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.