Okay. Good afternoon, everybody. Welcome to today's AOAAM and ORN's webinar on benzodiazepines and opioid maintenance treatment, the risks and the benefits, by Dr. Tae-Woo Park. I know him as Ted. My name, Ted Park. My name is Julie Kimmick and I'll be your moderator for this session. This is the first of a six-hour webinar series on hot topics in the treatment of opioid use disorder. Funding for this initiative that was made possible in part by a grant from SAMHSA, the views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services, nor does the mention of trade names, commercial practices or organizations imply endorsement by the U.S. government. I'd like to go over a couple of housekeeping things here to start. The webinar will be recorded and accessible on the AOAAM website. During the webinar, please ask questions for the presenter in the Q&A box. Questions will be answered at the end of the session or next week during our follow-up session. If you have housekeeping questions, like you're having problems with the audio or something like that, please enter them in the chat box. As a note, all participants have been muted and your cameras are off as this session is being recorded. I'd like to introduce Dr. Ted Park. He's an addiction psychiatrist and a researcher. He is certified by the American Board of Psychiatry and Neurology in general adult psychiatry and addiction psychiatry. He attended Case Western Reserve University School of Medicine and completed a general psychiatry residency and addiction psychiatry fellowship at Western Psychiatric Institute and Clinic at the University of Pittsburgh Medical Center. After he completed his clinical fellowship, he completed the Veterans Affairs Interprofessional Advanced Fellowship in Addiction Treatment at the Boston VA Health Care System. During his research fellowship in Boston, Dr. Park conducted studies on mental health and addiction in primary care settings and the risks of benzodiazepine use in patients taking opioids for pain and addiction. Dr. Park was also at Brown University and during that time his research focused on patients, assisting patients in reducing benzodiazepine use and opioid maintenance treatment. So I'd like to turn it over to Dr. Park who's going to talk today about benzodiazepines and opioid maintenance treatment. Thanks, Dr. Kimmick. And thanks for the ORN to give me the opportunity to talk today about a topic that is very, that I'm very close to. Let Dr. Kimmick already said this. I have no disclosures to report and apparently neither does Dr. Kimmick. So I want to start with this slide because I think it reflects a lot of people's experience. It certainly reflected mine. I took this from a Psychiatric Times article, an editorial piece or commentary where the author described a spectrum of attitudes toward benzodiazepine prescribing. And in this spectrum, there were more liberal prescribers and there were more conservative prescribers. And the conservative prescribers would only prescribe in very select situations like alcohol withdrawal, acute psychosis, acute mania, that sort of thing. And then more liberal prescribers would be prescribing in a long-term fashion and even to those who had substance use disorders. And when I was finishing up my clinical fellowship and I moved to Boston, in Pittsburgh where I was doing my clinical work, I'm sorry, training, I found that the providers tended to be, and my attendings tended to be very conservative in their benzo prescribing. So it was a real eye-opening experience when I moved to Boston where I was working in a methadone clinic and the attending there was prescribing benzodiazepine to almost all the patients in the clinic. And I was doing a research fellowship. It made me really wonder, can we do this safely? And so I started to do a series of studies that I'm going to talk about today that described sort of my journey with studying this topic area. So the first study that we set out to do was just to estimate the prevalence of benzodiazepine co-prescribing among people who were receiving methadone or buprenorphine in the VA nationwide. And we broke this up. If you know the VA system, they break up their geographical areas by VISN. And so that's what we did. We looked at VISN by VISN to see how much co-prescribing of benzodiazepine was going on. And what we found was that in buprenorphine, it ranged from 11% to 39%, depending on the VISN, and 7% to 24% in methadone, depending on the VISN. So there was this geographical variation in co-prescribing. And in some VISNs, it was always a minority, but it was sometimes quite a substantial minority. And the way we interpreted this variation in practice was that it reflected prescriber uncertainty. Is it safe to prescribe benzodiazepines to people on methadone? People weren't necessarily sure. And so that really did sort of set me off onto this path of wanting to know whether it was safe or not. Now, around the same time, there was an increasing prevalence of not just prescribing benzodiazepines for people in opioid maintenance treatment, but a larger population of patients who were receiving opioid analgesics for pain. So from 2002 to 2014, benzodiazepine co-prescribing increased by 41%, from 6.8% to almost 10%. And between 2001 to 2010, benzodiazepines were co-prescribed at 16% of chronic pain visits. Benzodiazepine use was more common in those with a substance use disorder history and in people who had higher opioid doses. So presumably, this high-risk group, high-risk for overdose among the opioids for pain group, that the high-risk group were more likely to be getting benzodiazepines, which could be compounding the risk of overdose. And when you looked at the data, I think many of you are familiar with this data. It just shows that on the y-axis here is the number of overdose deaths, and on the x-axis is time. And you can see that, of course, we've seen this great growth in overdoses, not just in amongst all drugs, but particularly in this time period, we