Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression.
BACKGROUND
Despite the longer duration of the depressive phase in bipolar disorder and the frequent clinical use of antidepressants combined with antipsychotics or mood stabilizers, relatively few controlled studies have examined treatment strategies for bipolar depression.


OBJECTIVE
To examine the use of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression.


METHODS
Double-blind, 8-week, randomized controlled trial.


METHODS
Eighty-four sites (inpatient and outpatient) in 13 countries. Patients A total of 833 randomized adults with bipolar I depression with a Montgomery-Asberg Depression Rating Scale (MADRS) score of at least 20. Intervention Patients were randomly assigned to receive placebo (n = 377); olanzapine, 5 to 20 mg/d (n = 370); or olanzapine-fluoxetine combination, 6 and 25, 6 and 50, or 12 and 50 mg/d (n = 86).


METHODS
Changes in MADRS total scores using mixed-effects model repeated-measures analyses.


RESULTS
During all 8 study weeks, the olanzapine and olanzapine-fluoxetine groups showed statistically significant improvement in depressive symptoms vs the placebo group (P<.001 for all). The olanzapine-fluoxetine group also showed statistically greater improvement than the olanzapine group at weeks 4 through 8. At week 8, MADRS total scores were lower than at baseline by 11.9, 15.0, and 18.5 points in the placebo, olanzapine, and olanzapine-fluoxetine groups, respectively. Remission criteria were met by 24.5% (87/355) of the placebo group, 32.8% (115/351) of the olanzapine group, and 48.8% (40/82) of the olanzapine-fluoxetine group. Treatment-emergent mania (Young Mania Rating Scale score <15 at baseline and > or =15 subsequently) did not differ among groups (placebo, 6.7% [23/345]; olanzapine, 5.7% [19/335]; and olanzapine-fluoxetine, 6.4% [5/78]). Adverse events for olanzapine-fluoxetine therapy were similar to those for olanzapine therapy but also included higher rates of nausea and diarrhea.


CONCLUSIONS
Olanzapine is more effective than placebo, and combined olanzapine-fluoxetine is more effective than olanzapine and placebo in the treatment of bipolar I depression without increased risk of developing manic symptoms.
Tohen
Mauricio
M
Lilly Research Laboratories, Indianapolis, IN 46285, USA. m.tohen@lilly.com
Vieta
Eduard
E
Calabrese
Joseph
J
Ketter
Terence A
TA
Sachs
Gary
G
Bowden
Charles
C
Mitchell
Philip B
PB
Centorrino
Franca
F
Risser
Richard
R
Baker
Robert W
RW
Evans
Angela R
AR
Beymer
Karin
K
Dube
Sanjay
S
Tollefson
Gary D
GD
Breier
Alan
A
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage* / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001569:Benzodiazepines; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy*; D003863:Depression / Q000175:diagnosis / Q000188:drug therapy; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010890:Pirenzepine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D005473:Fluoxetine; D001569:Benzodiazepines; D010890:Pirenzepine; D000077152:Olanzapine