Hello and welcome. I'm Dr. Benjamin Druss, Professor and Rosalind Carter Chair in Mental Health at the Rollins School of Public Health at Emory University and Health Systems Expert for SMI Advisor. I am very happy that you are joining us for today's SMI Advisor webinar. How much benzodiazepine prescribing is the right amount of prescribing? SMI Advisor, also known as the Clinical Support System for Serious Mental Illness, is an APA and SAMHSA initiative devoted to helping clinicians implement evidence-based care for those living with serious mental illness. Working with experts from across the SMI clinician community, our interdisciplinary effort has been designed to help you get the answers you need to care for your patients. Now, I'd like to introduce you to the faculty for today's webinar, Dr. Donovan Most. Dr. Donovan Most is a geriatric psychiatrist at the University of Michigan and the Ann Arbor VA with two primary research interests. First, he is exploring the determinants and outcomes of potentially inappropriate psychotropic prescribing in older adults with a particular focus on benzodiazepines. In addition, he is interested in the factors that drive overuse of medical services by older adults with dementia. Dr. Most, thank you for leading today's webinar. Thank you very much for the invitation and thanks to everyone who's joined us today. So here's my disclosure slide, which is pretty straightforward and we can get on to the talk. So I'm hoping at the end of our time together, you'll have a better sense for some basic epidemiology of benzodiazepine use. I'm hoping that you'll have a good understanding of what are really the common indications for use and the risks of that use, along with evidence specifically for those with serious mental illness. And then finally, if you are potentially considering a taper with one of your patients, to leave you with some suggestions and ideas about how you might do that. So to start with some of the epidemiology, so this is from a paper published now about five years ago, using data that's back from 2008 from a large basically prescription database. And what you see is on the x-axis, you have age, so 18 all the way at the left, up to 80 years all the way at the right. And basically it's just a straight line going up across age with women being prescribed. This is the prevalence of past year use of benzodiazepine by age. So women have about twice the prevalence of use of men and it just goes up with age. So as a geriatric psychiatrist, it kind of hurts my heart a little bit that the oldest adults who are the most at risk for harms for benzos are the most likely to be exposed. It's pretty unbelievable, frankly, that an 80-year-old woman, 12% of them in the past year were prescribed benzodiazepine. This is a more recent analysis that we actually published now about two years ago, using data from 2015 and 2016 from a nationally representative survey that asked questions about a variety of prescription medications, including benzodiazepines. And they describe use either as prescribed, so you take it just the way that your physician prescribes it. And they also ask about misuse. And misuse is both defined as either it's your medication that you were prescribed, but you're taking it differently, either more frequently, a different amount than how it was prescribed, or you weren't prescribed the medication, but you're taking it anyways. So those are sort of the two flavors of misuse. And again, this is grouped by age categories on that x-axis. The misuse bar is sort of the orange bar. So two things, two big points to point out here. First is on the right, you see those two red arrows. So this is just to show that use among middle-aged adults really has caught up to use among older adults, and is basically as much or even more. And so for me, who generally sees adults over 65, I could snap my fingers and stop benzo use, but the problem's not going to go away because we have this cohort of adults aging in to being sort of an older adult, so 65 or over. And as long as use continues in them, use among the oldest adults is going to continue to be an issue to address. The second piece is that red arrow for the 18 to 25 year olds. That's not really an age group that I treat a lot, but if I did, I would really want this to be on my mind. So you can see there that half of benzo use among this youngest group of adults is misuse. And so that also means that kind of any estimate you see of benzo use that's only based on prescriptions is really missing the boat and is missing like half of the amount of use that this youngest group of adults is using. So then just two slides that touch on the issue of prescribing by race and ethnicity. So this is from that study that I just showed you where we looked at use overall, and I have this red box around the race ethnicity breakout. And basically what you can see is the arrow is pointing. So this is the odds of use, the likelihood of use among different racial or ethnic groups compared to white patients. And so you can see basically black patients have about half the odds. All of these non-white groups have significantly lower likelihood of benzodiazepine use in the past year. And then this is a little bit of a flip side. So this is a different paper we did where we looked at patients who were on chronic use. Their criteria was more than 120 days prescribed in the past in a year, in a one-year period. And then we looked at over the next year how many of those chronic users have their benzo discontinued. And so here the African-American group has higher odds, which means that compared to white patients, black patients were more likely to have their benzodiazepine discontinued. So on one hand, you might say, I haven't gotten to the slide about harms yet, but on one hand you could say, well, maybe it's a good thing if non-white patients are being less exposed, you know, exposed to fewer harms. On the other hand, it's a bad thing that if people who really need these medications aren't getting them, that's a bad thing. And I guess regardless of whether it's good or bad, if these differences are being motivated by racism, obviously that would be a bad thing if that's what's informing the decision. Just I can tell you from here locally from a study that we did, just a small sort of pilot intervention study looking at chronic use here