saw a lot of prescription opioid overdoses. So one of the first studies that we set out to do was really to examine the risk of benzodiazepine co-prescribing in people who are getting opioids for pain. So the research questions we were asking were, is benzodiazepine co-prescription in patients receiving opioids for pain associated with increased risk of aberrant drug behaviors? So examples of aberrant drug behaviors would be early refills, selling or diverting their medications, or illicit drug use. And also, we were interested, of course, in whether or not prescribing benzos had an association with overdose death. So this is, I'm just going to really briefly go over the results of these studies, because it's not the main direction of the talk, but I think it does inform it somewhat. Now, this was the results for the study when we looked at a small sample of primary care patients who were getting opioids for pain. And what we found was that the risk of an early refill, of an early opioid refill, was increased with the associated, I'm sorry, the benzodiazepine prescription was associated with an increase in early refills, but was not associated with cocaine use. And in the larger study, this was a VA-based study, we did look to see if benzos were associated with overdose death. And in this larger study, we used something called a case cohort design, where we looked at all the VA patients who died of a drug overdose during 2004 to 2009, there were 2,400 of those individuals. And then we looked at annual 5% random samples of the base population, ending up with 420,000 unique patients. This was the whole cohort, plus the 2,400. And what we were looking at were, we were comparing times, so current times, so these were times when individuals were actively exposed to benzodiazepines. Former involved times when people who had formerly been prescribed a benzodiazepine, but weren't currently prescribed. And then there were times when people who had never been prescribed a benzodiazepine were included. And we were comparing these three different groups. And then we looked at the benzodiazepine dose, and we broke that down by diazepam dose equivalents. And this was our result. What we found was that, and I think the real headline here is that when you are currently being exposed to a benzodiazepine prescription, you were at four times higher risk of dying of an overdose. And then when we looked this, broke it down by dose, we found that there was a dose effect, that is, the higher the dose, the higher the risk of overdose. And around the time these publications were coming out, the New England Journal published an article or a commentary about our other prescription drug problem, describing benzodiazepines as an epidemic. There were increasing deaths related to benzodiazepines. So this is from NIDA, actually it's from the CDC, where they found that these blue bars are the total number of benzodiazepine-related overdoses was increasing over time amongst both men and women. And somewhat related to that, in Massachusetts in 2013 to 2014, over half of all opioid-related deaths had benzodiazepines in the top screen. And 22% of those had benzodiazepine prescriptions within three months of death. So most likely, this increase in benzodiazepine-related mortality was being driven by opioid-related deaths. So in terms of prior work that had been done around benzodiazepines and overdose in opioid maintenance treatment, benzodiazepine use in methadone maintenance treatment was associated with increased risk of overdose death. And that was in two studies, one a cohort study in Scotland and another case control study in England. Now, the question, I think a logical question is, if benzos are so bad and have these risks, why are people being prescribed them? Why are up to 40% of people in the VA on buprenorphine being prescribed them? Well, one of the big reasons is because benzodiazepines are effective. And this is from a meta-analysis that looked at generalized anxiety disorder, panic disorder, and social anxiety disorder. And what they found was that according to the clinical trials, benzodiazepines are effective treatments for anxiety disorders. And I think we can all understand that anxiety and relapse can go together, that anxiety is associated with relapse and poor treatment outcomes in substance use disorders. One study found that there was five times increased risk of readmission for alcohol treatment. Another study found that anxiety symptoms were associated with worse addiction treatment outcomes. And so I think it's important to understand that patient-centered treatment it's important to understand that patients can often suffer. And it's very common for people to have anxiety and to treat that anxiety. It's very important, not just because it's the right thing to do to treat their anxiety disorder, but also because it can lead to relapse. Another thing that I was very interested in and that we examined in the study that I'm about to talk about was whether or not there was a relationship between benzodiazepines and treatment retention. And at that point in time, there had been one study out of the UK that found that benzodiazepine prescription was associated with increased methadone treatment retention, but it was really unknown in the buprenorphine patient population. So I'm going to talk about two studies in depth today. One of them is a quantitative study, and in this we looked at the relationship between benzodiazepines, buprenorphine, and overdose death. And so the research questions we were asking in this study, is benzodiazepine prescription associated with increased risk of overdose or all-cause mortality in patients receiving buprenorphine treatment? And also is benzodiazepine prescription associated with improved treatment retention amongst those receiving buprenorphine? So in Massachusetts, a law was passed in 2015 to study the opioid overdose epidemic. And a part of this law was creating a data warehouse, or a data