Narrator - Dr. Abel 00:00 Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. Narrator - ? 00:11 This podcast is provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 00:17 This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - ? 00:27 And now on to the show. Dr. Sean Kane 00:31 Welcome to HelixTalk episode 68 I'm your co host, Dr. Kane. I'm Dr. Schuman, and I'm Dr. Patel. And if you haven't heard already, we have an audio upgrade courtesy of our dean, Dr. Mark Abel. We really appreciate his support and helping us come up with new equipment to help HelixTalk sound as good as it possibly can. So thank you very much. Speaker 1 00:52 All right, so today I'm really excited to introduce HelixTalk episode number 68 hooked on a feeling how to discuss benzodiazepine tapers with your patients now. Dr. Sean Kane 01:02 Dr. Schuman, I can't emphasize enough how important of a topic this is, as we'll talk about, benzodiazepines are incredibly common. Patients can become dependent on them, and one common clinical conundrum is, how do you get off of these benzodiazepines? So I'm really excited to hear your personal practice and some background on the topic. Speaker 1 01:19 So this, yeah, this is something that we it's come up a number of times in our facility, as well as overall nationwide, as a concern. And so in this episode, we're going to talk about the current state of benzodiazepine use, expected trends in prescribing, both currently and in the future, as well as risk associated with use. And then lastly, we'll discuss techniques for ensuring a benzodiazepine taper is performed in a safe manner with the lowest risk of harm. Speaker 2 01:41 And something tells me that we didn't arrive to that stage, just because, you know, I think there's some historical content to it, and I think our audience will appreciate if you can go over that a little bit Speaker 1 01:53 too, certainly. So when I was in in pharmacy school, one of the things they would show us were some of these old timey ads for different substances. And one of these is the idea about, quote, mother's little helper. And this is a name that was given to various benzodiazepines, or other sedative hypnotics, dating back for, really, since the 60s and 70s, Dr. Sean Kane 02:12 with the thought that if you're a mother, you have a stressful job, and that these benzodiazepines are kind of the little secret that the mom has to make her life tolerable. Speaker 1 02:22 Yeah, this goes all the way back to a movement into the suburbs and changes in business roles, and both from a lot of gender roles, males in the workplace adjusting to their promotions and so with nerves, and then women getting adjusted to again life in somewhat of a more rigid social structure, and then also raising children. And if you look at the advertisements, they're actually, I mean, now there's they're so outdated, it's laughable, but maybe a little bit horrifying at the same time, about really promoting this as a safe alternative to other illegal substances, or, you know, instead of alcohol, that this is, this is something safe, like we done in a pill form every day, multiple times a day just to deal with your quote nerves. Speaker 2 03:02 And so what we are seeing right now is the result of the decades of use and those individuals who will, let's say we're in their 20s and back in 1968 now they're in their 70s, and we as medical providers have to deal with their consecutive use of these agents. Dr. Sean Kane 03:21 So correct me, if I'm wrong, Dr. Schuman, but I believe benzodiazepines are fairly frequently used by the US patient Speaker 1 03:28 population, right? So that's you know, really, since the 1980s there's been this thought about, okay, maybe we shouldn't use these medications as much. However, at the same time, it really hasn't curbed their use. So one in 20 US adults currently uses a benzodiazepine. And not only that, but there was a 67% increase between 1996 and 2013 so again, in spite of the growing accumulation of data, the rate still went up. Speaker 2 03:53 And I know beers criteria is the criteria that defines the use of medications and appropriate or any inappropriate medications in elderly patients. And according to the 2015 update at the of the beers criteria, it showed that 9% of the older individuals are still using some form of prescribed benzodiazepines, right? Speaker 1 04:15 And what's interesting about that is that was not the first time that the beers criteria really discussed these medications, but it to show that it's still continuing to be an issue. In fact, they list a lot of different medications that are considered potentially inappropriate or inappropriate prescribing, and benzodiazepines are 20 to 25% of that total volume. Dr. Sean Kane 04:33 So clearly, these are extremely common medications. They're widely used, and there we understand that there are significant risks associated with them at a minimum, and I'm sure we'll talk more about it, but just for inappropriate use in elderly patients, let alone some of the other side effects that we worry about as well, right? The elderly Speaker 1 04:50 was that was one of the first places to start with. Again, you think about individuals that