Augmentation Trial of Prazosin for Post-Traumatic Stress Disorder (PTSD)

This is a 15-week randomized parallel design, double-blind, placebo-controlled augmentation
trial of prazosin to evaluate the efficacy and tolerability of prazosin augmentation in the
treatment of PTSD trauma-related nightmares, sleep disturbance, global function and sense of
well-being, and other clinical features and comorbidities of PTSD. Participants will be 210
OIF/OEF soldiers and veterans who have suffered war zone trauma. Participants will be
randomized 1:1 to prazosin or placebo and all previous psychotropic medications and/or
psychotherapy will be maintained constant. Randomization will be stratified by site and use
of an antidepressant.

Inclusion Criteria

- Age >18 years;

- Clear evidence of exposure to one or more war zone trauma events sufficient to satisfy
DSM-IV criterion A1 for diagnosis of PTSD;

- DSM-IV diagnosis of PTSD derived from the CAPS; CAPS total score >50;

- CAPS Recurrent Distressing Dreams item score >5 (of maximum score of 8);

- stable dose of non-exclusionary medications and psychotherapeutic treatment for at
least 4 weeks prior to randomization;

- good general medical health.

- Female participants must agree to use a reliable form of birth control during the
study.

Exclusion Criteria

- Psychiatric/Behavioral - meets DSM-IV criteria for current schizophrenia,
schizoaffective disorder, psychotic disorder, delirium, or any DSM-IV cognitive
disorder; substance dependence disorder within 3 months or any current substance
dependence; current cocaine or stimulant abuse; severe psychiatric instability or
severe situational life crises, including evidence of being actively suicidal or
homicidal, or any behavior which poses an immediate danger to patient or others.

- Medical - acute or unstable chronic medical illness, including unstable angina, recent
myocardial infarction (within 6 months), congestive heart failure, preexisting
hypotension or orthostatic hypotension, chronic renal or hepatic failure,
pancreatitis, Meniere's disease, benign positional vertigo; narcolepsy, or diagnosed
sleep apnea; allergy or previous adverse reaction to prazosin or other alpha-1
antagonist.