Risperidone Augmentation for PTSD

This is a multi-center, two-phase study to evaluate the efficacy and safety of risperidone augmentation to sertraline treatment of Post-Traumatic Stress Disorder (PTSD). In the first phase, all patients will be assigned to take open label sertraline for 8 weeks (up to 200 mg/d). Those who have not achieved a significant decrease in their PTSD symptoms by week 8 will be entered into the second phase. In the second phase, patients will continue with the sertraline, but will then be randomly given either risperidone (up to 3 mg/d) or matching placebo in double-blind fashion.

Inclusion criteria

• Signed consent prior to any study procedures being done
• Male or female outpatients between 18-65 years of age
• Trauma experienced meets trauma defined by DSM
• Meets criteria for DSM-IV PTSD as a result of civilian trauma
• CAPS Score of greater than or equal to 50 at screening and baseline
• Able to swallow whole capsules
• Fluency in both written and spoken English
• Negative urine drug screen at screening visit
• If female of childbearing potential, must have negative serum pregnancy test at screening visit and must agree to use a medically accepted means of contraception throughout the study and for 30 days after completion of the study
• To be include in Phase 2, must complete Phase I and must have less than 70% reduction from baseline on the CAPS

Exclusion criteria

• Pregnant women or those likely to become pregnant, or nursing mothers
• Medical instability (clinically significant hepatic, cardiac, or pulmonary disease, HIV, uncontrolled hypertension, diabetes or thyroid conditions, seizure disorders, clinically significant laboratory abnormalities at screen
• Primary psychotic disorder, or history of schizophrenia, other psychotic disorder, bipolar disorder, or cognitive disorder
• Those considered a risk for suicidal or homicidal behavior (the clinician will immediately, upon assessing a risk for suicidal or homicidal behavior, refer the patient for further evaluation and probable hospitalization)
• Hypersensitivity or other contraindication to sertraline or risperidone
• Meeting DSM-IV criteria for drug or alcohol dependence within 3 months of study entry
• Those who are still experiencing an ongoing traumatic stressor (domestic violence/elder abuse) who will need to focus on safety (the clinician will make referrals as appropriate)
• DSM-IV primary diagnosis of any other anxiety disorder or major depressive disorder
• Current use of antipsychotic, or other psychotropic medications, or supplements with known psychotropic effects
• Current involvement in litigation related to PTSD
• Current psychotherapy aimed at treating PTSD
• PTSD as a result of combat-related trauma
• Previous failure to respond to sertraline-risperidone combination at therapeutic dose