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 72 I'm your co host, Dr. Kane. I'm Dr Speaker 1 00:35 Schuman, and I'm Dr. Patel, all right, and I'm excited to bring today's episode, which is titled, Drop It Like It's Hot: prazosin and the 2017 VA/DoD PTSD guidelines. Dr. Sean Kane 00:48 Dr. Schuman, did I hear you say prazosin? Speaker 1 00:52 I could say both, depending upon what you prefer. This is. This is an interesting one. There's a lot of different ways to say it, but one, one good drug, kind of Dr. Sean Kane 00:59 tomato, tomato, tomato, Speaker 1 01:01 or potato, potato. That works too. Dr. Khyati Patel 01:05 So it sounds like it's hot because there are new guidelines, and seems like we're dropping something, aka, Praise the Sun, yes. Speaker 1 01:12 So what we want to do here is really go through there have been some surprising changes that came out right at the end of June, beginning of July of 2017, and so starting a new year, kind of a new changes. Want to go through there and talk about what they did with that medication, maybe some of the other ones, and then go through what that means moving forward for clinical practice and the management of PTSD. Dr. Sean Kane 01:30 So Dr. Schuman, and I'm going to hold my hand up and say, I almost never see any PTSD patients in my neck of the woods, because many times they're intubated on receiving sedatives and things like that. So I'm actually really excited to hear about kind of general management of PTSD. So for the listeners who aren't in a VA psych-type clinic, I think that they can get a lot of value out of understanding the overall management and really some of the nuances of these new guidelines, and why. Sometimes guidelines aren't exactly black and white, like many people want them to be, I Speaker 1 02:03 think that's a great overview. And first, what I want to do is just go into a little bit of the background about what we're talking about when we say PTSD or Post Traumatic Stress Disorder. It's actually now classified as a traumatic stress disorder rather than an anxiety disorder, and what it requires is you have an exposure to a traumatic event, either directly or even now hearing about it from another individual. So your classic example is going to be the 911, dispatcher or someone who hears about a loved one who had something very horrifying happen that can still lead to as long as you have more than a month, month of symptoms that can still classify as PTSD. And when we say symptoms, what we're talking about are classic flashbacks or intrusive symptoms. There's hyper arousal, or alterations in arousal, feeling constantly on edge or on guard. Then there's avoiding people or events that maybe remind you of it. So again, if we're talking about a car accident, avoiding that intersection, maybe even avoiding that type of vehicle or that color vehicle, and then some changes in cognition and mood. You know, it shatters your idea about what's considered safe and unsafe. Maybe your idea about that I'm a bad person because this happened around me, or the world is no longer safe. So all those things occur in a constellation of symptoms, what we call PTSD. Dr. Khyati Patel 03:15 So now, Dr. Kane, you said you don't deal with this patient population as much in my clinic. It's family practice. You know, we may see some patients who have this condition, but we don't see it whole lot. So you obviously, being at the VA, deal with a lot of this patient population. Can you tell us a little bit about what's the prevalence? How many times do you get to see this patient? Speaker 1 03:32 So it's tricky, because, you know, some of it is, I get, you know, an observer bias in that, you know, I see a lot of it because I see those that have serious symptoms and present that the range in the populations, and this is one to anywhere from, say, around 6% to 12 to 15% and most of the time, the civilian population and the combat population are not that far off. You know, there were some older studies in the in the Vietnam era that were, you know, up to 15 16% even enduring now, but overall, it's still somewhere between that six to 15% range, both civilian and combat. Dr. Sean Kane 04:05 That kind of surprises me a little bit, because when I think PTSD, I think of combat veterans who have had these very traumatic experiences. But it's interesting that you're saying that non combat experiences have a pretty good incidence rate of PTSD as well, right? Speaker 1 04:21 And that's, and that's, as some have said, you know, that may also be under reported, because there's still a lot of stigma, you know, we even see now, and, you know, in media and in national news about there's a lot of stigma associated with different types of abuse, and it's not even when people are always willing to come forward at the time. So a lot of times it can go kind of behind the scenes or under the surface for years. Dr. Sean Kane 04:41 So clearly today we're talking about the new guidelines, but in order to see where we're at now, I think it's important to know where we've been. So can you tell us just very generally, when did the old guidelines come out, and what did they kind of say about PTSD management? Sure. Speaker 1 04:53 So in 2010 the recent guidance, which we had been using, you know, when I was in school and as a resident and now practicing, got for. Putting under those, they would classify agents as significant benefit, some benefit, no benefit, unknown benefit. And our mainstays of treatment were SSRIs — examples include Prozac (fluoxetine) and Paxil (paroxetine). And our SNRIs, that's going to be your venlafaxine, which is your Effexor, maybe duloxetine, which is Cymbalta, and those are the mainstays of treatment, general symptoms. And then we had a few other medications, something like prazosin, specifically for sleep and nightmare symptoms, was called some benefit. And then mirtazapine as well, maybe for its antidepressant properties in a different mechanism of action. And some other classes, MAOIs, TCAs, older medications, which worked but had side effects. And then there were our no benefit medications, like our benzodiazepines, that which actually caused harm. And then Depakote, Topiramate, Risperidone, and then a lot of, pretty much anything else which had unknown benefit. There was a lot of unknowns and gray area within there. So I think I want Dr. Sean Kane 05:56 to touch on that just for a second, because when I think anxiety, you know, we've talked about benzodiazepines before for anxiety, and I appreciate that PTSD is no longer under the anxiety umbrella. But if you were to just ask me, without knowing anything about PTSD, what seems like a reasonable treatment strategy, I would assume that benzos would be advantageous, but you're actually seeing that benzos may cause harm in PTSD. Speaker 1 06:18 And this is what gets at a couple of things, one of which is going to be some of the societal concerns, which is how a lot of individuals self medicate. We have so many of our veteran and I speak of veterans because that's the general population. I work with so many individuals who self medicate with alcohol, heroin, other substances to dull things. And so we know about some of the pharmacodynamic interactions with opioids and alcohol, and what it does with benzodiazepines. The other piece of it is, as we said, is PTSD is no longer seen simply as this hyper arousal, but this mixed arousal. So we have a decreased cognition, decreased functioning in the front of the brain, and then higher, you know, over functioning in the the middle of the brain, the limbic system, fear processing. So because of that, you have some measures of the brain that actually have decreased cognition, and then the argument becomes okay. So a benzo as a medication that has a shotgun effect push, you know, decreases stimulation overall, that's actually hindering in the part of the brain that has to process through the trauma. And so in the long run, you may not be able to fully come to grips with what happened, because that part of the brain just is dulled by benzos, just like alcohol would. Dr. Khyati Patel 07:20 So it actually worsens the the whole process, and therefore they're called, known to be causing harm in this patient. Speaker 1 07:28 I've actually done studies finding that the psychotherapy can be inhibited in that population. Dr. Sean Kane 07:33 So then I have to ask, because my supposition is that benzos are good for PTSD. Is it common for patients with PTSD to be given benzos, even though the guidelines would recommend against it. Speaker 1 07:46 It was until about a year and a half, two years ago, when the VA in particular started looking at these psychotropic drug safety initiatives. And one of the ones that was really targeted was that specific population, geriatric population, with benzodiazepines and PTSD and benzodiazepines. So as a result of that, our prescribing rates have cut down tremendously, well above 50% I would say. Dr. Sean Kane 08:06 And again, we see non VA, non veteran type patients with PTSD. So I don't know, you know, are those non VA type patients getting benzos inappropriately then? Because again, that would be the thought of what you should give them. Speaker 1 08:21 Right from my from just anecdotal experience from a number of our clients and veterans, I would still say that maybe there is some lag as far as recognizing the data thus far. And so again, you know some people who go out of the system, and it appears to be a little bit easier in that, in that setting, but I believe you know, as a whole, the evidence still applies for any type of post traumatic stress disorder. Dr. Khyati Patel 08:43 So the updated guidelines were released in June 2017 and they're based on the evidence that was available until March 2016 and this is a little bit of an issue, because I'm thinking that in the practice, we were using the DSM five criteria for diagnosing and treatment, but then the studies that they've looked at through March may have been looking at the older DSM criteria, which was number four, right? Speaker 1 09:07 And that's one that we'll kind of have to see in the future how that plays out. But what we had is these kind of overlapping