Prazosin vs Paroxetine in Combat Stress-Related Post-Traumatic Stress Disorder (PTSD) Nightmares & Sleep Disturbance
The purposes of this study are:
- to 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 Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF).
- to evaluate the effects of the selective serotonin reuptake inhibitor (SSRI) paroxetine on behavioral symptoms and overall function in this population.
Stress Disorders, Post-Traumatic
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Placebo-Controlled Trial of Prazosin vs. Paroxetine in Combat Stress-Related PTSD Nightmares and Sleep Disturbance|
- Change in Combat Trauma-related Nightmares Will be Assessed by the Clinician Administered PTSD Scale (CAPS) Recurrent Distressing Dreams Item at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]Item B-2 "recurrent distressing dreams of the event" is a single item from the Clinician Administered PTSD Scale. The rating consists of two parts: Frequency and Intensity. Symptom frequency rated 0 to 4. Symptom intensity rated 0 to 4. Frequency plus Intensity ratings equal the total score. A higher score is worse; a lower score is better. This outcome measure evaluates the change in score from Baseline to Week 12.
- Change in Sleep Will be Assessed by the Pittsburgh Sleep Quality Index at Week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Pittsburgh Sleep Quality Index is a self-report questionnaire assessing sleep quality and disturbances over a 1-month time interval. A global score is obtained by summing the seven component subscales (total score range: 0-21). A score of 5 or less indicates good sleep quality. A score of more than 5 indicates poor sleep quality. Change is measured from Baseline to Week 12.
- Change in Global Trauma-related Symptom Severity and Functioning Will be Assessed by the Clinical Global Impression of Change at Week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]The Clinical Global Impression of Change is a 7-point scale that rates global change compared to baseline (1=markedly improved, 2=moderately improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=moderately worse, 7=markedly worse). The CGIC is used to determine the impact of treat effects on meaningful and distinct change in overall sense of well-being and functioning. This outcome measure evaluates change from baseline to Week 12.
- Additional Data on Change in Nightmares Will be Assessed by the PTSD Dream Rating Scale and Nightmare Frequency Questionnaire at Weeks 6 & 12 [ Time Frame: 6 and 12 weeks ] [ Designated as safety issue: No ]
- Change in Depressive Symptoms Will be Assessed by the Hamilton Depression Rating Scale at Weeks 6 & 12 [ Time Frame: 6 and 12 weeks ] [ Designated as safety issue: No ]
- Change in Quality of Life Will be Assessed by the Quality of Life Inventory at Weeks 6 & 12 [ Time Frame: 6 and 12 weeks ] [ Designated as safety issue: No ]
- Study Days Completed as an Indicator of Medication Tolerability at Weeks 6 & 12 [ Time Frame: 6 and 12 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||July 2004|
|Study Completion Date:||February 2008|
|Primary Completion Date:||February 2008 (Final data collection date for primary outcome measure)|
taken by mouth, twice daily, titrated up to efficacy or a maximum of 5 mg at 10a and 25 mg at bedtime for duration of study
Other Name: Minipress
Active Comparator: 2
20 mg taken at 10a for duration of the study
Other Name: Paxil, Paxil CR
Placebo Comparator: 3
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00202449
|United States, District of Columbia|
|Walter Reed Army Medical Center|
|Washington, District of Columbia, United States, 20307|
|United States, Washington|
|Madigan Army Medical Center|
|Fort Lewis, Washington, United States, 98431|
|Principal Investigator:||Murray Raskind, MD||Director, Mental Health Services and Director, Mental Illness Research, Education, and Clinical Center VA Puget Sound Health Care System|