Prazosin vs. Paroxetine in Combat Stress Symptoms in OIF/OEF Returnees
|ClinicalTrials.gov Identifier: NCT00261729|
Recruitment Status : Completed
First Posted : December 5, 2005
Last Update Posted : December 3, 2009
|Condition or disease||Intervention/treatment||Phase|
|Sleep Disorders Stress Disorders, Post-Traumatic||Drug: Paroxetine Drug: Prazosin Drug: placebo||Not Applicable|
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  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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||210 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Prazosin vs. Paroxetine in Combat Stress Symptoms in OIF/OEF Returnees|
|Study Start Date :||July 2004|
|Actual Primary Completion Date :||August 2007|
|Actual Study Completion Date :||December 2009|
paroxetine 20 mg
Other Name: Paxil
Placebo Comparator: 2
- CAPS recurrent distressing dreams item [ Time Frame: baseline, 6 weeks, 12 weeks ]
- Pittsburgh Sleep Quality Index [ Time Frame: baseline, 6 weeks, 12 weeks ]
- Clinical Global Impression of Change [ Time Frame: baseline, 6 weeks, 12 weeks ]
- Total CAPS [ Time Frame: baseline, 6 weeks, 12 weeks ]
- Quality of Life Inventory [ Time Frame: baseline, 6 weeks, 12 weeks ]
- Penn Alcohol Craving Scale [ Time Frame: baseline, 6 weeks, 12 weeks ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00261729
|United States, Washington|
|VA Puget Sound Health Care System, Seattle|
|Seattle, Washington, United States, 98108|
|Principal Investigator:||Elaine Peskind, MD||VA Puget Sound Health Care System, Seattle|