set, really. And it was subsequently called the Massachusetts Public Health Data Warehouse. And what this was, was it combined data sets from across different state agencies. The study that I'm going to talk about used the all-payer claims database in the state, the Registry of Vital Records and Statistics, which has to do with death records. In terms of, in this study, it has to do with cause of death. And they also looked at the prescription monitoring database to draw prescriptions from, controlled prescriptions. The acute hospital case mix, that's all the inpatient stays. And then the ambulance trip record information system and the Bureau of Substance Addiction Services. So this was a retrospective cohort study. We were looking at years 2012 to 2015. We included all adults with at least one buprenorphine prescription. And we included both buprenorphine and buprenorphine naloxone. And included, I'm sorry, excluded implant and patch formulations because those were typically being used for pain. And participants could have multiple treatment episodes and participants could have multiple treatment episodes that they could enter and they could exit and enter again into the cohort. The outcomes we were looking at, we looked at four outcomes. One was non-fatal opioid overdose. Another was fatal opioid overdose. We were also looking at all-cause mortality and then buprenorphine discontinuation. Our main exposure was concurrent benzodiazepine treatment. This was a Cox regression approach. We restricted to when patients were receiving buprenorphine. And then we adjusted for various demographic, patient demographics, health services use, and mental disorders. And so this is our sample that we were looking at. It was about 60, a little over 60,000 patients. People, women were more likely to get a benzodiazepine. So about 20, I believe 27% of the sample was getting a benzodiazepine at some point during the study period. Slightly older, this is the benzo group, slightly older and more likely to have a mental health condition or to be, had a recent mental health related encounter. Specifically, we were looking at acute encounters like ED visits and hospital stays. In terms of our outcomes, what we found was that there were 693 total non-fatal opioid overdoses, 183 fatal overdoses, and 369 all-cause deaths. Now, remember this is only during the time when people were on buprenorphine. And at the time, Massachusetts was having thousands of deaths total over that time period. So I think it's important to remember that these deaths, it was very rare for patients to have died of an opioid overdose while they were in treatment on buprenorphine. This is our final adjusted results. And what we found was that receipt of a benzodiazepine prescription was associated with twice the risk of a non-fatal opioid overdose, was almost three times increased risk of having a fatal opioid overdose, almost twice the increased risk of dying of any reason or any cause, but also was associated with a decreased risk of buprenorphine discontinuation, suggesting that there were risks. And I think that our findings sort of tracked what we had found in other populations who were getting opioids when it came to benzos. But we also found that there may be a potential benefit in that patients who received benzos tended to stay in buprenorphine treatment longer. And I think we all understand that buprenorphine works as a treatment in terms of decreasing the risk of overdose. And so other studies were coming out that were similar around the same time in Sweden. They published a study that found that there was around a two times increased risk of all-cause mortality when combining benzodiazepines with OMT. And most of these patients were getting methadone, I believe. And then out of the UK, another study came out that looked at the same topic area and found that there was about a three times increased risk of overdose death when combining benzodiazepines with, again, mostly methadone patients. And more recently, there was a study out of St. Louis that found that there was about a 1.5 times increased risk of non-fatal opioid, I'm sorry, non-fatal overdoses when combining high-dose benzos with buprenorphine. And what they also found actually was that there was an even smaller risk. It wasn't statistically significant, but probably in practicality, there was a slight increased risk of low-dose benzodiazepine prescription with buprenorphine. So just to sum up what, you know, some of the potential risks and benefits of benzo use in opioid maintenance treatment are, I mean, potentially it can increase the risk of overdose death and mortality in opioid maintenance treatment. And then I didn't talk much about this, but benzodiazepines are potentially addictive. So if you prescribe patients, especially this group who have a history of addiction, they may be more likely to become addicted to the benzodiazepine itself. And then in terms of potential benefits, these are efficacious treatments for anxiety and potentially prescribing benzodiazepines may improve treatment retention in opioid maintenance treatment. We also conducted a qualitative study. And what we did is we interviewed patients and providers about benzo use in opioid maintenance treatment. Sorry, this paper is no longer under review as published this year in the Journal of Substance Abuse Treatment. In terms of our research In terms of our research questions, what we're asking was that among patients and clinicians receiving and delivering opioid maintenance treatment, what were the motivations for benzodiazepine use and prescribing? And what are the patient and clinician understanding of the risks and benefits of benzodiazepine use? In this study, we interviewed 26 patients and 10 clinicians. And the patients were all receiving opioid maintenance treatment and were using benzodiazepines on a regular basis. And the clinicians were just clinicians all working in opioid maintenance treatment clinics. We sampled from one office-based