**Transcript of Cyberseminar**

**Spotlight on Women’s Health**

**Gender Differences in Psychopharmacologic Treatment among Veterans Diagnosed with Posttraumatic Stress Disorder (PTSD)**

**Presenter:  Nancy C. Bernardy, Ph.D.**

**June 10, 2014**

This is an unedited transcript of this session. As such, it may contain omissions or errors due to sound quality or misinterpretation. For clarification or verification of any points in the transcript, please refer to the audio version posted at www.hsrd.research.va.gov/cyberseminars/catalog-archive.cfm or contact Nancy.Bernardy@va.gov.

Moderator:	We are at the top of the hour so I would like to introduce our speaker, Dr. Nancy Bernardy, who is the PTSD Mentoring Program Director and is Associate Director for Clinical and Networking at the Executive Division at the National Center for PTSD at the White River Junction Vermont VA Medical Center. She is also an Assistant Professor in the Department of Psychiatry at the Geisel School of Medicine at Dartmouth Hanover in New Hampshire. Nancy, I am going to turn it over to you now and I will check on that audio.

*Dr. Bernardy:*	Alright Molly, thank you. It is the Geisel School of Medicine at Dartmouth but thank you so much. It is a real pleasure to be here today speaking during this series on women’s health. I first want to acknowledge my mentor and my collaborator on the work that I am going to be presenting, Dr. Matt Friedman, who is the past Executive Director of the National Center and he now serves as a psychiatric consultant for the PTSD Consultation Program. I am going to be saying more about that program later. He is also a psychiatric consultant for the National Center overall. 

We have worked closely with two clinical pharmacists in the Iowa City VA Medical Center...Drs. Brian Lund and Bruce Alexander, who also have collaborated on all of this work I will be presenting. 

I want to acknowledge Ms. Aaron Jenkyn, who is my research assistant who is so much more than a research assistant and very involved in this work and then Dr. Paula Schnurr, who had the wise advice to suggest to me that I explore the topic in gender differences in prescribing in PTSD and that is what I am going to be presenting to you overall today.

I want to thank Funding from the Department of Veterans Affairs Mental Health QUERI and we have a new project that is funded by the Mental Health, the Poly/Trauma and the SUD QUERI Programs. 

I briefly want to review the first line recommended pharmacologic treatments for PTSD, particularly reviewing the guidance around benzodiazepines and briefly go through our work examining prescribing practices overall in PTSD. Then I want to discuss the gender-specific findings and talk about possible explanations for those findings. Finally, I want to share some new work that we have done focused on polysedatives, again where we are seeing gender differences and implications for the way forward. 

It would help me to know what your primary role in VA is so if you take the time just to select this it will give me a sense of the audience.

*Moderator:*	Thank you, Nancy. It looks like the answers are streaming in for our attendees. Just simply click that circle next to the response that best encapsules your primary role in VA. It looks like the answers are streaming in so we’ll give people a few more seconds to get those in. Okay...they are still coming in. We’ve got a very responsive audience. We do appreciate your feedback. It does help us know who to gear this talk mostly towards. Alright...we’ll go ahead and end the poll. Nancy, do you want to talk through those results real quick?

*Dr. Bernardy:* 	It looks like we’ve got a majority of mental health clinicians, which is wonderful because that is really the group I wanted to reach, then followed by researchers, administrators, trainees and others. That is great, thank you.

I want to start with the pharmacotherapy table from the PTSD Clinical Practice Guideline that was published in 2010. I always like to point out the website for the guideline, which you can see here to show people that it is located at healthquality.VA.gov.  As you can see here, the first line recommended treatments are antidepressants for PTSD. The SSRI’s and the SNRI’s, specifically paroxetine, sertraline and venlafaxine.

I also want to point out that Prazosin is recommended there for nightmares related to PTSD with a B rating. We are not there yet with a stronger rating for Prazosin overall for PTSD symptoms but the think I really wanted to draw your attention to is the issue around benzodiazepines. The strength of the recommendation there on the left is a D and what that means is that the quality of the evidence is fair to poor but it also means that the recommendation is made against routinely providing this intervention to patients because they are either ineffective or harmful and in this case the authors of the clinical practice guideline made the point of putting the word harm in there for benzodiazepine. Also, right underneath that is a change in the recommendation regarding Risperidone, an atypical antipsychotic. Previously, atypical antipsychotics were recommended for people who were treatment resistant to SSRI’s as an adjunct treatment to antidepressants but after John Krystal’s large cooperative study came out in 2011 showing no benefit for Risperidone there was a change made to the Clinical Practice Guideline to put it in the same D category as benzodiazepines. 