locally of the different clinics within the health system that we looked at, the clinic that had the largest proportion of non-white patients actually had the lowest rate of benzo prescribing and the most sort of strict policies around prescriptions of controlled substances. And so it just makes you wonder about how use of these medications are viewed by different population groups, how providers view that and how it may influence their care. Okay. So after that little bit of background on the epidemiology, let's talk about what's so bad about benzos. Why is this guy talking about these for an hour? So again, as somebody who works with older adults, fall risk is a really big deal. And so when I work with medical students for residents, you know, they're thinking about a fall when a 20-year-old, 30-year-old falls. It's like, no big deal. Lots of people fall all the time. The problem is for older adults, it really can be like a life-altering event where you can have somebody who's really doing very well, they fall, God forbid they break a hip, and there's just significant morbidity and mortality associated with falls among older adults. So this is not a trivial concern. And in this meta analysis, they basically show that essentially the odds of fall associated with benzo exposure is significantly higher. So the 1.6 is the risk of falling if you are exposed to a benzo. Let me just talk to you about sort of two myths I think that are out there around benzo harms. So the first is the idea that short-acting benzos are safer and have less fall risk than long-acting benzos. And we've seen this when we look at benzo prescribing to older adults, that there hasn't been much change in overall use, but there has been a shift away from long-acting benzos. So I think that partly comes from this big early paper in 1989 that compared fall risk between long and short-acting benzos, and they found that the risk of hip fracture was elevated with long-acting benzos. However, in subsequent work that's happened since then with, say, more advanced observational methods, essentially it looks like short-acting benzos have essentially an equivalent fall risk to the long-acting medications. So it seems like clinicians got the initial message that short was safer than long-acting, but then they didn't really update it as new additional evidence came in that really there's a risk with any benzo. So the second one is this idea that short-term benzo use is safer, and an example is from this really, what was a very nice perspective in the New England Journal a couple years ago, and the quote here is, when they're used daily and for extended periods, the benefits diminish and the risks associated with their use increase. So I'm not entirely sure about that. So on one hand, you can say, so risk increases in the sense that my risk of a car accident, if I drive one day versus I drive every day for 30 days, sure, will be higher just by virtue of the fact that it's an activity that I do every day. On the other hand, what is not true is that your risk, say, of a fall-related injury on day seven of taking a benzo is lower than it is on day 30 or 90 of taking a benzo. So when they've looked at, again, going back to hip fracture risk and look at sort of risk during periods of exposure, your risk in your first week or two is as high or higher than it is for use that extends over a month. And I think that makes sense if you think about, so benzos work on the same receptor as alcohol. If you're not a drinker, one drink can have a significant effect, whereas if you have a glass of wine every night, a glass of wine might not affect you as much. And so that hopefully makes sense to folks that if you're early on in your benzo exposure, you haven't developed any type of tolerance yet, your risk potentially is as high or even higher early on with use. Okay, so going back to harms, I think one that people don't really think about a lot are increased risk of motor vehicle accidents. Again, you see odds ratio there is similar to the risk of fall-related injury. Interestingly, this risk is actually a little bit lower for older adults, and the odds ratio is even slightly higher for younger patients who are exposed to benzos. Overdose, particularly because of the opioid epidemic, is a topic that's been getting a lot of attention recently. So in this analysis looking at pharmaceutical-related overdose deaths, benzos are the number two medication after opioids. So when benzos were developed, they were a big advance because they're much safer than barbiturates. However, they're not completely safe and there is still risk. You can see that there's the risk of overdose with co-prescribing. So if you look at all opioid deaths, about 30% of opioid overdose deaths, there's also a benzo on board. And when you look at benzo overdose deaths, like three-quarters of them involve an opioid. However, that still means that there's a quarter of overdose deaths involving benzodiazepines that do not involve opioids. So while the overdose story is largely about opioids co-prescribed with benzos, it's not entirely related to opioid exposure. And there is some story with the benzos independent of opioids. And so in light of this increased risk, there's an FDA black box warning for co-prescribing of opioids and other CNS depressants, including benzodiazepines, since the fall of 2016. So then this final one, again, as a geriatric psychiatrist, is always surprising to me, the risk of impaired cognition that comes with benzo exposure. So I'll say there were several papers suggesting a link between benzo exposure and actually developing frank dementia. That I'd say at this point, based on the accumulation of evidence, looks less like there is a risk of actually benzos increasing the risk of dementia. However, we know that on a short-term basis, they absolutely do impair your cognition. It's the reason that midazolam or Versed gets used for procedural sedation is so you won't remember the colonoscopy that you're having. So in this meta-analysis of placebo-controlled studies comparing benzo to placebo, the authors write, these drugs consistently induce both amnestic or memory-related and non-amnestic cognitive impairments with evidence of a dose-response relationship. And it was a larger problem for adults over 65. And so this is actually a study, now almost 30 years old, where they