Olanzapine in the treatment of dopamimetic-induced psychosis in patients with Parkinson's disease

Background: Studies in elderly patients demonstrate antipsychotic efficacy and favorable safety profiles for olanzapine. We report results from two placebo-controlled, double-blind studies of olanzapine for treatment of dopamimetic drug-induced psychosis inpatients with Parkinson's disease (PD). Methods: Patients were treated with olanzapine or placebo for 4 weeks while dopamimetic therapy was held constant. Olanzapine was initiated at 2.5 mg/day, with 2.5-mg/day increases allowed every 3 to 4 days tip to the maximum dose of 15 mg/day. Results: Olanzapine patients showed significant improvements from baseline on positive symptoms and most efficacy measures, but no significant treatment-group differences were observed. Olanzapine performed significantly worse than placebo in both studies on the Unified Parkinson's Disease Rating Scale (UPDRS) total, Motor, and Activities of Daily Living scales, but not the UPDRS Tremor item or Complications scores. Corrected QT interval, vital signs, and body weight were not significantly different from placebo. Conclusions: These findings did not demonstrate superior efficacy of olanzapine for treatment of dopamimetic-induced psychosis in PD. The initial dose-titration schedule and mild baseline levels of psychosis may account for these findings. Future studies involving gradual dose titration are needed to explore further olanzapine's optimum use for patients with PD with treatment-related psychosis.