Clinical trial NCT00292370: Quetiapine Augmentation for Treatment-resistant PTSD
Official title: A Placebo-controlled Trial of Adjunctive Quetiapine for Refractory PTSD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Combat Disorders
Stress Disorders, Post-Traumatic
Keywords: Atypical Antipsychotics
Controlled Trial
Paroxetine
Quetiapine
Stress Disorders, Post-Traumatic
Treatment refractory
Treatment resistant
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: AstraZeneca
First posted: 2006-02-15
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Change in Clinician-Administered PTSD Scale for DSM-IV Total Score.
timeFrame: From baseline (week 8) to endpoint (week 16 or termination)
Secondary outcomes:
measure: Change in CGI-I
timeFrame: From Baseline (week 8) to Endpoint (week 16 or termination)
measure: Change in Mean PANSS Total and Subscores From Baseline to Endpoint
timeFrame: Baseline (week 8) to Endpoint (week 16 or termination)
measure: Change in Total Mean Hamilton Rating Scale for Depression (HAMD) Scores
timeFrame: From Baseline (week 8) to Endpoint (week 16 or Termination)
measure: Change in Total Mean Davidson Trauma Scale (DTS)
timeFrame: From Baseline (week 8) to Endpoint (week 16 or Termination)
measure: Change in Mean Q-LES-Q Score From Baseline to Endpoint.
timeFrame: From Baseline (week 8) to Endpoint (week 16 or termination)
measure: Change in Mean Scores of Pittsburgh Sleep Quality Index (PSQI) From Baseline to Endpoint.
timeFrame: From Baseline (week 8) to Endpoint (week 16)
measure: Change in Mean Sheehan Disability Scale (SDS) Scores From Baseline to Endpoint.
timeFrame: Baseline (week 8) to Endpoint (week 16 or termination)
measure: Change in Arizona Sexual Experience Scale (ASEX)
timeFrame: From Baseline (week 8) to Endpoint (week 16 or termination)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham VA Medical Center
state: Alabama
city: Tuscaloosa
country: United States
facility: Tuscaloosa VAMC
state: Alabama
city: Charleston
country: United States
facility: Ralph H. Johnson
state: South Carolina
Study officials:
affiliation: Ralph H. Johnson VA Medical Center
name: Mark B Hamner, MD BS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weathers FW, Keane TM, Davidson JR. Clinician-administered PTSD scale: a review of the first ten years of research. Depress Anxiety. 2001;13(3):132-56. doi: 10.1002/da.1029.