Clinically, post-traumatic stress disorder (PTSD) is characterized by re-experiencing the trauma, numbing of emotions, avoidance and increased arousal (e.g., startle reactions), with symptoms present for a minimum of one month. PTSD tends to be a chronic illness, with a lifetime prevalence of 5 to 12 percent and higher-than-average rates of psychiatric comorbidity. A previous empiric review published in 1992 identified five controlled trials that assessed pharmacologic treatment of persons with PTSD. Results revealed only modest improvement. The study population in these trials included only men, most of whom were combat veterans. Brady and associates conducted this randomized, controlled trial to determine if sertraline, a selective serotonin reuptake inhibitor, is efficacious in the treatment of persons with PTSD of moderate to marked severity.

Persons were enrolled if they had a diagnosis of PTSD of at least six months' duration and a severity score of at least 50 (on a 136-point PTSD scale). A variety of exclusion criteria were designed to ensure that other psychiatric comorbidities did not interfere with the study. For example, patients with a primary diagnosis of major depression or those undergoing cognitive-behavior therapy were excluded. Specifically, psychosocial, symptomatic and quality-of-life outcomes were examined. The trial was preceded by a placebo run-in period of two weeks. Patients were then randomized to receive 12 weeks of placebo or sertraline at a dosage of 25 mg per day for one week. At the discretion of the physician, the therapeutic regimen was increased weekly in 50-mg increments to a maximum of 200 mg per day. The Clinician Administered PTSD Scale (CAPS-2) was used to assess disease severity. Assessment of primary outcomes occurred at baseline, weeks 1, 2, 3, 4 and weeks 6, 8, 10 and 12.

Of the 187 patients randomized, 94 patients were randomized to receive sertraline and 93 were randomized to receive placebo; 93 sertraline-treated patients and 90 placebo-treated patients were available for at least one post-randomization efficacy assessment. No significant differences between the groups were evident at the beginning of the study. Those patients who received sertraline reported more insomnia than those who received placebo (16.0 versus 4.3 percent, respectively). Other adverse effects included headache, drowsiness or diarrhea but were not significantly different between the groups. Those patients who received sertraline had a mean weight loss of 2.9 lb (1.3 kg) compared with 0.7 lb (0.3 kg) for those in the placebo group. On three of the four main outcome measures, sertraline therapy was more efficacious than placebo. Improvement in primary and secondary outcome measures was also significantly better in the sertraline-treatment group, with a responder rate of 53 versus 32 percent. By week 2, patients receiving sertraline showed more improvement in CAPS-2 scores than those receiving placebo; this trend continued through the end of the study. The patient ratings revealed that sertraline was significantly better than placebo, with benefits in the areas of social and occupational functioning and perceived quality of life.

The authors conclude that sertraline is efficacious for the acute treatment of patients with PTSD. Further research is needed to determine if combination therapy (e.g., pharmacologic and behavior treatment) may be useful in certain patients.