Okay, it's five o'clock. We're going to begin our webinar today. Welcome. This is AOAAM and Opioid Response Network. Our webinar on benzodiazepines and opioid maintenance treatment, the risks and the benefits of case studies and question and answer period by Dr. Tebu Park. My name is Julie Timmick and I'll be your moderator for this session. This is the second of a six hour webinar series on hot topics and the treatment of opioid use disorder. You can see funding for this initiative was made part by a grant from SAMHSA and 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 US government. The earlier slides went over the housekeeping for this webinar here. And I'd like to introduce again today, Dr. Ted Park. He's an addiction psychiatrist and researcher. He's 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 as part of the University of Pittsburgh Medical Center. After completion of his clinical fellowship, he completed the VA Interprofessional Advanced Fellowship in Addiction Treatment at the Boston VA Healthcare 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 or addiction. So I'd like to welcome Dr. Park. Thanks, Dr. Kimmick. And thank you for the opportunity to talk about this topic. So today, so last week, for those who attended, I gave a general didactic about the risks and benefits of benzodiazepine use in opioid maintenance treatment. And this week, I'm going to go over a couple case studies of patients of mine. And at the end, I'm also going to bring up some questions that weren't addressed at last week's lecture. So I have no, neither Dr. Kamek or myself have any disclosures to report. So I'm going to dive right into the first case. The first case is a 50-year-old female and she came in reporting that her anxiety and panic had been out of control and I need to get back on my meds. So she had a long history of polysubstance use disorder, which I'm going to get into, into greater detail. And she was currently on buprenorphine maintenance treatment for opioid use disorder. Benzodiazepines had been prescribed or had been prescribed to her for the past 30 years. She has severe anxiety and panic attacks and agoraphobia with dizziness, flushing, shortness of breath, and fear of leaving her home. Benzodiazepines were helpful in reducing these symptoms, along with other symptoms. And she stated that benzodiazepines were the only thing that works because she had tried a bunch of other drugs and medications and benzodiazepines helped her the most. Now, she was prescribed clonazepam, two milligrams, three times a day for approximately 10 years. And then she switched providers when her old provider left and her new provider had her taper down to one milligram TID about eight years ago. So in the past, she had been prescribed both alprazolam and clonazepam, again, with doses up to one milligram TID. But when she was at one milligram TID and had this new provider eight years ago, the taper took from two milligrams TID to one milligram TID. The taper took two years, a very long time. The patient was against the taper from the beginning. And when she initially started the taper, she had an increase in anxiety and panic, had several lapses to opioids and cocaine across the two years that the taper took place. And she was supplementing her dose with benzodiazepines that she was buying off the street. Eventually, with help from her therapist, she stopped using drugs completely and her street benzodiazepines, in part because she had a daughter. Her daughter had had a daughter herself, and the daughter was saying she didn't want anything to do with her mother until she stopped using drugs. And that was a big motivation for her to stop. So she eventually accepted that she was going to be on one milligram three times a day, and she stopped using everything else. Now, before I saw her, that psychiatrist who had her on one milligram TID of clonazepam left her practice. And she was then transferred to another provider who immediately said one milligram TID is too much clonazepam. And that provider wanted to taper the clonapin further with the aim of discontinuation. Now, just a little bit of backdrop. So after the taper to one milligram TID of clonazepam, the patient did quite well. You know, the patient stopped using drugs, you know, was active or was retained in treatment, you know, just regular drug testing and really had done well up until this new provider said, let's get rid of the clonapin. That, of course, sparked a big reaction from the patient. The patient was against further taper reports, constant crying, feeling terrified, as well as intense drug cravings. And at that point, the patient came to me. So some substance use history. The patient has a very extensive substance use history. She had started using stimulants, cocaine, in particular, H-12, crack cocaine at age 14. And she had a very extensive substance use history. she had been using off and on for 30 years until about five years ago, five, six years ago. And cocaine was her drug of choice. She started using opioids in her 20s. She was prescribed a Percocet. I'm sorry, she had started using opioids regularly in her 20s. She was prescribed Percocet, then Dilaudid after a fall that broke her jaw after she became intoxicated from alcohol and other drugs at age 25. She was prescribed Dilaudid for about a year and then she was discontinued. That, she then, after she was discontinued, started to use heroin intranasally and progressed eventually to IV drug use. After about a year and a half of IV heroin use, she started treatment with buprenorphine and has been on buprenorphine for the past 15 years. Her last opioid use was approximately eight years ago. So it was around the time that she was tapering her benzos. In terms of benzodiazepines, she has a long history of benzo use as well. Some of it against her will. She was given by diazepam in her food by both her mother and her mother's boyfriend at a young age, at age 11. The mother's boyfriend was doing it so that she would fall asleep so that he could abuse her. The mother was giving her Alprazolam to calm her because at a young age, she was showing a lot of self-destructive symptoms. She started getting Alprazolam prescribed to her at age 18 and was taking more than prescribed right away. She described that she was parting and this was a sort of, she wasn't using them in a safe way. Let's put it that way. She was eventually transitioned to clonazepam two milligrams three times a day at age 26. That's when she really appreciated that it helped her symptoms and she started taking it responsibly. In terms of alcohol, she started drinking heavily at age 16. She was drinking about a six pack of beer a day. That accelerated over time to in her early 20s. She was drinking a fifth of liquor daily and she was kind of drinking off and on amongst other drug use until she completely stopped drinking at age 35. She had a pretty severe history of alcohol withdrawal. She reported delirium tremens as well as multiple inpatient detoxes for both benzodiazepines and alcohol. Marijuana, she used more consistently and regularly when she was younger. More recently, she only uses, she uses very occasionally a couple of times a month and purely as a recreational thing to sort of relax and have fun. She has a complicated mental health history. So she had a long history of childhood physical and sexual abuse. Her mother was 18 years old when she had her and was addicted to heroin and would leave the patient as a child with different people, different caregivers at different times for different periods of time. And sometimes she didn't know who these people were. Sometimes they were, oftentimes they were family members. Sometimes she didn't even know who they were. And based on that, due to that neglect, suffered a fair amount of abuse as a child. She reports being afraid a lot as a kid. She had a lot of generalized social anxiety as a child. She reports that her panic attacks started at age 11. She used to pull her hair and she cut herself frequently at age 11. And she reports that the self-harm sort of calmed some of her symptoms, her anxiety symptoms, gave her a sense of control over her life, which she lacked otherwise. And she reports that benzodiazepines helped, you know, prevent or reduce some of the speeds of self-harming behavior. She reports a long history of mood episodes. She had clear depressive episodes starting as a child and had manic episodes as well. She reports manic episodes with increased energy, decreased need for sleep and high irritability and anger. And these would last for several days in a row. Now, those symptoms have since declined and she was, in terms of her mood episodes, was under better control when I met her. She had a history of suicide attempts, five suicide attempts. The first was at age eight and most recently was over 20 years ago. So this was, it had been some time since she had contemplated suicide or had been hospitalized. She had three previous psychiatric hospitalizations. The last was about 15 years ago. Her medications when I met her, she was on aripiprazole, 10 milligrams daily, citalopram, 40 milligrams daily, bupropion, S-HARA, 150 milligrams, BID, gabapentin, 800 milligrams, BID, clonidine, 0.2 milligrams QHS, buprenorphine, naloxone, 16 slash four. And she, you know, she was also on, I forget to mention here, clonidine, but I didn't put it on the list. She was on two milligrams, she had been, by the time I'd see her, she had gone from three milligrams to two milligrams daily. She was also very well engaged in psychotherapy. She had had the same therapist for 10 years and she'd been meeting with him, this is an outside therapist, for 10 years, but more regularly over the past five, sometimes on a weekly basis, just depending on what was going on with her at the time. I know that during the pandemic, she was meeting with her therapist weekly. Surprisingly, she had no past medical history when I met her. In terms of her social history, she was living in her own apartment with her boyfriend of nine years, her daughter, and her granddaughter. So her daughter, who was 30 years old, ran away at age 15, but moved back four years ago. With her child, after the patient showed that she wasn't using drugs anymore. The patient has a GED, she went to college for a year. She's had several jobs in retail, restaurant, and office work. She stopped working about 20 years ago after being fired and she was able to get disability. So she's been receiving disability for mental health problems for the last 20 years. So on exam, she appeared 50 years old, she was crying, she was upset, she was anxious. It's very tangential, I think that is her baseline. And grossly, her cognition was intact. And again, she was coming because she had, she had had her Klonopin dose reduced from three milligrams to two milligrams. And she was very, very, very, very anxious. So she had her Klonopin dose reduced from three milligrams to two milligrams. And just a little bit more information, she, at this point, she was saying that she was gonna drop out of the clinic. She was saying her, to her buprenorphine provider, who was not her benzodiazepine prescriber, that she wanted to leave the clinic. She wanted to just find another provider because it was very important for her to be able to get this dose of Klonopin. And also was saying that she wanted to use, and there's a, she was in a great distress when I met her. And her buprenorphine prescriber actually reached out to me because I knew the buprenorphine prescriber and I also knew the benzodiazepine prescriber. And we came up with a plan afterwards. So just, this is, I've never done a Q&A, or I'm sorry, I've never done a case conference online like this, but I thought, you know, these are better with discussion. So any thoughts on how this patient should be treated or managed? I realized that this isn't the best format for this. So it looks like people are entering some things in the