may have been using them for decades on decades. Now those individuals are, well, getting into their 60s and over. So it becomes that about rethinking them and then out of that. And so in previous episodes, we talked, for example, about opioid prescribing. So just a shout out to our episode 61 we did a full discussion of the CDC 2016 guidelines for opioid prescribing. Well, they also focus throughout about benzodiazepines, discussing what is the risk of benzodiazepines contributing to that opioid induced risk of decreased respiratory drive, worsening sleep apnea. So one of them's problematic. Two of them is definitely something we need to avoid. And so that, I think, has been the latest real push towards, let's look at being careful these medications. Speaker 2 05:36 And a result of that, too, a lot of the prescription drug monitoring programs now not only track the use of opioids and morphine equivalents, they also track if the patient is on concomitant benzodiazepines and warn the provider, "the patient is also using benzodiazepines in addition to opioids." Dr. Sean Kane 05:56 Dr. Schuman, I know that PTSD is one of your areas of expertise, and something that is very common in a VA patient population. I understand that there's new guidelines regarding benzodiazepines for PTSD and the VA patient population, certainly. Speaker 1 06:10 So there were again, rumblings of change in recommendations for the last couple years, but just in June, they came out with the 2017 updates, and for the first time, medications are now considered second line for PTSD management, taking a backseat to psychotherapy for core symptoms as well as for insomnia. And what they continue to recommend is benzodiazepines as having strong evidence against their use, both as monotherapy or as adjunct therapy as well. Dr. Sean Kane 06:36 I just want to emphasize that so you're saying, not only are they not recommending it because of a lack of efficacy, but they're actually recommending against the use of benzodiazepines, Speaker 1 06:44 correct and that's because what they actually finding out that it's not just a safety concern, that they can actually worsen the outcomes. The main thing, and the one that I really try to discuss with with my patients, is the idea that it may interfere with psychotherapy. So a lot of what's done to really get the core of PTSD is for the individual to understand and process through the trauma that's occurred, and what that has to it has to occur on multiple levels of the brain. There's the ability to, you know, to control one's heart rate and one's respiratory rate, as well as the idea about processing through it on a higher cognitive level. And if somebody is cognitively slowed from medication that processing can't occur, or they've actually shown, is the ability for fear extinction to occur. So the ability to separate out that horrible past association. So when you hear a car backfire and you think gunfire, just separate that out and realize that's not happening. That's not gunfire. That ability, that extinction has been shown to it occurs less commonly with benzos, they really impair that healing. Dr. Sean Kane 07:43 So are we at the point not to get too much into PTSD? But are we at the point where we have good data that shows, in terms of a randomized fashion, that benzodiazepines aren't effective for PTSD, or is this more our current clinical experience combined with a lack of efficacy, of proving benzodiazepines are efficacious. Speaker 1 08:02 There actually are randomized trials. So they have looked at it as an adjunct, and again, finding that that interference in published studies with individuals looking at that psychotherapy component. Speaker 2 08:11 And so, you know, some of the concerns we just discussed, however, we have some concrete concerns with the long term use of benzodiazepines, such as dementia, fall risk, and, you know, elderly patients, and we want to discuss a little bit of those concerns and details and kind of form a base as to why we're talking about benzo tapers today, correct? Speaker 1 08:32 And so, Dr. Patel, you're exactly right. There are numerous concerns with benzodiazepines about cognitive impairment now out of that, but one of the things I always try to do is look at the truth versus myth. And one of the things is, in 2014 the British Medical Journal put out a fairly landmark paper exploring the relationship between benzodiazepines and dementia, and what they found was a significant association between benzodiazepine use and a subsequent diagnosis of Alzheimer's disease among community dwelling patients greater than 66 years of age. And initially, that was when there was a lot of press about it. But what but what was also discussed in multiple commentaries since then is the idea that a lot of times, agitation and restlessness are prodromal symptoms that can occur initially before a diagnosis of of Alzheimer's occurs. And so if somebody is getting a benzodiazepine for the agitation and the restlessness, and then they develop later on. Dementia. That doesn't necessarily mean the medication treats it. It means that you were treating the symptoms earlier and the disease was going to occur regardless. And so that's