buprenorphine clinic and one local methadone clinic. And the interviews were conducted and transcribed by myself and two research assistants. And we had developed a semi-structured interview based on topic areas that we had chosen a priority. All the transcriptions were reviewed by myself and entered into this qualitative software, qualitative software that we had developed. And we also developed a qualitative software, qualitative study software called Indivivo. The data analysis was largely guided by thematic analysis. We coded, me and the research assistants, we coded and developed, we coded the interviews or the transcripts of the interviews and developed a codebook. And then after coding, we identified major themes that we found in the relationships between them. So again, there were 26 patients, 10 clinicians. The mean patient age was 43, 43 years old. 65% of the patient sample was receiving methadone and about half were being prescribed benzodiazepines. The rest had either been prescribed them in the past and were no longer using them or were taking benzodiazepines that they had obtained off the street. The clinicians included addiction specialists, physicians, both psychiatrists and internists, nurses, and addiction counselors. So I'm just going to go through some of the themes that we, we, that came out of the interviews. So one of the main motivations, I think this is pretty straightforward, is that patients were taking benzodiazepines to feel calmer. Without the benzos, I feel like I had a lot more panic attacks. I had a lot more going on in my head and I felt like I couldn't get my head to stop racing. So I would say that I was a lot more pent up and fearful when I wasn't on the benzos. Another motivation was to get high. When I got on methadone, yes, definitely, because I didn't know that when you take a benzo on methadone, you get this high feeling because they say it's like twice as much as you take. So if you take one Klonopin, it has the effect of two. So in the beginning, I definitely took them to get that high feeling and get a head change. Another, so those are motivations. Some consequences that we found were that people became over sedated when they combined the medications. When I overdo them, I'm falling asleep on the train, getting woken up. There's been periods where I get on the train at three o'clock in the afternoon and I get woken up at one in the morning trying to get off the train. But patients also talked about how benzos did help them feel normal. Just simple little things like walking down the street would really bother my anxiety. And now I don't have that feeling anymore. I feel like I'm able to do normal things. Other patients spoke about benzodiazepines helping with drug cravings. I think that they've helped me. I don't have cravings. I know that methadone helps with that. But the two together combined, the two together combined helped me not to have the anxiety and not to have the cravings. One of the major themes that we discovered looking at these interviews was that patients often learned how to use benzodiazepines safely. My experience has been to take them as needed. And I can kind of tell if I take them too long or taking too many during the day, I'll be more sleepy and out of it. But I don't want to be out of it. I just kind of want to be calm and be neutral. I think they're a good thing and they're a bad thing. It just depends on where you are in your life or your addiction. I really like this quote because I feel like it does kind of reflect the yin and yang or the good and the bad or, you know, the sort of duality that benzodiazepines can be for patients. But it is what we did find very commonly was that patients entering into treatment tended to, you know, who were starting off like in methadone or, you know, entering in early recovery tended to have problems taking benzodiazepines safely while patients who were further along in their care tended to do better with them. In a sense, they learned how to sort of minimize some of the risks on their own. There was also a strong sort of desire from a lot of the patients to stop using benzodiazepines. Some of the reasons were wanting to be substance-free. I'd like to not be taking them. I'd like by then to have found a way to get through these negative feelings without taking a pill. Another was needing to be dependent on providers. That is that patients didn't want to be dependent on providers. And that was one of the reasons why they would want to stop taking benzodiazepines. Not really, other than the fact that five years from now, a doctor might say, hey, we're taking you off of them, which was something that happened to a lot of the patients that we interviewed. Another group of patients talked about how stopping benzodiazepines would reflect some sort of accomplishment. Of course, I would love to quit benzodiazepines, nothing more than to just have the White House with a picket fence and a family and be able to be content and happy. But until that happens, I get stuck in my head way too much. All right, so when we looked at the provider interviews, one of the main things that really struck me was that patients and providers had different priorities and goals. So these are from some provider interviews. My understanding of the research is that benzodiazepines are not good long-term treatments for anxiety and they're better for a short-term treatment. And long-term, the risks outweigh the benefits. Because we're the medical professionals. Patients, they're not thinking about benzos, I mean about safety. They're just like, oh my God, I'm always anxious. I have to have this for me to be calm. That's where their mind is. I mean, it seems like most people that I've encountered want to stay on them indefinitely. And that might conflict with what my goals are for the patient, based on maybe what they're presenting with. And so I just wanna reflect on this a little bit. I think that maybe thinking about this, it's quite obvious, and