Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzipine HGGW Study Group

Arch Gen Psychiatry. 2000 Sep;57(9):841-9. doi: 10.1001/archpsyc.57.9.841.


Background: We compared the efficacy and safety of olanzapine vs placebo for the treatment of acute bipolar mania.

Methods: Four-week, randomized, double-blind, parallel study. A total of 115 patients with a DSM-IV diagnosis of bipolar disorder, manic or mixed, were 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 score. Response and euthymia were defined, a priori, as at least a 50% improvement from baseline to end point and as a score of no less than 12 at end point in the Y-MRS total score, respectively. Safety was assessed using adverse events, Extrapyramidal Symptom (EPS) rating scales, laboratory values, electrocardiograms, vital signs, and weight change.

Results: Olanzapine-treated patients demonstrated a statistically significant greater mean (+/- SD) improvement in Y-MRS total score than placebo-treated patients (-14.8 +/- 12.5 and -8.1 +/- 12.7, respectively; P<.001), which was evident at the first postbaseline observation 1 week after randomization and was maintained throughout the study (last observation carried forward). Olanzapine-treated patients demonstrated a higher rate of response (65% vs 43%, respectively; P =.02) and euthymia (61% vs 36%, respectively; P =. 01) than placebo-treated patients. There were no statistically significant differences in EPSs between groups. However, olanzapine-treated patients had a statistically significant greater mean (+/- SD) weight gain than placebo-treated patients (2.1 +/- 2.8 vs 0.45 +/- 2.3 kg, respectively) and also experienced more treatment-emergent somnolence (21 patients [38.2%] vs 5 [8.3% ], respectively).

Conclusion: Olanzapine demonstrated greater efficacy than placebo in the treatment of acute bipolar mania and was generally well tolerated.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / psychology
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Olanzapine
  • Pirenzepine / adverse effects
  • Pirenzepine / analogs & derivatives*
  • Pirenzepine / therapeutic use
  • Placebos
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Severity of Illness Index
  • Sleep Wake Disorders / chemically induced
  • Treatment Outcome
  • Weight Gain


  • Antipsychotic Agents
  • Placebos
  • Benzodiazepines
  • Pirenzepine
  • Olanzapine