Quetiapine Augmentation for Treatment-resistant PTSD

VA Office of Research and Development124 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

124

Conditions

Combat Disorders Stress Disorders, Post-Traumatic

Interventions

Open Label (OL) ParoxetineDRUG

Open-label Paroxetine

PlaceboDRUG

Double-blind placebo taken with OL paroxetine

QuetiapineDRUG

Double-blind quetiapine taken with OL paroxetine

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (3)

Birmingham VA Medical Center

Birmingham, Alabama, United States

Tuscaloosa VAMC

Tuscaloosa, Alabama, United States

Ralph H. Johnson

Charleston, South Carolina, United States

Outcomes

Primary Outcomes

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

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.

Time frame: From baseline (week 8) to endpoint (week 16 or termination)

Secondary Outcomes

Change in CGI-I

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.

Time frame: From Baseline (week 8) to Endpoint (week 16 or termination)

Change in Mean PANSS Total and Subscores From Baseline to Endpoint

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.

Time frame: Baseline (week 8) to Endpoint (week 16 or termination)

Change in Total Mean Hamilton Rating Scale for Depression (HAMD) Scores

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.

Data from ClinicalTrials.gov

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