especially maybe with your own patient interactions, this happens. But what we really found was that patients tended to focus more on the benefits of taking benzodiazepines over the risks. They were aware of the risks, but they were more focused on how it could help them. While providers were much more concerned about the risks of benzodiazepines rather than the benefits, and sometimes questioned the benefits. And you can imagine that in a situation, in a scenario like that, if that's happening every day in the clinic, and there's this sort of disagreement right from the start, you can see how this can be a difficult clinical situation for both the patient and the provider. So just a summary of the qualitative study, opioid use disorder patients use benzodiazepines both in safe and unsafe ways. Patients learn to use benzodiazepines safely and are more able to do so when stable in opioid use disorder treatment. Patients commonly aspire to discontinue benzodiazepines. And that really has, I think if you're experienced in treating people with buprenorphine or methadone, this has more to do, I think, with just patients not wanting to be on medications at all. And I'm sure you've had situations where patients will enter treatment very early in recovery, say, how long can I, when can I get off of this medication? And that's, I think, a fairly common theme that a lot of patients deal with. And then lastly, patients prioritize the benefits of benzodiazepine therapy and providers prioritize the risks. So I'm just gonna briefly go through some sort of practical approaches on prescribing benzodiazepines to people with opioid use disorder. This is the last part of the talk. And I think probably the healthiest way, not just the healthiest, but maybe the smartest way to approach this difficult clinical situation is using a risk-benefit framework. I've been talking a lot about risks and benefits, and I think it really applies when it comes to how you're gonna actually deal with patients. And the important thing here is you're judging the treatment, not the patient. So it would be inappropriate to be asking the following questions. Is the patient a good or bad person? Does the patient deserve benzodiazepine treatment? Should this patient be punished or rewarded? Should I trust them? Maybe more appropriately, I think we should be thinking about these patients and we should be asking, do the benefits of this treatment outweigh the risks in this patient or to society as a whole? So in terms of just a preliminary guideline for prescribing generally, some of the research that I've been looking at today that we did, I think it's a good rule of thumb to not prescribe to people who are actively using illicit opioids. Because what we found was that people who are actively using illicit opioids really had problems controlling their benzo use or using them in safer ways. And so I think it's a good rule of thumb to not prescribe to people who are actively using illicit opioids really had problems controlling their benzo use or using them in safer ways and tended to misuse them. And then I like to prescribe only after trying non-benzodiazepine alternatives. I think that makes sense. You're going from, your algorithm is going from safe to less safe. And so you would start with SSRIs, SNRIs and other medications. If you have access to psychotherapy, I think that could be very helpful. If you can get the patients to engage in it. So safe to unsafe, or less safe, I should say. And then in terms of when, if you do decide to prescribe a benzodiazepine, you really want to assess the potential benefits. So you assess current function and then you ask what can the patient expect to do with their medication that they can't do now. And you can think of the medication prescription as a test. And then after that test, you assess benefit. So, or the opposite of benefit, right? You can assess harm. So you reassess factors affecting symptoms. You reattempt to treat on the underlying disease and comorbidities. And you could consider increasing the dose as a test. And if there's no effect, that means there's no benefit. And the benefit then can't outweigh the risks. And so you'd want to discontinue the medication. And then likewise, you're assessing for potential risks. And those risks might be sedation, overdose, et cetera, addiction or diversion. It's important to use a consistent approach across your patients, but you want to set the level of monitoring to match the risk. And when the risks outweigh the benefits, you stop the medication. And in terms of, I mentioned monitoring, you would use monitoring and universal precautions in a lot of respects. We're a bit lucky in opioid maintenance treatment because we're, well, this is pre-pandemic, where we're getting regular drug testing. We often have, we're often more than just one physician or one prescriber. We have, like, especially in methadone, there's a number of ancillary staff and there's nurses and there's a lot of people who can place eyes on the patients. And increasingly, even in buprenorphine treatment, we're having more and more nursing staff, MAs, therapists, et cetera, who are also working with the patient and can help with this monitoring process. So, but specifically, some clinics use contracts or agreement forms. Most use drug screening. In terms of safe prescribing, you can prescribe small quantities. You can ask patients to come more frequently. You can do pill counts, which can be a bit onerous at times, but some clinics have the ability to do this. And of course, you can check the prescription monitoring database for any abnormalities in terms of control prescriptions. Now, I mentioned that if the risks outweigh the benefits or there are no benefits, then you should just stop the medication. Of course, that's easier said than done for patients who are, who have been taking benzodiazepines regularly. This is, I think amongst psychiatrists, it's one of the hardest things we have to do. And there