1183 A Randomized, Double-blind, Placebo-Controlled Trial of Doxazosin for Nightmares and Sleep Disturbance in PTSD
Anne Richards, Leslie Yack, Anthony Santistevan, Emily Berg, Steven L Batki, Karen H. Seal, Thomas C. Neylan
Sleep May 1, 2025 DOI: 10.1093/sleep/zsaf090.1183 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 65 |
| Population | Trauma-exposed adults (60 veterans, 21 female) with full or subclinical PTSD and prominent nightmares |
| Intervention | Doxazosin |
| Dose | maximum dose of 10mg daily |
| Measures | CAPS-4 nightmare items, Nightmare Distress Questionnaire (NDQ), Pittsburgh Sleep Quality Index (PSQI), sleep diary mobile phone application |
| Topics | Dreaming PTSD |
| Key findings | Doxazosin, compared with placebo, reduced wake after sleep onset and nightmare severity and increased sleep maintenance on daily sleep diary measures, but did not significantly change validated measures of nightmare distress or sleep quality, which the authors attribute partly to robust placebo effects. The authors suggest doxazosin may improve some sleep properties and distressing dream severity. |
Abstract
Nightmares and non-nightmare sleep disturbances are a core feature of posttraumatic stress disorder. Effective treatments remain elusive. Doxazosin is an alpha-1 adrenergic blocker with demonstrated promise, but there is a dearth of evidence from randomized controlled trials on its effectiveness. We report findings from a randomized, double-blind, placebo-controlled trial evaluating the effectiveness of doxazosin for nightmares and non-nightmare sleep disturbances. 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 10mg daily. Primary outcomes were nightmare frequency and intensity (CAPS-4), nightmare distress (NDQ), and sleep quality (PSQI). Secondary outcomes were derived from a sleep diary mobile phone application developed by our group and included the weekly number of distressing dreams, worst distressing dream severity, and properties of sleep (sleep latency, wake after sleep onset, sleep maintenance, and total sleep time). For outcomes with two measurements, baseline-adjusted ANCOVAs were used to estimate treatment differences in change from baseline. For outcomes measured at three or more time points, linear mixed effects models were used to model change from baseline. All models adjusted for baseline values of the dependent variable of interest. Compared to placebo, participants randomized to doxazosin showed greater reduction in wake after sleep onset (adjusted p = 0.02), greater increase in sleep maintenance (adjusted p = 0.047), and greater reduction in nightmare severity (adjusted p < 0.001) over the course of the trial as measured by a daily sleep diary. That said, validated measures of nightmare distress (CAPS-4 nightmare items, nightmare distress questionnaire) and sleep quality (Pittsburg Sleep Quality Index) 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. Results suggest that doxazosin may be effective for improving properties of sleep quality and reducing distressing dream severity in those with PTS and highlight the utility of a daily mobile sleep diary application, in contrast with retrospective reporting, for detecting effects. U.S. Department of Defense Grant W81XWH-17-1-0234 (PI: Richards)
Comparable studies
Other randomized controlled trials on PTSD, most cited first.