tolerance and withdrawal were normal and benign. They certainly occur commonly, but are they benign? I think the first, another step back question is, is long-term opioid therapy effective for chronic non-cancer pain? And I think we have some clues lately. Purdue Pharma back in 96 didn't really do comparative effectiveness trials, but Erin Krebs and her colleagues in VA have done one since. And for opioid-naive patients with either osteoarthritis or low back pain, if they're randomized to immediate-release OxyContin versus non-steroidal anti-inflammatory drugs, and given really state-of-the-art care to emphasize non-pharmacologic therapies and other movement therapies and that sort of thing, the NSAIDs are equally effective in pain function and somewhat better in pain intensity and better in terms of adverse events. So we've been prescribing a potentially toxic medication for non-life-threatening conditions, and from a public health perspective, it's been a disaster. And should we really even continue? Is it safe? As opioid pain reliever sales increased tenfold from 1990 to 2007, drug treatment admissions quadrupled and drug overdose deaths quadrupled. That was from Susan Oki's viewpoint in the New England Journal in 2010. We all know the rest of the story since then. Withdrawal is common. Is it benign? There's evidence that withdrawal predicts the other symptoms of OUD. And is tolerance benign? The risk of aberrant behaviors, as they say in the pain literature, the other OUD symptoms and overdose risk and falls and lots of other negative consequences increase in a dose-dependent manner, which means as the tolerance increases, the risk of these adverse events increase. So I'm arguing that maybe we shouldn't make an exception, that these two things really aren't benign. And then I don't want to go into a lot of detail about this. This is the next iteration from the industry. So this is an industry-sponsored study that was published by Debbie Hassan and colleagues in 2022 in our Green Journal, comparing further modifying the DSM criteria to say, but is the motivation for this criterion because of desire to relieve physical pain or is it because of desire to relieve emotional pain? Dr. Compton's already told us it's hard. The brain overlaps what those are. We can't really tell the difference very well. They also wanted to measure convergent validity, saying, well, patients who are taken from a substance use disorder treatment program, their symptoms converge with antisocial personality disorder. To me, this was kind of a crazy design that just perpetuates the stigma that drug addiction is a sociopathic personality disorder. So I'll just leave that to say the opioid pain manufacturers are still looking for ways to modify what we think of when we think of addiction so that they can continue to market their products. So can opioid-induced pain, that's what I've just said, be distinguished? One important thing to note is that pain is part of opioid withdrawal. After you start the opioids, because you want pain relief, once you develop tolerance and you experience withdrawal, you experience pain. And what I think might be an important distinguishing characteristic is Aaron Krebs taught us that if you have opioid-naive patients and you randomize them to NSAIDs or opioids, they're both equally effective. But for patients on long-term opioid therapy, the only thing that relieves their pain is the opioid, like Ms. Morris. I think that's because what she has is opioid-induced pain. She has a drug-induced condition in which her pain has been created by hypersensitization of neural circuits from long-term exposure to opioids. And of course, the only thing that relieves opioid withdrawal really effectively is more opioids. So do tolerance withdrawal and pain-motivated behaviors predict the risk of other opioid-related adverse events? Yes. Do patients on chronic pain treated without opioids manifest the DSM-5 pain-motivated criteria? That's the real question. That would be the right control group, is ask those PRISM-OP questions of patients whose chronic pain is managed without opioids, and do they have those aberrant behaviors? So I leave you back with these questions for discussion more broadly with the whole group. Is there a need to change the DSM-5 SUD diagnosis? We'd like to hear from you. In what ways? Are we happy with it the way it is? I'll just ask for a show of hands. Are we happy with DSM the way it is and DSM-5? Have we finally hit the sweet spot where we're capturing disease and not missing folks and not mischaracterizing them? No, nobody's happy with it. Okay. So now please speak up. And I don't know if our AV folks, oh, we have one microphone here. Please speak up. What ways do we need to change it? Mike Dawes, Addiction Psychiatry, BU and VA Boston. We wrestle with this a lot too, similar to you folks. I talk to our pain medicine folks a lot, and I think we're working formulation is you do the DSM the best it is, but you also look at function and impairment and how that factors in. So, and I mean, to do it well, I think you need to go back again and come up with some validated measures for impairment as well as the degree of pain and do item response theory for that and to see how it falls out, because it's really an empirical question. And that's something probably DSM, whatever is going to need to do. But I think better assessment of the functionality is really the key and asking yourselves, you know, does buprenorphine, sublocate, you know, all of these, do they help and what else can help? So, a lot of this is an empirical question that needs to be addressed. Thank you, Dr. Dawes. Hi there, Taras Reshduka from Queen's University, Canada. First of all, I would like to admire your fearless approach to the case, because most of us, if we hear about a case like this, a patient presents into a clinic, we cringe a little bit, because we know it's not going to be an easy ride. I just want to be a bit controversial here. So, question about taking patients off oxycodone. It's very arbitrary how we arrive to that decision. You presented the case with someone who had relatively good social adaptation skills. She was doing yoga, gardening, right? She was complaining of pain, and as you know, pain is a part of life, right? You were born in pain, you die in pain. So, why this decision made so unilaterally? Where is the approach to patient-centered care? She doesn't want to go off this medication. So, the question is to the group, are we treating our own anxiety, because policymakers saying, you know, this is not cool anymore, right? So now, I have a lot of students, I work in academic centers, I have a lot of young students becoming residents, leaving into independent practice, go into primary care, and the first thing that they do, they see a 75-year-old on benzos, or 65-year-old with rheumatoid arthritis on oxycodone, they're trying to take them off. So, what about the risk and benefits of this intervention? I've seen this 75-year-old of oxazepam being admitted with withdrawal seizures, and later with severe anxiety to inpatient psychiatric ward, and the patients who are off opiates, they go to the streets, there's meds available everywhere, and they overdose because they have not been properly educated. So, we as a profession, how we are preventing of do no harm. So, it's, ethically, it's very challenging case. I don't know, I don't think I have a question for you specifically, because I don't think, you know, anyone has an answer, but I just want us to stimulate some thinking. The question for Will, what's the high dose of buprenorphine for pain management? That's very straightforward question. Thank you. Really great points, and I would say, right, so, you know, if you take a case like Miss Morris, with her and many others like her, I would say, honestly, I wish she had never been started on opioids. I think where things got with these folks is really a failure of our system, but when we're meeting them where they are, I think that is a different question. You know, we've got to, and I guess the way we approached her, I would say, and I would invite Dr. Eaton's comment here, too, is that, like, we have something we think will be better for you. We have an approach that we think would be better than where you are now, but we don't better than where you are now, and starting with the offer of gain framing, you know, and if she disagrees, then if there's no overwhelming, compelling reason to force her, I mean, if she's having significant problems where it would be below the standard of practice to continue her opioids, then we must act, but if there's nothing like that, then it's really a matter of if she doesn't want to do it, we can't force it, but in this case, we did we force it? We gave her a constrained choice. Yeah, we gave her a constrained choice of, yeah. You know, I think your point is very well taken, and I think this is something that the field is really trying to figure out, benefits versus harm, and who gets to decide, you know, who's benefiting and what are the harms? This is a 59-year-old woman who's receiving quite high-dose opioids, and as she stays on it long-term, the harms are likely to continue to mount. It is not clear that, you know, she still has quite a bit of pain, still has a lot of anxiety related to things, and so there was really just a belief that we could hold her hand, that we could add a lot of additional support, we could provide evidence-based chronic pain, and we could get her to a safer place, and we could do so very slowly and gradually, but you're right, she kind of didn't take to that very well, and it was very difficult. So the alternative, I guess, that you're proposing is that we keep people on high-dose oxycodone for years and years and years and hope for the best, and I'm not sure that, you know, we just don't know. I don't think we know the outcome of that coin toss. Yes. So your other question was about high-dose buprenorphine, and really that's all of our pain formulations are really low-dose. Transnormal buccal buprenorphine, the highest we really can get is less than four milligrams sublingual buprenorphine. For somebody who's been maintained on 270 milligrams morphine equivalents, that dose of buprenorphine isn't going to touch her. So we really do have to go for the off-label sublingual buprenorphine products if we're going to really match her opioid needs. Was that, did you want to say something else? I want to add one reflection from what Dr. Drexler highlighted for us. The treatment guidelines that the VA promulgated and what CDC has now promulgated in two different versions are mostly around when you're first starting somebody on a pain medication. So avoiding opioids to begin with is a very clear message. I could say the same thing about benzodiazepines, where many of us have struggled with, what do you do with a patient who's been on them and is now older and beginning to fall down because of them? And yet when you taper them, they have horrible withdrawal symptoms, as we heard, and may end up in the emergency department or worse because of withdrawal. And the taper from a benzo is even more difficult than an opioid taper. So that's just an example of how avoiding this is an important lesson, I think, for all of us. I really appreciated the history in this area. When we look at how China responded to their opioid crisis around the turn of the 19th to 20th century, they stopped all opioids. But for the large population that was currently taking them, they allowed them to continue. So there was a population gradual reduction over time. I don't know enough about it to have the details. But in some ways, the patient you described is somebody who was, sounds like, probably mistreated 10 or 15 years earlier, when there might have been alternatives that could have suited her just as well and might not have left her with this risk 15 years later. But we're in the uncomfortable position, and really the thorny position, of how do you manage it? I would like to say that research will have the answers to this. And I think we will have research that can shed light on it and maybe provide some alternatives. But in some ways, that's what the issue around transition to buprenorphine is all about. And how do we create a system where high-dose buprenorphine might be acceptable for these persons on high-dose opioids that don't really have an opioid use disorder? Because as much as we talked about it, that patient didn't. Please. Hi. Kevin Severino, Yale University. Great talk. Just to follow up on the previous discussion, could you clarify for me when the patient was on their 180 milligrams of immediate release of oxycodone, what was their level of pain and what was the evidence of impaired function at that point? So when they came to us, they continued to have muscle spasms. They continued to have low back pain. But they were functioning okay. They were going out with friends. They were doing, loved to garden. And they were doing all right. They came to us, mostly they'd been on it for seven years. Cancer was in remission. So the original reason for having started was no longer particularly relevant. And they were on very high doses. Right. Was she seeking in any way higher dose? Nope. No. So I do question the idea that we came to the conclusion that harm outweighed benefit at that point. And then the other thing is I do wonder how much we'd be discussing the need for a new diagnosis if we didn't have the stigma of what it means to ascribe an opioid use disorder. So if this were ascribing SI joint dysfunction, even diabetes, aside from insurance issues, we might think about it differently. We might just take the practical approach. Let's give her an OUD so we can use the high dose but we still put our substance use disorders in this different category, both for us and the patients where we're a little afraid to ascribe those. And I understand that. Thanks. Thanks, Kevin. I am mindful of time. We'll stick around for more questions. But if people need to leave, that's fine as well. I also want to say this case. We can talk about the particulars of the case. It mostly was illustrative to have a conversation around what to do. There are a lot of patients that do have harms that are outweighing the benefits and you need to begin to initiate a taper and it's still quite the struggle. So I just want to say, so I'm Dina, work in West Virginia, and I am so happy we have this discussion today because my colleague and I actually were med psychers and addiction psychiatrists. We run clinics like this and we have many patients who their PCPs no longer prescribe high dose narcotics and then they come and they know me and Dr. Naza and they just kind of send them to our clinic and we're like, well, oh my God, we'll be diagnosed because they definitely don't meet addiction criteria, but yeah, definitely mild SUD. So for documentation purposes and for legal purposes, what we do is say you have mild opioid use disorder, not addiction, you have chronic pain, you're not a candidate for buccal, you're not a candidate for the patch because your equivalents don't kind of meet up with that. And we do get buprenorphine. And so we're pretty careful in how we document because other prescribers looking at that will think if you have OUD and don't say not addiction, then all of a sudden, you know, you're treated differently. There's a stigma around that. So question number three, a separate diagnosis, maybe more so because of the stigma related to it and to those with opioid use disorders. But in terms of what it is physiologically, to me, it's pretty much the same. I don't know if we need a separate thing other than just associated with the stigma, but I'm so happy we had this conversation. And please don't report us to the CDC. Okay. Thank you. Hi, I'm Marcus Vicari. I'm a PGI3 psychiatry resident at Beth Israel in Boston. Yeah, so coming back to my second question, I think it applies to everybody. This was just really helpful because it applies to kind of a case that I saw on Monday. So I guess I'm wondering, you know, what do you do when things are a little bit, how would you kind of characterize this when things are a little bit more murky, even than this case where I had, like, let's say the patient is taking, not being pushed to come off of the dose, but is taking an extra dose because they know that they have built up tolerance and that they felt, okay, this is no longer helping for my pain as much, so they start taking more, but then run out, like, two to three days early. And then, so I was just really having difficulty kind of assessing how do you kind of really