Prazosin vs. Paroxetine in Combat Stress Symptoms in OIF/OEF Returnees

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00261729
Recruitment Status : Completed
First Posted : December 5, 2005
Last Update Posted : December 3, 2009
Information provided by:
VA Office of Research and Development

Brief 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.

Condition or disease Intervention/treatment Phase
Sleep Disorders Stress Disorders, Post-Traumatic Drug: Paroxetine Drug: Prazosin Drug: placebo Not Applicable

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 210 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Arm Intervention/treatment
Experimental: 1
Drug: Paroxetine
paroxetine 20 mg
Other Name: Paxil

Placebo Comparator: 2
Drug: placebo
placebo capsules

Experimental: 3
Drug: Prazosin

Primary Outcome Measures :
  1. CAPS recurrent distressing dreams item [ Time Frame: baseline, 6 weeks, 12 weeks ]

Secondary Outcome Measures :
  1. Pittsburgh Sleep Quality Index [ Time Frame: baseline, 6 weeks, 12 weeks ]
  2. Clinical Global Impression of Change [ Time Frame: baseline, 6 weeks, 12 weeks ]
  3. Total CAPS [ Time Frame: baseline, 6 weeks, 12 weeks ]
  4. Quality of Life Inventory [ Time Frame: baseline, 6 weeks, 12 weeks ]
  5. Penn Alcohol Craving Scale [ Time Frame: baseline, 6 weeks, 12 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Hazardous duty in Iraq or Afghanistan with the US Armed Forces during Operations Iraqi Freedom and Operation Enduring Freedom
  • Exposure to at least a moderate level of combat (>5 on Revised Combat Exposure Scale)
  • Good general medical health
  • Stable dose of non-excluded medications for at least 4 weeks prior to randomization
  • >5 on CAPS recurrent distressing dreams item
  • >5 on CAPS difficulty falling or staying asleep item

Exclusion Criteria:

  • Acute or significant chronic medical illness, preexisting hypotension or orthostatic hypotension, pancreatitis, gout, M ni re's disease, benign positional vertigo, narcolepsy, or any other unstable medical condition.
  • Women of childbearing potential with either positive pregnancy test or refusal to use effective birth control method will be excluded.
  • Lifetime schizophrenia, schizoaffective disorder, bipolar disorder, psychotic disorder or any DSM-IV cognitive disorder, current delirium, substance dependence disorder within 3 months of the study, severe psychiatric instability or severe situational life crises, including evidence of being actively suicidal or homicidal, or any behavior which poses an immediate danger to patient or others.
  • Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist or paroxetine or any other SSRI, no concurrent use of another alpha-1 antagonist agent, no concurrent use an antidepressant (other than trazodone prescribed for sleep).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00261729

United States, Washington
VA Puget Sound Health Care System, Seattle
Seattle, Washington, United States, 98108
Sponsors and Collaborators
US Department of Veterans Affairs
Principal Investigator: Elaine Peskind, MD VA Puget Sound Health Care System, Seattle

Publications of Results:
Other Publications:
Responsible Party: Peskind, Elaine - Principal Investigator, Department of Veterans Affairs Identifier: NCT00261729     History of Changes
Obsolete Identifiers: NCT00240201
Other Study ID Numbers: MHBA-025-05S
First Posted: December 5, 2005    Key Record Dates
Last Update Posted: December 3, 2009
Last Verified: December 2009

Keywords provided by VA Office of Research and Development:
Sleep Disorders
Stress Disorders, Post-Traumatic

Additional relevant MeSH terms:
Stress Disorders, Traumatic
Sleep Wake Disorders
Stress Disorders, Post-Traumatic
Pathologic Processes
Trauma and Stressor Related Disorders
Mental Disorders
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Antihypertensive Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists