Fluoxetine versus placebo in posttraumatic stress disorder.

Background: This study was designed to address the efficacy and tolerability of fluoxetine in patients with posttraumatic stress disorder (PTSD) as diagnosed using the Structured Clinical Interview for DSM-IV Axis I Disorders and the Clinician-Administered PTSD Scale (CAPS). The patient population included both civilians and combat veterans.

Method: This was a double-blind, randomized, placebo-controlled study conducted in Europe, Israel, and South Africa, primarily in war-torn countries. Patients were predominantly male (81%) and white (91%), with 48% exposed to a combat-related traumatic episode. Patients were randomly assigned to 12 weeks of acute treatment with fluoxetine, 20 to 80 mg/day (N = 226), or placebo (N = 75). The primary efficacy measurement was the mean change from baseline in the Treatment Outcome PTSD rating scale (TOP-8) total score, which was analyzed using a repeated-measures analysis of variance. Secondary assessments included the CAPS, the Davidson Trauma Scale, the Clinical Global Impressions-Severity of Illness scale (CGI-S), the CGI-Improvement scale (CGI-I), the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Rating Scale for Anxiety (HAM-A), and the Hopkins 90-Item Symptom Checklist-Revised.

Results: Fluoxetine was associated with a greater improvement from baseline in total TOP-8 score than was placebo. This difference was statistically significant by week 6 of treatment (p < .001) through the end of the acute phase of the study (week 12; p = .006). Compared with placebo, fluoxetine was also associated with significantly greater improvement in CAPS total score as well as intrusive and hyperarousal subscores and in CGI-S, CGI-I, HAM-A, and MADRS scores (p < .05). The presence of dissociative symptoms at baseline appeared to be a predictor of high placebo response. The mean fluoxetine dose at endpoint was 57 mg. There were no clinically significant safety differences.

Conclusion: Fluoxetine is effective and well tolerated in the treatment of PTSD. Most PTSD patients will respond satisfactorily at doses in the upper normal range for the usual antidepressant doses of fluoxetine.