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Quetiapine Augmentation for Treatment-resistant PTSD

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.
 
ClinicalTrials.gov Identifier: NCT00292370
Recruitment Status : Completed
First Posted : February 15, 2006
Results First Posted : July 1, 2014
Last Update Posted : October 16, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
VA Office of Research and Development

Brief Summary:
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 or disease Intervention/treatment Phase
Combat Disorders Stress Disorders, Post-Traumatic Drug: Open Label (OL) Paroxetine Drug: Placebo Drug: Quetiapine Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 124 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Placebo-controlled Trial of Adjunctive Quetiapine for Refractory PTSD
Study Start Date : January 2006
Actual Primary Completion Date : December 2008
Actual Study Completion Date : May 2009


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Change in Clinician-Administered PTSD Scale for DSM-IV Total Score. [ Time Frame: From baseline (week 8) to endpoint (week 16 or termination) ]
    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 :
  1. Change in CGI-I [ Time Frame: From Baseline (week 8) to Endpoint (week 16 or termination) ]
    Clinical Global Impressions Scale and Global Improvement Subscales (CGI-I) is a 7-point scale which was used to assess overall improvement. The scores range from 1 to 7, with 1 indicating very much improved and 7 indicating very much worse.

  2. Change in Mean PANSS Total and Subscores From Baseline to Endpoint [ Time Frame: Baseline (week 8) to Endpoint (week 16 or termination) ]
    Positive and Negative Symptom Scale (PANSS). A 30-item clinician administered rating scale for which positive, negative and general subscales are scored from 30 to 210 with a higher scores indicating greater severity of symptoms.

  3. Change in Total Mean Hamilton Rating Scale for Depression (HAMD) Scores [ Time Frame: From Baseline (week 8) to Endpoint (week 16 or Termination) ]
    Hamilton Rating Scale for Depression (HAMD) was used as a measure of depression. Scoring is based on a 17-item scale. Eight items are scored on a 5 point scale from 0= not present to 4= severe. The scoring is based on the first 17 items. Scores of 0-7 normal, 8-13 is mild depression, 14-18 moderate depression, 19-22 severe depression and 23 and above very severe depression; the maximum score being 52 on the 17-point scale.

  4. Change in Total Mean Davidson Trauma Scale (DTS) [ Time Frame: From Baseline (week 8) to Endpoint (week 16 or Termination) ]
    The DTS is a 17-item self-rated scale that measures the frequency and the severity of DSM-IV PTSD symptoms. Items are rated on 5-point frequency (0 = "not at all" to 4 = "every day") and severity scales (0 = "not at all distressing" to 4 = "extremely distressing"). The DTS yields a frequency score (ranging from 0 to 68), severity score (ranging from 0 to 68), and total score (ranging from 0 to 136). A higher score indicates higher frequency and severity. It can be used to make a preliminary determination about whether the symptoms meet DSM criteria for PTSD. Scores can also be calculated for each of the 3 PTSD symptom clusters (i.e., B, C, and D).

  5. Change in Mean Q-LES-Q Score From Baseline to Endpoint. [ Time Frame: From Baseline (week 8) to Endpoint (week 16 or termination) ]
    Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) a self-rated 14-item questionnaire designed to assess the degree of enjoyment and satisfaction of various aspects of daily functioning. Each question is rated on a 5-point scale with scores ranging from "1 = very poor" to "5 = very good". The minimum raw score on the Q-LES-Q-SF is 14, and the maximum score is 70. A lower score indicates worsening and a higher score indicates better quality of life.

  6. Change in Mean Scores of Pittsburgh Sleep Quality Index (PSQI) From Baseline to Endpoint. [ Time Frame: From Baseline (week 8) to Endpoint (week 16) ]
    The PSQI is one of the most frequently used self-rated sleep questionnaire. Total score ranging from 0 to 21. Higher scores are representing worse sleep quality.

  7. Change in Mean Sheehan Disability Scale (SDS) Scores From Baseline to Endpoint. [ Time Frame: Baseline (week 8) to Endpoint (week 16 or termination) ]
    The SDS is a brief 3-item questionnaire that was used as a self-report to assess the degree to which psychiatric symptoms have disrupted the patient's work, family/home responsibilities, and social life. Score ranging from 0 (no impairment) to 30 (most severe).

  8. Change in Arizona Sexual Experience Scale (ASEX) [ Time Frame: From Baseline (week 8) to Endpoint (week 16 or termination) ]
    The ASEX is a brief 5-item rating scale that assesses five global aspects of sexual dysfunction. Score is 5 and the maximum score is 30. Lower scores indicate more positive sexual experiences.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

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 ClinicalTrials.gov identifier (NCT number): NCT00292370


Locations
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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
VA Office of Research and Development
AstraZeneca
Investigators
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Principal Investigator: Mark B Hamner, MD BS Ralph H. Johnson VA Medical Center
Additional Information:
Publications:
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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT00292370    
Other Study ID Numbers: CLIN-006-04F
First Posted: February 15, 2006    Key Record Dates
Results First Posted: July 1, 2014
Last Update Posted: October 16, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by VA Office of Research and Development:
Atypical Antipsychotics
Controlled Trial
Paroxetine
Quetiapine
Stress Disorders, Post-Traumatic
Treatment refractory
Treatment resistant
Additional relevant MeSH terms:
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Disease
Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Combat Disorders
Pathologic Processes
Trauma and Stressor Related Disorders
Mental Disorders
Quetiapine Fumarate
Paroxetine
Antidepressive Agents
Psychotropic Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Antidepressive Agents, Second-Generation
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors