Future Directions
Investigators could explore the higher all-cause mortality rates in the SSRI/SNRI, benzodiazepine, and opioid therapy group, as this study did not assess cause of death in these patients. Whether any patients died of reasons directly attributable to benzodiazepines or opioids is unknown.
That SSRIs and SNRIs are the only established first-line pharmacologic treatment options for PTSD symptoms partly accounts for the widespread use of benzodiazepines in this population. For that reason, beyond characterizing the many risks associated with using benzodiazepines to manage these symptoms, there is a huge need to research the viability of other pharmacologic agents in treating PTSD. This is especially important given the slower onset to efficacy of the SSRIs and SNRIs; per estimates, only up to 60% of patients respond to SSRIs, and 20% to 30% achieve full remission of PTSD.12 Furthermore, these rates likely are even lower for combat veterans than those for the general population. Several trials discussed in a 2009 guideline review of the treatment of patients with acute stress disorder and PTSD have called into question the efficacy of SSRIs for combat-related PTSD.13 In these randomized, controlled trials, change in PTSD symptom severity as measured with CAPS was not significantly reduced with SSRIs compared with placebo.
A systematic review revealed that, of the nonantidepressants used as adjuncts in treating patients who do not achieve remission with SSRIs, the atypical antipsychotic risperidone may have the strongest supporting evidence.12 However, the present study found high rates of antipsychotic use in the SSRI/SNRI, benzodiazepine, and opioid therapy group, which also had the highest all-cause mortality rate. The safety of risperidone as an alternative treatment needs further evaluation.
Some prospective studies have suggested that the α1 blockers doxazosin and prazosin, the latter of which is commonly used for PTSD nightmares, also may improve PTSD symptoms as assessed by CAPS.14,15 Although these results are promising, the trials to date have been conducted with relatively small sample sizes.
With more veterans being treated for PTSD within the VA health care system, the central treatment goal remains: Adequately address the symptoms of PTSD while minimizing the harm caused by medications. Prescribers should limit benzodiazepine and opioid use in this population and consider safer nonpharmacologic and pharmacologic treatment options when possible.
Conclusion
Combat veterans with PTSD who are prescribed benzodiazepines and/or opioids in addition to first-line pharmacotherapy are at significantly increased risk for overall and mental health hospitalization.