Quetiapine Augmentation for Treatment-resistant PTSD

Phase 4

Completed

Conditions: Combat Disorders
Stress Disorders, Post-Traumatic

Interventions: Drug: Open Label (OL) Paroxetine
Drug: Placebo
Drug: Quetiapine

Registration Number: NCT00292370

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 124

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: Open Label (OL) Paroxetine	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.
Arm 2 OL Paroxetine + DB Placebo	Open Label (OL) Paroxetine	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.
Arm 2 OL Paroxetine + DB Placebo	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.
Arm 3: OL Paroxetine + DB Quetiapine	Open Label (OL) Paroxetine	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.
Arm 3: OL Paroxetine + DB Quetiapine	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.

Primary Outcome Measures

Name	Time	Method
Change in Clinician-Administered PTSD Scale for DSM-IV Total Score.	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

Name	Time	Method
Change in CGI-I	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.
Change in Mean PANSS Total and Subscores From Baseline to Endpoint	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.
Change in Total Mean Hamilton Rating Scale for Depression (HAMD) Scores	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.
Change in Total Mean Davidson Trauma Scale (DTS)	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).
Change in Mean Q-LES-Q Score From Baseline to Endpoint.	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.
Change in Mean Scores of Pittsburgh Sleep Quality Index (PSQI) From Baseline to Endpoint.	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.
Change in Mean Sheehan Disability Scale (SDS) Scores From Baseline to Endpoint.	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).
Change in Arizona Sexual Experience Scale (ASEX)	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.

Trial Locations

Locations (3): Tuscaloosa VAMC
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Tuscaloosa, Alabama, United States
Ralph H. Johnson
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Charleston, South Carolina, United States
Birmingham VA Medical Center
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Birmingham, Alabama, United States