Q&A. Okay. Yeah. Well, in terms of for Venzo use, that's a great, great comment. I haven't told you if the Venzo use was causing any problems. It hadn't been really causing any problems. It was treating her anxiety. It was, you know, she wasn't misusing it. So there was no real aberrant drug taking behavior like early refills. Again, she wasn't using any illicit drugs and we had monitoring of this because she was active in or engaged in opioid maintenance treatment. The provider was working off of just the belief that these medications shouldn't be combined. And therefore it was pushing for a taper. I'm sorry, it wasn't pushing for a taper, it demanded a taper. Close monitoring. Absolutely. I think anybody who is getting a co-prescribed benzodiazepine while they're in opioid maintenance treatment should be closely monitored because there are risks associated with Venzo prescribing. Discharge to another practice. You know, we were really trying to keep this patient who had been really engaged, well engaged with opioid maintenance treatment for years now and was doing well. We would prefer to not have this patient go to another outside practice given that she had already had good relationships with some of her providers. But yes, I mean, she was gonna force that issue, I think, if we hadn't acted. Inpatient care. You know, I think that if there was a motivation on her part to discontinue the benzodiazepine, inpatient is an option. Although my feeling, inpatient in order to help her detox off the benzodiazepine that is. She didn't quite need psychiatric inpatient care at that point because I didn't sense that she was gonna harm herself or that she was unsafe at home. The issue, maybe I can go into this later in a second. I'll go into this a little bit later about inpatient care in a second case. Clear indication for erythrofresol, she had a diagnosis of bipolar disorder. Complicated history, but is it wise to keep her on benzos? That's the question. That's why I'm really raising this case. And I will touch on that in a little bit. Legal issues, no. She didn't have any outstanding legal issues. And she was really able to function at home. She was able to help take care of her granddaughter. She was a good partner. I mean, she had a lot of anxiety still and would have period bouts of mild depression. But you know, yeah, she was functioning well. My heart was, yeah, she was really, she's a really sympathetic person. I mean, she has been through, I mean, I really have to give it, I gave credit to her, just because she's been through so much. And she's been able to get through it. And so, I think that she felt a sense of betrayal, I think, from her providers, because she'd been really doing well. And this was more sort of external from her in terms of wanting to, other people wanting her to get off the benzodiazepine. And then slowly tapering her. Yeah, I mean, I think that that is an option. It can be addressed with the patient. I'll go into that a little bit more. I've had benzo prescribers who never checked urine. When we started buprenorphine and started urine screens, we found they were substituting street Xanax. Yeah, I mean, it's very possible that this patient has been, you know, getting street benzodiazepines and supplementing, or, you know, has been, the problem is that the urine drug tests are very particular for benzodiazepines. And since I don't have a slide on that later, I can talk about that just briefly now. So, the benzodiazepine immunoassays, which are the qualitative tests, you know, do they have benzodiazepines in their system or not, were really designed for diazepam, which is one of the older benzodiazepines. So, diazepam and diazepam-like benzodiazepines, like L-Prazolam, the immunoassay does a very good job of detecting whether or not someone's using a benzodiazepine or not. For the newer benzodiazepines, like clonazepam and lorazepam, the urine drug tests, the immunoassays, don't do a very good job. So, for those benzodiazepine types, it's much better to get some kind of mass spec liquid chromatography or gas chromatography, a mass spec, to get an accurate reading of whether or not someone is using or not, or taking them or not. All right, let's see. I would try everything I can to help her. It seems to really want help. She's currently compliant. I agree with all of that. It's far safer to prescribe immunotherapy or methadone with benzodiazepine use, either illicit or illicit, rather than full agonist opioid use with heroin and fentanyl. Her overdose risk would be much higher with heroin and fentanyl use and benzos than on either beep or meth. And that is very true, and definitely, I think, should be part of the risk-benefit calculation that we should be making as prescribers. Is it safer for this patient to disengage with care and use illicit drugs, you know, and get street benzos? If that's the comparison, then, obviously, it's much better to give her benzodiazepines in the setting of buprenorphine, because the other is more risky. Let's see. Holistic approaches. I can't get into that right now. Does your clinic prescribe other psych medications with buprenorphine? Yes. Continuing clonazepam with post-mortem and continuing to encourage tapering very slowly, I think that's a good approach. I will talk about Z-drugs at the very end, and then not be sure about the amount of benzos taken by, that's true, this, again, it's hard to know exactly how many benzos someone's taking. You can take a look at somebody's overall sort of, usually somebody who is taking street benzos to supplement their prescription or even not supplement prescription are aiming to use the drug in a misused way or an unsafe way. And typically, those patients will reveal themselves in a sense, because if you're misusing benzos, you're over-sedated, you don't look like you can have an appointment because you're falling asleep or you're having, or you're doing reports or you're ending up in an emergency room and you're getting reports