The purpose of this study is to determine whether prazosin will reduce the incidence of
nightmares, sleep disturbance, and overall symptoms in combat trauma-exposed individuals
The combat stress-related nightmares and sleep disturbance that often follow exposure to
military combat are distressing and frequently persistent symptoms that impair quality of
life and both occupational and social (e.g., family) function. One of the most frequently
reported and most troubling symptoms of PTSD is trauma-content nightmares. These nighttime
symptoms have been notoriously resistant to treatment with psychotropic medications such as
anxiolytics, the SSRIs, and sedating antihistamines such as cyproheptadine. The SSRIs
sertraline (Zoloft®) and paroxetine (Paxil®) are the only drugs FDA approved for PTSD. This
approval was based on modest overall PTSD improvement compared to placebo in large
multicenter trials that enrolled almost exclusively noncombat trauma subjects.
Placebo-controlled SSRI trials for PTSD in combat veterans have been negative or equivocal.
Neurobiologic data suggest that combat stress-related nightmares and sleep disturbance in
PTSD are related to enhanced central nervous system (CNS) adrenergic activity, particularly
at night. Prazosin is a CNS-active, non-sedating alpha-1 antagonist that has long been
generically available for the treatment of hypertension and benign prostatic hypertrophy. We
recently demonstrated in Vietnam combat veterans with chronic PTSD that prazosin is robustly
effective for previously treatment refractory combat trauma related nightmares, sleep
disturbance and overall PTSD severity and functional impairment.
The goal of this study is to evaluate the efficacy and tolerability of prazosin compared to
placebo for combat stress-related nightmares, sleep disturbance and overall function in
combat-trauma exposed persons with PTSD.
Primary outcome measures will be Clinical Global Impression of Change, Recurrent Distressing
Dreams and Difficulty Falling and Staying Asleep items of the CAPS, total CAPS (exclusive of
the dreams and sleep items), and the Pittsburgh Sleep Quality Index. Depression and quality
of life also will be assessed.
- Combat-trauma exposed persons with a diagnosis of PTSD
- No diagnosis of lifetime schizophrenia, schizoaffective disorder, bipolar disorder,
psychotic disorder, or any DSM-IV cognitive disorder; current delirium, or substance
dependence disorder within 3 months of the study or current substance use other than
alcohol (no more than 2 drinks/day); severe psychiatric instability or situational
life crises, including evidence of being actively suicidal or homicidal, or any
behavior which poses an immediate danger to patient or others
- In good general medical health (no acute or significant chronic medical illness,
including unstable angina, recent myocardial infarction, history of congestive heart
failure, preexisting hypotension [systolic <110] or orthostatic hypotension [systolic
drop > 20 mmHg after two minutes standing or any drop with dizziness];
insulin-dependent diabetes mellitus; chronic renal or hepatic failure, pancreatitis,
gout, Meniere's disease, benign positional vertigo, narcolepsy, allergy or previous
adverse reaction to prazosin or other alpha-1 antagonist, or any unstable medical
- Stable dose of nonexcluded medications for concurrent stable medical conditions for
at least 4 weeks prior to randomization.
- Specific criteria used to validate presence of combat stress-related nightmares and
sleep disturbance will include: score > 5 (of a maximum score of 8) on the CAPS
Recurrent Distressing Dreams item. (CAPS score >5 places subjects in the upper third
of nightmare severity) or score > 5 (of a maximum score of 8) on the CAPS Difficulty
Falling or Staying Asleep item.