actually had older adults, I believe it was in long-term care settings, some of whom they randomized to stopping their benzos. And when they compared them to patients who didn't stop their benzos, they found significant improvement in memory, immediate recall, total digits or digit span. These patients appeared more alert and less forgetful. The improvement was noticeable to nursing staff and family members. And so when you work with older adults, one of their biggest concerns is about cognitive impairment. And so it really is just baffling that we expose something like 10% of older adults to medications that we know impair their cognition. So then after we think about those risks, what about the evidence for benefit? So we'll start with PTSD. So the VA and the Department of Defense understandably have a really big interest in treating PTSD. And so they update and review the evidence and update their treatment guidelines regularly. So their recommendation for benzos for PTSD or acute stress is a strong against due to lack of evidence for effectiveness and because risks outweigh potential benefits. And then they also have this sentence in there about preclinical evidence suggests benzos may interfere with extinction or fear conditioning. And so, okay, so the preclinical generally means animal studies. And to give you an example of what they mean here. So if you think about an animal study where basically they expose a stimulus, so maybe a noise or a light with an injury or some type of harm to the animal. So then when the animal sees that, hears that noise, they associate it with the injury. And the whole point of exposure therapy, like you practice with patients is that as you gradually re-expose the patient to the stimulus, but they don't experience the harm, gradually sort of that fear response to the stimulus will be extinguished. So what they're showing in animal studies is that after the trauma, if you give the animal a benzo, they have a harder time or a longer time extinguishing the startle response, the stress response to the stimulus when the injury occurred. So this as a clinician makes me worry that after a traumatic event, if you're providing patients with benzos, you're potentially prolonging the period of time that it takes them to recover from that trauma. So what about generalizing generalized anxiety disorder? So this is from a systematic review and that analysis that was published in the Lancet two years ago. So they found, and typically in these studies, they both compare the symptom response and also oftentimes drop out due to side effects. And so they find that duloxetine, pregabalin, venlafaxine and escitalogram had a good balance of being both effective and acceptable or not a lot of dropout because of side effects. And then they say paroxetine and benzos were effective, but they were poorly tolerated when compared with placebo. So benzos did not come out of this analysis as being a recommended treatment. So then what about panic disorder? So this is now about five years old, the Cochrane systematic review, or let's say the choice of which or whether to prescribe an antidepressant and or benzo cannot be made on the basis of the review. So when is the right answer for use of benzos and anxiety disorders? So the American Geriatric Society years criteria, which again is specifically focused on older adults, they say, we still find that benzos are appropriate. They have an appropriate role for severe generalized anxiety disorder. And then there was a recent date in the New England Journal about five years ago. And they say, the authors say there's been some controversy about the long-term use of benzos. However, these agents can with careful monitoring be used on a long-term basis in selected patients with treatment resistant generalized anxiety disorder. Okay. So then how do you operationalize treatment resistant? So this is from the let's see, the British Society of Psychopharmacology, excuse me, British Association of Psychopharmacology. And in their practice guidelines, this is how they operationalize it. So they basically say multiple trials of essentially at least two medications from two different classes or with two different mechanisms of action and psychotherapy. And then at that point, you might consider someone to have treatment resistant anxiety that would benefit from use of a benzodiazepine. But just to be clear, that recommendation was not one for PTSD. So then what about insomnia, which is the other reason that benzos are really commonly prescribed? So this is a meta-analysis looking specifically at placebo-controlled trials of sedative hypnotics for older adults, so 65 and over with insomnia. And so these are the sort of summary findings around the benefits. So there was a small improvement in sleep quality with a tiny effect size. Sleep time increased 25 minutes, which I think is really striking to think about. Sometimes I think patients and providers can have almost kind of magical beliefs about how helpful these medications are. But again, compared to placebo, it was not even a half an hour of improvement. And then the number of nighttime awakenings decreased by a mean or an average of less than one time, fewer awakenings compared to placebo. And then how about the risks? So nearly five times higher adverse cognitive events, nearly four times higher daytime fatigue, nearly three times, two and a half to three times higher psychomotor events. And this is where you get your worry about risk of falls and fractures. And so for me personally, that is a difficult risk-benefit discussion to justify, I think, use of these medications given really the very small benefits that have been demonstrated and potentially very worrisome harms. So the American College of Physicians regularly publish practice guidelines. And so for chronic insomnia, their first top-line recommendation is CBT for insomnia. And then on the medication question, because everyone always wants to know about medications for sleep, they basically include medications with this very hedgy recommendation, where they say, we recommend a shared decision-making approach, discussion of benefits, harms, costs, to decide whether or not to add pharmacological therapy in whom CBT has already been tried alone and it was unsuccessful. And then that recommendation, they say it's a weak recommendation based on low-quality evidence. So I suspect that there were a number of fights amongst the members of this panel as they were trying to come up with these guidelines for whether or not to even include medications at all. OK, so then what do we know about real-world outcomes? So part of the challenge with benzos is because they've been around for a longer time, there isn't a huge body of placebo-controlled trials to inform our evidence base. And so what you're left with are observational data analyses, which always have limitations and drawbacks, because it's not the gold standard of randomizing patients, the placebo versus the medication. But anyways, I wanted to go through a few of these studies. So this is an analysis looking in patients with schizophrenia who were already on an antipsychotic. And then they looked at what happened, what were real-world outcomes with various different medications added on top. So again, everyone was on an antipsychotic. And then they looked at patients who were also on an antidepressant, also on a benzo, also on a mood stabilizer, or also on a second antipsychotic. They looked at time to psychiatric hospitalization. And they looked at time to ED visits. And what you'll notice is in both of these images, the benzodiazepine is the bottom line. So that means that patients who received an antipsychotic and a benzo basically ended up being hospitalized sooner. And they ended up being seen in the ED sooner than patients who were on any of these other combinations of medications. What about dementia? So this is an area that I think about a lot. So they looked at patients who were already on an antipsychotic. And then they looked at when either an antidepressant was added or a benzodiazepine was added. When you compared an antipsychotic alone to an antipsychotic plus a benzo, they had nearly double the increased risk of death. Obviously not a good outcome. What about depression? So the idea here, and this used to be, maybe still is in some practice guidelines, so patients with depression frequently have comorbid anxiety. And or when you start them on an antidepressant, sometimes there can be a little bit of increased restlessness, a little bit of treatment-induced anxiety or akathisia because of the serotonergic antidepressant. And so the idea was that you could potentially start a new benzo at the same time as you started the new antidepressant. This would increase the likelihood of patients tolerating the antidepressant. So then in the long run, they were able to maintain their treatment for depression longer in the hopes of improving their symptoms. And so in this study, they basically looked at a huge group of people who were started on a new antidepressant during about a 15-year period of time. And then they essentially compared people who were just started on a new antidepressant with people who were started also on a new benzo at the same time. And so basically 10% of people who started an antidepressant were also put on a benzo at the same time. And then so the whole point of this, or the whole idea behind this, is that by starting a new benzo at the same time, you're increasing the likelihood that they'll stay on their antidepressant. Turns out when they looked at these groups, so antidepressant alone versus antidepressant plus a benzo, they looked at them at three months and at six months, and there was no difference in the likelihood of still being on the antidepressant at that point. What they did find is that of those people who were started on a new benzo, 12% of them went on to become a long-term benzo user. So they looked at the number of days prescribed with the initial benzo supply. And basically the more days that you got, the more likely it was that you would go on to become a long-term benzo user. And so this analysis basically shows the benzo, starting the benzo, had no improvement, no benefit in people continuing their antidepressant. On the other hand, you do have a group of people that you basically turned into long-time chronic benzo users. And so then what about bipolar disorder? So this is a secondary analysis of the STEP-DD study. So commonly, benzos get prescribed particularly to help with the manic or hypomanic phase of the illness. And they found that for patients who were enrolled in the study, about a quarter of them, once they reached remission, a quarter of them were prescribed benzodiazepines. And then it turns out that that group ended up having a higher risk of going on to experience a subsequent mood episode. And so what the authors say is that benzos may be associated with greater risk of recurrence of a mood episode, or alternatively, at a minimum, the benzo is a marker of more severe course of illness. So that really is the caveat for all of these studies that I've just described, this idea that in the real world, the patients who are getting the benzos are the more sick, the more ill patients. I'm not sure if I totally buy that specifically, say, for the schizophrenia study. So I would imagine that the patients who were on two antipsychotics, I think it's harder to argue that the benzo plus antipsychotic is a sicker group than the two antipsychotic group. In any event, I just don't think it's entirely encouraging that in all of these studies, in every one of them, the patients who were also prescribed a benzo basically had worse outcomes. In every diagnosis that we just looked at, it's worrying that the signal from the observational evidence basically all goes in the same direction, which is that it seems like outcomes are worse for the folks who are on the benzos. So going back to the slide about what's so bad about benzos after we talk about all these specific harms, it turns out that the evidence base for the way that the medications are most commonly used is really pretty slim, whereas it seems like the evidence for harms just continues to accumulate. And so how do you think about what the risk-benefit discussion looks like in the face of so much evidence that potentially harms are worse with benzo exposure? So now I'm going to make a very big jump over the discussion that happens between you and your patient when you decide whether or not tapering a benzo is the appropriate and the right thing to do, and talk to you a little bit about what a taper might actually look like. So I think the first part of it is to reassure both patients