I wanted to start with...what is the problem with this guidance? We probably every 2-3 weeks get an email here at the National Center from a clinician in the VA saying...I have a patient who is 65-years-old with PTSD who has been on chronic benzos for the last 15-20 years. He is doing well. Why would I want to rock the boat and try to stop those? And so...it is contentious, this role about benzos and PTSD. What small clinical trials have been done...and these are listed in the Clinical Practice Guideline...have shown that there is no benefit of benzodiazepines in either alleviating the overall PTSD symptoms or in preventing PTSD. What is obvious is that there is an evidence-based literature regarding the significant risk of chronic benzodiazepines that is large, is a very clear literature and is growing rapidly. Combined with the lack of evidence of efficacy from the trials that have been done in PTSD plus this clearly evidenced high risk profile, we see support for the Clinical Practice Guidance against their chronic use. Perhaps the developers of the Clinical Practice Guidelines should think about, in the upcoming one, including that literature as part of the guideline to show the concerns about the safety of benzodiazepines overall.

So what else do we know about benzodiazepines in PTSD? Well, we think they are commonly prescribed to manage the symptoms of insomnia and anxiety but we know now that there are better treatment options for both of those symptoms that include safer medication options and psychotherapy options. The issue around anxiety is an interesting one. It is very possible that what appears to be anxiety to the clinician and the patient is actually part of that hyper-arousal cluster of symptoms that if the person gets an evidence based PTSD treatment that will decrease and be resolved through therapy. It is all the more reason to try to get people into an evidence-based psychotherapy for PTSD. Also, we know that there are two common comorbidities often associated with PTSD...mild traumatic brain injury history and substance use disorder...that are contraindications to benzodiazepine use. However, what I am going to show is it is that very group of patients who are receiving these at higher rates. There is some limited clinical evidence that benzodiazepines can reduce the effectiveness of the evidence-based cognitive behavioral treatments, prolonged exposure [audio drops] processing therapy that are recommended and that has been seen in real world patients. 

Most of us know about these adverse effects of benzos...intolerance and dependence, pretty severe withdrawal symptoms can be seen and also the dramatic rebound so that once patients do quit them they see a return to the insomnia and anxiety that may even be higher than what was previously reported. There is also risk of accidents and falls in older adults but the most adverse effect may be this issue of cognitive fogginess. The cognitive impact that benzodiazepines have on the patient...part of this growing literature of concern is listed there in the bottom bullet. There is new evidence suggesting an increased risk of dementia associated with chronic benzodiazepine use. This is of particular concern in PTSD patients where we have also seen an association with an increased risk that is two times greater in older Veterans with PTSD. There is increasing evidence of detrimental effects on the immune system. This is seen in rates of infection with patients who are on chronic benzos...and also this is true also in patients who are on Zolpidem, which I am going to talk about later and significantly higher rates for mortality have been associated with long-term use of benzodiazepines overall as well as a brand new paper that came out two weeks ago showing this relationship for patients who are prescribed benzodiazepines for sleep. 

It is, I think, evident of VA’s commitment of women’s health needs that things like this series are being organized. We know that women are now the fastest growing cohort within the Veteran community. They represent approximately 16% of the returning Veterans from Iraq and Afghanistan and when we began this work there was virtually none done to examine the role of pharmacotherapy in the management of PTSD in women Veterans.

I wanted to just share a couple of slides that Dr. Rani Hoff from NPEC had shared with us recently. To give you an illustration of what is happening with the numbers of Veterans in VHA with a diagnosis of PTSD, starting at the beginning of the wars in Iraq and Afghanistan and you can see this dramatic increase in the Veterans diagnosed. That also may look like a small blip at the bottom in women (the red line there) but actually that number is going up from 10,000 in 2003 to almost 50,000 in 2013 and showing that in another way  you can see the percentage of Veterans with a diagnosis of PTSD by year and as you can see what is happening, that top line reflects the rates in female Veterans and we have a much greater increase there taking place in our women Veterans coming in for treatment in VHA whereas the total number in males is pretty close and close to 10%.

