Quetiapine Augmentation for Treatment-resistant PTSD

A Placebo-controlled Trial of Adjunctive Quetiapine for Refractory PTSD

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.

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.