and, frankly, the providers that patients can be tapered off of benzos. I think there's this perception, both among patients but also among providers, that the wheels are really going to fall off if someone stops their benzoidazepine. So I just want to present a little bit of data that suggests that that's actually not true. And so this is a study where they basically had over 100 chronic benzo users. So the average here was these patients had been on their benzo for more than 13 years, which I think it's part of where the worry about what will happen when they stop comes from, because many times patients have been on these medications for a really long time. So it's not surprising that they might get a little bit attached and wonder about what things will look like when they're off. So they did a gradual paper over at least two months. In a couple of slides, I'm going to suggest to you that I think that was probably kind of fast, but the minimum here was two months. And so what they found, not surprisingly, is that the group that stopped their benzo had improved performance on cognitive function compared to those who continued their benzo. And then this point is really important, is that anxiety, irritability, lack of energy was worse in the group that continued their benzo, and there was no change in sleep. So this is, I think, a big concern that both patients and providers have, is that when they stop their benzo, they're going to get more anxious. They're going to get more irritable. Their sleep is going to be terrible. And in this analysis, that is not what they found. So this is another more recent study where they were tapering patients off of chronic benzodiazepines. They have over 500 chronic users in three different study arms. So there was the usual care, or kind of the placebo arm, and then there were two different intervention groups. So both groups got the information that's here in the box. So it was largely a sort of patient educational intervention around the potential risks associated with use, reassurance about reducing the medication, and then self-help leaflet. So probably, I would imagine, covered the sort of basics of sleep hygiene. And then one group had scheduled follow-up visits with their regular provider, and the other group just got information and written instructions. Of course, they could see their provider, but it wasn't part of the study that they had scheduled ongoing follow-up. And after a year, nearly a half of the two intervention groups stopped their chronic benzo. The usual care group, only 15% stopped. And what they found is that there was, in people who stopped, there was no increase in their anxiety or depression scores, there was no more sleep dissatisfaction, and there was no increased alcohol consumption compared to baseline. That's another big concern is that if I stop the benzo, my patient's gonna start drinking or using marijuana. So in this study, at least, they didn't collect information about marijuana, but at least for alcohol, they did not see that increasing. So I think this is another important piece of data to help kind of reassure patients and the providers that patients really can do very well after they stop their benzo. I think this is another interesting piece of information. So they looked at 12 months at how many patients had been started on an antidepressant. So this is another issue that we'll talk about in a couple of slides about whether or not you need to substitute or add on another treatment to replace the benzo. And what you find is that in the group that had regular follow-up with clinicians, more of those patients ended up starting an antidepressant than the group that did not have regular scheduled follow-up with their clinicians. And I really think that this speaks to clinicians feeling that they need to do something to help the patient. And if they're not prescribing something, they're not helping them. And so this is a common concern and question, like, do I need to replace the medication? If I'm taking one thing away, I probably need to give them something else. And I think clinicians minimize the benefit of education and just listening and being with their patient during the process. They think that that's not enough. And so you see more prescribing of other medications in the group of patients that had more contact with clinicians. Okay, what about the idea of medications to actually help with the taper? So I think it's really, the way that I think about this is you want medication that would be driven by the original indication for the prescription. The problem is a lot of the time, it's hard to know why exactly the benzo was started in the first place. So here are two studies to show what I'm talking about. So the one is one that we did now, I guess, about 10 years ago, where these are older adults across the state of Pennsylvania who are newly started on the psych med. And we did, it was a telephone-based sort of mental health screening interview that we did with them. And among folks who were started on an anxiolytic, less than 5% met criteria for a generalized anxiety disorder or panic. And then a colleague, also Weekers, did a study looking in the VA, and there, in veterans who were receiving a benzo or another anxiolytic, about a quarter of them didn't have a mental health diagnosis. So less of a problem in the VA, but still a significant proportion of folks prescribe medications who don't have a clear diagnosis. And so, and then also, even if you do know why the benzo was started, for people who've been on the medication for five, 10, 15 years, there's just no way to know how they're actually gonna feel when their brain isn't receiving this sort of chronic inhibitory medication that is, that's what the benzo is doing. So my preference, my recommendation is a little bit more of a watchful waiting approach. Okay, so you and the patient have decided to taper now. What would you do? The very, very, very most important thing, I would say, is to go slowly. So patients have been on these medications for decades. So I can think of only a very select number of situations where it would really be like an emergency to try to take them off of the medication. And then I think the other important thing for both you and the patient to remember is that there's meaningful harm reduction just from reducing the dose. Most, that