A double-blind, randomized, placebo-controlled trial of doxazosin for posttraumatic distressing dreams and sleep disturbance in men and women with posttraumatic stress.

Study objectives: Distressing dreams and sleep disturbance more broadly are core features of posttraumatic stress disorder. Effective treatments remain elusive. Doxazosin is an alpha-1 adrenergic blocker with demonstrated promise for PTSD, but there is a dearth of evidence from randomized controlled trials. The current randomized, double-blind, placebo-controlled trial evaluated the effectiveness of doxazosin for distressing dreams and sleep disturbances in adult men and women with trauma history and prominent distressing dreams.

Methods: N = 65 trauma-exposed adults (60 veterans, 21 female) with full or subclinical PTSD and prominent nightmares were randomized to either placebo (N=32) or doxazosin (N = 33) titrated to a maximum dose of 10 mg daily. Prespecified primary outcomes were distressing dream frequency and intensity (CAPS-IV), and sleep quality (PSQI). Prespecified secondary outcomes were distressing dream frequency, worst distressing dream severity, and properties of sleep (sleep latency, wake after sleep onset, sleep maintenance, and total sleep time) measured daily using a sleep diary mobile application.

Results: Compared to placebo, CAPS-IV nightmare and PSQI sleep quality outcomes did not differ significantly over the course of the trial between treatment groups (adjusted p's > 0.05), in part due to robust placebo effects in these measures. In contrast, participants randomized to doxazosin showed a greater increase in sleep maintenance (adjusted p = 0.047) and greater reduction in worst distressing dream severity (adjusted p < 0.001) over the course of the trial as measured by a daily sleep diary. These effects predominated in males and were moderated by baseline standing orthostatic systolic blood pressure.

Conclusions: Doxazosin demonstrated statistically significant, clinically modest effects on prespecified sleep diary measures of distressing dream and sleep outcomes relative to placebo, but no effects based on clinical interview and survey measures. Ongoing research is therefore critical to improve treatment options for both males and females, for whom treatment benefits may differ, and to improve measurement in distressing dreams research so as to further develop targeted and effective treatment solutions.

Clinical trial registration: Registry: ClinicalTrials.gov; Name: A Randomized Controlled Trial of Doxazosin for Nightmares, Sleep Disturbance, and Non-Nightmare Clinical Symptoms in PTSD; Identifier: NCT03339258; URL: https://clinicaltrials.gov/study/NCT03339258.