from different places. So this patient, on the other hand, had been in a clinic and stable for several years, and those things weren't happening. And so I felt fairly confident that this patient wasn't taking medications off the street. Sino problem with continuation of panazepam and alternate treatment of anxieties. Successful, patient stable with no reports of sedation or intoxication, no events of aversion, continue close monitoring and coordination of care with all prescribers critical. I agree with all of those points. I'm just gonna go on here. So just again, when you're weighing the risks and benefits, I talked about this in the last talk last week. So some potential risks with benzo use, you can increase the risk of overdose death and mortality in opioid maintenance treatment when people use benzos on top of their opioid maintenance treatment. There is a risk of becoming addicted to the benzodiazepine, but there are benefits as well. Benzodiazepines are efficacious treatments for anxiety and in this case, distress. It treated her distress. It did in her case, prevent drug cravings, and it can overall population level can improve retention in opioid maintenance treatment. So one question I think that's worth asking for this patient and someone commented on this, if there were any signs of problems with the benzodiazepine is, does this patient have benzodiazepine use disorder? I pulled up the DSM-5 criteria just to kind of help us and I think it's good to revisit it. I will say this before I get into these criteria. It can be hard to diagnose benzodiazepine use disorder in somebody who is being prescribed benzodiazepines for treatment of some condition. Just like a parallel would be, it is hard to detect opioid use disorder in someone who is receiving chronic opioid analgesics for pain. When people sometimes have exacerbations of pain or in this case, anxiety, they may act like behave in ways that are similar to someone who's addicted to those drugs. But anyway, so the DSM-5 diagnostic criteria, problematic pattern of use leading to clinically significant impairment or distress manifested by at least two of the following in a 12 month period, taken in larger amounts over a longer period than intended, persistent desire on successful efforts to cut down or control use, great deal of time spent on obtaining substance, craving for the substance, recurring use resulting in failure to fulfill major role obligations, continued use despite recurring social or interpersonal problems, recurring use in situations in which it's physically hazardous, continued use despite knowledge of having a recurrent problem caused by use. And then there's tolerance and withdrawal, but these criteria are only used who aren't prescribed benzodiazepines. So using these criteria, I did not feel that she had benzodiazepine use disorder. You could make the argument that she had unsuccessful efforts to cut down or control use, but she wasn't really having problems controlling the use. She wasn't taking more than prescribed. She was taking her prescribed amount. If any, well, anyway, I'll keep going here. I just wanted to reference a couple clinics. There's a couple studies out there. These are mostly observational studies. These aren't randomized trials, so they have some limitations, but there were a couple reports of these clinics that used a benzodiazepine maintenance treatment, and I thought it would be worthwhile just kind of reviewing them really quickly. So there was a clinic in Tel Aviv, a methadone clinic in Tel Aviv, and they had 66 patients with benzodiazepine use disorder. They offered one of two treatments, clonazepam detox or clonazepam maintenance. Again, this was not a randomized trial. The detox group received an eight-week taper of clonazepam. The maintenance group started at clonazepam, two milligrams TID, and then gradually tapered them to an individual maintenance dose, and then they kept on, they stayed on that dose. Medication was taken while observed, so this might not have as much relevance to people who are working in methadone clinics, but the medication was taken while observed on the weekdays only. They were given weekend after take-homes. Now, their primary outcome, they've labeled failure. So they define that by excessive benzodiazepine use by patient self-report or clinician observation two times. During the study period, and what they found was that at 12 months, 86% of the detox group had failed, failed, I should say, and 34.6% of the maintenance group had failed. So fewer of the maintenance group failed treatment, that is, didn't have these episodes of excessive benzodiazepine use. So that's one clinic that seems to suggest that at least in these methadone patients, you could maintain them if you're dosing them almost daily and observing it. Now, a second clinic in London was doing a very similar thing. They reported 278 patients, 80 had never received a benzodiazepine, 71 had briefly or occasionally received a benzodiazepine, and 127 received a benzodiazepine maintenance. Now, what is benzodiazepine maintenance? In this case, it was up to 30 milligrams per day of diazepam or eight milligrams per day of Klonopin. They had observed daily dosing until all illicit drug use had stopped. And at that point, because they were checking their drug screens, and at that point, they started getting take-homes. And they got more and more take-homes as they continued to do well in terms of their drug screens. And what they found when they looked at the results for these different groups, were the maintenance group at baseline had higher incidence of alcohol use disorder, injection drug use, and psychiatric disorder. So this benzodiazepine maintenance group tended to have, was a more severely ill group. But when they looked at the outcomes, the maintenance group had better treatment retention compared to other groups, and lower in-treatment mortality compared to the group that never received a benzodiazepine. And then