periods where we had an old guideline at least in 2010 new diagnostic criteria in 2013 new guidelines in 2017 so we're not going to pretend that all the data we're referring to came out between 2013 and 2017 so there's going to be, you know, a small amount of nuclear really. None of the studies were in that in between period. We're still all using older criteria. So as time goes on, that may change the population that's being assessed based upon that criteria, which could change who is included and excluded. Dr. Khyati Patel 09:41 So the bottom line is, is there a change in the way we diagnose patients with PTSD between the two criterias? Speaker 1 09:49 Yes, there are, overall, there's still a fair amount of overlap, but there is some some difference in terms of how they're diagnosed. So what are the new guidelines saying Dr. Schuman? So the first big piece of it is the first kind of bomb. Shows one I actually totally agree with, which is the idea starting right now medications are no longer first line for treatment of PTSD. Dr. Sean Kane 10:07 So as a pharmacist, I just want to make sure I understand this. No meds for PTSD Speaker 1 10:13 as the first one. So what they say now is individualized, trauma focused psychotherapy is now recommended over pharmacotherapy, with the idea being is to get through and go through and process those wounds. A lot of times, when I speak to our patients, talk about the idea of a band aid, is that what you have is a wound. Sometimes that wound has been sitting there for years and years, and you've tried to cover it up. A lot of times you got to get at it, peel it apart, you know, this old band aid, clean up what's in it. It's going to be nasty and hurt, but that piece of it to help recover, and that, again, needs to really sit down and talk through with somebody and process what happened. And so that becomes your first line treatment, because of better evidence in treating some of the core symptoms. Again, all those, the hyper arousal, the cognitive functioning, the avoidance, the re experiencing longer duration of response, and as well as, other than, you know, some some discomfort, fewer side effects from those treatment options. Dr. Sean Kane 11:07 And just to clarify, this is not done in conjunction with, like, an SSRI or something. This is first line, no drugs, psychotherapy, right, correct? Speaker 1 11:15 And actually, we'll get to this later. Is there's not even enough evidence about the combination. And that goes to this idea about needing more data. So right now, the only thing they have evidence for is, yes, just on its own, psychotherapy, apart from medications, is considered first line. But what they've said is that may not always be available. When we think about, you know, individuals who, by nature of their symptoms, prefer to be reclusive, it is tough to then say we're gonna sit down with you every single week for 20 sessions, or we're going to go through and do Cognitive Processing Therapy. Does it sound like a plan? And you say, No way, just give me a pill, send me out my way. And so there is some difficulties, and if it's not preferred by the patient or not available at that point, pharmacotherapy or other types of psychotherapy can be considered as well as you can consider pharmacotherapy for breakthrough symptoms. That's not something that's specifically mentioned in the criteria or the guidelines, but it is something that's alluded to, and it's something we will do in practice as well, but that becomes kind of your main stage of treatment moving forward. Dr. Sean Kane 12:15 So then if we are reaching for drug therapy, let's say they either aren't good candidates for psychotherapy, or they failed psychotherapy. What are some of the first line agents that we're considering for this PTSD patient population? Speaker 1 12:28 One thing, actually, before I even mention that, is, is we a lot of times think insomnia is the big one. Okay, well, what if they have insomnia? Well, actually, they're even they say no cognitive behavioral therapy over medications for insomnia too. So even if you say, they say, All right, one form of psych, if you need to do something else, from Sonic, do a different form of psychotherapy, and then may consider medication. So as far as, yeah, what we're talking about, this is where they got specific, one of the things, so we said SSRIs and SNRIs were kind of those biggest level of evidence, strong evidence. Well, now they've gone in and saying, we're just going to pick a certain agents within those classes which have the studies no longer a blanket effect, sertraline, paroxetine, fluoxetine, venlafaxine, those are the four medications with strong evidence. Everything else dropped from Dr. Sean Kane 13:12 that interesting. So within those four agents, you know, three of the four are SSRIs, and then the fourth one, venlafaxine (Effexor), is an SNRI. You know, we've talked about depression before, and kind of pros and cons, side effects and things like that, within those four what things stand out to you in terms of when you might pick one over the other, and Speaker 1 