New Coprescription of Opioids and Benzodiazepines and Mortality Among Veterans Affairs Patients With Posttraumatic Stress Disorder

Background: Opioids and benzodiazepines are commonly coprescribed medications. The mortality risk associated with their concurrent use is unknown.

Objective: To estimate the all-cause mortality risk for patients newly prescribed opioids and benzodiazepines concurrently relative to patients prescribed benzodiazepines only, opioids only, or neither medication.

Methods: This propensity score-matched, retrospective, cohort study included 17,476 patients receiving Veterans Affairs (VA) health care between October 1, 2009, and September 30, 2011, and diagnosed with posttraumatic stress disorder identified using ICD-9-CM code 309.81. One-year total and cause-specific mortality was assessed by hazard ratios and subhazard ratios, adjusted for propensity score, age, baseline psychiatric and medical comorbidity, and daily medication dose.

Results: Concurrent users (n = 4,369) were propensity score matched 1:1 with benzodiazepine-only users, opioid-only users, and nonusers. One year after medication start, the concurrent cohort had higher rates of all-cause mortality (116 deaths) relative to benzodiazepine-only (75 deaths; adjusted hazard ratio = 1.52; 95% CI, 1.14-2.03), opioid-only (67 deaths; 1.76; 95% CI, 1.32-2.35), and nonuser (60 deaths; 1.85; 95% CI, 1.30-2.64) cohorts. Risk of overdose death was greater among patients in the concurrent cohort relative to patients in the benzodiazepine-only (adjusted subhazard ratio = 2.59; 95% CI, 1.00-6.66), opioid-only (2.58; 95% CI, 1.09-6.11), and nonuser (9.16; 95% CI, 2.27-37.02) cohorts. For circulatory disease-related deaths, the adjusted subhazard ratio for concurrent medication users was 1.81 (95% CI, 1.01-3.24) relative to nonusers.

Conclusions: New coprescription of opioids and benzodiazepines was associated with increased all-cause mortality and overdose death compared with new prescription of benzodiazepines only, opioids only, or neither medication and increased circulatory disease-related death relative to neither medication.