they also found that, interesting, that mortality rate increased for all the groups, for those who dropped out of methadone, but it increased much at a greater, much greater rate among those in the benzodiazepine maintenance group after leaving treatment. So again, mortality rate, once people left methadone, as expected, mortality rate went up, but it went much higher for the people who were getting benzodiazepines prescribed by the clinic regularly. So I wanted to throw these in there just to show that it is possible that patients can be maintained on benzodiazepines, and sometimes the outcomes can be beneficial. Now, these were fairly unsophisticated analyses, and especially this last study didn't really control for confounders. So I will put that as another limitation. So back to the patient, in terms of her clinical course, as some had suggested, I did increase the Klonopin back to one milligram TID, the patient stabilized, and she still remains in treatment after a year post that dose change. There hasn't been any evidence of illicit drug use. Despite some mood fluctuation during the pandemic, she's done quite well. And really the reason why I wanted to bring this case up was because I think that if you were going to force a taper of benzodiazepines against the patient's will, then you shouldn't do it without just cause, or explicit and specific cause. So if your cause is because on a population level, benzodiazepines have been found to increase the risk of bad outcomes. I don't think in this particular case that that's a good reason to force a benzodiazepine taper. I think if the patient had signs of misuse, had overdosed or had been taking more than prescribed, then I think a discussion about a benzodiazepine taper should be discussed or should be considered. Not in this case when someone had shown years of stability and doing well. So all I'm saying here is that I had presented data that benzodiazepines can be risky, but I do think that you should apply that data on a case-by-case basis. And that's the overarching point of this case. In the interest of time, I'm just gonna push on here. So the second case is a 33-year-old male. This was a patient who stated upfront that benzos are my drug of choice. I love benzos. He was using to lessen his chronic agitation and restlessness, but he also had a lot of negative consequences of benzodiazepine use. It made him forgetful. He would lose things. He'd become overstated. He'd been fired at work because he was intoxicated from overuse of benzodiazepines. And so when we saw him, he had left early from inpatient detox for benzodiazepines about a month ago. He left after five days of a seven-day taper protocol, citing issues and conflict with the system. And we were seeing him in an emergency room-based bridge clinic. So it's a bit of a unique clinic, but people can come in on a walk-in basis. So when we evaluated him, so after he had left that inpatient detox, he had immediately restarted using benzodiazepines. And so we were able to see that he had a lot of issues with his body. So after he had left the detox, he had immediately restarted using benzodiazepines. He reported that he'd been using them since college. He uses as much as he can get, sometimes five to 10 milligrams of alprazolam or clonazepam per day. Recently, he had been using about four milligrams or of alprazolam or clonazepam per day. His longest period of abstinence was a few months while in jail. Most of his periods of abstinence were in sort of supervised settings or controlled environments. That is, he had no seizures or hospitalizations. He did have report one blackout and was considered an overdose from the benzodiazepines. So in terms of his substance use history, started using prescription opioids in college. He partied a lot, dropped out after five semesters. At age 22, he began using intranasal heroin and then slowly progressed to IV drug use. His prior medication for opioid use is sort of history. He had been getting buprenorphine for about six to seven years total. He was in methadone maintenance in 2010 on a max dose of 105 milligrams daily. But most recently, again, he was on buprenorphine. His last use of heroin and phenol was about two months prior to the presentation. And again, he was currently on maintenance buprenorphine, eight milligrams a day. In terms of stimulants, he began using cocaine in college. He used crack cocaine twice within the last month, but he stated that he doesn't really use it very often. He did occasionally use street Adderall. Last use was about four weeks ago. Denied alcohol use, was smoking marijuana daily, been doing that for some time. And smoked a pack a day. Terms of his mental health, psychiatric history, he had endorsed symptoms of generalized anxiety disorder, but denied other symptoms of different anxiety disorders, including panic, PTSD, or social anxiety disorder. He reported past diagnosis of ADHD and had been treated with stimulants in the past as a child in his childhood. Has had symptoms of depressive disorder in the past, but wasn't depressed currently. Denied any manic symptoms, denied history of suicide attempts or psychiatric hospitalizations. Terms of his past medical history and medications, he had no significant past medical history and was not taking any or was not being prescribed any medications aside from the buprenorphine. In terms of his social history, he was a high school graduate, dropped out of college. I'm sorry, but that's not very clear. He dropped out of college after two and a half years. His first year he did quite well, but then after that was his performance declined as he started using more drugs. Since then he'd been working different jobs in food delivery, sales, and factory work. Most recently he worked in an auto parts store, but was fired due to intoxication. He subsequently lost his housing, became homeless, and was at the time sleeping in his mother's backyard. He had a somewhat complicated relationship with his