13:30 that's, that's a great thing. So one of the things we look at is, is a big thing is going to be weight gain, sedation, sexual functioning. So something like, If weight gain is the big concern, paroxetine is probably not going to be the best option. Moving for the others are fairly weight neutral, sedation becomes a big one generally. Again, we'll hit on paroxetine, even though it has FDA approval, is one poorly tolerated, and you still have more weight gain, more sedation with that one in the highest rate of sexual dysfunctioning. So from there, the more activating agents would be certainly in the flux the chain. Believe it or not, venlafaxine seems to have some of the higher rates of sexual dysfunction. I would argue, a lot of it is maybe under dosing it. And so it's one that you kind of toast that line between SSRI and then really doesn't become an SNRI until a dose of 150, to 225, milligrams. So especially if you're playing in these low doses, it's it's right up, right with the others, and not any more well tolerated. Dr. Khyati Patel 14:24 That's good information to have. So basically, what you're saying, we pick the agents based on their side effects and what suits for the patient. So individualizing therapy is important here, and Speaker 1 14:32 that's a big thing throughout this is a common theme, is individualized therapy. Dr. Sean Kane 14:36 Again, the older guidelines had SNRIs, SSRIs, and now they're being much more specific. Duloxetine, or Cymbalta, for example, was not listed on the new guidelines. Is it because of a lack of efficacy or just a lack of data to support its use? Speaker 1 14:49 And here's a great point — the difference between no evidence of benefit versus evidence of no benefit. With duloxetine, it's simply that there is no good data. Some experts have noted we have had so few high-quality trials over the last 10 years, so absence of evidence does not necessarily mean absence of effect. Dr. Khyati Patel 15:18 So we talked about these mono therapies. There specific SSRI or SNRI agents. Are there any other agents that the guidelines mentioned that are, either the guidelines are for it or against it, that we want to have our listeners to also focus on? Speaker 1 15:32 Yeah, there are. There's a couple of unique ones. One of them is some weak evidence against use and that they specifically mentioned quetiapine. Not shocking. I've kind of on past podcasts. We've talked about PTSD and atypical antipsychotics. The one thing to note on this is that there was a very positive study in favor of the use of quiti Iping. But that study came out right after, like, really, within a few months period. I believe after this paper kind of set off their their cut off for when new data. And so because of that, the echotyping study is excluded from this paper. It's they mentioned it only to say that they're not discussing it. So that's kind of something to take with a grain of salt, overall, really, not a lot. You know, recommendation is to pretty much avoid these medications in PTSD, in practice, you'll see them. It'll be interesting to see moving forward, what happens? Because I said, as I said, despite kind of the guideline recommendations, there are still some publications which have come out very much in support of it, especially that this new photographing one. Dr. Khyati Patel 16:30 I mean, just talking from chronic disease management, you know, metabolic issues, but photographing are very common. So I'm kind of glad to see that, you know, not a lot of patients are going to be on it. Speaker 1 16:40 And the other interesting one is citalopram. So this is one that, again, was lumped in initially with all the other SSRIs, but then there was a recent meta analysis that seemed to show that it failed to separate from placebo. And you combine that with the concerns about Qt prolongation at those higher doses above 40 milligrams, and so this one became a weak evidence against you. So that's something to point out. You know, grant, we still use it a number of individuals, but it's going to be interesting to see, you know, with time, as we change to reflect those which do have the higher level of evidence, those four we previously discussed, Dr. Sean Kane 17:13 are there any other agents that were discussed in the guidelines that you think are worth mentioning? Speaker 1 17:17 Another interesting one is Topiramate. So the VA had done and the same area up in Washington State, which is really interesting when we talk about prazosin, and it really became widely used up there; they did some of the studies looking at Topiramate, some found benefit, but overall they showed limited change in overall PTSD symptoms. But the overall change in PTSD symptoms, not really any benefit with Topiramate and even even in those with comorbid alcohol use disorder. So really, for the most part, now that one again, weak evidence against you, specifically for PTSD. Dr. Sean Kane 17:49 And again, in thinking about, like the side effect profile of an SSRI versus Topiramate, you see a lot of cognitive dysfunction with Topiramate. So in my mind, without good