have been a number of clinical trials that have looked at how to discontinue benzodiazepines. Almost none of them were done with patients who had substance use disorders or were in opioid maintenance. What they did find in that, and so this is mostly adults in primary care or general medicine or older adults who are regularly using benzos, sometimes for sleep, sometimes for anxiety. Gradually, I mean, this is sort of, I think that some of the meta-analysis of these studies were pretty obvious. The first one was that gradual benzodiazepine tapers are more effective than routine care. You know, it's interesting. The literature doesn't really define questions like, you know, should we switch them to a long-acting benzodiazepine? How long should the taper be? What else should we be giving them in terms of medications and other treatments? The one other treatment that seemed to really help people successfully discontinue benzodiazepines was adding a psychosocial intervention to the taper to help patients complete the taper and continue to be benzodiazepine-free at three or six months, I think sometimes up to a year follow-up. So, and that intervention, the psychosocial intervention, the most studied were CBT or variants of CBT. And I believe that that's what I have for you today. So I think there is some time to answer questions. Okay, thank you so much, Dr. Park. That was a great overview of the research and the work that you've done and the research that you've reviewed as well. We do have some questions. Somebody had asked, in the VA study, were deaths of the same demographics as a random comparison sample? Yeah, it was the same group. So all of the people who died were of the same sort of larger cohort. We were just sampling, we sampled both from the, so there's a larger base population of people who are using opioids for pain or taking opioids for pain. And I wish I had the table here of the people I don't think I have a table comparing the demographics of the people who died and people who didn't die. But yes, we were sampling from the same base population, both the cohort and the cases. Maybe that would be something to you next week if you wanted to have that table on the slides or something like that, and you wanted to go over it, we could always do that too. Go ahead. Next question was, does retention in treatment account for those who died? Does retention in treatment account for those who died? I.e., was the denominator those who remained alive or was it all patients in the associated studies? Can you repeat? Let me see this. I can't look at this one. For the Q&A. Does retention in treatment account for those who died? The denominator of those who remained alive or was it all patients in the, I see. So in that respect, so in these studies, if someone dies, they're censored and no longer contribute to the study. They don't contribute person time to the study. I'm not sure if that gets at your question, but in that sense, the answer is yes, it does account for the people who died. Okay. Next one was, did the benzodiazepine overdose deaths have buprenorphine in their system at the time of death? Were they taking the buprenorphine or was it just prescribed since prescribed doesn't really mean it's taken? You're absolutely right. And this is a major, this is not, it's not to say a major flaw, but it's a flaw of all pharmacoepidemiology studies when you look at prescriptions because unfortunately we can't, and actually this, you know, this goes for randomized control trials as well. They're not regularly testing. You know, if you did a randomized control trial of benzodiazepine prescribing, you don't always do a test to see if there's benzos in their system. But in the same respect, no, we don't have that data. We're making assumptions in terms of whether or not they're taking the benzos. They could not be taking them. And oftentimes we don't expect 100% adherence to the treatment. So, you know, some people are taking more, some people are taking less, some people could be supplementing off the street. So that is a limitation of the study. Okay. Let's see. Somebody had commented, I wonder if it's truly possible to take benzodiazepines PRN long-term or ideal because many of my patients are prescribed them TID long-term and come into the clinic appearing sedated. So I think that was more just a comment there. How much time do you recommend the patient try an SSRI and psychotherapy before considering benzos? Does this vary based on the diagnosis? So in terms of how much time, I mean, you know, generally speaking for an SSRI, you're gonna wanna want the patient to be on medication for something like six to eight weeks and at an effective dose or a potentially effective dose. So I would at least give it that much amount of time. And, you know, sometimes, you know, this is a, it's a variable group. There are a number of, there's a substantial group of patients who are gonna be coming from day one saying, I've tried, you know, I've tried Prozac, I've tried Zoloft, I've tried Slex, I've tried Effexor. And then you say, have you tried Cymbalta? And they say, yes, I've tried that one too. And then, and then they're really, some of them will be more straightforward and ask about whether or not they can receive a benzodiazepine. You know, other people will talk about how their past experiences with benzodiazepines are very helpful. I don't necessarily, you know, that right there, in those situations, you're gonna have to use clinical judgment. I think that sometimes it's better to sort of try something documented. And then if that's not gonna work, then you can move on. I think the risk there is that patients will just at that point. And I've had that happen many times before. But I think it's important, you know, just like all the same principles in terms of patient engagement and trying to keep them engaged and trying to get them to understand that you're trying to help them, you understand their condition and that you will try what's