Nefazodone in patients with treatment-refractory posttraumatic stress disorder.

Abstract

Posttraumatic stress disorder (PTSD) is a highly prevalent and often chronic disorder among combat veterans, persisting in as many as 15% of Vietnam veterans for at least 20 years. Treatment response in veterans with combat-related PTSD has been disappointing. Although anxiolytics, anticonvulsants, antipsychotics, and antidepressants have been tried, none has been consistently associated with improvement in all primary symptom domains (i.e., intrusive recollections, avoidance/numbing, and hyperarousal). This open-label study evaluated the use of nefazodone in a group of Vietnam veterans with chronic, treatment-refractory symptoms of PTSD. Male outpatients with DSM-IV PTSD who had failed a minimum of 3 previous medication trials were eligible for the study. Nineteen Vietnam combat veterans entered the study and were treated with nefazodone, 100-600 mg/day, for 12 weeks. PTSD symptoms, anxiety, depression, sleep, sexual functioning, and adverse events were assessed weekly. Severity of depression lessened, as did PTSD symptoms of intrusive recollections, avoidance, and hyperarousal. Depressive symptom severity as measured by the Beck Depression Inventory decreased by a mean of 30%. Similarly, there was an overall drop in the intensity of PTSD symptoms as measured by the Clinician Administered PTSD Scale of 32% with a 26% improvement for symptoms of intrusion, 33% for avoidance, and 28% for arousal. In addition, improvements in sleep and sexual functioning were reported. The mean daily dose of nefazodone after 12 weeks was 430 mg (range, 200-600 mg/day). The most frequently reported side effects were headaches (53%), dry mouth (42%), and diarrhea (42%), but side effects tended to be mild and transient. In this group of Vietnam veterans with chronic treatment-refractory PTSD and multiple comorbid Axis I psychiatric disorders, nefazodone was well tolerated and effective. Larger, controlled studies are warranted.