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


CONCLUSIONS
Olanzapine demonstrated greater efficacy than placebo in the treatment of acute bipolar mania and was generally well tolerated.
Tohen
M
M
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285. USA. m.tohen@lilly.com
Jacobs
T G
TG
Grundy
S L
SL
McElroy
S L
SL
Banov
M C
MC
Janicak
P G
PG
Sanger
T
T
Risser
R
R
Zhang
F
F
Toma
V
V
Francis
J
J
Tollefson
G D
GD
Breier
A
A
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010919:Placebos; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012720:Severity of Illness Index; D012893:Sleep Wake Disorders / Q000139:chemically induced; D016896:Treatment Outcome; D015430:Weight Gain
D014150:Antipsychotic Agents; D010919:Placebos; D001569:Benzodiazepines; D010890:Pirenzepine; D000077152:Olanzapine