A Placebo-Controlled Study of Nefazodone for the Treatment of Chronic Posttraumatic Stress Disorder

Abstract

Nefazodone is a unique serotonergic antidepressant that acts as both a presynaptic serotonin reuptake inhibitor and a postsynaptic 5-hydroxytryptamine 2A receptor antagonist. Based on the positive results of open-label trials of nefazodone, including one from our group, we tested nefazodone's efficacy in the treatment of posttraumatic stress disorder (PTSD) under placebo-controlled conditions. Forty-one patients with chronic PTSD, predominantly male combat veterans, were enrolled in a randomized, double-blind, placebo-controlled 12-week trial of nefazodone. The primary outcome measure was the Clinician-Administered PTSD Scale. Fifteen patients were randomized to placebo and 26 were randomized to nefazodone. In a repeated-measures analysis of variance with last observation carried forward, patients on nefazodone showed a significant improvement in the percentage change of Clinician-Administered PTSD Scale Total score from baseline compared with those on placebo (P = 0.04; effect size = 0.6). Sample size was not powered to test group differences in the Clinician-Administered PTSD Scale criterion B, C, or D subscale. However, the criterion D subscale showed significant improvement in patients treated with nefazodone compared with those treated with placebo (P = 0.007). In addition, the Hamilton Rating Scale for Depression showed significant improvement compared with placebo (P = 0.008). The nefazodone group also reported an improvement on the PTSD Checklist (self-report scale; P = 0.08) and the Clinician-Administered Dissociative States Scale (P = 0.06). This pilot study supports the efficacy of nefazodone for the treatment of PTSD. However, larger placebo-controlled studies in more diverse patient population are warranted.

Treatment of Post-Traumatic Stress Disorder Nightmares at a Veterans Affairs Medical Center

“…Davidson cited a DPCT study by Davis et al [108] with 26 nefazodone subjects and 15 controls. The nefazodone treatment group had improved total scores from baseline compared with those in the placebo group ( p = 0.04 at effect size of 0.6).…”

Advances in the Management of Treatment-Resistant Anxiety Disorders

“…Bupropion is not effective for PTSD as demonstrated in two RCTs (118,119), although the primary focus of one trial was smoking cessation (119). Two RCTs of nefazodone support its use in PTSD (120,121), and an open-label study of 19 veterans in whom three previous medication trials had failed (122) suggests that nefazodone may have a role in treatment-refractory PTSD, although its widespread clinical use is limited by potential hepatotoxicity. Although widely used as an augmenting agent for insomnia in PTSD (123,124), trazodone has only been studied in one very small (Nϭ6) open-label trial (125) and not in any controlled studies.…”

Targeting memory processes with drugs to prevent or cure PTSD

“…Nefazodone, a 5-HT reuptake inhibitor/5-HT 2A antagonist, showed promising results in a small PTSD pilot study [114], although this drug has fallen out of favor because of liver toxicity issues. Positive findings were also reported for mirtazapine, an antidepressant with antagonist actions at multiple 5-HT 2 receptor subtypes as well as at a 2 -adrenergic receptors [115].…”