had to have been teased out. And there have been follow up studies since then that have somewhat some of them have have agreed with the study, but others, especially some fairly well controlled studies, have disagreed with and found that there is not this huge Association, and thus, right now, it's one that we can't say for sure that they can actually cause dementia, but we certainly know that they reduce sensory processing, concentration, problem solving and working memory. So those are all very real concerns. I just want to make sure that we don't put fears out there that may not be backed up by the current literature. Dr. Sean Kane 09:59 And there are a number of other adverse effects of benzodiazepines that we think about — fall risk is definitely one of them, which is one of the reasons why the benzodiazepines as a drug class are on the Beers Criteria. But really, when you think about fall risk, it's not just the fact that a patient falls, but more commonly, elderly patients are on anticoagulants. The risk of bleeding is higher with that fractures, elderly patients are more likely to have fractures of long bones or hips, and even patients who are driving with benzodiazepines at some level, you know to what you were discussing. Dr. Schuman the fact that cognitive processing is delayed, potentially could result in a car accident or just impairment of your driving ability in general. Speaker 2 10:41 Yeah, and this, this finding was actually a little bit interesting to me, that they are actually associated with increased risk of suicide. So I understand that they might be on concomitant antipsychotics or some of antidepressant type medication which increases the use. But can you provide some explanation as to how benzos are directly associated with increased risk of suicide. Speaker 1 11:03 Certainly, there's a couple different hypotheses about it. One of them is the idea about behavioral disinhibition. So what we a lot of times think about, what puts the rain on our behavior sometimes, is our frontal cortex. And so if our frontal cortex, with our executive functioning, is blunted from the benzodiazepine, you can actually then lead to behavioral disinhibition, and then that can lead to an individual acting out something somewhat impulsively, such as a frustration, to then lead to a suicide attempt, as well as other depressive symptoms. These medications are CNS depressants as well, and so that extends to a lot of different thought patterns, again, very similar to what we would say with alcohol. And then there's the flip side of it that acute withdrawal, or somebody who's using or abusing the medication taking multiple doses and then runs out, you can see a rebound anxiety. And then lastly, you can also see the overdose on the benzodiazepine. Is how the individual decides to try to commit suicide. So then there's also that concern too, about providing the individual now with a means to committing suicide. Speaker 2 12:00 And then there is always that dependence or the use disorder that we talk about, how you know, opioids are a means of a potential drug abuse or overuse. Benzos are in that similar category as well, right? Speaker 1 12:16 And one of the big things is, and one of my pet peeves when discussing with patients and providers is always to be clear about the terminology we use so many times a patient will be will be told, okay, you've been on these for years, you're probably addicted, or you're addicted right now, and that, that kind of statement right there is immediately going to put the patient on the defensive, and it's going to be really hard to establish that valid therapeutic relationship. And so that's where try to discuss terms like dependence or physical dependence, we have statistics say over 50% of individuals that receive the medication will be physically dependent, not meaning, again, it doesn't necessarily show that it was directly on the person that they decided that they were going to go ahead and do that, but that it does occur. And thus to discuss, you know, how that is potentially a problem, and then work with the individual to understand the risks of that and what what the fallout could be, and then come up with a plan. Dr. Sean Kane 13:04 And just for clarity, when you say physically dependent, that means that if you withdraw the benzodiazepine, they'll have some symptom of withdrawal from not having the benzodiazepine correct, and Speaker 1 13:13 sometimes because it was providing some semblance of a benefit for that individual. And that's to say that they're not necessarily addicted, but it was doing something, and the substance that was doing something for them isn't there anymore, and so they're going to have a period where they're not Dr. Sean Kane 13:25 doing as well off of it. So clearly, being on a benzodiazepine is a big deal in the first place, but if you're already on a benzodiazepine, given that it's fairly common that a body can become physically dependent on that benzodiazepine, it's important to figure out how, if the patient's ready, how do you actually get off of a benzodiazepine without causing these suicidal ideations or these withdrawal symptoms? What is the typical process for that? Speaker 1 