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 in patients 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 up 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.

A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia.

BACKGROUND: An intramuscular (IM) formulation of olanzapine has been developed because there are no rapid-acting IM atypical antipsychotic drugs currently available in the United States for treating acute agitation in patients with schizophrenia. METHODS: Recently hospitalized acutely agitated patients with schizophrenia (N = 270) were randomized to receive 1 to 3 IM injections of olanzapine (2.5, 5.0, 7.5, or 10.0 mg), haloperidol (7.5 mg), or placebo within 24 hours. A dose-response relationship for IM olanzapine in the reduction of agitation was assessed by measuring the reduction in Positive and Negative Syndrome Scale Excited Component (PANSS-EC) scores 2 hours after the first injection. Safety was assessed by recording adverse events and with extrapyramidal symptom scales and electrocardiograms at 24 hours after the first injection. RESULTS: Olanzapine exhibited a dose-response relationship for reduction in agitation (F(1,179)= 14.4; P<.001). Mean PANSS-EC reductions 2 hours after the first injection of olanzapine (2.5 mg = -5.5; 5.0 mg = -8.1; 7.5 mg = -8.7; 10.0 mg = -9.4) were superior to those with placebo (-2.9; P =.01 vs olanzapine at 2.5 mg; P<.001 for each other olanzapine dose) but not with haloperidol (-7.5). A dose of 5.0, 7.5, or 10.0 mg of olanzapine caused a greater reduction in agitation than placebo 30 minutes after the first injection. There were no differences between treatment groups for hypotension, the most frequently reported adverse event, or for clinically relevant changes in the QTc interval. There was a greater incidence of treatment-emergent parkinsonism during treatment with IM haloperidol (16.7%) than with 2.5 (P =.03), 5.0 (P =.03), or 7.5 mg (P =.01) of IM olanzapine (0%) or with placebo (0%) (P =.01). CONCLUSIONS: Intramuscular olanzapine at a dose of 2.5 to 10.0 mg per injection exhibits a dose-response relationship in the rapid treatment of acute agitation in patients with schizophrenia and demonstrates a favorable safety profile.