Efficacy and safety of sertraline treatment of posttraumatic stress disorder - A randomized controlled trial

Context Despite the high prevalence, chronicity, and associated comorbidity of posttraumatic stress disorder (PTSD) in the community, few placebo-cont rolled studies have evaluated the efficacy of pharmacotherapy for this diso rder. Objective To determine if treatment with sertraline hydrochloride effective ly 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 J une 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 Manua l of Mental Disorders, Revised Third Edition diagnosis of PTSD and a Clinic ian 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 hy drochloride in flexible daily dosages of 50 to 200 mg/d, following 1 week a t 25 mg/d (n=94); or placebo (n=93). Main Outcome Measures Baseline-to-end-point changes in CAPS-2 total severit y score, Impact of Event Scale total score (IES), and Clinical Global impre ssion-Severity (CGI-S), and CGI-Improvement (CGI-I) ratings, compared by tr eatment 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 signif icance (mean change from baseline to end point, -16.2 vs -12.1; P=.07). Usi ng 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 fro m 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 reexperi encing/intrusion (P=.14). Sertraline was well tolerated, with insomnia the only adverse effect reported significantly more often than placebo (16.0% v s 4.3 %; P=.01). Conclusions Our data suggest that sertraline is a safe, well-tolerated, and effective treatment for PTSD.