slide of the harms that I showed you, almost every one they've shown that the risk of bad outcomes is higher with a higher dose. And so from a harm reduction perspective, a lower dose is a great goal and a great outcome. This might be, again, my work with older adults that influences this thinking. If you do decide with the patient to do a taper, I would recommend that you only prescribe one or two steps at a time because you might wanna modify it as you go. And you ultimately don't want the patient to have a whole bunch of different pill bottles around with different steps in the taper because that will just lead to confusion. And then there's also, of course, the worry about diversion, misuse, who else is in the household. And so in general, I think you wanna go just a couple steps at a time, only have them have on hand a couple steps at a time to try to keep things more simple. So this is an example of a taper schedule from what's called the Empower Intervention by Cara Canenbaum, who's a geriatrician in Canada. This was a direct-to-patient intervention where they basically sampled patients from community pharmacists who were chronic benzo users, and then they just mailed the patient's education about the risks and harms of benzos that presented a schematic of a tapering schedule. And they said, you should just talk to your doctor or pharmacist about maybe whether you might wanna taper. So this is the schematic that they presented where they have outlined a reduction of about half, 50% reduction in the first month, and then basically over the next several months, a more gradual tapering off process. Again, this is just a schematic, so I don't think literally they were tapering patients this way. In general, I think you wanna go with a regimen where in a given week, the patient's taking the same thing every day. Here are the pills. You have some days of a half pill, some days of a quarter pill. That's probably a little bit more confusing than you wanna do. So you would maybe wanna become good friends with your clinical pharmacist and figure out how you can get to sort of shave off the amount of benzodiazepine you wanna shave off each week. This is another resource that I would refer you to called the Ashton Manual. This is a woman who is a physician in England who really developed this amazing resource that's available for free online here at this website that gives just a really nice sort of overview of the mechanism of benzodiazepine. There's a chart with equivalents between different types of benzos. And what she suggests is a slower taper than that Empower schematic. So where basically you cut about 5% every one to two weeks and then it cut about 2.5% of the original dose than every one to two weeks. So you end up with, unlike the Empower, which I think was completing the taper in about four months, here completing a taper at a minimum would be five months up to even over a year, depending on how rapidly you went with the patient. So I think these are really the critical pieces of the taper, is that, essentially, the patient who perhaps has become accustomed to taking the Benzo and potentially even sees themselves as needing the Benzo, you're essentially helping them learn to cope without the medication. And so as part of that process, it's really important to keep the taper moving forwards. It can pause. You can slow things down. But you don't want to go backwards. You don't want escape pills. Because essentially, you're helping the patient learn to be able to come up with some alternative coping strategies. And you want them to unlearn seeing the Benzo as an important coping strategy. And if you and the patient agree to do escape pills, they're seeing the Benzo pill as their coping strategy. And that's what you're trying to help them learn a new habit. So then what about the issue of switching to a long-acting Benzo for the taper? So in the EMPOWER study, the majority of people stayed on their current Benzo. So most of these folks were on, I believe, either like lorazepam or alprazolam. Very few of them, less than 5%, were on a long-acting Benzo. So in other words, the vast majority of people completed the taper on their current Benzo. And for the majority, their current Benzo was a short-acting Benzo. So kind of in a real-world setting, people completed their tapers on short-acting Benzos. I also think, again, it leads to less confusion and potential, keeps people from having sort of maybe an old supply of one Benzo and then getting into like switching them to a new Benzo for a taper. That can be a whole complicated process. And then again, people will have multiple different types of medications on hand, which can be confusing. I just wanted to revisit this study that we spoke about a couple slides back, where the chronic users were tapered off. And there was the one intervention arm that was mostly education and the other intervention arm that had follow-up visits with the clinicians. And I have pointed out that more of the patients who saw their clinicians got put on antidepressants. So it turns out when you look at switches to long-acting Benzos, more of those patients were also switched to long-acting Benzos. So again, I think this speaks to the clinician's very good motivation and desire to help. But again, sometimes I think we can get into a habit where we see helping as doing things with medications or adding medications. And again, the switch to long-acting Benzos is consistent with that hypothesis. What about the idea of adding medications to help with the taper process? So not that you need to replace the Benzo with something, but by adding something on, it will make the taper smoothly. So this is a table from the VA, where I do my clinical work, has an academic detailing service that really has tremendous, tremendous resources available for clinicians. And they basically did a review, a literature review of the evidence out there. And essentially, they said there's really limited and conflicting evidence. And their bottom line was that a gradual taper was the best way to do a taper. And there wasn't really good evidence to support the need to add on anything additional. So I think the final points that I would make about the taper is really part of it is about dealing with the patient and your own anxiety about it, and the belief that the patient will do OK without it, that