necessary in order to help them. And sometimes that alone will keep them engaged in the clinic whether you give them a benzo or not. Okay. Somebody had commented that in their experience, anxiety in patients on methadone or buprenorphine was directly dependent on low or insufficient dose of the medication for opioid use disorder and greatly improved with methadone or buprenorphine dose increase due to improved withdrawal symptoms and anxiety as symptoms of opioid withdrawal. So wondering if you had a comment on that. Yeah, I mean, I think at least in my experience that opioids can be an anxiolytic. And I think that quite obvious when it comes to short acting elicit opioids that patients are not, and are probably escaping from some of their anxiety symptoms or their trauma symptoms by using opioids. In terms of methadone and buprenorphine, I think in particular buprenorphine has limited, most likely limited effects when it comes to being an anxiolytic, especially for patients who are, I found that patients wishing for methadone or buprenorphine tend to have an onset of anxiety symptoms maybe that were being suppressed by methadone. And also we have dose limits when it comes to the partial agonist and there's a ceiling effect. And so even if it did have an anxiety, anxiolytic effect is probably, it has a limitation. And, but I do think that what you're saying there or writing there is not untrue. We had a question about the study. Did your study include patients that were taking benzos illicitly? Or if not, do you feel the data would correlate? Some of my patients are taking benzos illicitly and I'm concerned since I'm prescribing their buprenorphine and the overdose and death risk they're worried about, but I feel it's less dangerous than heroin plus a benzo. What are your thoughts on this? So the studies did, we're only looking at prescribed benzodiazepines because this is a limitation of using these sort of large administrative databases. A lot of these were put together for insurance purposes and don't have a lot of the clinical data like drug tests. So we don't know if they were using illicitly or we don't have a great signal of whether they were using illicitly. And so we primarily were studying prescribed benzos. In terms of what you're writing there, there's a couple of things that it makes me think of. One is, I've had a lot of patients who take benzos illicitly or buying from the street or getting them from their family members. And they're not necessarily using them in ways that I would worry about. That is, they're using them in sort of controlled fashions, not a big dose, but are really trying to treat some underlying condition. And sometimes they're just using it sporadically when they have a panic attack or they're having real problems sleeping or that sort of thing. And they're not taking them in large quantities. And so the question there would be, as the provider, is it better or safer to be the prescriber rather than them getting illicitly off the street, which has its own risks? And I think that's something that you'd have to consider as the provider. And then the other part of that is the risk of, I think you're absolutely right. The risk of, in fact, this has been shown in the research is that people who take benzodiazepines in the absence of buprenorphine who have an opioid use disorder are at higher risk of overdose than people who are taking benzodiazepines in the setting of receiving buprenorphine. So, and that suggests that when someone's in buprenorphine, they're getting, they're engaged in clinical treatment and engaged in maybe a larger, sort of more sort of coordinated and has more of a clinical infrastructure to help take care of the patient rather than someone who's maybe just, getting benzodiazepines from one provider, not in opioid use disorder treatment, despite having opioid use disorder. Those people tend to be at higher risk. Now, I have a couple of question statements and it seems like they're related to states. One is Ohio law restricts concurrent prescribing of MAT and benzos. I think after 90 days to taper, it requires prescription only by a board certified addictionologist or psychiatrist with addiction certification. Is this the case in most states? I am unaware of this law. Dr. Kermit, do you know this law? No, I'm not sure. I'm originally from Ohio too. I went to medical school there. That's something new for me. I haven't heard that. I mean, I know that in Massachusetts, for example, the attorney general here was going after certain clinics that were, had really abnormal prescribing practices when it came to benzos and opioids. But I don't know about a state that has a law like this since we certainly don't have it here. Okay. And there was one about Oregon. So I was trying to find that one again. Let's see. It was somewhat of a similar. Yeah, I'm reading it now. Yeah, the Oregon Medical Board. Yeah, well, often sanctioned providers that prescribe benzos and suboxone, force tapers, transfer care to another provider. I don't know how to ask this, but how do I avoid getting in trouble? Should I just document well, use low doses of benzos, like less than two milligrams of Klonopin per day? You know, I, it's funny because I think that some of the research that I've published has had an impact on like, has had some policy impact. So for example, the medical board might, or in Ohio too, Oregon and Ohio might be doing some of this because we've, and others have found that there's this increased risk associated with the co-prescribing. But I think that those studies only tell really sort of half the picture. It's really hard to, without a randomized trial, to study this topic area. It's specifically to study the benefits or the potential benefits of benzodiazepine prescribing. Now I'm not up here saying that everybody should get a benzo. You know, I think that, but I do think that it can be done, prescribed to a select group of patients who could do pretty well and get benefits. And there's