Nefazodone in patients with treatment-refractory posttraumatic stress disorder

Background: 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 w ith combat-related PTSD has been disappointing. Although anxiolytics, antic onvulsants, antipsychotics, and antidepressants have been tried, none has b een 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 vet erans with chronic, treatment-refractory symptoms of PTSD. Method: Male outpatients with DSM-IV PTSD who had failed a minimum of 3 pre vious medication trials were eligible for the study. Nineteen Vietnam comba t veterans entered the study and were treated with nefazodone, 100-600 mg/d ay, for 12 weeks. PTSD symptoms, anxiety, depression, sleep, sexual functio ning, and adverse events were assessed weekly. Results: 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%. Simi larly, there was an overall drop in the intensity of PTSD symptoms as measu red by the Clinician Administered PTSD Scale of 32% with a 26% improvement for symptoms of intrusion, 33% for avoidance, and 28% for arousal. In addit ion, improvements in sleep and sexual functioning were reported. The mean d aily 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. Conclusion: In this group of Vietnam veterans with chronic treatment-refrac tory PTSD and multiple comorbid Axis I psychiatric disorders, nefazodone wa s well tolerated and effective. Larger, controlled studies are warranted.