PTSD: National Center for PTSD
Use of Benzodiazepines for PTSD in Veterans Affairs
Use of Benzodiazepines for PTSD in Veterans Affairs
- 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).
In This Article
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.
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