mother. He wasn't allowed in the house. He had recently broken up with his girlfriend, had a newborn baby who he had seen about a month prior the baby was being cared for by the baby's mother. So on initial exam, he was easily distracted, but cooperative, slurred speech, tangential, was forgetting things quickly and required for going redirection. In terms of assessment, we diagnosed him with severe benzodiazepine use disorder as his primary substance use disorder. No history of complicated withdrawal. Had overdosed in the past. Was intoxicated on benzodiazepines. Had been unable to complete a recent inpatient detox program. Had moderate opioid use disorder in early admission and was on stably on buprenorphine. And he was seeking outpatient withdrawal management for benzodiazepines. So just some questions for discussion. Is this patient a candidate for outpatient benzodiazepine detox? And how should he be treated? I'm just gonna make a comment, Dr. Park here. When you read the Q&A, the audience can't see them. So could you read those aloud? Oh, yeah, sure. Does he truly want help? Yes, this patient wanted, was motivated to stop taking benzodiazepines. At this point, he, you know, that's why he went to the inpatient detox. He felt that he was out of control with his benzodiazepine use. He was able to reflect that it was having a lot of negative effects on his life and wanted to discontinue. I think he should be admitted. One person said, I think he should be admitted for inpatient treatment. Well, he had tried to do inpatient treatment and it didn't work out. Now that shouldn't mean that he shouldn't go try another inpatient treatment. I think that there's a possibility that that could work. I will say this, there have not been any trials that compare inpatient versus outpatient detoxification. Now, there are some indications, you know, there are some recommendations by ASAM, for example, that can help you determine whether or not someone would be better off inpatient versus outpatient. I think there are safety issues. You know, if this person had had severe withdrawal in the past with seizures and other medical complications, you might, that might be a indication for somebody going inpatient for their detox or, you know, had severe sort of, you know, mental health issues or other medical issues, you know, you might want to put them, you might want to recommend inpatient at that point. Now this patient didn't have any of those. So you could do the inpatient detox, they would accept him. But in this case, I think that an outpatient detox is or was an option. And the other thing here is that typically with, and this is a generalization, I don't know if there's evidence for this. But it's, I feel that shorter tapers, like one week, which this would have been two weeks, may be less effective long-term in terms of successfully taking somebody off of a benzo versus a longer taper. And I think that, you know, patients tend to develop, you know, I'm going to stop there. That is my belief. I think a longer taper has better results if you looked on the aggregate. In terms of using a gabapentin protocol, that's an interesting suggestion. I don't know if gabapentin protocols have been used in benzo tapers. I know that obviously benzodiazepines have been used in terms of getting people off of benzodiazepines as well as phenobarbital. But I don't, unless there's been something recent, oh, you know, I think there has been some small studies that looked at gabapentin and found some success in terms of benzodiazepine detox. So that could be an option. And then treating ADHD and GDD in the meantime, that is something that we did. Using the Ashton manual protocol, it's been a while since I've looked at that. Benzodiazepines are his drug of choice, correct. Most outpatient detox programs are too short for somebody, um, sorry, that question disappeared. You know, there are programs, ambulatory detox programs that can last a while. And I'll talk about what we did for this patient. Phenobarbital detox, as I mentioned, there is some evidence that that can be effective. I would do that in the inpatient unit. Inpatient because he's still kind of homeless. That's a good point. If someone doesn't have stable housing and are unlikely to show up for their ambulatory visits, then an inpatient detox may be appropriate. Very short prescriptions, one to three days of medication at pharmacy until they can manage more days at a time to stabilize use of longer activating benzo and slower taper over months to years, most likely to be successful. That's interesting. We will, I will talk about what we did. That isn't that far off from what you're suggesting. And then our medical staff made a decision to not approve any prescriptions for alprazolam as well as evidence of illicit alprazolam use shown in UAs due to our own data showing increased overdose and deaths. We do take action. This is about alprazolam versus other benzodiazepine types. And it's a little bit perpendicular to this case, but I will talk about that at the end if there is time. I think there is some interest on the relative risks of different benzodiazepine types. And then lastly, he will need a very long treatment and long-term treatment facility for stabilization in control environment. Well, I'm here to tell you that that was not the case for this patient. So in terms of approaches to benzodiazepine withdrawal management, there is, you know, in terms of the taper rate, there is little data on how fast you should discontinue somebody off of benzodiazepines. I think in most clinical trials, what they have done is reduce, use a gradual reduction approach 25 to 50% every one to two weeks over six to 10 weeks. Six to 10 weeks seems to be the sort of most commonly used aim for how fast clinicians would taper their patients. Although those studies are primarily not in people with substance use disorders. And these were not people necessarily with benzodiazepine use disorder. These were people, oftentimes