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Use of Benzodiazepines for PTSD in Veterans Affairs

 

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This section is for Researchers, Providers, & Helpers

This section is for Researchers, Providers, and Helpers

Use of Benzodiazepines for PTSD in Veterans Affairs

Key Points

For Your Clients

  • The VA/DoD Practice Guideline for PTSD recommends against the use of benzodiazepines for treatment of PTSD.
  • The evidence is mounting on the harms associated with chronic benzodiazepine use in patients with PTSD.
  • Despite the lack of efficacy of benzodiazepines for PTSD and potential harms associated with chronic use, 30% of VA PTSD patients had a prescription for benzodiazepines in fiscal year (FY) 2012.
  • VA is making efforts to reduce use of benzodiazepines among patients with PTSD through several different initiatives.

Evidence on the Use of Benzodiazepines for PTSD

The VA/DoD 2010 Practice Guideline for the Management of PTSD strongly recommends against the routine use of benzodiazepines in Veterans with PTSD (1). The recommendation was based on unproven efficacy of benzodiazepines and well-known risks for abuse and dependence.

There have been two placebo-controlled randomized clinical trials of benzodiazepines for treating PTSD. Both had negative findings. Alprazolam (Xanax) had no benefit in alleviating PTSD symptoms (2), and clonazepam (Klonopin) had no benefit for the treatment of PTSD-related sleep dysfunction (3). Findings from research using VA administrative data of Veterans in care for co-occurring PTSD and substance use disorder (SUD) also do not support the use of benzodiazepines in PTSD (4). A recent meta-analysis of 18 studies with over 5,200 participants found benzodiazepines to be ineffective for PTSD treatment and concluded the risks associated with their use outweigh potential short-term benefits (5).

Despite the lack of efficacy of benzodiazepines for the treatment of core PTSD symptoms (intrusion, avoidance, alterations in cognitions and mood, and hyperarousal) or sleep dysfunction, VA clinicians continue to prescribe benzodiazepines for PTSD patients (30% in 2012; 6) -- presumably for symptomatic control of insomnia and anxiety due to the rapid short-term relief offered by benzodiazepines. However, it is now recognized that any benefit of benzodiazepines for these associated symptoms rapidly dissipates, leaving a patient to continue taking the medication to avoid withdrawal and rebound effects (7). The common practice of allowing patients to take benzodiazepines on an as-needed basis can lead to fluctuating blood levels that can worsen anxiety and cognitive impairment (8).

Problems Associated With Long-Term Benzodiazepine Use

There is a large literature documenting the harms of long-term benzodiazepine use (defined as > 3 months). This is especially true for older patients, who are at increased risk for motor vehicle crashes (9-10). Older patients taking benzodiazepines are also 2 to 3 times more likely to fall (11) and have 50% higher risk of hip fractures, even at modest doses with short-acting agents and short-term exposures (12-13). Cognitive dysfunction (including feelings of fogginess and confusion) is a common effect of long-term benzodiazepine use (14). Chronic benzodiazepine use can also cause anterograde amnesia (15) and is associated with elevated risk of dementia and Alzheimer’s disease (16-17). Importantly, there is a 50% increase in overall mortality rates associated with long-term benzodiazepine use (18).

There are also PTSD-specific problems. The cognitive effects of long-term benzodiazepine use among Veterans with PTSD are particularly concerning. PTSD itself is a risk factor for dementia, with older Veterans with PTSD nearly twice as likely as Veterans without PTSD to develop dementia (19). Increased disinhibition among those Veterans who are already high in aggression is another important concern. Increases in aggressive behavior were found among Veterans receiving benzodiazepines who were aggressive prior to treatment (20). Benzodiazepines are contraindicated in obstructive sleep apnea and chronic obstructive pulmonary disease (21), disorders commonly observed in Veterans with PTSD (22-24).

The long-recognized risks of abuse and dependence associated with use of benzodiazepines have particular relevance for Veterans with PTSD, who often have a co-occurring SUD. Pre-existing diagnosis of SUD may increase the risk of being prescribed high daily benzodiazepine doses for extended periods of time (25). Veterans who are on concurrent opioids and benzodiazepines are at increased risk for adverse effects including death from drug overdose (26-27).

Studies are mixed on whether benzodiazepines interfere with evidence-based cognitive-behavioral therapies (CBT) for PTSD, especially exposure-based therapies (28-30). There is some evidence that daytime dosing and long-acting benzodiazepines appear to interfere with the mental processes necessary to benefit from psychotherapy (5).

Safe and Effective Treatment Options

The VA/DoD Clinical Practice Guideline recommends evidence-based psychotherapeutic interventions (1), including the two treatments disseminated in VA’s national evidence-based practice initiative, Prolonged Exposure and Cognitive Processing Therapy (31). A meta-analysis of treatments for PTSD suggests psychotherapy is more effective than medications (32). Recommended medications for PTSD include antidepressants such as sertraline (Zoloft) and paroxetine (Paxil) (1). Safer and more effective treatment options for the specific symptoms often targeted by clinicians with benzodiazepines exist (33). For anxiety, psychotherapy options include CBT, CBT for Anxiety, or Stress Inoculation Training. Medication options include selective-serotonin reuptake-inhibitor antidepressants such as sertraline (Zoloft) and paroxetine (Paxil) or the serotonin-norepinephrine reuptake-inhibitor venlafaxine (Effexor) (34). For insomnia, CBT for insomnia is highly effective (35). Other forms of CBT may be helpful. Medication options include older antidepressants such as trazodone, doxepin, or amitriptyline; prazosin for trauma-related nightmares; or diphenhydramine (Benadryl) (36).

Steps Taken by VA to Improve Prescribing Practices

As a result of efforts taken by VA, the latest data from June 2013 to September 2015 indicate the overall number of Veterans with PTSD who received an outpatient benzodiazepine prescription is down by 11,697 (VA Psychotropic Drug Safety Initiative). However, there is an increased trend of benzodiazepine prescriptions for women Veterans (37).

Given the lack of efficacy of benzodiazepines for the treatment of PTSD and the potential harms noted above, VA pharmacotherapy safety initiatives have identified potential subgroups of patients that are most at risk of adverse effects from long-term benzodiazepine use. These subgroups include patients with co-occurring TBI, co-occurring current or lifetime substance use disorder, and women Veterans. Other high-risk groups include older Veterans and those with a history of chronic pain who are on other sedatives (38).

The Psychotropic Drug Safety Initiative is a nationwide psychopharmacology quality improvement program launched in 2013. The program supports VISN and facility psychopharmacology quality improvement initiatives by providing data on national, VISN, and facility-level performance on prescribing measures; facilitating clinical review of Veterans who may benefit from improvement in their psychotropic medication regimen via actionable patient lists on a Clinical Management Dashboard; providing feedback and technical assistance for quality improvement action planning; coordinating a national learning collaborative; and providing training and educational resources. One of the prescribing measures addressed in the program is use of benzodiazepines in patients with PTSD. There are also measures addressing use of benzodiazepines in older Veterans, regardless of PTSD diagnosis.

The Opioid Safety Initiative, established in 2012, has worked to support clinicians to reduce the use of opioids for chronic pain and offer safer, alternative treatment options. Co-prescribing of opioids and benzodiazepines has been a specific focus of these efforts because of the increased risk of overdose when these medications are taken together. As a result, the latest VA data from July 2012 to December 2014 indicate overall opioid use in the VA healthcare system is down, with 29,281 fewer patients receiving opioids and benzodiazepines together.

The National Academic Detailing Service, developed through Pharmacy Benefits Management, has also focused on benzodiazepine use in patients with PTSD. The Academic Detailing program works by having clinical pharmacists meet with individual clinicians to review caseloads and suggest options for specific patients. Suggestions may include safe tapering strategy guidance as well as information on recommended alternative treatment strategies. Development of PTSD-specific clinician dashboards and patient reports are in progress and are scheduled for national rollout by the end of 2015. The dashboards will provide clinicians the ability to conduct proactive, population level management of specific classes of pharmacotherapy for their patients with PTSD.