assess the criteria because, you know, most of the tolerance withdrawal is related to the prescribed opioids, but then, you know, they wouldn't be going into withdrawal if they, you know, weren't taking the extra five milligrams of oxycodone of their 40 milligram per day prescription in addition to 180 milligrams of morphine they send to release per day. So yeah, that kind of got into more even trickier waters in, like, how would you, I guess, navigate characterizing that whereas, like, there is a component of the patient, like, doing, you know, taking more than what is actually prescribed, so not actually following the prescription. And but still the majority of what they're taking is prescribed. In general, the way we will make a pitch to a patient is it is clear that you're having a great deal of pain. It sounds like the oxycodone works for you, but it's starting to lose its effectiveness. The dose that you were on, you're probably developing some tolerance. You're wondering if perhaps a higher dose would work. I have a better medication for you, I think, a medication that will be longer acting, a medication that's going to be much safer, and I think it's going to really help you in this situation so that you're not running out or you're not needing more. And perhaps because it's so long acting, you're not going to be thinking about taking the medication so often. Patients usually, Dr. Becker and I published just that patients really like having an alternative. Not many patients love being on opioids. They say the reason I'm on this opioid is because while I have chronic pain, but also nothing else works, and if I stop, it's no good either. And so a lot of patients feel stuck, and that's often the phrase that we will use, you feel stuck. And honestly, I can't tell you how many patients, when we say that, often will get tears in their eyes and say, yes, I feel stuck. And so when they have an alternative that probably will work better, my son's calling, asking for internet access. Anyway, they're very happy. I got a call during my presentation from my wife to ask whether today was the day to change the cat litter. Thank you. Last question. Hi, Bill Jangvro. I'm an addiction psychiatrist from Thomas Jefferson University in Philadelphia. Great talk. Thank you for bringing up these really difficult cases. I guess I have more of a comment about how to, I mean, one thing that we've all kind of hinted at, a lot of us have hinted at, is just discussing with a patient an exit strategy, maybe. I had a very similar case presented to me from a primary care doctor, a woman who has been on, I mean, literally 400 morphine milligram equivalents per day of oxycodone. She's got obstructive sleep apnea. There's nothing really horrible right this moment. I mean, she's living, she just stays at home, but the doctor is getting kind of concerned about continuing to prescribe this, and the patient wants to come off, but is also afraid. The way I kind of brought it up was, well, where do you see yourself in five years, in 10 years, do you still want to be on this? You're saying you're in 10 out of 10 pain, and yet you're on an extremely high dose of this medication. Maybe this is not that effective for you, and it's hard to get that buy-in, and we're still struggling with her. I mean, the long-term plan is to try to get this woman onto buprenorphine, but I think we have a ways to go, because she's just on so much oxycodone and oxycontin right now. But I was just thinking maybe that is something that we can all kind of agree on, is that you should just keep having these discussions with patients over time, and then hopefully it doesn't come to having to make an ultimatum. And maybe not just with chronic pain patients, but even in our opioid treatment program, we have patients on methadone who have been abstinent from non-medical opioids for decades, and they're getting older. They can't make it to a methadone program every day, or it's getting very difficult. They have loosened the federal regs in terms of take-home bottles, but it's hard to get there. And I'll say the same thing to them. Do you want to be on 200 milligrams of methadone when you're 70 years old, when you're 80 years old? These patients are aging, and they're surviving. We've actually done somewhat of a good job of keeping patients with OUD alive, I think, in some of our opioid treatment programs. So I guess, again, it's just more of a comment about maybe a different way of looking at it, rather than trying to separate it and figure out is it this or that, which is very challenging, is just to keep having these discussions and saying, you know, eventually we should try to get you off of this if we can. And the more time we devote to it, the easier it'll be, because, you know, maybe we can just take off like a milligram every couple of months or even every couple of years, rather than waiting until there's a crisis, you know, and you're falling and hitting your head, and nobody's willing to prescribe it. Let's do it on your terms now. So sorry about my long-winded comment, but thank you. Thank you. Thank you all very much for joining us today.

long-term opioid therapy

chronic pain

DSM-5

opioid use disorder

diagnostic frameworks

addiction specialists

pain management

buprenorphine

tolerance

withdrawal symptoms

public health

treatment ethics

patient-centered approach

pharmaceutical interests

diagnosis

Dr. Will Becker

Dr. Wilson Compton

Dr. Karen Drexler

Dr. Ellen Edens

Condition X

tolerance and withdrawal

prescription opioid dependence