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A Randomized Controlled Trial

Kathleen Brady, MD, PhD; Teri Pearlstein, MD; Gregory M. Asnis, MD; Dewleen Baker, MD; Barbara Rothbaum, PhD; Carolyn R. Sikes, PhD; Gail M. Farfel, PhD

JAMA. 2000;283:1837-1844.

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.

Author Affiliations: Departments of Psychiatry, Medical University of South Carolina, Charleston (Dr Brady), Butler Hospital, Providence, RI (Dr Pearlstein), Montefiore Medical Center, Bronx, NY (Dr Asnis), Emory University, Atlanta, Ga (Dr Rothbaum); Posttraumatic Stress Disorder Unit, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio (Dr Baker); and Pfizer Inc, New York, NY (Drs Sikes and Farfel).

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Placebo Effect in Posttraumatic Stress Disorders
Barry Krakow, Michael Hollifield, Teddy D. Warner, Kathleen T. Brady, Terri Pearlstein, Gregory M. Asnis, Dewleen Baker, Barbara Rothbaum, Carolyn R. Sikes, and Gail M. Farfel
JAMA. 2000;284(5):563.
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JAMA. 2000;283(14):1905-1906.
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