Olanzapine versus lithium in the maintenance treatment of bipolar disorder: a 12-month, randomized, double-blind, controlled clinical trial.
OBJECTIVE
The authors compared the efficacy of olanzapine and lithium in the prevention of mood episode relapse/recurrence.


METHODS
Patients with a diagnosis of bipolar disorder (manic/mixed), a history of two or more manic or mixed episodes within 6 years, and a Young Mania Rating Scale total score > or =20 entered the study and received open-label co-treatment with olanzapine and lithium for 6-12 weeks. Those meeting symptomatic remission criteria (Young Mania Rating Scale score < or =12; 21-item Hamilton depression scale score < or =8) were randomly assigned to 52 weeks of double-blind monotherapy with olanzapine, 5-20 mg/day (N=217), or lithium (target blood level: 0.6-1.2 meq/liter) (N=214).


RESULTS
Symptomatic relapse/recurrence (score > or =15 on either the Young Mania Rating Scale or Hamilton depression scale) occurred in 30.0% of olanzapine-treated and 38.8% of lithium-treated patients. The noninferiority of olanzapine relative to lithium (primary objective) in preventing relapse/recurrence was met, since the lower limit of the 95% confidence interval on the 8.8% risk difference (-0.1% to 17.8%) exceeded the predefined noninferiority margin (-7.3%). Secondary results showed that compared with lithium, olanzapine had significantly lower risks of manic episode and mixed episode relapse/recurrence. Depression relapse/recurrence occurred in 15.7% of olanzapine-treated and 10.7% of lithium-treated patients. Mean weight gain during open-label co-treatment was 2.7 kg; during double-blind monotherapy, weight gain was significantly greater with olanzapine (1.8 kg) than with lithium (-1.4 kg).


CONCLUSIONS
These results suggest that olanzapine was significantly more effective than lithium in preventing manic and mixed episode relapse/recurrence in patients acutely stabilized with olanzapine and lithium co-treatment. Both agents were comparable in preventing depression relapse/recurrence.
Tohen
Mauricio
M
Lilly Research Laboratories, Indianapolis, IN 46285, USA. m.tohen@lilly.com
Greil
Waldemar
W
Calabrese
Joseph R
JR
Sachs
Gary S
GS
Yatham
Lakshmi N
LN
Oerlinghausen
Bruno Müller
BM
Koukopoulos
Athanasios
A
Cassano
Giovanni B
GB
Grunze
Heinz
H
Licht
Rasmus W
RW
Dell'Osso
Liliana
L
Evans
Angela R
AR
Risser
Richard
R
Baker
Robert W
RW
Crane
Heidi
H
Dossenbach
Martin R
MR
Bowden
Charles L
CL
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control* / Q000523:psychology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008094:Lithium / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D000077152:Olanzapine; D011569:Psychiatric Status Rating Scales; D055502:Secondary Prevention; D016896:Treatment Outcome
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D008094:Lithium; D000077152:Olanzapine