Quetiapine Augmentation for Treatment-resistant PTSD

VA Office of Research and Development

Status and phase: Completed; Phase 4

Conditions: Combat Disorders; Stress Disorders, Post-Traumatic

Treatments: Drug: Placebo; Drug: Open Label (OL) Paroxetine; Drug: Quetiapine

Study type: Interventional

Funder types: Other U.S. Federal agency; Industry

Identifiers

NCT00292370

CLIN-006-04F

Details and patient eligibility

About

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.

Full 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.

Enrollment: 124 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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124 participants in 3 patient groups, including a placebo group

Arm 1: Open Label (OL) Paroxetine

Other group

Description:

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.

Treatment:

Drug: Open Label (OL) Paroxetine

Arm 2 OL Paroxetine + DB Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Open Label (OL) Paroxetine

Drug: Placebo

Arm 3: OL Paroxetine + DB Quetiapine

Experimental group

Description:

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.

Treatment:

Drug: Quetiapine

Drug: Open Label (OL) Paroxetine