Due to the significant risks associated with benzodiazepines and the lack of evidence for their effectiveness in the treatment of PTSD, it is worthwhile to implement strategies to carefully assess and consider alternate treatment options and to minimize new benzodiazepine prescriptions whenever possible. Strategies to taper existing benzodiazepine prescriptions are effective despite the fact that it is difficult and time-consuming work (39-43). Ultimately, the results of VA’s efforts should result in continued decreases in utilization of these potentially harmful medications and facilitate effective treatment options among Veterans with PTSD who use VA care.

References

  1. U.S. Department of Veterans Affairs and Department of Defense. (2010). VA/DoD Clinical Practice Guideline for Management of Post-Traumatic Stress Disorder. Retrieved from https://www.healthquality.va.gov/Post_Traumatic_Stress_Disorder_PTSD.asp
  2. Braun, P., Greenberg, D., Dasberg, H., et al. (1990). Core symptoms of posttraumatic stress disorder unimproved by alprazolam treatment. Journal of Clinical Psychiatry, 51, 236-238. Retrieved from http://www.psychiatrist.com/jcp/Pages/home.aspx
  3. Cates, M. E., Bishop, M. H., Davis, L. L., et al. (2004). Clonazepam for treatment of sleep disturbances associated with combat-related posttraumatic stress disorder. Annals of Pharmacotherapy, 38, 1395-1399. doi:10.1345/aph.1E043
  4. Kosten, T. R., Fontana, A., Sernyak, M. J., et al. (2000). Benzodiazepine use in posttraumatic stress disorder among veterans with substance abuse. Journal of Nervous and Mental Disease, 188, 454-459. Retrieved from https://www.ptsd.va.gov/professional/articles/article-pdf/id22290.pdf
  5. Guina, J., Rossetter, S. R., De, R. B., et al. (2015). Benzodiazepines for PTSD: A systematic review and meta-analysis. Journal of Psychiatric Practice, 21, 281-303. doi:10.1097/PRA.0000000000000091
  6. Lund, B. C., Bernardy, N. C., Alexander, B. A., et al. (2012). Declining benzodiazepine use in veterans with posttraumatic stress disorder. Journal of Clinical Psychiatry, 73, 292-296. doi:10.4088/JCP.10m06775
  7. Lader, M. (2011). Benzodiazepines revisited--will we ever learn? Addiction, 106, 2086-2109. doi:10.1111/j.1360-0443.2011.03563.x
  8. Cloos, J.-M. (2010, July). Benzodiazepines and addiction: Myths and realities (Part 1). Psychiatric Times, 26-29. Retrieved from http://www.psychiatrictimes.com/
  9. Ray, W. A., Fought, R. L., & Decker, M. D. (1992). Psychoactive drugs and the risk of injurious motor vehicle crashes in elderly drivers. American Journal of Epidemiology, 136, 873-883. doi:10.1093/aje/136.7.873
  10. Hemmelgarn, B., Suissa, S., Huang, A., et al. (1997). Benzodiazepine use and the risk of motor vehicle crash in the elderly. JAMA, 278, 27-31. doi:10.1001/jama.1997.03550010041037
  11. Glass, J., Lanctot, K. L., Herrmann, N., et al. (2005). Sedative hypnotics in older people with insomnia: Meta-analysis of risks and benefits. BMJ, 331, 1169. doi:10.1136/bmj.38623.768588.47
  12. Wang, P. S., Bohn, R. L., Glynn, R. J., et al. (2001). Hazardous benzodiazepine regimens in the elderly: Effects of half-life, dosage, and duration on risk of hip fracture. American Journal of Psychiatry, 158, 892-898. doi:10.1176/appi.ajp.158.6.892
  13. Chang, C. M., Wu, E. C., Chang, I. S., et al. (2008). Benzodiazepine and risk of hip fractures in older people: A nested case-control study in Taiwan. American Journal of Geriatric Psychiatry, 16, 686-692. doi:10.1097/JGP.0b013e31817c6a99