Because we are interested in these things at the National Center for PTSD and developing products and thinking about ways to reach clinicians, I was really interested in having you indicate which method you prefer learning clinical information. Do you prefer to take part in webinars such as this or do you really like to get written materials? Books or journal articles? Do you like to get things on your mobile app...so do you prefer to have an iPod cast that you can listen to or something for your iPad? Do you prefer sort of the older fashioned live lecture grand rounds with case presentations that make it real for you or face-to-face discussions such as that might happen with a pharmaceutical company representative or an expert staff member? If you would just please click one of those and let us know what you prefer.

*Moderator:*	Thank you. It looks like once again the answers are streaming in. We have a very response audience and we do appreciate that. Also glad to see that webinars are a front runner in this poll.

*Dr. Bernardy:*	It looks like they like this so that is good news, Molly. Thank you.

*Moderator:* 	I’ll go ahead and end it.

*Dr. Bernardy:*	Okay.  So, what I wanted to show you is first starting out with our work we initially looked at benzodiazepine use in Veterans with a PTSD diagnosis and this work was published by Dr. Lund in 2012. We saw this nice decrease in prescribing among Veterans with PTSD overall so those are the rates from 37% down to 31% in 2009. What happened, though, is when we put this next to a graph where it shows a number of patients who were on medications for PTSD and saw the increase in the number of Veterans coming in to VHA for services you can see what happens there. We weren’t quite certain if we were actually observing a good news story and could say that benzodiazepine use was decreasing or were we actually seeing an increase. Clearly, there were many more patients being prescribed benzodiazepines.

We wanted to try to see what medications were being substituted for benzodiazepines if they were decreasing. We looked at overall prescribing trends in Veterans with PTSD and again this is sort of a mixed good news/bad news story. We found that the proportion receiving either the SSRI or the SNRI’s which were the top recommended pharmacotherapy treatments increased almost 10% to almost 60% of Veterans who were getting meds in _____ [00:17:01]. This was good news for us. This represented an increase of more than 46,000 Veterans receiving what we recommended as first line treatment. In addition to this overall decrease in benzodiazepine rate of prescribing we saw the overall frequency of atypical antipsychotic use declining from 20% in 1999 to approximately 14% in 2009. What we did see happening, however, was when Zolpidem or Ambien, as it is commonly known, was added to the formulary in 2008 we saw prescribing triple for that drug suggesting to us that there was a sleep problem related to PTSD that prescribers are really struggling with to address. The part of the good news is that Prazosin use has expanded nearly sevenfold so from the time that Dr. Rosenheck and colleagues did their study and saw _____ [00:18:12] around the Seattle area, we are actually seeing a much broader dissemination of Prazosin around the country and that is good news for its use with trauma related nightmares. 

This is just a graphic of what I presented. However, I do want to point one thing out there. This is the line that reflects the benzodiazepine use and as you can see here, looking at polypsychopharmacotherapy across the board benzodiazepines are the second most commonly prescribed medication in PTSD patients. We were still concerned that 30% of these patients actually were too high a rate to be observing.

We next looked to see where the medications were coming from. One of my colleagues and I looked at this and the bottom line of this paper is that the vast majority of the psychotropic medications for PTSD are coming from mental health providers. You can see the breakdown there on the differences. This were confirmed for us that Veterans are frequently being prescribed medications that are not supported by the Clinical Practice Guideline and most of the prescriptions are being written by mental healthcare providers. 

We next turn to look at predictors associated with benzodiazepine prescribing and these are patient level correlates. These are the data that I presented after the presentation polisher came up to me and said...You’ve got to look at this issue with women. As you can see, the patient characteristic associated with benzodiazepine use included female gender, Veterans over 30 years of age, those living in a rural residence, a service connection greater than 50%, Vietnam era service and a duration of a PTSD diagnosis over three years. They weren’t really new to treatment. They had been in the system for a while. What I did not list here which makes sense was that there was also a comorbid anxiety disorder associated with increased prescribing. 

Let’s turn to the paper that you will be able to get that was published in the Journal of General Internal Medicine looking at gender differences in prescribing. We looked at the background on this and what we found was that women disproportionately receive prescriptions for psychotropic medications across the board so 1:4 American women receive these medications compared to about 15% of men. This is particularly true of antianxiety drugs. You can see those numbers there. It is particularly in what I like to think of as middle aged women 45-64...compared to a rate that is approximately half that seen in men. I should say that this is not an issue that is unique to the United States. This is true in most developing countries and it has been documented particularly in Europe, although Europe has really gotten ahead of us in trying to do something about this and there has been a lot of work looking at reducing benzodiazepine prescribing in the European countries and some of the work I am going to share with you in a bit.

