Trauma-related nightmares and sleep disturbance are among the most characteristic and treatment-resistant PTSD symptoms in Veterans. However, the only current FDA approved drug treatments for PTSD (SSRI antidepressants) do not specifically target nightmares. Therefore, these medications often provide incomplete relief for PTSD symptoms.
Clinical and preclinical data suggest that increased responsiveness to central nervous system (CNS) norepinephrine (NE) contributes to the pathophysiology of PTSD and – importantly – to these treatment-resistant nighttime symptoms. Prazosin is an alpha-1 adrenoreceptor antagonist that can be used to decrease the responses to NE in the central nervous system. Many clinicians are more familiar with the use of prazosin for the treatment of hypertension or benign prostatic hypertrophy (BPH). In recent years, these uses of prazosin have been usurped in clinical practice by more effective antihypertensive agents and by agents for BPH that do not cross the blood-brain barrier.
However, these features of prazosin: low cost, decades of clinical safety experience, somewhat unimpressive potency in hypertension, and activity within the CNS make it an appealing medication for the treatment of nightmares in PTSD.
Previous research by VA scientists found that prazosin improves sleep and reduces nightmares for veterans with PTSD. (Biological Psychiatry, 2007, 1(8):928-34) Dr. Murray Raskind and Dr. Elaine Peskind, working at the Seattle VA, demonstrated that prazosin is well tolerated and substantially reduces PTSD trauma nightmares and sleep disturbance in Veterans. Moreover, prazosin improved global clinical status (sense of well being and ability to function) compared with placebo. Prazosin is an attractive medication because of its low cost, decades of clinical safety experience and minimal side effects at the low doses used. Even though these studies have resulted in wide spread adoption of prazosin in PTSD treatment, because only specific symptoms of PTSD were evaluated in the studies, prazosin can not yet be considered a treatment for PTSD.
About the Study
The VA Cooperative Studies Program sponsored a project entitled “Prazosin and Combat Trauma PTSD” — a nationwide project to investigate the therapeutic efficacy of prazosin for veterans with combat-related PTSD. The goal of CSP #563 (“PACT”) was to conduct a rigorous, randomized, double-blind, parallel-group, placebo-controlled trial of prazosin in a large multi-site study of Veterans with nightmares as a prominent feature of their war-zone PTSD. The treatment period lasts 6 months.
As one of the project’s leading participating sites, Long Beach VAHS enrolled participants who served in a range of military conflicts and settings, and represented various age ranges.
The study was designed to demonstrate both the short-term and long-term effectiveness of prazosin for PTSD. The study’s research design encompassed a shorter-term, more tightly controlled efficacy component and a longer-term, more real world, effectiveness component. Primary outcomes include trauma nightmares, sleep disturbance, and global clinical status. Secondary outcomes included total PTSD symptoms, comorbid depression, quality of life, and physical functioning.
Enrollment closed for this project and data analysis is underway.
However, a parallel study conducted with active duty personnel by the same investigators – a 15-week randomized controlled trial– demonstrated that prazosin was effective for trauma nightmares, sleep quality, global function, CAPS score, and the CAPS hyperarousal symptom cluster. Prazosin was well tolerated, and blood pressure changes did not differ between groups.
Data from that study can be found online in the 2013 Sept edition of the American Journal of Psychiatry: http://ajp.psychiatryonline.org/article.aspx?articleid=1712525