  14. Stewart, S. A. (2005). The effects of benzodiazepines on cognition. Journal of Clinical Psychiatry, 66 (Suppl 2), 9-13. Retrieved from http://www.psychiatrist.com/jcp
  15. Curran, H. V. (1991). Benzodiazepines, memory and mood: A review. Psychopharmacology, 105, 1-8. doi:10.1007/BF02316856
  16. de Gage, B. S., Begaud, B., Bazin, F., et al. (2012). Benzodiazepine use and risk of dementia: A prospective population based study. BMJ, 345, e6231. doi:10.1136/bmj.e6231
  17. de Gage, S. B., Moride, Y., Ducruet, T., et al. (2014). Benzodiazepine use and risk of Alzheimer’s disease: Case-control study. BMJ, 349, g5205. doi:10.1136/bmj.g5205
  18. Kripke, D. F., Langer, R. D., & Kline, L. E. (2012). Hypnotics' association with mortality or cancer: A matched cohort study. BMJ Open, 2, e000850. doi:10.1136/bmjopen-2012-000850
  19. Yaffe, K., Vittinghoff, E., Lindquist, K., et al. (2010). Posttraumatic stress disorder and risk of dementia among US veterans. Archives of General Psychiatry, 67, 609-613. doi:10.1001/archgenpsychiatry.2010.61
  20. Shin, H. J., Rosen, C. S., Greenbaum, M. A., et al. (2012). Longitudinal correlates of aggressive behavior in help-seeking U.S. veterans with PTSD. Journal of Traumatic Stress, 25, 649-656. doi:10.1002/jts.21761
  21. Mazza, M., Losurdo, A., Testani, E., et al. (2014). Polysomnographic findings in a cohort of chronic insomnia patients with benzodiazepine abuse. Journal of Clinical Sleep Medicine, 10, 35. doi:10.5664/jcsm.3354
  22. Hawkins, E. J., Malte, C. A., Grossbard, J. R., et al. (2015). Prevalence and trends of concurrent opioid analgesic and benzodiazepine use among Veterans Affairs patients with post-traumatic stress disorder, 2003-2011. Pain Medicine. doi:10.1111/pme.12787
  23. Spitzer, C., Koch, B., Grabe, H. J., et al. (2011). Association of airflow limitation with trauma exposure and post-traumatic stress disorder. The European Respiratory Journal, 37, 1068-1075. doi:10.1183/09031936.00028010
  24. Williams, S. G., Collen, J., Orr, N., et al. (2015). Sleep disorders in combat-related PTSD. Sleep and Breathing, 19, 175-182. doi:10.1007/s11325-014-0984-y
  25. Hermos, J. A., Young, M. M., Lawler, E. V., et al. (2007). Long-term, high√Ę‚ā¨¬źdose benzodiazepine prescriptions in veteran patients with PTSD: Influence of preexisting alcoholism and drug-abuse diagnoses. Journal of Traumatic Stress, 20, 909-914. doi:10.1002/jts.20254
  26. Park, T. W., Saitz, R., Ganoczy, D., et al. (2015). Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: Case-cohort study. BMJ, 350, h2698. doi:10.1136/bmj.h2698
  27. Hawkins, E. J., Malte, C. A., Grossbard, J., et al. (2013). Comparative safety of benzodiazepines and opioids among Veterans Affairs patients with posttraumatic stress disorder. Journal of Addiction Medicine, 7, 354-362. doi:10.1097/ADM.0b013e31829e3957
  28. van Minnen, A., & Hagenaars, M. (2002). Fear activation and habituation patterns as early process predictors of response to prolonged exposure treatment in PTSD. Journal of Traumatic Stress, 15, 359-367. doi:10.1023/A:1020177023209
  29. Rosen, C. S., Greenbaum, M. A., Schnurr, P. P., et al. (2013). Do benzodiazepines reduce the effectiveness of exposure therapy for posttraumatic stress disorder? Journal of Clinical Psychiatry, 74, 1241-1248. doi:10.4088/JCP.13m08592