13:50 One of the big pieces of it, a lot of times, is education, open discussion. When we get consulted, discuss this with a patient. A lot of you know the first thing to do is discuss with them what's going on, find out what they're using the medication for, and openly discuss the risks and benefits. Because whether it's, you know, actually doing something, not there's a lot of subjectivity as this medication is working for me, to understand what the individual feels that it's doing, and then discussing is that something actually provided by the medication? Is it more of a placebo effect, and what was going on there? And then discuss them, looking at some of the alternatives. You know that these medications do have some benefit short term on on treating anxiety or insomnia. But the thing about moving beyond, we're moving beyond just simply trying to treat the symptoms and we want to actually treat the process within the body or the brain, or the maladaptive behaviors that are leading to to the to the anxiety or the insomnia, which is leading to the medication use. Speaker 2 14:44 I like the approach over here. You said you you want to involve the patient, and that's more of that motivational interviewing or shared decision making technique. And it kind of reminds me that it's very similar to smoking cessation, oh yes, that if your patient is not on board with. This process, it's you're gonna have a very tough time getting through this benzo taper process. Speaker 1 15:05 In fact, I use some of the same language to talk about the ask, advise, assess, assist, arrange. Those same framework is used in taping somebody off of benzodiazepines. You're exactly right. Dr. Patel, Dr. Sean Kane 15:16 so what, what kind of timeframe are we thinking when we talk about the withdrawal phenomenon that can happen that clearly telling the patient about the time frame is important and some of the symptoms are important if they do experience these withdrawal symptoms that they should probably contact their provider and maybe slow down their benzodiazepine taper. But what is the time frame and what should they be looking out for? Speaker 1 15:37 Some general estimates is that it can take up to seven days for the withdrawal to occur. Again, it may take only a day or two for some of these short-acting agents, I think of something like alprazolam, which has a fairly short half-life. It may only take a number of half-lives of the drug — a couple of days — for that to occur. But it may take up to seven days with these longer-acting medications. And then it can even last anywhere from four days. So again, something like alprazolam all the way up to 14 days for diazepam, so you have a very protracted or longer period of withdrawal. And if it were to occur, you would have symptoms like irritability, insomnia, acute anxiety. And these are the big ones. And the other thing about it too is when these symptoms occur again, a lot of times, the individual may not even know or have a specific reason why they're taking the medication, but the minute you take it away, the individual become generally restless. Now they say, aha, that's why I needed the medication. I can never get off of it. I got anxious, or I was anxious. I didn't have my benzodiazepine, and it needs to go, you know, so therefore I need to have it again. And so by doing an inappropriate tape for the first time, you may have lost the individual indefinitely on whether or not they're really going to try it again. Dr. Sean Kane 16:44 And just to clarify, because I think that if a provider or patient doesn't know enough about the pharmacokinetic profile of these drugs, they may not associate their symptoms two weeks later being associated with the fact that they stopped their diazepam two weeks ago, meaning that their withdrawal symptoms take a while to start kicking in for some of these agents, and they may not have that temporal relationship to really build that cause and effect scenario with them, certainly. Speaker 1 17:12 And another concern that individuals will have. Some individuals have this this anxiety about getting anxiety when they don't have the medication, and that's where it's so important to discuss what the medication and is also discuss what you're going to do in the absence of the benzodiazepine. So again, if a number of people that say, you know, well, I just keep one in my in my pocket and definitely never use it, but I just the mere fact that it's there is an encouragement to me, and so to figure out a way using, you know, maybe that's more of a psychotherapy component that can be utilized for that individual to find other ways of coping with stressors and getting at the heart of what is leading to that fear of unpreparedness. Speaker 2 17:47 And some of the more pronounced withdrawal symptoms could be things such as seizures or paresthesias or flu like symptoms or weakness. So they maybe feel like they are knocked off their feet because they're not using these medications, right? Speaker 1 18:00 And so the thing is, is to be very frank with the individual about what to expect is, you know, I don't like the idea about that I'm a salesman and that I have a quota of individuals to get off of the medication. That's not what this is about. But of letting the individual know these are the risks and the benefits, but really emphasizing, you know, why we're doing this, but don't try to hold back from them any of the real concerns about about withdrawal, but explain we're going to do this in a way that we're going to minimize it. Dr. Sean Kane 18:22 Going to minimize it. I just want to emphasize that, because I think it's really important when we talk about goals of therapy for pharmacotherapy, one of our goals here is to not have the patient go through these withdrawal symptoms. They may have some of them to a mild extent, but our goal is to have very minimal withdrawal symptoms. The way that we do that is by very slowly tapering down, as opposed to just cutting the patient off and saying, Sorry, you know, deal with it. This is what's going to happen, right? Yeah. And that Speaker 1 18:47 actually brings us to another interesting point. Is when looking at doing the tape, or one piece of evidence that individuals consider is switching to a long acting benzodiazepine. So if, perhaps, if the concern is that we're just going to start slowing down the frequency, and now we're going to have periods where the anxiety is not treated, or there's withdrawal in the middle of certain days. What about using a long acting medication? And I like the theory of it. I love the you know, longer half life also means there's less of that immediate reward effect you take the medication, since it has a slower onset and a slower offset, you don't get that contextualization. But oh, I took the medication. Now I feel better. It went away. Now I feel bad. Therefore, I need another dose. The only problem with that is the evidence actually isn't there. Surprisingly, in 2006 there was a Cochrane Review, and that really didn't show any kind of benefit of doing that switch. And since then, there's really not been a lot of additional data. So that's an area of a weakness in the literature. We need more data looking at that to see is if better studies or different approaches can can change that shift. But right now, some do it, but there's, again, not a strong evidence to support Speaker 2 19:51 it, and this technique is probably not appropriate for all patients, especially those with hepatic impairment or renal impairment, where these metabolites. May accumulate even further, expanding the withdrawal symptom range, or put them at a harm's way. So again, this is not, not only it's not proven, but it's not for all patients. Speaker 1 20:11 So Right? And my other concern with it too is the fact that you're also, you know, with a lot of inner patient variability, the concern that now, if you're switching from an individual medication, individual feels is working to one that may not you're also running the risk of now first thing we do is destabilize their anxiety. Right off the bat with switching meds and then and now we've again, we've wavered in the patient provider relationship. So I think for that reason, I'm usually more akin to stick with the current patient's medication, but then work on making adjustments from there. Dr. Sean Kane 20:39 So Dr. Schuman, if we go off of that viewpoint where you're going to keep the patient on whatever benzodiazepine they're on, even if it's a very short acting benzo like alprazolam, what is a typical scenario, given that there's not one size fits all, but what is a typical starting point in terms of what that tapering regimen might look like? Speaker 1 20:57 So one of them is, one way of looking at is to start off with something along the lines of a 25% dose decrease, and a lot of it is going to depend upon the dosage form of the medication, what it's available. And can you split the dose, things like that, but doing something like a 25% reduction in dose, and then wait a little bit, wait two to four weeks, for example, see how the individual is responding, and then gradually do another 25% decrease in the dose. Wait two to four weeks, see how the individual is responding and bring it down slowly until you've come out, until the individuals discontinued the medication. Speaker 2 21:31 And any any criteria that you use to taper off, any percentages that you use to taper off, I'm assuming that they're going to be in accordance with either psychotherapy or repeat follow up with the provider to make sure they're not experiencing any withdrawal symptoms. Speaker 1 21:45 Correct? That's that's a big point, Dr. Patel, is that this is all part of a close follow up, whether we're doing a telephone follow up or in person follow up is we're assessing, how are you doing? Had you know, have you noticed any anxiety coming back? Have you noticed any, you know, change in mood, you know, with also looking for some of those withdrawal symptoms, but potentially also the reinforcement see is, do you feel better? There's the flip side of it too, is, do you feel less, you know, cognitively impaired or less groggy? You know, be careful. We don't want to add a leading question so that we're trying to promote a certain, you know, for them, get them to say the right answer, but really to discuss with them. And then something we'll get to in the end, too, is also the idea about that we're using substitutionary methods, whether it's pharmacotherapy or psychotherapy. We're not doing this in a vacuum, where all we're doing is taking away this benzo and then that's it. We have other treatment options, other evidence based therapies that can be utilized. Dr. Sean Kane 22:41 So with that in mind, during the benzodiazepine tapering process, if a patient does want to pursue adjunct therapies, what are some of the options to help control those withdrawal symptoms without basically going backwards and going back to the previous tapering dose that the patient was on? Well, as for Speaker 1 22:58 withdrawal symptom prevention, there's really three medications that have been trialed. Carbamazepine has been used, actually, at doses of 200 800 milligrams a day, and that's been found to be effective in decreasing severity of withdrawal. Unfortunately, there are not a lot of studies. There's a it's a handful of studies, really, generally two to three with each of these medications, but that has shown some benefit. Melatonin is another interesting one more for the insomnia component, if an individual is using the the benzodiazepine for insomnia, to use melatonin, two to five milligrams, some studies, I believe, have used immediate release. The majority have used to control the release melatonin, which for formulary restrictions. I think it may be difficult to procure that one. But again, the evidence really is mixed. As far as that benefit in there. One study was very clear that did not show benefit at all. Others have shown some benefit. The one that I find the most intriguing is pregabalin (and gabapentin has also been studied). With that in mind, they've trialed pregabalin at 300 to 600 milligrams a day during a 12-week taper, and they found that there was an increase in the number who were able to remain benzodiazepine-free. The study wasn't adequately powered, so it didn't come with significance, but there was a difference of about 14% in the number of patients who were able to again, to discontinue that benzodiazepine. So I think that's a promising thing Speaker 2 24:20 to consider. And you mentioned that some patients are using benzodiazepine more for sleep, so there were some mixed evidence for the melatonin use in those patients. But we definitely don't want to switch them from benzodiazepines to one of the Z‑drugs, like zolpidem or eszopiclone, and make sure that we're not getting them off of benzodiazepines and on to something else that could also be addictive, right? Speaker 1 24:43 Dr. Patel, that's a huge point. Even beyond addiction or dependency is the idea that some Z‑drugs have shown concern for sleep apnea and other adverse effects. So again, to make sure we're not trading one problem medication for another, and then the next guideline comes out and says, don't use that one. And now, six months later. Back for the same thing we're doing now and again, the patients is looking at, you know, what are we doing? We just, we just did this, Dr. Sean Kane 25:05 and thinking about what happens after that. Benzo is gone. Hopefully the patient had an indication for the benzodiazepine in the first place. And I still remember back to my pharmacotherapy lecture for anxiety. I was shocked that the first line therapy for anxiety was not a benzodiazepine, but it was something like an SSRI or an SNRI. And I think that providers and definitely patients are going to have this knee jerk reaction to anxiety equals benzo, and that there's no other options. And that's simply not true, and we have great evidence that these other drugs are more efficacious for that certainly. Speaker 1 25:38 So some of those examples for PTSD, again, SSRI or SNRI. Insomnia — we talked about some of the medications, doxepin for example, or melatonin; anxiety disorders — SSRIs, SNRIs, buspirone and hydroxyzine. But the big thing to not forget about is psychotherapy. Really number one should be especially for PTSD and insomnia, number one should be cognitive behavioral therapy. And you know, this is a plug for our colleagues out there in psychology and psychiatry is really working that inter professionalism, interdisciplinary treatment is to say we've got a patient. We're going to work together as a team to find these other effective treatments. We've had some benefit with the number of individuals getting off through the use of these other treatment modalities as well, is to find ways of addressing those feelings of anxiety that really are at the heart of it, and brand kind of bringing down that, that stress response, that need, that knee jerk reaction then becomes, you know, I have anxiety. I should, you know, to take something for but to find other positive adaptations that can occur. Speaker 2 26:39 Brought up a really good point Dr. Kane earlier about how the primary medication, or the first‑line medication, for generalized anxiety disorder is really the SSRIs to go with. And I still find myself educating my fellow providers in the clinic that, no, no, don't. Don't prescribe a short, even a short‑acting benzo PRN, and if they have truly been diagnosed with anxiety, behavioral therapy plus an SSRI could be a better option to go with. Dr. Sean Kane 