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Comparative Safety of Benzodiazepines and Opioids Among Veterans Affairs Patients With Posttraumatic Stress Disorder

Hawkins, Eric J. PhD; Malte, Carol A. MSW; Grossbard, Joel PhD; Saxon, Andrew J. MD; Imel, Zac E. PhD; Kivlahan, Daniel R. PhD

doi: 10.1097/ADM.0b013e31829e3957
Original Research

Objectives: Although Veterans Affairs (VA) patients with posttraumatic stress disorder (PTSD) are prescribed benzodiazepines and opioids in addition to recommended pharmacotherapies, little is known about the safety of these medications. This study compared the 2-year incidence of adverse events among VA patients with PTSD exposed to combinations of selective serotonin reuptake inhibitors (SSRIs) or serotonin/norepinephrine reuptake inhibitors (SNRIs), benzodiazepines, and opioids.

Methods: This retrospective cohort study used VA administrative data from 2004 to 2010 to identify and follow 5236 VA patients with PTSD with new episodes of (1) SSRIs/SNRIs only; (2) concurrent SSRIs/SNRIs and benzodiazepines; and (3) concurrent SSRIs/SNRIs, benzodiazepines, and opioids. Outcome measures were the 2-year incidence and adjusted hazard ratios (AHR) of mental health and medicine/surgery hospitalizations, emergency department visits, harmful events (eg, injuries and death), and any adverse event after adjustment for demographics, clinical covariates, and adverse event history.

Results: Compared with SSRIs/SNRIs only, the adjusted risk of mental health hospitalizations (AHR: 1.87; 95% confidence interval [CI]: 1.37–2.53) was greater among patients prescribed SSRIs/SNRIs and benzodiazepines concurrently. The AHR of mental health hospitalizations (AHR: 2.00; 95% CI: 1.35–2.98), medicine/surgery hospitalizations (AHR: 4.86; 95% CI: 3.30-7.14), emergency department visits (AHR: 2.01; 95% CI: 1.53–2.65), any harmful event (2.92; 95% CI: 2.21–3.84), and any adverse event (AHR: 2.65; 95% CI: 2.18–3.23) were all significantly greater among patients prescribed SSRIs/SNRIs, benzodiazepines, and opioids than among those prescribed SSRIs/SNRIs only.

Conclusions: Concurrently prescribing SSRIs/SNRIs, benzodiazepines, and opioids among patients with PTSD is associated with adverse events. Although efforts are warranted to monitor patients who are prescribed combinations of these medications to prevent adverse events, these results should be interpreted with caution until they are replicated.

From the Health Services Research & Development (EJH, CAM, JG, DRK), Seattle, WA; Center of Excellence in Substance Abuse Treatment and Education (EJH, CAM, AJS, DRK), VA Puget Sound Health Care System, Seattle, WA; Department Psychiatry and Behavioral Sciences (EJH, AJS, DRK), University of Washington, Seattle; and Department of Educational Psychology (ZEI), University of Utah, Salt Lake City, UT.

Send correspondence and reprint requests to Eric J. Hawkins, PhD, VA Puget Sound Health Care System–Seattle Division (S116ATC), 1660 S. Columbian Way, Seattle, WA 98108. E-mail:

The authors declare no conflicts of interest. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or University of Washington.

Received January 16, 2013

Accepted May 30, 2013

© 2013 American Society of Addiction Medicine