We know that women suffer more frequently from psychiatric disorders then men so when we were trying to think about this we wondered if there was greater diagnostic frequency of those disorders that would account for this difference. Were there gender differences in acceptance and receipt of mental health treatment? There was some evidence that yes...as in most cases with healthcare women are more willing to go to a doctor and do something about a problem so was it the fact that they were coming in and getting treatment and, in fact, are we seeing under treatment of men with PTSD or is this actually a gender based inequity? 

The general methodology, and I don’t want to spend a lot of time on this because it is in all of our papers...but basically this is administrative work using the large database that is available through pharmacy and we looked at this first from a time period of a decade. We started in 1999, went through 2009 and some of the later work I am going to show you has been extended into 2011. We used Veterans who had at least one encounter coded for PTSD from inpatient discharges and outpatient encounters. We primarily looked at psychotropic prescribing in most of this work but we included Prazosin based on the fact that we were seeing this story that seemed to point to prescribing for sleep problems and we wanted to see what was happening with the use of Prazosin. 

This is again from the demographic characteristics of the gender differences paper. What I want to point you to is the fact that the women are almost a decade younger than the male Veterans. The women primarily live in urban areas compared to the rural residences of men. The women are post-Vietnam era, which is not surprising, and they have a lower service connection then the men do. They also have newer diagnoses then the men.

When we looked at comorbidities across the board, the top diagnoses, women significantly had greater comorbidities of depression, anxiety disorder, panic disorder, GAD and OCD and social phobia. Again, this is often seen in work looking at PTSD. What you see at the bottom is that men were higher in substance use disorder diagnoses as well as history of traumatic brain injury although the differences were not that large in those two. 

These are the results when we looked at the different medications...and we looked at them in four different time points across that decade so that we could get a trend across the time. What you will see is that we have had a nice increase in antidepressant prescribing for women that we also saw in men; it is just that the women are getting higher rates of antidepressants. When we got to benzodiazepine that is where we saw the big difference in the trend. Women here are getting an increase in benzodiazepines across the time period whereas in men, you see this nice return down to lower than 30% that we had previously reported. We have got this very different profile going on in women with benzos. In atypicals we also saw higher rates in women from 1999 to 2003 and what happened is that rate of atypicals stays elevated in women whereas in men we see this gradual decline in atypical antipsychotic prescribing. Zolpidem, again, you see this picture of a huge increase in prescribing for both men and women after it was made available on formulary but you see there that the difference in women is really striking. Finally, in Prazosin, women are receiving an increase in Prazosin but it is not as high as what we are seeing in men and that is the only place where we saw men’s receipt of medication higher was with the use of Prazosin. This is just in a graphic depiction of what I showed you. Again, what I want to point out...this middle line here is where you see the differences in benzodiazepines and that very different profile in women compared to what we have observed in men.

We next looked at independent predictors of gender differences. We looked at demographic characteristic and psychiatric comorbidities for the SSRI’s, the benzodiazepine and atypical antipsychotics. What we found was that age had a substantial impact on both benzodiazepines and atypicals. The good news is that younger, reproductive aged women had lower rates of receipt of both of those medications. Unfortunately, we are seeing an increase with age in women for benzodiazepines which is an area of concern. The atypicals, on the other hand, show this nice inverted U pattern where you have lower rates seen in younger women, increased in middle aged and decreased in older for both men and women. Finally, the bottom one makes sense. You see an increased percentage of VA service connected disability contributing to this increase in prescribing of all medications for both men and women perhaps reflecting the complexity of those patients.

We then looked at independent predictors of the psychiatric comorbidities and saw that they had a significant impact. The likelihood of SSRI and SNRI use was threefold higher in patients with co-occurring depressive disorder. Again, that makes sense that you would see more of those in those patients. The benzodiazepine use was more common for all anxiety disorder comorbidities particularly with panic disorder, again reflecting an appropriate indication and an elevated prescribing of atypical antipsychotics was observed in both men and women with co-occurring substance use disorder. Traumatic brain injury history was associated with increased prescribing across all medication classes except for that SSRI use in women and again, that is something that we would say is really contraindicated in this CPG where guidance _____ [00:29:50] traumatic brain injury is really that go low, start low, go slow recommendation and so that is an area that we think needs to be addressed. We saw benzodiazepine use actually higher for women with co-occurring substance use disorder which again is contraindicated whereas we saw the opposite for men. We saw both this increase in prescribing of women with a history of a TBR, with a history of a current substance use disorder which is an area of concern and a place where we might need more education.

We next looked at the contribution of these differences to what we had seen in the men. The differences in SSRI prescribing were largely attributable to differences in comorbidity which I just mentioned. You can see here the unadjusted rate for SSRI. When you put in comorbidity it brings it down to 1.13 after adjustment for the comorbidity. In contrast, when you adjusted for demographic variables it really had no effect of prescribing of SSRI’s across genders. When we looked at benzodiazepines, however, there were competing effects seen. When you adjusted for demographics, when you go from this unadjusted rate of 1.47 down to demographics you see that there is an increased impact of gender whereas adjustments for the comorbidity decrease the impact. The net result of that simultaneous adjustment for these effects was a persistence in the gender based discrepancy in benzodiazepine prescribing which could not be explained by differences either in demographics or the comorbidity so that gender effect is persisting in the benzodiazepine prescribing. Finally, gender differences in atypical prescribing were primarily attributable to demographic characteristics that you can see from the shift of 1.31 to 1.08 after adjustment. 

When we look at this overall, again we are seeing this overall receipt of women Veterans getting all psychotropic meds. The increases of SSRI, SNRI reflect this positive shift to evidence based care. We were seeing approximately 18,000 women who had previously not been on SSRI’s receiving what are the first line recommended meds and when adjusted for comorbidities there were still higher frequencies of SSRI’s and SNRI’s in women. It is possible that men may stay away from those medications because of concerns about side effects so, again, this question remains about are men being undertreated with the SSRI’s for PTSD. 

When we looked at the prescribing of atypical antipsychotics we again observed this comparable guideline concordant pattern with atypicals being reduced but yet we saw this increase in women that stayed elevated compared to what is happening in men. When we adjusted for demographic characteristics there were still elevations in frequency for women that were not accounted by more severe service connected disability. We weren’t quite certain what was going on with the atypical antipsychotics. We thought that they might be targeting insomnia symptoms, however, we looked at low dose quetiapine to try to test that and we found no differences there. So, again, we are not quite certain what accounts for this gender difference.

I do like to make the point that atypical antipsychotics were recommended adjunctively to SSRI’s in the CPG before that work done by Dr. Krystal so prescribing clinicians were prescribing what was recommended in the guideline until it was modified in 2012. Clearly, concerns about side effects should always be considered when you are talking about prescribing atypical antipsychotics. 

The prescribing of benzodiazepines is where we see the significant exception. We saw decreased prescribing in men but we saw this steady increase in women despite the Clinical Practice Guideline recommendations of harm and not only did we see that across the board in women but we are seeing it in women with co-occurring substance use disorder or a history of a traumatic brain injury _____ [00:35:12] indicated. This issue about age also appeared to be a related factor. It is encouraging that we are seeing reduced rates in women who are of reproductive age but those women who are older is an area of concern and then having a greater service connection contributed to elevated prescribing which again suggests that these are complex patients that clinicians are trying to target perhaps other symptoms. 

So, what were the possible reasons for this discrepancy or disparity? It is possible that it may be symptom differences and Matt King, at our Women’s Division in Boston has done some nice work with Amy Street and Patty Resek [PH] looking at symptom differences and we know that women may exhibit higher rates of distress. This was also speculated by Dr. Karen Seel [PH] in some of the work that she has done. We know from Matt King’s work also that men are reporting more nightmares. That may be contributing to this increased use of Prazosin in males as opposed to women but they also report more numbing and hyper vigilance. There is some old work from some Dutch researchers that suggested that clinicians may also prescribe benzodiazepines in women for sort of vague symptoms that are not an indication for their use...so symptoms such as headache, fatigue, chest pain, vertigo...all of those symptoms have been indicated to have benzodiazepines used where there really is no evidence that they can be helpful at all for those symptoms. 