  30. Rothbaum, B. O., Price, M., Jovanovic, T., et al. (2014). A randomized, double-blind evaluation of D-cycloserine or alprazolam combined with virtual reality exposure therapy for posttraumatic stress disorder in Iraq and Afghanistan War veterans. American Journal of Psychiatry, 171, 640-648. doi:10.1176/appi.ajp.2014.13121625
  31. Karlin, B. E., Ruzek, J. I., Chard, K. M., et al. (2010). Dissemination of evidence√Ę‚ā¨¬źbased psychological treatments for posttraumatic stress disorder in the Veterans Health Administration. Journal of Traumatic Stress, 23, 663-673. doi:10.1002/jts.20588
  32. Watts, B. V., Schnurr, P. P., Mayo, L., et al. (2013). Meta-analysis of the efficacy of treatments for posttraumatic stress disorder. Journal of Clinical Psychiatry, 74, e541-550. doi:10.4088/JCP.12r08225
  33. Bernardy, N. C., & Friedman, M. J. (2015). Psychopharmacological strategies in the management of posttraumatic stress disorder (PTSD): what have we learned? Current Psychiatry Reports, 17, 564. doi:10.1007/s11920-015-0564-2
  34. Baldwin, D. S., Anderson, I. M., Nutt, D. J., et al. (2005). Evidence-based guidelines for the pharmacological treatment of anxiety disorders: Recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology, 19, 567-596. doi:10.1177/0269881105059253
  35. Morin, C. M. (2015). Cognitive behavioral therapy for chronic insomnia: State of the science versus current clinical practices. Annals of Internal Medicine, 163, 236-237. doi:10.7326/M15-1246
  36. Rosini, J. M., & Dogra, P. (2015). Pharmacology for insomnia: Consider the options. Nursing, 45, 38-45. doi:10.1097/01.NURSE.0000460712.06302.19
  37. Bernardy, N. C., Lund, B. C., Alexander, B., et al. (2013). Gender differences in prescribing among veterans diagnosed with posttraumatic stress disorder. Journal of General Internal Medicine, 28 (Suppl 2), S542-548. doi:10.1007/s11606-012-2260-9
  38. Bernardy, N. C., Lund, B. C., Alexander, B., et al. (2014). Increased polysedative use in veterans with posttraumatic stress disorder. Pain Medicine, 15, 1083-1090. doi:10.1111/pme.12321
  39. Morin, C. M., Bastien, C., Guay, B., et al. (2014). Randomized clinical trial of supervised tapering and cognitive behavior therapy to facilitate benzodiazepine discontinuation in older adults with chronic insomnia. American Journal of Psychiatry, 161, 332-342. doi:10.1176/appi.ajp.161.2.332
  40. Tannenbaum, C. (2015). Inappropriate benzodiazepine use in elderly patients and its reduction. Journal of Psychiatry & Neuroscience, 40, E27-28. doi:10.1503/jpn.140355
  41. Pollmann, A. S., Murphy, A. L., Bergman, J. C., et al. (2015). Deprescribing benzodiazepines and Z-drugs in community-dwelling adults: A scoping review. BMC Pharmacology and Toxicology, 16, 19. doi:10.1186/s40360-015-0019-8
  42. Vicens, C., Bejarano, F., Sempere, E., et al. (2014). Comparative efficacy of two interventions to discontinue long-term benzodiazepine use: Cluster randomized controlled trial in primary care. The British Journal of Psychiatry, 204, 471-479. doi:10.1192/bjp.bp.113.134650
  43. Tannenbaum, C., Martin, P., Tamblyn, R., et al. (2014). Reduction of inappropriate benzodiazepine prescriptions among older adults through direct patient education: The EMPOWER cluster randomized trial. JAMA Internal Medicine, 174, 890-898. doi:10.1001/jamainternmed.2014.949
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