older adults who were prescribed benzodiazepines for various conditions, such as anxiety and insomnia. And they would use different protocols to try to get patients off of the benzodiazepines. And the tapers would typically, would last six to 10 weeks in these clinical trials. These taper rates may be different for people with different comorbidities. But that the taper rate can be modified based on the patient's ability to tolerate withdrawal symptoms. So I think it should be sort of fashioned on a case-by-case, designed on a case-by-case basis. So there may be withdrawal symptoms during the taper. These withdrawal symptoms are typically worse with longer duration of benzodiazepine use prior to the taper. So there are subjective symptoms that can worsen as the dose nears zero. So you can slow the taper towards the end of the taper. So typically, you might wanna go, you could go faster with your taper rate in the beginning of the taper and slow it down towards the end. In terms of choice of benzodiazepine, there are no clinical trials comparing benzodiazepine, different benzodiazepine types for tapering purposes. If the patient is largely taking short-acting benzodiazepines, you can switch to a longer-acting benzodiazepine. And there is some rationale to this because short-acting benzodiazepines are associated with higher dropouts in benzodiazepine discontinuation trials. They're associated with worse rebound anxiety and more severe withdrawal symptoms. So it might be a good idea to switch them. Now, I have also seen clinical trials, successful clinical trials of benzodiazepine discontinuation when a majority of the patients were taking L-Prazolam and were kept on their L-Prazolam. The protocol was just to keep them on the medication they were prescribed. In terms of frequency of monitoring, you know, as outpatient, I think weekly visits are preferred over longer time between visits. But you can do it on a, you know, if your clinic is busy and you can't see that patient every week, then you may be able to see them every other week. But I would give one week prescriptions in that case. Daily monitoring is even better. I mean, if you could do daily monitoring, that would be great, but it's often not feasible in most clinics. And then the taper rate should correspond to, and the frequency of monitoring should probably, should try to be corresponding to how much the patient is withdrawing in terms of symptoms. In terms of adjunctive therapy, so there've been multiple meta-analyses that have looked at benzodiazepine discontinuation trials, but there's little evidence of effectiveness for adjunctive medications as a whole. Then again, there aren't enough trials, really. You know, there've been a number of trials, but they, you know, there's only like one or two that look at one drug and, you know, one or two that look at another drug. So they're all kind of spread out in terms of, there aren't like, you know, a bulk of trials that have looked at specific drug types. And the study populations are often heterogeneous. Like I said, there aren't that many randomized trials of benzodiazepine discontinuation of people who have substance use disorders. And it's mostly trials in older adults or general medicine. In terms of psychosocial interventions, there has been evidence that adding a psychosocial intervention can improve the success rate of benzodiazepine discontinuation. CBT is the best study and has felt to be, and has been effective, but other effective options have been relaxation therapy, often paired with psychoeducation. So back to the case, this patient agreed to an outpatient benzodiazepine taper, and he agreed to come in almost daily. So the clinic was open from Monday through Saturday, where he would get a daily benzodiazepine prescription, and they got biweekly urine drug screens. He agreed to abstaining from opioids, screened benzodiazepines, alcohol, or other sedative products. But he did state that he was gonna continue to use marijuana or cannabis. And that clinic prescribed his buprenorphine as well. I'm sorry, that clinic is the clinic that he was getting his taper in. So the proposed taper, he was currently taking approximately 550 milligrams of benzodiazepine daily. So a five-week taper was proposed where they cut by 10 milligrams each week. And in the last week, he was taking five milligrams for the final week. In terms of his clinical course, his adherence to taper was pretty good overall. Somewhat surprisingly, even though he was homeless, he was showing up every day pretty consistently. He did use illicit clonazepam twice, use cocaine twice, and Adderall twice. But we just pushed on with the taper. He was, again, homeless, staying in a shelter or the street throughout the taper. He did have the taper lengthened by approximately a week at various time points due to an increase in withdrawal symptoms. But he did complete his taper on day 40. I've been continuing to manage this patient and two years post-detox, he remains abstinent from benzodiazepines and other drugs. His anxiety is adequately treated with SSRI. He was diagnosed with ADHD and he was receiving stimulant treatment. He is receiving stimulant treatment. He's employed and he's back together with his girlfriend, living with her and having a family. Living with her and helping to raise their child. So this patient did quite well with this outpatient taper. And I think it goes to show that if someone's motivated, he was very motivated. People can successfully discontinue benzodiazepines. All right. Let me go through some questions here. Which SSRI? Prozac, I believe. And interestingly, we did have to lower his dose. He was having some side effects. He stopped it completely because he felt that he didn't need it. But then most recently asked to restart it because he was feeling like he was just more depressed lately and felt different without the Prozac. Let's see. After taper was done, any episode of relapse? No, this patient has not