Doxazosin XL Reduces Symptoms of Posttraumatic Stress Disorder in Veterans With PTSD: A Pilot Clinical Trial

Background: Serotonin and norepinephrine reuptake inhibitors are effective first-line agents for the treatment of posttraumatic stress disorder (PTSD), but treatment is associated with a range of side effects that limit treatment adherence. Prazosin, an alpha(1)-noradrenergic antagonist with a half-life of roughly 2-3 hours, has shown promise in the treatment of sleep disturbance and nightmares. Doxazosin extended release (XL) is also an alpha(1)-noradrenergic antagonist but with a half-life of approximately 15-19 hours. Methods: We conducted a double-blind, placebo-controlled, within-subjects trial to characterize the impact of doxazosin XL on PTSD symptoms. Participants (N = 8) were diagnosed using DSM-IV criteria. They completed the study twice, once during treatment with doxazosin XL and once during treatment with matched placebo, with a 2-week washout separating the 2 episodes. Doxazosin XL was titrated from 4 mg/d to 16 mg/d over 12 days. After 4 days of treatment at 16 mg/d or the equivalent number of placebo capsules, PTSD symptoms were assessed using the Clinician-Administered PTSD Scale (CAPS(17)) and the PTSD Checklist-Military version (PCL-M). Repeated measures analysis of variance were used to evaluate effects of treatment, time, and treatment x time. This study was run from November 20, 2013, to June 31, 2014. Results: Doxazosin XL treatment was associated with a nonsignificant treatment x time reduction in ratings on the CAPS hyperarousal subscale (P < .10) (but not on the CAPS Total score) and with significant treatment x time reductions in PCL-M ratings (P = .002). Conclusions: Doxazosin XL may be an effective alternative to prazosin for the treatment of some PTSD symptoms. (C) Copyright 2016 Physicians Postgraduate Press, Inc.