27:08 And to that point, then, you know, we still have benzos on the market. They're not going to go away anytime soon. What is the true role of benzodiazepines with these, you know, anxiety type disorders, and if we were to see those, what are some steps, even simple steps, that we can take to make sure that it's prescribed appropriately? Speaker 1 27:25 That's a great point. And so I'm going to mirror it back to our discussions about the CDC guidelines and opioids, the same ideas we're not just talking about. You know, a lot of times it's very hard to change paradigm for an existing patient. One thing we can do, as we encourage patients to look at the risk and benefit is looking at future practice. And so just like with changing what we consider acute pain and what we treat it with, we're looking the same thing as acute anxiety, no more than six weeks. Really is for these benzodiazepines, their role should be, as for somebody who comes in with profound, very significant, very severe anxiety, or insomnia, you know, there's generally a reason we talked about is insomnia usually has a reason behind is we're going to use the medication the short term, and we're going to find out what's causing the insomnia, and we're going to address that, and with we're going to use evidence based treatments for anxiety. But yes, some individuals are so agitated or restless or anxious they can't perform psychotherapy just yet, and so to kind of get the individual a bit calmer, bit more stabilized until either the psychotherapy can begin to work, or until the those few weeks before the SSRI or SNRI takes effect, that may be the window of time where a benzodiazepine could be utilized. But big thing is that you're very clear up front with the patient that this is the plan a short period of time, and from there, we're going to continue to work on these other treatment modalities. Dr. Sean Kane 28:40 Now, Dr. Schuman, is there kind of a well accepted time frame in which physical dependence develops with benzodiazepines? Is six weeks short enough time that patients aren't likely to need that tapering regimen, or is six weeks long enough that you probably do need a taper at that point? Speaker 1 28:57 Generally, at that time period, I believe in most individuals would be fine at that point to be able to discontinue it again. A lot of it is going to be, is going to be the individual having a fear, not necessarily, of the physical withdrawal, but then there's gonna be psychologically that, again, that anxiety about not having the medication, which does result in an anxiety, and then that may justify the individuals saying, well, that's that's why I need it. And so you have to kind of work against that by coming up with would be in the PTSD program, say, other tools in the toolkit, and so to really come use those other tools, Speaker 2 29:26 yeah, and just like the opioid medications or any pain medications too, like you tell them, Yes, the instruction says take it every four to six hours, or take it twice a day. But you don't really need to take it if you're not feeling anxious, you know. So it's really the PRN use that we need to stress when we were prescribing it. Speaker 1 29:41 For some individuals, what I've discussed with them as part of it is, write down how you were feeling around that time when you took it. And let's see, what was it, you know, what were the thought patterns that led to your use of that medication? And then what else can we do, then to push against those negative thought patterns in the future? Dr. Sean Kane 29:57 So, Dr. Schuman, I know that you went. Is a talk about this one trial called the Empower trial, that we'll definitely reference in our show notes at HelixTalk.com but what's kind of the 30,000 foot view of what was the Empower trial, and why does it matter for clinical practice? Speaker 1 30:11 That's a great question. So the Empower trial was one utilizing both pharmacy and medical providers to look at if direct patient education could be used to help with the de prescribing of benzodiazepines. Well, they gave the individuals in the study was an eight page book where they talked about the harms of the medication, you know, things like, did you know that these medications can cause dependency? Did you know about the high risks of falls, or the concerns about suicidality, cognitive functioning, and maybe the lack of long term efficacy and evidence. It also would discuss what are some alternative treatments, what are the recommendations on tapers — and their taper lasted 21 weeks in the study. Much of these other things we discussed were presented in a booklet that was visually appealing to the individual. And then they're also advised to discuss the book with their pharmacist and or the psychiatrist. And those who received the direct education were over eight times more likely, so the an odds ratio eight times more likely to discontinue the medication regimen. So 5% versus 27%. Forty‑two percent of them did have some withdrawal effects, but none required hospitalization. A few patients received substitutional medications, but over well, these, these tapers were very, very well received. And the big piece of it was sitting down with the