used benzodiazepines according to his report and testing since this detox was done. I'll be honest with you. This is a success story that doesn't, I would say that for a patient like this with other core morbidities, although he was fairly healthy for, he's young and fairly healthy. This kind of success story doesn't often happen. I think it's less than half, less than 50%. What kept him on track? At this point, he had a lot of insight into sort of the effects of benzodiazepine. He also wanted to reunite with his girlfriend. He also wanted to, you know, he had a new child and that was a big motivation for him as well. Did you find the support system plays a role in their success? No, I think that a support system in general is associated with better success in just about treating any problem, especially substance use or psychiatric problem. In this case, he actually didn't have much support and really leaned on the clinical staff for support. I think daily visits really helped this patient stay on track. All right, so it is 555. I thought that I would maybe address a couple questions from the last talk, maybe ones that I think have relevance to today's questions. I think some people had some interest in discussing the difference between, or the risks, the relative risks of different benzodiazepine types. So a couple thoughts on that. And there was someone, I think you commented on alprazolam in particular. And I will say this, there have, so there are studies out there, there are human laboratory studies that have asked the question, do patients or people who have substance use disorders and people who don't have substance use disorders have different preference for different drugs? They're blinded, these are blinded studies, they don't know what's ahead of them, in front of them, and they take pills and then they mark down which they liked and which they didn't like or whatever had preferences. And what those human laboratory studies seem to show overall is that patients prefer diazepam over other benzodiazepine types. Some studies have shown alprazolam to be their preference. Now, there are different reasons for this. Those medications, especially diazepam, are highly lipophilic, which allows them to cross the blood-brain barrier even more easily and can have a faster onset of action. So that faster onset of action means you can get relief from anxiety, for example, or you can just feel whatever the subjective feeling from that benzodiazepine will be from that particular individual faster. Now, in terms of, I mentioned risks of short-acting medications. Alprazolam does have a reputation for doing this as well, having this like fast onset of action. And therefore, these medications that have faster onset of action are likely to have higher abuse liability or misuse liability. And so that goes as well to alprazolam. There's mixed evidence about alprazolam and the risks of alprazolam, but I would say that the preponderance of the evidence seems to suggest, and at least my anecdotal information is that alprazolam has greater risks. Now, in terms of medications that have potentially lower risks, if I'm treating somebody for anxiety, I tend to go with planazepam because it's longer acting, has a longer duration of anxiolytic effect and has a slower onset of action and therefore potentially has a lower risk of misuse. Now, when we did our study looking at benzodiazepine use in people who were taking opioid analgesics for pain and we looked at overdose risk, we found that there wasn't actually that much difference in terms of the benzodiazepine type and risk of overdose. Let me see if there's something else that... Someone asked about benzodiazepine receptor agonists like Z-drugs and what the risks of those were. So, there have been a couple of studies that have looked at this in terms of people who are getting opioid maintenance treatment. I don't think that question has been asked. It could be wrong about people who are taking opioids for pain, but in turn, there are two studies, cohort studies that have looked at Z-drugs and both were associated with increased risk of drug overdoses, drug overdose mortality in particular. Just sort of other studies that have looked at similar drugs and this is not a similar drug, but it's oftentimes prescribed in this patient population, gabapentin or pregabalin. Gabapentinoids were also, I might be misremembering this, but I believe they're also associated with an increased risk of overdose death. And in one other study, they looked at pregabalin specifically and they found that that was increased with drug overdoses in people who were on opioid maintenance treatment. The bulk of these patients were on methadone, not buprenorphine. All right. It is, it is six o'clock. Okay. Thank you very much, Dr. Park, for that very great case discussion. And we had a lot of participation from our participants, which we really appreciate. I think that in the past couple of weeks, we've really learned a lot about benzodiazepines and methadone maintenance and buprenorphine maintenance treatments. And I really appreciate you taking the time out to do this webinar. I'd just like to remind everybody that next week, we're going to have another webinar and it's going to be on methadone maintenance. And our presenter is going to be Dr. Sarah Kawasaki. And she's going to be talking about her experience working in a methadone or opioid treatment program during COVID and the lift of the temporary lifting and suspension of the regulations and what their program has, you know, how that's affected their program and participation and adherence to the program. So I invite you all to come and see us again next week at about five o'clock, five o'clock Eastern. Okay. So thank you. Thanks. Bye everyone. Bye-bye.

benzodiazepines

risks and benefits

opioid maintenance treatment

Dr. Tebu Park

case studies

outpatient tapering

supportive therapy

individualized treatment

monitoring progress

benzodiazepine use disorder