Clearly, what we are seeing here is something related to difficulties around sleep symptom management. This extraordinary 10% increase in Zolpidem use or Ambien in women from the time it was put on the formulary confirms how much sleep difficulties are part of the clinical presentation of PTSD and there is growing concerns that this may not be a good substitute. There is a new literature about Zolpidem that is expressing concerns about its long-term use. There is also new guidance for women because of symptoms that they have in the morning where they are still groggy, having difficulty driving etc. that bring concerns to its use. Again, we are not quite sure why Prazosin use is the exception and more widely used in men unless it is this issue with more nightmares.

It is also possible that there may be gender specific mechanisms of taking part here in this difference. There is some work showing that gender specific mechanisms may underlie the relationship between sleep impairment and the development of PTSD. When I looked in the literature of comparisons of PTSD patients and sleep symptoms overall there are discrepant findings and it is a little hard to come away from that with a clear picture but it looks as if males with PTSD report more PTSD related sleep disturbances overall whereas in women it may not be PTSD that is driving the discrepancy but actually maybe things related to age and gender contributing to this so sex hormone factors of things related such as menopause may be driving the symptoms in women although we know that men also report sleep difficulties related to age so it is difficult to know exactly what is going it but it may be the case that women again are more willing to take medications for sleep. We also don’t know if they are having an opportunity to take part in psychotherapies aimed at sleep at the rate that men are. 

I just want to mention there are clearly limitations of using administrative data. We can examine trends here but it is very hard to determine justifications for use of these medications by prescribing clinicians. Trying to capture insomnia is also really complex when you are looking at administrative data. It is not easy to capture that trying to look at comorbidities particularly when it is a symptom related to PTSD and really it might even be difficult trying to do this from chart reviews. There may be other co-occurring disorders that are relevant that we did not capture that we could be contributing to this and we can’t really confirm the timing. A current, active disorder such as current SUD versus a history or the severity of the co-occurring disorders such as the traumatic brain injury or substance use disorder we can’t really tell from the data that we had access to. Clearly, we don’t have an easy way to find out if these patients have been able to engage in the evidence-based cognitive behavioral treatments which would be an important factor in looking at this work.

The conclusions of this paper looking at gender differences...it is important to try to determine in future work reasons for this increased prescribing of benzodiazepines for women with PTSD. It may be that the complexity of these patients are causing clinicians to respond to treatment failures by indiscriminately trying different non-appropriate, or non-recommended medications and I think it is also important to look at receipt of cognitive behavioral therapy for insomnia which has a growing efficacy behind it and gender differences in response to that treatment. We need work done looking at provider education about this growing reproductive aged cohort to inform clinicians about gender differences and side effects of these psychotropic medications, dosing information sex differences, pharmacokinetics to insure quality PTSD care for our women Veterans. 

So, I am curious if you think that it would be helpful to have a way to look at provider prescribing and give clinicians’ feedback about their providing. Do you think that if we could come up with a tool that would do this...would it be helpful for showing providers that they are outliers in their prescribing or would this not be used because the data is too difficult to acquire in our healthcare practices or is it a bad idea? Overwhelmingly, of the people who voted Molly...it looks like they think it would be helpful to show providers this information which is growing and encouraging.

*Moderator:*	Thank you. Although results are still coming in it looks like we do see the general trend so I’ll go ahead and close that now.

*Dr. Bernardy:*	What I want to do next is briefly tell you the findings about polysedative prescribing. This is a new paper that we have just had published in pain medicine. We know that PTSD is complicated by these co-occurring conditions of chronic pain, insomnia, the brain injuries and other mental health disorders that are usually treated by sedating medications. There is a growing concern about the use of these sedatives in patients with PTSD. There has not been very much work done in this area. Karen Seel came out with her paper in 2012 where she noted an increased prescribing of opioids in patients with PTSD, adverse outcomes and then she looked at that and found that concurrent use was also seen with sedative hypnotics. Eric Hawkins did a nice small cross sectional study that found that almost 50% of Veterans with PTSD were taking benzodiazepines with concurrent opioids and there is recent work done by Dr. Park and others in the VA that noted considerable regional variability of this overlap of benzodiazepines and opioid agonist therapies which we think reflects uncertainty of guideline recommendations.