they won't decompensate terribly during the taper process. They won't be calling the office all the time because they're feeling really uncomfortable. By doing a slow taper, you're doing your best to minimize the likelihood that they'll experience any types of withdrawal symptoms. And then I just leave you with these final pearls from Dr. Ashton, which are just to be confident. I think these really apply to both the patient and to you, to the clinician, to be confident about the process, to be patient. Again, a slow taper is likely to mean the patient experiences less withdrawal. And so a slow taper will be a better tolerated taper. And then it can be very different. Different patients will be able to tolerate different parts of the taper process. And so you want to take a personalized approach to each patient. This, I think, also speaks to the art of tapering. So in this paper, they had 171 patients who were in a benzo discontinuation program. It was a four to six week taper. So hopefully, I've convinced you after the last couple of slides that that is much faster than I would recommend for a taper. And they basically looked at people who had to stop the taper early. They looked at people who stopped the taper late, who I wouldn't necessarily call this a failure. I would say this is a good harm reduction paper. And then they looked at the people who were able to get off completely. And what they found is that the group that stopped early actually had the lowest physician rated withdrawal severity. So I think that really speaks to the idea that I think it was sort of about this idea of the patient's mastery and sense of control over the situation. Something about it led them to not feel like they could tolerate the taper process, even though based on an objective measure, the withdrawal that they were experiencing wasn't really that severe. This is the final thing that I will leave you with, is please, please, please do not taper patients against their will. A too rapid benzodiazepine taper, just stopping someone's benzodiazepine taper can be fatal. Stopping someone's opioid can precipitate withdrawal and make them incredibly uncomfortable. It shouldn't be fatal. A benzo abrupt stop can be fatal, because the brain is used to chronic suppression of its electrical activity. That's what the benzo does. If you take that away, all of a sudden, the brain is like, what is going on? And you can have withdrawal seizures, and they can be fatal. So do not, please do not stop a benzo abruptly. And also, in rare cases, it would be a good idea that you would just take a patient off of their benzo. Hopefully, we can learn from what's happened with the opioid epidemic that just stopping people's medications against their will usually does not have good consequences. I wanted to leave you with a couple final resources. So I mentioned the VA's Academic Detailing Service. So they have really tremendous materials that are available to everyone for free. These are your taxpayer dollars at work. If you're at the VA, you can see the printed materials. For everybody else not at the VA, this is all available online for you to print out. I've included the URL here. So when you get to this first page, you see if you click on this catalog, it will open up the PDF. And you can go through the table of contents. And you can see all the different topics that they cover and have materials on. So if you click on that benzodiazepines topic, it will take you to a bunch of different resources, including both patient and physician or clinician facing materials, including a handout like this that shows a little infographic about potential risks for patients. This is more a clinician facing resource to sort of help think about how you would script a conversation around benzos. And then they have a benzo conversion chart and a little bit of an outline for a sample paper schedule. So I would highly recommend that folks take a look at these resources. And then if people aren't aware, the VA has also developed a number of phone apps. So this is the CBTI Coach, which is just a really great resource that you could encourage patients to download that has a lot of information about sleep hygiene. It has a little sleep log where you can track how much time are you in bed, how much time are you sleeping. So anyways, there's, again, a variety of resources available through the VA. So in summary, I'm not sure if I left you with an answer for what's exactly the right amount of benzo prescribing. Hopefully, I've convinced you that probably it's less than the amount of prescribing that's currently going on. Particularly, we're in communities that seems like those most at risk are the people who are getting exposed the most. Hopefully, I've convinced you that there's potential mismatch between the evidence supporting use and the amount of use that we're seeing. Hopefully, I've convinced you that people really can stop their benzos. The most important thing is to not do it too quickly. I personally would suggest that you would aim for no faster than four months. And there's no shame in one that goes on over years, maybe with some frequent pauses in the course of it. I think the simplest option is just to use the currently prescribed benzo. There's not really good evidence to support adding something on to help with the taper. I think this is really important is it's a process that you're helping see the patient through and helping them kind of learn how to not see that benzo as an external thing that they need. I would also recommend this watchful waiting approach and not jumping to a substitute right away. Because again, I think you just really, even if you do know exactly why the benzo was prescribed five or 10 years ago, you just don't know how the patient's going to feel now without it. And so rather than start something right away, I would say go through that gradual slow taper process and then reevaluate as you go. And then finally, there are patients for whom benzo use is appropriate. So please, I don't want the take home to be that Donovan Most thinks that everyone should have their benzos stopped. That is not what I'm saying. What I am saying is that I think that again, based on the evidence we have, I think we just need to recalibrate a little bit and readjust who is getting these. And finally, if you and a patient do decide to taper and don't get completely off, that is not a treatment failure. That is absolutely a success from a harm reduction perspective. Here are some resources that hopefully will be helpful for folks. And with that, I will turn it over. Thank you for such an interesting and helpful presentation, Dr. Most. Before we shift into Q&A, I want to take a moment and let you know that SMI Advisor is accessible from your mobile device. Use the SMI Advisor app to access resources, education, and upcoming events, complete mental health rating scales, and even submit questions directly to our team of SMI experts. Download the app now at smiadvisor.org forward slash app. Now comes the Q&A portion of the presentation. Please feel free to submit your questions by typing them into the question area found at the lower portion of your control panel. I see one question that's about downloading the VA education materials. And the slides from the presentation today are available in the handouts area, which is in the lower portion of your control panel. So if you are able to download those, you can get the URL for that resource, as well as a number of others that Dr. Most had referred to. So while we wait for other questions to come in, I'll start with a question for you, Donovan. So if you inherit a patient who's already on benzodiazepines, how do you think about having the discussion with them about those risks and benefits of staying on them versus discontinuing the medications? Yeah, so I think that's a really common concern, because a lot of times, especially I think among younger physicians, they generally are a little more, I think, anti-benzo, and so more frequently are inheriting patients, and they're starting them themselves. And also, I think it's important to note that the vast majority of benzos are prescribed by primary care providers who have such an incredibly difficult job and so many things that they're trying to manage and handle for their patients. I think the relationship with the patient is probably, in some ways, one of the most important ingredients of a successful taper. And so 100%, I would not say this is something you want to bring up at your first visit with a patient. I think it would depend on what else do they have going on medically, building up a bit of a relationship with the patient, and then starting to talk with them about getting a sense of why were they prescribed it, what happened to that original symptom, how are they feeling, would they consider maybe cutting down to start the discussion. I would feel more strongly about a taper, say, in somebody who's co-prescribed an opioid, who needs to be on the opioid. So that's, I think, a good opportunity for some shared decision making in co-prescribed, patients co-prescribed benzos and opioids to help talk with them about which one do they think has been the most beneficial. Because with the black box warning, you really wouldn't want them to be on both of them. So I guess after I have a relationship with the patient, I would wonder about, is there particular reasons that I think this person is especially at high risk for harm related to the benzo? Are they co-prescribed other medications? Do they have PTSD? Do they have a substance use disorder? And then decide in the grand scheme of what's going on with this patient clinically, how important is stopping or at least reducing the benzo to help me prioritize how important it should be. Thanks so much. Really helpful. So we have a number of questions. We probably won't have time to get to all of them, but there's a lot of interest clearly in this topic. What one of the questions is about the potential for depression, major depression, as a result of chronic benzodiazepine use. What's your view on that as a potential problem? I mean, so benzos are their CNS depressants. And so in the way that you would worry about chronic regular alcohol use potentially contributing to depression or poor mood, that's how I would think about chronic use of benzos. And so yeah, I guess that's kind of the short and simple answer is it's a CNS depressant. It reduces electrical activity broadly in the brain. And I ultimately would be most concerned about why were they on it clinically? What's the reason for being on it would be my main concern. Great. I'm not sure if I totally answered that or not. Yeah, no, that was really helpful. And then there's a question about kind of low dose in terms of harm minimization. And how low would you see a low dose being? How low is low? So that's a good question. And I guess it depends partly on the patient's age. I mean, I guess I would say there's no dose that I would consider a safe dose. I think essentially the risk of potential harm essentially increases with the dose that the person's being exposed to. And so in general, if they need to be on something, a lower dose, less regular use is probably a safer way to go. But I wouldn't say it's like they're safe up until you get to like they're safe until you cross like four milligrams of parazepam a day or something. And then they start being less safe. There is not a threshold like that. Great. Thank you so much. So I'm mindful that we're just about at time. So with that, we won't be able to get to all the questions. But if you do have follow up questions about this or other topics related to evidence-based care for SMI, we do have a consult service. We have clinical experts who are available for online consultations. So any mental health clinicians can submit a question and receive a response from one of our SMI experts. Consultations are free and confidential. SMI Advisor is just one of many SAMHSA initiatives that are designed to help clinicians implement evidence-based care. We'd encourage you to explore the resources available on the Mental Health Addiction and Prevention PTCs, as well as the National Center for Excellence for Eating Disorders and the Suicide Prevention Resource Center. These initiatives cover a broad range of topics from school-based mental health through the opioid epidemic. Thank you for joining us. Until next time, take care. For more information, visit www.samhsa.gov.

Dr. Benjamin Druss

Rosalynn Carter Chair in Mental Health

SMI Advisor webinar

benzodiazepine prescribing

evidence-based care

serious mental illness

Dr. Donovan Most

geriatric psychiatrist

benzodiazepine epidemiology

tapering strategies