efficacy data. Why would you go to that drug when you could potentially reach for your SSRI, for example, Unknown Speaker 18:07 totally agree, Dr. Khyati Patel 18:09 we kind of set the background for benzodiazepine. You know, we're kind of moving away from there. Are there any other agents that they strongly recommend against? Speaker 1 18:16 Well, so there's a few of them. The main ones, as you mentioned, is benzodiapine, strong evidence against use as monotherapy. And then the other one right now is ketamine, and this is one that's been a hot topic right now for depression ketamine infusion clinics. And then lately is the idea about using ketamine and other NMDA antagonists as a way of working in individuals who do have, you know, again, some aversion to psychotherapy. And it's really interesting, even MDMA is being trialed as well, with the idea being, if you can kind of give, you know, more of an excitatory system to get the individual, you know, almost more hyper aroused to where they're more willing to discuss and process through these traumas, by allowing things to bubble up. And as you can imagine, in the wrong setting, that could be very detrimental to an individual who's maybe using the medication inappropriately and not in the right context, and then now is unable to deal with all the symptoms that's bringing up. And so if it was being used, it's going to be in a very close clinical setting and combined with psychotherapy. But that's, again, very, very, very early on in development, and at this point, kind of to get ahead of things. The VA is really advising against it at this point, till we can kind of get an idea how safe it is and make sure that the right environments are being used. Dr. Sean Kane 19:34 So Dr. Schuman, I know that you mentioned just kind of a lack of overall good quality data or studies to support specific, you know, approaches to the treatment of PTSD. Where are we at in terms of other data for other agents, or where things are headed in the next Speaker 1 19:51 decade, let's say, and that's, again, that's another frustrating thing is that, you know, based upon what were some fairly strict criteria for inclusion into the these guidelines, a lot. Medications were excluded and not even mentioned. So examples are clonidine and propranolol as two of these alpha and beta adrenergic agents. Respectfully, wish to try to work on that hyper arousal symptom. Those medications have been widely used in clinical practice. Personally, we've had some some good success with the propranolol, for example, and we have a couple providers who use clonidine very as actually their preferred agent in the clinic. However, big quality studies just aren't available, and so those two agents weren't even discussed in the guidelines, which is kind of sad, because, again, it it's not indicative of where practice is. Dr. Sean Kane 20:33 That's really too bad, too, because if you think about it, like this is not a rare condition, right? Like this is common enough that with the proper funding, you could be able to study these in high quality randomized control trials, but for whatever reason, we're not seeing that kind of study being done, right? Speaker 1 20:51 And so that's actually to that point is brings us, I think, to a good transition to talking about praise, and is the is okay, what happens if we do try to get one of those big studies. So this agent is just for you know, an old quick overview, is a centrally acting alpha one blocker, originally used for treatment of high blood pressure, not really a great agent there, started to be used for treatment of benign prostatic hyperplasia, found benefit there, and then, kind of anecdotally discovered its benefit for treatment of PTSD symptoms. Dr. Sean Kane 21:23 So given that it's been used more for a psych indication, can I assume that it crosses the blood Speaker 1 21:29 brain barrier, and that's that's been the one of the big thing with it, and so that's where they know to the benefit, but because it still has systemic effects, that's what's why blood pressure becomes a concern. So one of the dose limiting issues have been orthostasis. I've seen doses up to 10. I think 16 milligrams the highest I've seen. There are case reports up to 50 milligrams being utilized most of the time. 510, 15 is the norm. Dr. Sean Kane 21:53 So Dr. Sherman, how would you doses of somewhere between five to 15 milligrams for PTSD compared to other labeled indications of prazos and like for hypertension or BPH, things like that. Speaker 1 22:05 For BPH, a lot of times you're doing divided doses to account for its shorter Half Life and duration of effect. So you're talking maybe two, four or six milligrams in in two divided doses twice daily. For PTSD symptoms, generally, with some exception, it's used as a one time dose at bedtime to account for some of those nighttime hyper arousal symptoms and try to avoid the residual hypotension and or the stasis in the mornings after so I Dr. Sean Kane 22:31 assume that if we've used it historically, we must have at least some data to support its use, and then something must