Prazosin vs. Paroxetine in Combat Stress Symptoms in OIF/OEF Returnees
Condition: Sleep Disorders; Stress Disorders, Post-Traumatic
MeSH terms: Sleep Wake Disorders; Parasomnias; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Study type: Interventional

Summary: 
      Evaluate the efficacy and tolerability of the drug prazosin compared to placebo for combat
      stress-related nightmares, sleep disturbance and overall function in recently combat-exposed
      returnees from OIF and OEF. To evaluate the effects of the SSRI paroxetine on behavioral
      symptoms and overall function in this population.
    

Detailed description: 
      Trauma-related nightmares and sleep disruption that follow combat exposure are distressing
      and frequently treatment resistant symptoms that impair quality of life and overall function.
      These symptoms closely resemble core nighttime symptoms of posttraumatic stress disorder
      (PTSD), and are increasingly recognized in returnees from Operation Iraqi Freedom (OIF) and
      Operation Enduring Freedom (OEF). Prazosin, a generically available brain active alpha-1
      adrenergic receptor antagonist, markedly reduced or eliminated combat trauma-related
      nightmares and sleep disruption in 23 of 25 combat-exposed returnees from OIF at Madigan Army
      Medical Center (MAMC). The use of prazosin in OIF returnees was based on clinical efficacy of
      prazosin for trauma-related nightmares, sleep disturbance, and overall function in Vietnam
      combat veterans with chronic PTSD. The only drugs FDA approved for PTSD are the selective
      serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine. However, SSRI effectiveness
      in combat trauma PTSD, especially for nighttime symptoms, remains questionable.

      This is a placebo-controlled clinical trial of prazosin vs. the SSRI paroxetine for combat
      trauma-related nightmares, sleep disturbance, and overall posttraumatic stress disorder
      (PTSD) clinical severity in OIF/OEF returnees. Both neurobiologic considerations and our
      preliminary clinical treatment data provide support for the proposed trial. Preclinical and
      clinical studies suggest a role for increased central nervous system (CNS) adrenergic outflow
      and/or responsiveness in PTSD pathophysiology. Possible mechanisms include alpha-1 adrenergic
      receptor-mediated effects on sleep physiology, corticotropin releasing hormone secretion, and
      disruption of cognitive processing.

      Here we propose a double-blind, placebo-controlled parallel group 12 week clinical trial of
      prazosin vs. paroxetine to test the following hypotheses:Hypothesis 1. Prazosin will be more
      effective than paroxetine or placebo for reducing frequency and intensity of combat
      trauma-related nightmares (as measured by the "distressing dreams" item of the Clinician
      Administered PTSD Scale [CAPS]).

      Hypothesis 2. Prazosin will be more effective than paroxetine or placebo for improving sleep
      quality (as measured by the Pittsburgh Sleep Quality Index [PSQI]).

      Hypothesis 3. Prazosin will be more effective than paroxetine or placebo for improving
      overall clinical status (as measured by the Clinical Global Impression of Change [CGIC]).

      Hypothesis 4. Prazosin will be better tolerated than paroxetine as measured by days retained
      in the study and frequency of adverse events. Primary outcome measures will assess
      trauma-related nightmares, sleep disturbance and change in global clinical status: these will
      include the CAPS [59] Recurrent Distressing Dreams item, the PSQI (60) and the CGIC (58)
      score. Secondary outcome measures will include total CAPS score, the CAPS subscale scores
      (Reexperiencing/ Intrusions, Avoidance/Numbing, and Hyperarousal), the Nightmare Frequency
      Questionnaire (NFQ), Insomnia Severity Index, and measures of depressive signs and symptoms,
      quality of life, and number of study days completed.
    

Intervention name(s): Paroxetine; Prazosin; placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): paroxetine 20 mg; Prazosin; placebo capsules
Other intervention name(s): Paxil
Intervention MeSH terms: Prazosin; Paroxetine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Paroxetine; Prazosin; Sleep Disorders; Stress Disorders, Post-Traumatic