Quetiapine Augmentation for Treatment-resistant PTSD

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00292370
First received: February 13, 2006
Last updated: June 27, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to compare the response of veterans with PTSD without an optimal response to paroxetine to quetiapine augmentation versus placebo.


Condition Intervention Phase
Combat Disorders
Stress Disorders, Post-Traumatic
Drug: Open Label (OL) Paroxetine
Drug: Placebo
Drug: Quetiapine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Placebo-controlled Trial of Adjunctive Quetiapine for Refractory PTSD

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Change in Clinician-Administered PTSD Scale for DSM-IV Total Score. [ Time Frame: From baseline (week 8) to endpoint (week 16 or termination) ] [ Designated as safety issue: No ]
    The Clinician-Administered PTSD Scale for DSM-IV (CAPS) is described in the National Center for PTSD Instruction Manual (November 2000) as a semi-structured clinical interview designed to assess the seventeen symptoms for Post Traumatic Stress Disorder (PTSD) outlined in the DSM-IV, along with five associated features. Ratings are made on a 5 point continuum from the lowest frequency or intensity to the highest. Total CAPS score is a summed score that ranges from 0 to 136 where 0 is asymptomatic and higher scores equal more severe PTSD symptomatology. Also, a change in total CAPS score of 15 points was proposed as clinically significant change.


Secondary Outcome Measures:
  • PANSS,HAMD,CGI,DTS, PSQI,PSQI-A, Dream/Sleep Diary,Q-LES-Q,SDS,ASEX,AIMS, BAS, SAS [ Time Frame: Baseline to endpoint change scores ] [ Designated as safety issue: No ]

Enrollment: 124
Study Start Date: January 2006
Study Completion Date: May 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm 1: Open Label (OL) Paroxetine
Open-label Paroxetine In Phase I, eligible participants will take open-label (OL) Paroxetine (up to 60 mg) daily for 8 weeks. Participants who are refractory (less than 30% reduction in CAPS scores or a minimum CAPS of 50 at week 8) and have PTSD symptoms of at least moderate severity on CGI-S will be eligible for Phase II.
Drug: Open Label (OL) Paroxetine
Open-label Paroxetine
Other Name: Paxil
Placebo Comparator: Arm 2 OL Paroxetine + DB Placebo
In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of placebo for 8 weeks in a double-blind (DB) fashion.
Drug: Open Label (OL) Paroxetine
Open-label Paroxetine
Other Name: Paxil
Drug: Placebo
Double-blind placebo taken with OL paroxetine
Other Name: sugar pill
Experimental: Arm 3: OL Paroxetine + DB Quetiapine
In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of quetiapine (up to 800 mg daily) for 8 weeks in a double blind fashion.
Drug: Open Label (OL) Paroxetine
Open-label Paroxetine
Other Name: Paxil
Drug: Quetiapine
Double-blind quetiapine taken with OL paroxetine
Other Name: Seroquel

Detailed Description:

This is a two-site study designed to evaluate the efficacy and safety of quetiapine augmentation of paroxetine treatment in veterans with PTSD who have failed to respond to paroxetine treatment.

In Phase I, eligible patients will take open-label paroxetine (up to 60 mg daily) for 8 weeks. Patients who are refractory (less than 30% reduction in CAPS scores or a minimum CAPS score of 50 at week 8) and have PTSD symptoms of at least moderate severity on CGI-S will be eligible for the second phase. In Phase II, patients will continue taking open-label paroxetine and will be randomized to the addition of quetiapine (up to 800 mg daily) or placebo for 8 weeks in a double-blind fashion.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Veteran age 18 to 75.
  • Competent to give informed consent.
  • Meeting DSM-IV criteria for PTSD.
  • Minimal CAPS score of 50 at baseline.
  • If female of childbearing potential, patient must have a negative pregnancy test and, if sexually active, be using a medically approved contraceptive method.
  • Patients who have not taken psychiatric medications within 1 week prior to study entry (except fluoxetine [5 weeks])

    • monoamine oxidase inhibitors (MAOIs [4 weeks])
    • depot neuroleptics [4 weeks])
    • or any investigational drug within 30 days prior to study enrollment.
  • To be eligible for Phase II

    • patients must be refractory to paroxetine in Phase I, as defined by less than 30% reduction in CAPS scores or a minimum CAPS score of 50 at week 8
    • must have PTSD symptoms at least moderate severity on CGI-S
    • and must have been compliant with study medicine in Phase I, as defined by taking at least 80% of prescribed doses.

Exclusion Criteria:

  • History of sensitivity to paroxetine or quetiapine.
  • Failure to respond to a prior adequate therapeutic trial i.e. minimum of 8 weeks at maximum tolerated dose of paroxetine (up to 60 mg daily) or quetiapine (up to 800 mg daily).
  • Women who are

    • breast-feeding
    • pregnant
    • expect to become pregnant during the course of the study
    • or are sexually active and are not using a medically acceptable method of birth control.
  • Presence of clinically significant hepatic

    • cardiovascular
    • or other medical conditions that may prevent safe administration of paroxetine or quetiapine
    • or any other clinically significant unstable medical conditions.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00292370

Locations
United States, Alabama
Birmingham VA Medical Center
Birmingham, Alabama, United States, 35233
Tuscaloosa VAMC
Tuscaloosa, Alabama, United States, 35404
United States, South Carolina
Ralph H. Johnson
Charleston, South Carolina, United States, 29401-5799
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Mark B Hamner, MD BS Ralph H. Johnson VA Medical Center
  More Information

Publications:
Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00292370     History of Changes
Other Study ID Numbers: CLIN-006-04F
Study First Received: February 13, 2006
Results First Received: February 14, 2014
Last Updated: June 27, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
Atypical Antipsychotics
Controlled Trial
Paroxetine
Quetiapine
Stress Disorders, Post-Traumatic
Treatment refractory
Treatment resistant

Additional relevant MeSH terms:
Combat Disorders
Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Anxiety Disorders
Mental Disorders
Paroxetine
Quetiapine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants

ClinicalTrials.gov processed this record on July 20, 2014