individuals and discussing it well. They the main, I guess, the main point of it was that for every four patients who received the booklet, one patient was able to discontinue and remain benzodiazepine free until until the six month assessment piece. Dr. Sean Kane 31:36 So two questions for you. One, is this booklet something that someone can see, is it available publicly, or was it restricted to this study? Speaker 1 31:44 Unfortunately, as far as I can tell, the booklet itself was restricted. I tried to find it within a trial, and I found some general discussions of it. But what I have done is, through the VA, for example, has a department of what they look at is an academic detailing, providing some evidence, and there's a number of patient and provider friendly handouts. And so that's another thing we will have linked up to our website, and that's something that actually, even if you're not at the VA, you can still access that through the link, and that has a number of nice visuals that can be utilized to discuss it too, with patients. Dr. Sean Kane 32:12 And then the other thing that I just wanted to highlight is that we're looking at benzodiazepine discontinuation rate of 5% versus 27% meaning that even with our very aggressive booklet therapy, we still weren't able to get three quarters of the patient population to stop their benzodiazepine, which I think highlights part of the problem is that this is really, really, really difficult to deal with, and maybe they ended up on a lower dose or things like that. But this very much speaks like smoking cessation, to me, were our best quit rates and some of our most aggressive regimens that we can give a patient approach about one in four, which is not very good at all. Speaker 1 32:49 And Dr. Kane, while you brought up another good point, which is the idea that, just like with smoking cessation, this is not a one time shot. Well, we tried it once, it didn't work, so I guess we'll keep going indefinitely. This is just like with and do a ton of smoking cessation, I believe you all do as well, is the idea is that you fall you get back up again. We try this again later on. Maybe this wasn't the right time, but we still need to agree that it's important, and we'll look at doing it again. There's a couple of individuals that I've tried three, four or five times, and we just it hasn't been the right time, or the substitutionary treatment we found wasn't really working. So now we're trying psychotherapy and attempting that and then seeing what we can do from there. But we keep trying because we emphasize the importance Dr. Sean Kane 33:30 of it. I think this topic is incredibly important, and as we mentioned, we will have references in our show notes at HelixTalk.com just to kind of wrap up a couple key concepts. Dr. Schuman, what are some of the things that you think are the most important take home points from today's discussion? Speaker 1 33:45 I think the big one is, again, the benzodiazepine use has been clearly associated with risks of falls, altered mental status, impaired cognition, dependence, and one that is, I think about a lot of interference with psychotherapy. So there are reasons why we want to reconsider their use. Speaker 2 34:00 But at the same time, you know, we have that social and cultural history that we see now, the individuals are using these medications for decades, and that has been associated with hesitancy to consider this discontinuation. Dr. Sean Kane 34:14 And then third is, you know, these tapering regimens is not one size fits all, generally speaking, a 25% dose reduction over a couple weeks is kind of a starting point, but really it's the close follow up is pivotal to making the tapering regimen successful. So the length of the taper, the degree that you drop, the dose per week, or per every other week, should be very patient specific, in collaboration with the patient, as opposed to kind of on your own, and this is what you do for every patient, right? Speaker 1 34:45 And then, just like when we talk about again with opioids, is we're making sure that as we're withdrawing this medication, that alternative treatment status strategies are utilized for any emergent or underlying anxiety or insomnia. And then, really the ideal focus is on non pharmacologic methods. Working with your psychologist or psychotherapist for things like cognitive behavioral therapy. Dr. Sean Kane 35:05 So that concludes today's episode. Hopefully you've appreciated our upgrade and audio quality, and if you did, we would love to hear about it by a five star review in iTunes. Those help other healthcare providers find our show and also helps motivate us to continue with the work that we do for these HelixTalk episodes. We're on Twitter at HelixTalk, HelixTalk.com with that, I'm Dr. Kane, Unknown Speaker 35:28 I'm Dr. Schuman, Unknown Speaker 35:29 and I'm Dr. Patel, and with that, study hard. Narrator - Dr. Abel 35:33 If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five star review in the iTunes Store, search for HelixTalk and place your review there Narrator - ? 35:44 to suggest an episode or contact us. We're online at HelixTalk.com thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.