a way to do it that can minimize risks. Now, I think it's unfortunate though, that like this has led to policies that seem a bit, that could have destabilizing, a destabilizing effect on patients. You know, this is, you've probably encountered patients who have been taking benzodiazepines for a long period of time, who've been prescribed them, have been stable, have not used any illicit drugs and have been doing quite well. And you can imagine in a situation like that, if a board of medicine is saying, you know, you got to take those patients off, you're essentially forcing these patients into tapers against their will. And you could do some damage in terms of where they are in their recovery. So I generally don't agree with that approach. It sounds like there was somebody in the audience too, and a few people agreed, gave us the thumbs up on his question. In patients who've been on benzos for a prolonged period of time, maybe years, even decades, I found in 40 years of addiction practice that it's virtually impossible to taper them off with benzodiazepines, even with prolonged inpatient or residential treatment. My practice has become one of harm reduction as long as there's no evidence of significant over sedation. You know, I think that, you know, so there's a couple of things going on. I think that there is, it depends on the sample of patient. So of course, if you're not looking at addiction population, there's plenty of evidence that you can taper people off with benzos long-term. Although the risk of relapse is quite high, and that being said. But, you know, there's long-term sort of studies that have looked at patients entering a trial of benzo discontinuation and being able to successfully be discontinued years later. So I do think that it's possible. I do also think it's possible for our patients in terms of our addiction patients. Now, I don't, those long-term studies have not typically included addiction patients. So I'm leaving the opportunity or the possibility that Dr. Wartenberg here is stating that, you know, that is very difficult. And I don't disagree with that. In terms of the practice of harm reduction, I wholeheartedly support. I think that you really do. I think in that risk benefit sort of approach, that framework, you do have to wonder, you know, if patients are going to be taking these medications off the street and are gonna get them off the street which has risks, take them in sort of unsupervised ways, you do have to wonder, is it better? Is it not better to be, have that patient in your care where you're prescribing, you're regularly testing them and you have some impact in terms of their treatment and how the benzodiazepine is being managed. And I think it's an important question to ask. Yeah, it looks like we have four minutes left. So I think maybe just this one last comment here, question, and then we'll, any questions that were unanswered today, we can roll them over into next week. But this kind of dovetails off of what you were saying about benzos off the street. Any thoughts on prescribing to people who are using illicit benzos in addition to opioids, both on admission and in methadone or buprenorphine treatment? In my area of Central Texas, we have a lot of pressed fake Xanax with fentanyl in them. If patients are ready to take a longer acting benzodiazepine in a regular and safer manner, I generally prescribe as the risk of continuing illicit Xanax is so high. The studies you mentioned besides yours didn't seem to address illicit benzodiazepine use. So, yes, this is an issue here as well in Boston where people are taking pressed pills that have fentanyl in them, and that can lead to overdose. That can lead to problems in terms of people who have legal issues or have connections with departments of children's and families, et cetera. So these tests are important even if it's only a small amount of fentanyl that they're taking inadvertently. So there are risks with these pressed pills. And I think I had earlier mentioned about how to, the question is, what do you do in those situations? Should you take over and manage the benzodiazepine treatment? And I really do think it has to do with your clinical judgment and weighing the risks and benefits about whether or not you think you can do it safely. And I think the comparison, what you're comparing there is, is it safer for you to be the prescriber than for the patient to be getting illicit benzodiazepines and potentially taking these pressed pills off the street. So I think that in those situations, if that's ongoing, and you generally have very little sort of, it's hard to say, the most direct way or the most direct intervention in those situations oftentimes is for you to become the prescriber. And so what I would suggest that if you're going to do that, then you try to do that as a test and see if you can do it safely and see if the patient can adhere to the sort of treatment guidelines that you set up. Okay. Well, thank you very much for your webinar today. Now we are going to have a webinar next week and Dr. Park is going to have case discussion and also continue answering questions that may not have been answered during today's session or that people might think of in the upcoming days. So if you do have a question for Dr. Park that you'd like to have answered, you can go to the AOA website where you registered for this webinar and on the education page, enter the question on the discussion board and we'll pass them along to him on Monday. So make sure you get your questions into us by Monday. And then on next Wednesday, August 25th at five o'clock, we're going to reconvene and talk about this very important topic again and expand upon it. So thank you very much for attending and we'll see you next week. Thanks, Dr. Park. Bye.

benzodiazepines

opioid maintenance treatment

risks and benefits

geographical variation

aberrant drug behaviors

qualitative study

calmer and manage anxiety

practical approaches

risk-benefit framework