Effects of Prazosin and Other Alpha-1 Adrenergic Antagonist Drugs on Nightmares and Sleep Disturbances in Posttraumatic Stress Disorder
Olga Y. Ponomareva, Sean R. Stetson, Bruce Meltzer, Kelly Kim, Gary B. Kaplan
Journal of Clinical Psychopharmacology March 12, 2026 DOI: 10.1097/jcp.0000000000002164 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Randomized Open-label Peer reviewed |
|---|---|
| Interventions | Prazosin Doxazosin Terazosin Tamsulosin |
| Topics | Dreaming PTSD |
| Keywords | Prazosin Posttraumatic stress Adrenergic antagonist Sleep system call Anesthesia Adrenergic receptor Endocrinology |
| Key findings | Prazosin has the best evidence base for treating PTSD-related nightmares, and alternative alpha-1 blockers may be effective when prazosin is not feasible. |
Abstract
PURPOSE/BACKGROUND: Chronic insomnia causes malaise and is associated with depression, irritability, cognitive impairment, impaired alertness, and substance abuse. Individuals with posttraumatic stress disorder (PTSD) often have both inadequate and fragmented sleep, putting them at elevated risk for these consequences. Sleep abnormalities in patients with PTSD include frequent trauma-related nightmares, prolonged sleep latency, frequent interruptions, early awakening, nighttime behavioral disorders, and disruptions of sleep cycles. Here, we review the pharmacological treatment for nightmares with an emphasis on noradrenergic (NA) signaling, following the clinical observation that medication treatment with alpha-1 adrenergic blocking agents, such as prazosin, improves nightmares. METHODS/PROCEDURES: We discuss the randomized controlled trials (RCTs) examining prazosin's impact on nightmares, including its efficacy and safety, and the limitations of the studies. In addition, we review the accumulating evidence from case reports, chart review, and small studies for several other anti-alpha-1 agents (specifically doxazosin, terazosin, and tamsulosin) and their efficacy in treating nightmares in PTSD. FINDINGS/RESULTS: RCT studies for prazosin suggest clinical efficacy for PTSD-related nightmare disorder in subpopulations of individuals with this condition. Case studies, pilot, and open label trails suggest possible clinical use of terazosin, tamsulosin, and doxazosin in PTSD-related nightmares, however, further RCTs are needed. IMPLICATIONS/CONCLUSIONS: When available and clinically tolerated, prazosin continues to have the best evidence base for use in PTSD-related nightmares. When prazosin use is not feasible, alternative alpha-1 blockers may be effective in a subset of patients.
Comparable studies
Other narrative reviews on PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic Psychiatry's Brave New World. | 2020 | Review | |
| Reviewing the Potential of Psychedelics for the Treatment of PTSD | 2020 | Review | |
| Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA. | 2016 | Review | |
| MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms? | 2018 | Review | |
| Clinical applications of hallucinogens: A review. | 2016 | Review |
Citations in the library
Cites 7
- Pharmacotherapy for sleep disturbances in post-traumatic stress disorder (PTSD): A network meta-analysis. Sleep Medicine July 1, 2024
- Therapeutic Effects of Tamsulosin in Nightmare Disorder: A Randomized, Double Blind, Placebo-Controlled, Cross-Over, Pilot Study. Drug research February 1, 2024
- The Effects of Pharmacological Treatment of Nightmares: A Systematic Literature Review and Meta-Analysis of Placebo-Controlled, Randomized Clinical Trials. International Journal of Environmental Research and Public Health December 31, 2022
- Doxazosin improved COVID-19 associated nightmare in a patient with major depressive disorder: a case report with a positive rechallenge. International Clinical Psychopharmacology July 1, 2021
- Doxazosin for the treatment of nightmare disorder: A diary-based case study. SAGE open medical case reports 2020
and 2 more in the library