Olanzapine versus placebo in the treatment of acute mania

Objective: The primary intent of this study was to compare the efficacy and safety of olanzapine and placebo in the treatment of acute mania. Method: The design involved a random-assignment, double-blind, placebo-controlled p arallel group study of 3 weeks' duration. After a 2- to 4-day screening per iod, qualified patients were assigned to either olanzapine (N=70) or placeb o (N=69). Patients began double-blind therapy with either olanzapine, 10 mg , or placebo given once per day. After the first day of treatment, the dail y dose could be adjusted upward or downward, as clinically indicated, by on e capsule (olanzapine, 5 mg/day) within the allowed range of one to four ca psules. The primary efficacy measure in the protocol was defined as a chang e from baseline to endpoint in total score on the Young Mania Rating Scale. Clinical response was defined a priori as a decrease of 50% or more from b aseline in Young Mania Rating Scale total score. Results: The olanzapine gr oup experienced significantly greater mean improvement in Young Mania Ratin g Scale total score than the placebo group. On the basis of the clinical re sponse criteria, significantly more olanzapine-treated patients (48.6%) res ponded than those assigned to placebo (24.2%). Somnolence, dizziness, dry m outh, and weight gain occurred significantly more often with olanzapine. Th ere were no statistically significant differences between the olanzapine-tr eated and placebo-treated patients with respect to measures of parkinsonism , akathisia, and dyskinesias. No discontinuations of treatment due to adver se events occurred in the olanzapine treatment group. Conclusions: The resu lts from this study suggest that compared with placebo, olanzapine has supe rior efficacy for the symptoms of acute mania.