• Clinical Global Impression of Change [ Time Frame: Measured at Weeks 4 and 8 post-treatment ] [ Designated as safety issue: No ]
  
• Recurring Distressing Dreams and Difficulty Falling and Staying Asleep items of the CAPS [ Time Frame: Measured at Weeks 4 and 8 post-treatment ] [ Designated as safety issue: No ]
  
• Pittsburgh Sleep Quality Index [ Time Frame: Measured at Weeks 4 and 8 post-treatment ] [ Designated as safety issue: No ]
  

• Total CAPS score [ Time Frame: Measured at Weeks 4 and 8 post-treatment ] [ Designated as safety issue: No ]
  
• CAPS subscale scores ("Reexperiencing/Intrusions", "Avoidance/Numbing", and "Hyperarousal") [ Time Frame: Measured at Weeks 4 and 8 post-treatment ] [ Designated as safety issue: No ]
  
• Measures of nightmare frequency, depressive signs and symptoms, quality of life, and number of study days completed [ Time Frame: Measured at Weeks 4 and 8 post-treatment ] [ Designated as safety issue: No ]
  

Post-traumatic stress disorder (PTSD) is an anxiety disorder that can develop after exposure to a terrifying event in which grave physical harm occurred or was threatened. People with PTSD have persistent frightening thoughts and memories of their past ordeal and often feel emotionally numb, especially with people to whom they were once close. PTSD was first recognized in male combat veterans. Today, however, the majority of people who have PTSD are young women who have experienced non combat-related trauma, such as sexual or physical assault or a life-threatening illness or accident. The disorder can be short-lived, but PTSD can also become chronic, with long lasting symptoms that are often treatment-resistant, possibly causing severe functional disability. Frequent trauma-related nightmares and other debilitating sleep disruptions are examples of chronic PTSD symptoms for which an effective treatment has not been developed. Sertraline and paroxetine, both selective serotonin reuptake inhibitors (SSRIs), are the only drugs approved by the FDA for treating PTSD. Neither of them, however, has been effective in reducing PTSD-related sleep disruption. Studies have shown that the drug prazosin has been effective in reducing distressing trauma-related nightmares in older male combat veterans. This study will evaluate the effectiveness of prazosin in treating post-traumatic stress disorder caused by noncombat trauma in individuals already being treated with SSRIs.

Participants in this double-blind study will first undergo 12 weeks of treatment with psychotherapy and a standard SSRI. After 12 weeks, participants will be randomly assigned to receive either prazosin or placebo in addition to psychotherapy and standard SSRI treatment for a total of 8 weeks. Study visits will occur weekly for the first 12 weeks, and then at Weeks 1, 2, 4, 6, and 8 during the 8-week phase. Additionally, follow-up visits will be held 4 and 18 weeks post-intervention. PTSD symptoms, disorder severity, and frequency of sleep disturbances will be assessed.

Inclusion Criteria:

• DSM-IV diagnosis of PTSD, as derived from the Clinician-Administered PTSD Scale (CAPS)
• Stabilized on any necessary medications for at least 4 weeks prior to study entry
• Score of greater than 4 on the CAPS Recurrent Distressing Dreams item (maximum score of 8)
• Score of greater than 4 on the CAPS Difficulty Falling or Staying Asleep item (maximum score of 8)
• Agrees to use an effective form of contraception throughout the study

Exclusion Criteria:

• Any acute or significant chronic medical illness
• Any unstable medical condition
• Unstable angina, recent heart attack, history of congestive heart failure, pre-existing hypotension (systolic blood pressure less than 110 mm Hg), or orthostatic hypotension
• Insulin-dependent diabetes
• Chronic kidney or liver failure
• Pancreatitis or gout
• Meniere's disease, benign positional vertigo, or narcolepsy
• Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist
• Currently taking another alpha-1 antagonist agent
• Pregnant
• DSM-IV diagnosis of cognitive disorder, schizophrenia, schizoaffective disorder, bipolar disorder, or other psychotic disorder
• Current delirium
• Active substance dependence disorder within 3 months of study entry
• Current substance use other than alcohol (no more than 2 drinks per day)
• Severe psychiatric instability or situational life crises, including evidence of suicidal or homicidal ideation
• Currently taking any other psychotropic medication (e.g., antidepressants, benzodiazepines, anti-convulsants, anti-psychotics, sedating antihistamines, sedatives/hypnotics (exclusionary medications will be discontinued and participants will undergo a 2-week washout period before baseline assessments)