title: Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression.
abstract: 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.
authors: Lilly Research Laboratories, Indianapolis, IN 46285, USA. m.tohen@lilly.com
authors: Mauricio
authors: M
authors: Tohen
authors: Eduard
authors: E
authors: Vieta
authors: Joseph
authors: J
authors: Calabrese
authors: Terence A
authors: TA
authors: Ketter
authors: Gary
authors: G
authors: Sachs
authors: Charles
authors: C
authors: Bowden
authors: Philip B
authors: PB
authors: Mitchell
authors: Franca
authors: F
authors: Centorrino
authors: Richard
authors: R
authors: Risser
authors: Robert W
authors: RW
authors: Baker
authors: Angela R
authors: AR
authors: Evans
authors: Karin
authors: K
authors: Beymer
authors: Sanjay
authors: S
authors: Dube
authors: Gary D
authors: GD
authors: Tollefson
authors: Alan
authors: A
authors: Breier
mesh_terms: 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
chemical_list: D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D005473:Fluoxetine; D001569:Benzodiazepines; D010890:Pirenzepine; D000077152:Olanzapine