Cooperative Studies Program #563 - Prazosin and Combat Trauma PTSD

Inclusion Criteria: * Age \>18 years. * Exposure to one or more life-threatening war zone trauma events per the Combat * Exposure Scale \[78\] and documented by Department of Defense (DD) Form 214, Combat Action Ribbon (Marines), Combat Infantry Badge (Army), or other clear evidence of war zone trauma exposure. * Eligible for VA health care. * Diagnostic and Statistical Manual of Mental Disorders (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). * Capable of giving informed consent. * Stable dose of non-exclusionary (see below) medications for at least 4 weeks prior to randomization. * Psychotherapeutic treatment stable for at least 4 weeks prior to randomization. * Good general medical health (see Medical Exclusion Criteria below). * Female participants must agree to use a reliable form of birth control during the study. Exclusion Criteria: Medical: * Acute or unstable chronic medical illness, including unstable angina, recent myocardial infarction (within 6 months), congestive heart failure, preexisting hypotension (systolic \<110) or orthostatic hypotension (systolic drop \> 20 millimeters of mercury after two minutes standing or any drop accompanied by dizziness); chronic renal or hepatic failure, pancreatitis, Meniere's disease, benign positional vertigo; narcolepsy. * Untreated sleep apnea, diagnosed by a sleep study, is exclusionary. Treated sleep apnea (e.g., Continuous Positive Airway Pressure, surgery) will not be exclusionary. * Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist. * Wounds requiring surgery, embedded shrapnel, and recent surgical amputation do not comprise an exclusion if the individual is otherwise medically eligible. * Women of childbearing potential with positive pregnancy test or refusal to use effective birth control method, or who are breastfeeding will be excluded. Psychiatric/Behavioral: * Meets DSM-IV criteria for current schizophrenia, schizoaffective disorder, psychotic disorder not otherwise specified (NOS), delirium, or any DSM-IV cognitive disorder. * Exclusion for psychotic disorder is not to be confused with combat trauma-induced reexperiencing symptoms (transient dissociative states or flashbacks), which will not be exclusionary. * Substance dependence disorder within 3 months or any current substance dependence (stable methadone maintenance will not be exclusionary). * 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. * Nonsuicidal depression comorbid with PTSD will not be exclusionary (see below). Medications/Therapies: * Current use of prazosin or other alpha-1 antagonist. * Previous adequate trial of prazosin for PTSD. * Subjects on trazodone will undergo a 2-week washout period before baseline assessment. (Combining prazosin and trazodone may increase risk of priapism). * Sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) will be not be permitted during the study dose titration period because of increased risk of hypotension in combination with alpha-1 blockers. Following achieving stable dose of study drug, sildenafil, tadalafil, and vardenafil will be permitted at 1/2 the usual starting dose. * Stimulants or alternative medications with stimulant properties (e.g., ephedra). * Recent exposure therapy and/or Eye Movement Desensitization and Reprogramming (EMDR). These therapies must have been completed \> 4 weeks before randomization. * Other psychotropic medications and/or maintenance psychotherapy at a stable dose for at least 4 weeks will not be exclusionary.