We propose a double-blind placebo-controlled augmentation trial of the generically available alpha-1 adrenergic antagonist prazosin in chronic posttraumatic stress disorder (PTSD) caused by noncombat (""""""""civilian"""""""") trauma. Primary target PTSD symptoms will be residual distressing trauma-related nightmares and sleep disturbance that persist despite a trial of the selective serotonin reuptake inhibitor (SSRI) paroxetine. Although several SSRIs are FDA-approved for PTSD, SSRIs (and other drugs) often are not helpful for these very distressing nighttime PTSD Symptoms. Preliminary studies in older male combat veterans with chronic PTSD demonstrated that prazosin (the only available alpha-1 antagonist that crosses from blood into brain) eliminated or Substantially reduced previously treatment resistant trauma-related nightmares and sleep disturbance that had been distressing and debilitating for many years. Prazosin also reduced overall illness severity and functional impairment, and was well tolerated. These beneficial prazosin effects are consistent with involvement of increased responsiveness of brain alpha-1 adrenergic receptors in PTSD pathophysiology. Here we will determine if these encouraging prazosin results also can be demonstrated in the generally younger and predominantly female population of persons with noncombat trauma PTSD who continue to suffer from residual distressing trauma related nightmares and sleep disturbance despite standard PTSD treatment. In a double-blind placebo-controlled parallel group 8-week clinical trial of prazosin augmentation (following a 12-week """"""""lead-in"""""""" of standard SSRI plus manualized psychotherapy treatment) the following hypotheses will be tested: Hypothesis 1: Persons with PTSD manifested by residual distressing trauma-related nightmares and sleep ? disturbance (despite SSRI treatment) randomized to prazosin augmentation will manifest a greater reduction in trauma related nightmares and sleep disturbance than those randomized to placebo augmentation. Hypothesis 2: Persons with PTSD manifested by residual distressing trauma-related nightmares and sleep disturbance (despite SSRI treatment) randomized to prazosin augmentation will manifest greater improvement in overall global PTSD severity and function than those randomized to placebo augmentation. Hypothesis 3: The time to study discontinuation (""""""""dropout"""""""") due to unacceptable adverse effects will not differ between PTSD subjects randomized to prazosin augmentation and those randomized to placebo augmentation. Primary outcome measures will be the Clinician Administered PTSD Scale (CAPS) Recurrent Distressing Dreams item, the Pittsburgh Sleep Quality Index, and the Clinical Global Impression of Change. Additional outcome measures will be the total CAPS score, the CAPS Difficulty Falling or Staying Asleep item, the three CAPS subscales (Reexperiencing/Intrusions, ? Avoidance/Numbing, and Hyperarousal), measures of nightmare quality and frequency, depressive signs and symptoms, and quality of life. Number of study days completed and adverse events also will be compared between groups. ? ?