When we looked at this polysedative prescribing we again looked at the demographic subgroups and I just want to show you that benzodiazepine prescribing, and I have got benzodiazepines here and opioids...the benzodiazepines...what you are seeing is actually (I should mention these are data that were two years later)...we are seeing this increase in prescribing in our women Veterans now at 44% compared to the 34% seen in males. We also see an increase in opioids in women compared to males. We see higher rates in rural areas (I have got these highlighted in the red), lower among older Veterans and we saw some very interesting differences in race, ethnicity and receipt of these medications. Primarily, they are being received by Caucasians but look at this rate in Native Americans of opioids which is a different area that is very interesting and people should be looking at some of this work.

When we looked at period prevalence of any concurrent polysedative use, the first thing I want to point out is that the cohort actually doubled from 2004 to 2011, and you can see those numbers at the top. What I want to show you is that by 2011, the concurrent use of more than three sedatives has increased from 9.8% to 12%. This may seem like a relatively small number but, again, when you look at those numbers of Veterans that are increasing that is up over 43,000 Veterans who are on more than three sedative medications concurrently and it represents a relative increase of over 25% because of the doubling of that denominator. 

When we looked at the trends in polysedative use overall, what we saw here and we compared prevalence and incidence...what we found was that benzodiazepines and atypical antipsychotics followed similar trends with gradual declines in both incidence and prevalence. The incident prescribing of skeletal muscle relaxants remained consistent, however, what we saw was the prevalence of opioid use increase from 30% to 35% in 2011...so that is this line here...despite more than a 25% relative decrease in incidence during this period. That suggested to us that they were actually shifting towards chronic prescribing of opioids. What we also then found when we looked at the frequency of concurrent prescribing of polysedatives by demographic subgroups, again we are seeing this increase in women compared to men and you can see here for two or more and then for three or more. Again, women are getting many more meds and they are concurrent. When we looked at what medications we were primarily observing this is what we found. They were primarily opioids and benzodiazepines and this percent of 15.9 is actually higher than what you would except to see based on the individual prevalence of both opioids and benzodiazepines. We know that it is a combination of two meds that are a particular concern around overdose. 

There has been previously work done in some series by Sally Haskell and Laurie Zephyrin looking at musculoskeletal pain. There are increased rates seen in women. This might be accounting for some of the increase of opioids but it really does not address this issue of concurrent sedative medications in women. We also have new data from Dr. Ronnie Hoff at _____ [00:49:41] showing that women are entering PTSD treatment with more severe pain then men so it is clearly a problem. We know that there is a significant pain burden associated with PTSD. This may be making treatment engagement for PTSD more difficult. There is a great deal we need to know about concurrent pain management with PTSD treatment in our specialty clinics and guidance for clinicians as how to best address PTSD and pain and it is possible that an improvement in PTSD symptoms may actually increase the perceptions and recognition of pain. It is, again, an area where we need a great deal more research particularly in our women Veterans.

So what have we learned overall from our work? We know that the provider location matters. It is primarily mental health doing the bulk of the prescribing of these medications except for the opioids which are primarily coming from primary care and it is critically important that we have that care coordinated. There is a reflection of the complex patient mix seen in this data and _____ [00:51:02] failure to effectively disseminate the guideline recommendations. Overall, women and comorbidities are presenting a dilemma and PTSD sleep also is causing problems. There is a lot of opportunity here for educational products and training. The good news is that OMHO has developed a psychopharmacology initiative. They are using academic detailing to try to address this problem. There is a lot of work happening around the opioid safety initiative as well. We are currently working on the development of shared decision making tools that, I think importantly will give information to Veterans and their family members about the risks of some of these medications and safer options and the issue about CBT protocols to address insomnia pain and anxiety is one that really needs to be done to try to help in tapering patients from these meds. 

Quickly, I want to share some references regarding new research that shows that patients can be tapered from benzodiazepines with actually relatively small work done by clinicians and it is really exciting to read these new studies showing that patients do want to be tapered and are willing to do the work to do that.

We have developed some tools here at the National Center that are available on our website for both providing clinicians as well as patients. Email me or you can get those off our website.

I just want to make the point that we do have a consultation program that offers prescribing consultation around medications. We have psychiatrists who can talk to you about these medication decisions and help. 

Finally, next week we have a talk on this topic and the consultation lecture series PTSD and Sleep Problems and then the following month we have one on Pain and PTSD so those coincide perfectly with what I am sharing. Here is the information about the website where we have fabulous materials and you can contact me at this address. Sorry Molly [laughter].

