Olanzapine-fluoxetine combination for the treatment of bipolar depression

Expert Opin Pharmacother. 2011 Dec;12(17):2751-8. doi: 10.1517/14656566.2011.632368. Epub 2011 Oct 28.


Introduction: Olanzapine-fluoxetine combination is one of only two products currently approved by the US FDA for the acute treatment of depressive episodes associated with bipolar disorder.

Areas covered: This treatment evaluation reviews double-blind randomized controlled trials of olanzapine-fluoxetine combination for bipolar depression. A total of three primary study reports are found in the peer-reviewed literature. Additional data regarding the trials are obtained from study synopses disclosed on the internet by the manufacturer and from product labeling.

Expert opinion: Number needed to treat for antidepressant response for olanzapine-fluoxetine combination versus placebo in the 8-week trials was 4 (95% CI 3 - 8), and that for remission was 5 (95% CI 3 - 8). Single-digit numbers needed to harm (NNH) values were observed for the treatment-emergent adverse events of weight gain (NNH 7, 95% CI 5 - 16) and diarrhea (NNH 9, 95% CI 5 - 30). NNH versus placebo for weight gain ≥ 7% from baseline was 6 (95% CI 4 - 10). When contrasted with lamotrigine, olanzapine-fluoxetine combination demonstrates statistically significantly greater improvement in depressive and manic symptoms but there is a higher incidence of treatment-emergent adverse events, weight gain and elevation in metabolic factors. Studies that directly compare quetiapine monotherapy with olanzapine-fluoxetine combination, the only two approved products for the treatment of bipolar depression, are not available. Nonetheless, indirect comparisons indicate similar efficacy outcomes but different tolerability profiles, with quetiapine principally being associated with sedation. Additional approved treatment options would be welcome.

Publication types

  • Review

MeSH terms

  • Animals
  • Antidepressive Agents, Second-Generation / adverse effects
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines / adverse effects
  • Benzodiazepines / therapeutic use*
  • Bipolar Disorder / drug therapy*
  • Dibenzothiazepines / therapeutic use
  • Drug Combinations
  • Fluoxetine / adverse effects
  • Fluoxetine / therapeutic use*
  • Humans
  • Quetiapine Fumarate


  • Antidepressive Agents, Second-Generation
  • Antipsychotic Agents
  • Dibenzothiazepines
  • Drug Combinations
  • olanzapine-fluoxetine combination
  • Fluoxetine
  • Benzodiazepines
  • Quetiapine Fumarate