Efficacy of olanzapine in acute bipolar mania - A double-blind, placebo-controlled study

Background: We compared the efficacy and safety of olanzapine vs placebo fo r the treatment of acute bipolar mania. Methods: Four-week, randomized, double-blind, parallel study. A total of 11 5 patients with a DSM-IV diagnosis of bipolar disorder, manic or mixed, wer e randomized to olanzapine, 5 to 20 mg/d (n = 55), or placebo (n = 60). The primary efficacy measure was the Young-Mania Rating Scale (Y-MRS) total sc ore. Response and euthymia were defined, a priori, as at least a 50% improv ement from baseline to end point and as a score of no less than 12 at end p oint in the Y-MRS total score, respectively. Safety was assessed using adve rse events, Extrapyramidal Symptom (EPS) rating scales, laboratory values, electrocardiograms, vital signs, and weight change. Results: Olanzapine-treated patients demonstrated a statistically significa nt greater mean (+/- SD) improvement in Y-MRS total score than placebo-trea ted patients (-14.8 +/- 12.5 and -8.1 +/- 12.7, respectively, P < .001),whi ch was evident at the first postbaseline observation 1 week after randomiza tion and was maintained throughout the study (last observation carried forw ard). Olanzapine-treated patients demonstrated a higher rate of response (6 5% vs 43%, respectively; P = .02) and euthymia (61% vs 36%, respectively; P = .01) than placebo-treated patients. There were no statistically signific ant differences in EPSs between groups. However, olanzapine-treated patient s had a statistically significant greater mean (+/- SD) weight gain than pl acebo-treated patients (2.1 +/- 2.8 vs 0.45 +/- 2.3 kg, respectively) and a lso experienced more treatment-emergent somnolence (21 patients [38.2%] vs 5 [8.3%], respectively). Conclusion: Olanzapine demonstrated greater efficacy than placebo in the tr eatment of acute bipolar mania and was generally well tolerated.