have changed for it to again be dropped from the guidelines. So give us some historical context here, certainly. Speaker 1 22:41 And so this is where I try to go into the story. Go into the story. So the name to know is Dr. Murray Raskind. He's a VA psychiatrist up at Puget Sound, Washington area, and that's where a lot of PTSD research comes from. He had put out a number of studies, 2003 2007 and then the big one in 2013 67 individuals randomized prazosin or placebo, and found significant superiority in total sleep quality and total scores on the CAPS, which is the main scale used for assessing PTSD, and on the hyperarousal subscale as well. So over across the board, did really, really well, and that was considered the one that validated it. And so say, keep doing what you're doing. And that was on top of his previous studies. Dr. Khyati Patel 23:23 So this study showed positive results with prazosin. However, what are the guidelines saying — they're downgrading it? Speaker 1 23:30 And so this is where it gets interesting. They said there's and this is where I, again, I was, I was personally shocked. There is weak evidence against use as mono therapy or augmenting agent for global PTSD symptoms, okay, and I perhaps because the main thing it's being used for is the nightmares. But then they went on to say and insufficient evidence for or against use in treatment of nightmares and again, and that was, that was the biggest shocker in there. Dr. Sean Kane 23:55 So then what changed? How did they decide to basically have this role reversal of the role of prazosin, given this fairly good data, what's new or different? Speaker 1 24:04 So what they said is, there is a large negative but unpublished trial, which completed about three years ago. The VA had done this, this pact study, where they had looked at prazosin and combat trauma, and that study showed it did not work. And the only problem with that is, when you look at their criteria for inclusion in the paper, they said, this study must be published on or after January 1, 2009 to March 2016, must be in English, and must be a full clinical study or systematic review. And so when I asked you guys, you know, in guidelines, how often do you see unpublished data being represented in guidelines, first and foremost, but then to use as a totally 180 degree reversal of clinical practice. Dr. Sean Kane 24:46 Um, never, yeah, that's not gonna happen. And then Speaker 1 24:49 that was, that was some of, one of the interesting things about it is it's it was totally, totally different. And you know also, why use unpublished data? And as well as one thing I wasn't able to kind of get from. There is, did that, did they use unpublished data from was that allowed for all the drug studies? Because I imagine, if we were to look at every other drug that was included in their study, there is bound to be unpublished data for each one of those. And was each one included or unfortunate? Is this, you know, is this a certain bias that was introduced by knowing that this study is available and so we're going to include it, versus looking and saying, all right, we're going to Include Unpublished studies from all of these as long as they meet our criteria. Dr. Sean Kane 25:26 So are you suggesting that if someone was involved in the guidelines that had intimate knowledge of the pact study, that maybe they would be more inclined to include that in the analysis? Speaker 1 25:36 And that's, that's what, that's what kind of concerned me. And there's even a mentioning that says one of the concerns of the older data is they were all done out of one VA and one provider that was the main author. And the thing about it is this new study was the same author, and so while it was a multi site study, it's still the same gentleman. Dr. Sean Kane 25:54 And for the listeners, I think it's important to talk about why there's a danger in including unpublished data, you know the peer review process, which is what happens during the publication process, is critically important for the scientific validity of a study. So during that peer review process, that's where you get challenged on your data. That's where they challenge your conclusions, your study methodology and things like that. And to have an unpublished study means that you haven't gone through that rigorous scientific process to basically make sure that you have the best quality study possible, so that you have this high quality or high level of evidence when that study gets published. Speaker 1 26:31 And I think that that's a kind of a good point to delve into a little bit about what this study looked in. So again, that's one of the things about it is, because it is unpublished, what we have to go off of, and this is something I believe we'll include in the listener. Notes. Is a link to the clinical trials page, which is essentially the only documentation we have for this study. And what they did is they looked at 300 they go 320 veterans randomized to prison or placebo, 26 weeks, 10 weeks of flexible dosing, one to 20 milligrams. But again, there's no, no discussion as far as what