Prazosin vs Paroxetine in Combat Stress-Related Post-Traumatic Stress Disorder (PTSD) Nightmares & Sleep Disturbance

NCT00202449 | Terminated Results DMC

• 3 other identifiers: Raskind 0046DoD #PR054292UW HS #04-1469-V 02
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Stress Disorders, Post-Traumatic; Sleep Disorders

Keywords

Prazosin; Paroxetine; Stress Disorders, Post-Traumatic; Sleep Disorders

Outcome Measures

Primary Outcomes (3)

• Change in Combat Trauma-related Nightmares From the Clinician Administered PTSD Scale (CAPS) Recurrent Distressing Dreams Item at Week 12

  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. Minimum = 0 Maximum = 8

  Baseline and Week 12

• Change in Sleep From the Pittsburgh Sleep Quality Index From Baseline to Week 12

  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.

  Baseline to Week 12

• Change in Global Trauma-related Symptom Severity and Functioning From the Clinical Global Impression of Change From Baseline to Week 12

  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 treatment effects on meaningful and distinct change in overall sense of well-being and functioning. This outcome measure evaluates change from baseline to Week 12.

  Baseline to Week 12

Study Arms (3)

1

EXPERIMENTAL

Prazosin

Drug: prazosin

2

ACTIVE COMPARATOR

Paroxetine

Drug: paroxetine

3

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

prazosin DRUG

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

Also known as: Minipress

1

paroxetine DRUG

20 mg taken at 10a for duration of the study

Also known as: Paxil, Paxil CR

2

Placebo DRUG

Placebo

3

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Acute or significant chronic medical illness, preexisting hypotension or orthostatic hypotension, pancreatitis, gout, Ménière'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 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (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 of an antidepressant (other than trazodone prescribed for sleep).

Sponsors & Collaborators

• Seattle Institute for Biomedical and Clinical Research: lead
• United States Department of Defense: collaborator
• VA Puget Sound Health Care System: collaborator

Study Sites (2)

Walter Reed Army Medical Center

Washington D.C., District of Columbia, 20307, United States

Location

Madigan Army Medical Center

Fort Lewis, Washington, 98431, United States

Location

Related Publications (4)

• Raskind MA, Peskind ER, Kanter ED, Petrie EC, Radant A, Thompson CE, Dobie DJ, Hoff D, Rein RJ, Straits-Troster K, Thomas RG, McFall MM. Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am J Psychiatry. 2003 Feb;160(2):371-3. doi: 10.1176/appi.ajp.160.2.371.

  PMID: 12562588 BACKGROUND

• Raskind MA, Thompson C, Petrie EC, Dobie DJ, Rein RJ, Hoff DJ, McFall ME, Peskind ER. Prazosin reduces nightmares in combat veterans with posttraumatic stress disorder. J Clin Psychiatry. 2002 Jul;63(7):565-8. doi: 10.4088/jcp.v63n0705.

  PMID: 12143911 BACKGROUND

• Raskind MA, Dobie DJ, Kanter ED, Petrie EC, Thompson CE, Peskind ER. The alpha1-adrenergic antagonist prazosin ameliorates combat trauma nightmares in veterans with posttraumatic stress disorder: a report of 4 cases. J Clin Psychiatry. 2000 Feb;61(2):129-33. doi: 10.4088/jcp.v61n0208.

  PMID: 10732660 BACKGROUND

• Peskind ER, Bonner LT, Hoff DJ, Raskind MA. Prazosin reduces trauma-related nightmares in older men with chronic posttraumatic stress disorder. J Geriatr Psychiatry Neurol. 2003 Sep;16(3):165-71. doi: 10.1177/0891988703256050.

  PMID: 12967060 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Sleep Wake Disorders

Interventions

Prazosin; Paroxetine

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Piperidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

High rate of early termination leading to small number of patients analyzed.

Results Point of Contact

• Title: Murray Raskind, MD
• Organization: VA PSHCS

Murray.Raskind@va.gov

206-764-2702

Study Officials

• Murray Raskind, MD

  Director, Mental Health Services and Director, Mental Illness Research, Education, and Clinical Center VA Puget Sound Health Care System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 20, 2005
• Study Start: July 1, 2004
• Primary Completion: February 1, 2008
• Study Completion: February 1, 2008
• Last Updated: July 10, 2018
• Results First Posted: July 12, 2012

Record last verified: 2018-06

Locations

US (2)