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A Double-blind, Placebo-Controlled Study

Mauricio Tohen, MD, DrPH; Thomas G. Jacobs, MAS; Starr L. Grundy, BScPharm; Susan L. McElroy, MD; Michael C. Banov, MD; Philip G. Janicak, MD; Todd Sanger, PhD; Richard Risser, MS; Fan Zhang, PhD; Verna Toma, BS; Judith Francis, MA; Gary D. Tollefson, MD, PhD; Alan Breier, MD; for the Olanzapine HGGW Study Group

Arch Gen Psychiatry. 2000;57:841-849.

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.

From the Lilly Research Laboratories, Indianapolis, Ind (Drs Tohen, Sanger, Zhang, Tollefson, and Breier; Mssrs Jacobs and Risser; and Mss Grundy, Toma, and Francis); the Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Mass (Dr Tohen); the Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio (Dr McElroy); Northwest Behavioral Medicine, Marietta, Ga (Dr Banov); and The Psychiatric Institute, Department of Psychiatry, University of Illinois, Chicago (Dr Janicak).

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