the average dose was utilized. So we know average dosing again, 510, 15 milligrams, we can look at what the average doses were in previous studies, but we can't compare to what the average dose was here, because up to this point, to my knowledge, we can't find it. Dr. Sean Kane 27:15 And you're kind of suggesting that if the average dose was like two milligrams, then maybe the effect was not observed because they didn't give the right Oh, totally. Speaker 1 27:23 And so again, is these things. I mean, I certainly think this is compelling data, but I would love to see it in a published format so we could give it the same rigorous overview. Dr. Khyati Patel 27:32 So including an unpublished trial in deciding which way the guidelines would go was probably not the right move. Are there any good things that the the guidelines did well, yeah. Speaker 1 27:42 And again, actually, first, just as your point was one of the statements, and it was kind of interesting, where they said the quality of the VA cooperative study could not be fully rated, as it was unpublished. However, the study design was impressive, and the cooperative studies are known for scientific excellence and methodological rigor, so we'll include them. And so again, my concern there was a little bit of a halo effect, which is, since these studies are usually good, we'll include it. So again, maybe a little bit of a preferential treatment compared to other unpublished studies and and to what you're saying. As far as the good things about it, I really did, like they did, say, this is not meant to be a standard of care. It's a general guide to best practice. And there was really a good emphasis on shared decision making. One of the big things I like throughout it is the ADA, hey, you should probably ask the patient, what are their concerns. Going back to, I believe, Dr. Kane, you mentioned the concerns with choosing one SSRI versus an SNRI. And Dr. Patel baby mentioned it too, talking the patient. These are the side effects. These are, this is our deck of cards. These are the agents we have to offer. Of these. Here's the good and bad of each one. What do you think? What is your deal breaker as an individual and allowing that to do it? And I think that's a very good thing. They allowed for it. Dr. Khyati Patel 28:51 And let's face it, PTSD is usually not long standing, meaning patients may have some other psychological, psychosocial issues, such as, you know, substance use disorder, sleep issues, depression, bipolar, etc. So kind of addressing those symptoms or conditions in general, along with PTSD, it's important Speaker 1 29:09 as well, right? And so they didn't say, Hey, we're going to provide guidance on how to treat all those things. But what they did say is, you need to treat all those things. You need to ask when you sit down, somebody, talk about their PTSD. Don't get so siloed you forget about substance abuse, anxiety, depression, sleep, making sure you're getting referrals, and again, outside of just the pharmacy realm, if it's insomnia, you know, do we have a sleep study? Do we have cognitive therapy on board? Should we get those things on board? Have we done a TBI screening? Have we assessed for what that could be contributing? What are the medical comorbidities and how do those Interplay into it? Dr. Sean Kane 29:44 So when I think of guidelines and guideline updates, one thing that always I think is interesting is that as soon as a new guideline comes out, people are quick to kind of jump off ship to whatever the new guideline says, even though sometimes the data that prompted that new guideline change has been out. For a while. So in this context, I think that it's important to think about, you know, one of the big changes here is unpublished data isn't even out yet, which is super interesting. So sometimes the guidelines aren't black and white. Must do this. And I think we've kind of reflected on, you know, these are guidelines, guideline being the operative word. They're not requirements. They're not black and white. These are not checklists, things like that. So, Dr. Schuman, in your practice, given that the guidelines have changed, has your personal practice or how you treat PTSD changed, Speaker 1 30:32 not a great extent, you know, one of the main things that we still, you know, one thing we have is kind of keeping an eye for, you know, what are these agents that do have the highest level of evidence? So we have been using a fair amount of duoxetine relative to venlafaxine, again, noting that there's an overall, you know, a dearth of a little bit of some of that evidence you may be wanted to really look at. Okay, maybe we should be focusing a little bit more on using our sertraline or our fluoxetine, maybe venlafaxine against some of the sexual side effects there. I'm not as big a fan of it as compared to other s NRIs, but that's something I think to be noting on. And then the big one, though, with prazosin is it really hasn't changed a lot. I may be slightly more inclined to consider one of these other alternative agents such as clonidine or propranolol, but