*Moderator:*	Not a problem at all. We do have some time for questions and comments. I know a large portion of our audience joined just after the top of the hour. To submit your questions or comments please use the Q&A box located on the right hand corner of your screen. Just type it into that lower box and press the speech bubble and that will get it submitted and we can answer it in the order that it was received. 

We did have a comment about someone asking for a little more focus on the women’s health portion in the first few minutes. I just want to remind our audience that we do run an entire women’s health series which this was a part of and we do encourage you to go to the online catalog and sign up for any women’s health topics, which we do cover a large range of, and you can also go to our archive catalog and filter just for the women’s health series and view all of our previous presentations since 2011. We do try and provide ample information about the important topic of women’s health.

Regarding the first question, “Dr. Bernardy...are there any data comparing rates of prescriptions between VA and the private sector?”

*Dr. Bernardy:*	Thank you for that question. We do know that overall for the gender differences women are prescribed more medications across the board in the civilian sector. Bob Rosenheck and colleagues had published some of that work. What we have wanted to try to do is to look for PTSD overall with Veterans who are newly returning from the Department of Defense because we were hearing from clinicians that they are inheriting patients on their caseload who are coming in on atypical antipsychotics, benzodiazepines and stimulants appeared to be a big problem but we have had difficulty trying to get access to data that would really support that. Right now we don’t know a great deal about that and also, the bigger issue is what are Veterans getting outside the VA? This issue about concurrent medications...there is some work trying to compare with databases that you can look at prescribing of these medications by community providers but it is difficult for us to know also what medications are being received outside of the VA.

*Moderator:*	Thank you for that response. The next submitter submits a comment and a question. “It is interesting that comorbid depression results in higher levels of appropriate prescribing for women with PTSD. Has anyone looked at gender differences in prescribing focused on those with and without primary diagnosis of depression?”

*Dr. Bernardy:*	I am trying to figure out if this is for PTSD which is what I...

*Moderator:*	You should be able to read it now. Do you see it off to the right?

*Dr. Bernardy:*	“Has anyone looked at gender differences in prescribing focused on those with...”. I’m sorry. I don’t know that literature. I would definitely assume so but my area really is in PTSD. I think it is a great point and something if anyone knows that would be wonderful to hear. 

*Moderator:*	Thank you. We do encourage your audience members if you have any further information on that and you can provide us a little info we do appreciate it. The next question...”Are there any biological differences in the way women deal with PTSD versus men?”

*Dr. Bernardy:*  	That is a very interesting question. When you started out with the first comment, Molly...I was going to say that there has been some lovely work done by Paul Schnerr here looking at health effects of PTSD overall which there is a growing literature about biological differences and the impact of those related to PTSD and actually that might be a wonderful topic for this series. There is some information and I actually would be happy to get some of that back. It is a very broad area.

*Moderator:*	Well, I am not sure if this hits the nail on the head but I do want to thank you for actually plugging one of our upcoming sessions that is presented at SGIM and it will be presented by Dr. Paula Schnerr and by _____ [00:58:26] and the title is *Implications of PTSD for Women Veterans Treated in Primary Care Settings*so we do encourage you to sign up for that one. It will be advertised in the next few days and you will be able to register in our online archive catalog. 

I am going to put up the feedback now so I want our attendees to please provide us your feedback because it is your questions and comments that really guide our program and decide which sessions which we should have presented. As I mentioned, we do have an entire women’s health series so you are going to get a monthly email for all the sessions coming up in July. You will receive that next week and we encourage you to take a look at that whole list and sign up for any sessions that interest you. Even if you sign up but are unable to attend the live presentation you do still receive an email with the handouts and the follow-up email with the link to the archives so it is worth signing up even if you are not sure you can make it to the live presentation.

We do have a minute or two left so I would like to let Dr. Bernardy make any concluding comments you may have.

*Dr. Bernardy:*	I appreciate this opportunity and I think we are constantly working here to try to improve the information that goes out to the field about PTSD and I do encourage people to take a look if they haven’t lately at our website. It is PTSD Awareness Month and there is a great deal of information there for clinicians that they can share in their local facility.

*Moderator:*	Excellent. I want to echo your thanks for the audience for joining us today and also to you, Dr. Bernardy...for lending your expertise to the field. We greatly appreciate your time and effort put in to presenting this. For our attendees, I am going to leave this feedback form up for a while so take your time. However, that does formally conclude today’s presentation so thanks once again to everybody and we will see you at our next session. 

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