Context: Despite the high prevalence, chronicity, and associated comorbidity of posttraumatic stress disorder (PTSD) in the community, few placebo-controlled studies have evaluated the efficacy of pharmacotherapy for this disorder.

Objective: To determine if treatment with sertraline hydrochloride effectively diminishes symptoms of PTSD of moderate to marked severity.

Design: Twelve-week, double-blind, placebo-controlled trial preceded by a 2-week, single-blind placebo lead-in period, conducted between May 1996 and June 1997.

Setting: Outpatient psychiatric clinics in 8 academic medical centers and 6 clinical research centers.

Patients: A total of 187 outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition diagnosis of PTSD and a Clinician Administered PTSD Scale Part 2 (CAPS-2) minimum total severity score of at least 50 at baseline (mean age, 40 years; mean duration of illness, 12 years; 73% were women; and 61.5% experienced physical or sexual assault).

Intervention: Patients were randomized to acute treatment with sertraline hydrochloride in flexible daily dosages of 50 to 200 mg/d, following 1 week at 25 mg/d (n=94); or placebo (n=93).

Main outcome measures: Baseline-to-end-point changes in CAPS-2 total severity score, Impact of Event Scale total score (IES), and Clinical Global Impression-Severity (CGI-S), and CGI-Improvement (CGI-I) ratings, compared by treatment vs placebo groups. Results Sertraline treatment yielded significantly greater improvement than placebo on 3 of the 4 primary outcome measures (mean change from baseline to end point for CAPS-2 total score, -33.0 vs -23.2 [P =.02], and for CGI-S, -1.2 vs -0.8 [P=.01]; mean CGI-I score at end point, 2.5 vs 3.0 [P=.02]), with the fourth measure, the IES total score, showing a trend toward significance (mean change from baseline to end point, -16.2 vs -12.1; P=.07). Using a conservative last-observation-carried-forward analysis, treatment with sertraline resulted in a responder rate of 53% at study end point compared with 32% for placebo (P=.008, with responder defined as >30% reduction from baseline in CAPS-2 total severity score and a CGI-I score of 1 [very much improved], or 2 [much improved]). Significant (P<.05) efficacy was evident for sertraline from week 2 on the CAPS-2 total severity score. Sertraline had significant efficacy vs placebo on the CAPS-2 PTSD symptom clusters of avoidance/numbing (P=.02) and increased arousal (P=.03) but not on reexperiencing/intrusion (P=.14). Sertraline was well tolerated, with insomnia the only adverse effect reported significantly more often than placebo (16.0% vs 4.3%; P=.01).

Conclusions: Our data suggest that sertraline is a safe, well-tolerated, and effective treatment for PTSD.