overall, we're not, I don't think we're going to stop using prazosin. And one thing they even noted in there is this doesn't mean get all your patients off of the medication. If they're on it, use your clinical judgment. Maybe, you know, and I think that's some of the heart of what they were getting at, is, if you have a patient on it right now, reevaluate what it's doing for them. And if it's not working, maybe consider bringing it off, trying an alternative. But then if they're not on it, I still think it's part of the it's part of the options, and I would still, again, use some of these other agents that have not as robust evidence. I think they're still maybe, maybe they get a little bit more play, because it's no longer praise us in with this great data and then everything else, but now maybe it levels the playing field a little bit, but we're still targeting, targeting that, um, that noradrenergic system. Dr. Sean Kane 32:11 And I will say that one of my biggest complaints of the new guidelines is a lack of a pronunciation guide for prazosin. Yep, clearly we've kind of struggled a little bit in how we want to talk about it, and there's no right answer. Speaker 1 32:28 And one of the things, I think another one, is really the idea about future studies, future research, the idea about looking at, you know, complex patient populations and utilizing the medications in a real world population, what do we got? What are we going to do looking at some of these other agents, I'm very much interested to see, you know, head to head studies looking at a clonidine or guanfacine or prazosin, or even, you know, developing a hierarchy of, if one adrenergic medication fails, where do we go from there? And unfortunately, there's just not a lot going there. And that's kind of what my heart is, is to see what do we do next? We have, again, these, this handful of agents, but let's, let's get some really good quality studies, and let's, let's keep, keep moving forward so that we, because so much of it is, we don't have this evidence or information. So let's, let's get some more information, and maybe soon, rather than later. Let's reevaluate where we're at in a couple of years. Dr. Khyati Patel 33:23 And I just can't help but notice the fact that the guidelines have suggested psychotherapy as the mainstream of therapy for PTSD patients, and apologizing in advance for getting a little bit more political. But as we know, with the new healthcare reform and things that are changing, there's not whole lot of allocation in the budget towards mental health coverage. And so if you're saying that these patients need to go see somebody and do all these psychotherapies and stuff, it's very important that we advocate for patients getting the coverage for this psychotherapies as well. Speaker 1 33:55 Certainly, this is a team based approach, and you know the system, you know we need to be coordinating, whether it's social workers and therapists and psychologists, psychiatrists, pharmacy working together here to hit it from different modalities, even though, again, the problem is, they even admitted there's no real good studies looking at concomitant psychotherapy and medication. So again, it's it seems to make sense. But even there, we need to do more assessments and studies there as well. Dr. Sean Kane 34:24 So Dr. Schuman, to kind of wrap things up, what are some of the big take-home points in your mind for these new 2017 PTSD guidelines? Speaker 1 34:33 Again, the big one is the overall re examining of praise in and moving it down to essentially a kind of neither for nor against approach to it. And then being careful, though, how you take that, that it doesn't mean that we need to get everyone off of it, and it just, we just need to have maybe a little bit more of a critical eye on the data that's available. And moving forward, be thinking about other modalities. And then the other piece of it is going to be within our SSRI, is it. SNRIs, maybe we need to be focusing a little bit more on those that have been studied, as well as encouraging further research into those that haven't been studied. So our duloxetine or desvenlafaxine, certain other medications and newer agents, and then lastly, continuing to avoid use of benzodiazepines, while, while, I must say, while being careful to discuss with the patient, the client, why this is and so to try to avoid fear tactics about death and overdoses, and really focus on the lack of benefit, as well as the potential interaction negatively with psychotherapy. Dr. Sean Kane 35:39 So for the listeners that want to actually read the 2017 PTSD guidelines. We'll have a link on our website, HelixTalk.com again. This is episode 72 and we'll also have a link to the clinicaltrials.gov page for the PACT trial, which is that unpublished trial referenced in the 2017 guidelines. So with that Happy New Year, I'm Dr. Kane, I'm Dr. Schuman and I'm Dr. Khyati Patel 36:01 Dr. Patel, and as always, study hard. Narrator - Dr. Abel 36:04 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 - ? 36:15 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.