title: Olanzapine plus fluoxetine for bipolar disorder: a systematic review and meta-analysis.
abstract: BACKGROUND
  Olanzapine plus fluoxetine combination (OFC) is one of the current approaches for treating the depressive phase of bipolar disorder. Our objective was to synthesize the evidence on the efficacy of OFC therapy in bipolar depressed patients.
  
  
  METHODS
  We searched for randomized controlled trials (RCTs) on MEDLINE, Embase and other databases. Independent researchers selected the studies and extracted the data. The GRADE approach was used to assess the quality of the evidence. The Mantel-Haenszel random effect model was used to perform the meta-analyses.
  
  
  RESULTS
  From 627 unique records retrieved, four RCTs were included (1330 patients). OFC improved the response compared to olanzapine (relative risk [RR]=1.58; 95% confidence interval [95% CI]: 1.27, 1.97) and to placebo (RR=1.99; 95% CI: 1.49, 2.65) but not to lamotrigine (low-quality evidence). Similar results were found for remission and relapse rates. No differences were identified for levels of depression and mania symptoms (low-quality evidence) and incidence of mania (moderate-quality evidence). Adverse effects were more common in patients treated with OFC than in those treated with lamotrigine (RR=1.13; 95% CI: 1.04, 1.23), but no difference was found relative to the patients treated with olanzapine (low-quality evidence).
  
  
  CONCLUSIONS
  Despite the totality of the evidence included, there are few RCTs available regarding the efficacy of OFC therapy for bipolar depression. The risk of attrition and reporting bias is also a concern.
  
  
  CONCLUSIONS
  OFC therapy improved the response, remission, and relapse rates among other outcomes. However, a worse profile of adverse reactions was observed in some comparisons. These data clarify the therapeutic use of OFC as an option to olanzapine in bipolar depression. The quality of the evidence could be improved by additional comparisons and higher rates of treatment adherence.
authors.affiliation: University of Brasilia, Brasilia, DF 70904-970, Brazil.
authors.forename: Marcus T
authors.initials: MT
authors.lastname: Silva
authors.forename: Ivan R
authors.initials: IR
authors.lastname: Zimmermann
authors.forename: Tais F
authors.initials: TF
authors.lastname: Galvao
authors.forename: Mauricio G
authors.initials: MG
authors.lastname: Pereira
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D004338:Drug Combinations; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D004338:Drug Combinations; C492572:olanzapine-fluoxetine combination; D005473:Fluoxetine; D001569:Benzodiazepines