Onset of antidepressant effect of olanzapine and olanzapine/fluoxetine combination in bipolar depression. Academic Article uri icon

start page

  • 618

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  • 627


  • The current analysis investigated the onset of antidepressant effect of olanzapine/fluoxetine combination.Data for these post hoc analyses were obtained from a clinical trial comparing olanzapine, placebo, and olanzapine/fluoxetine combination in bipolar depression (BD). Subjects were 833 patients with a DSM-IV diagnosis of bipolar I disorder, depressed. The Montgomery-Asberg Depression Rating Scale measured depressive symptoms. Multiple analytic methods were applied, including traditional (mean differences) analysis, pattern analysis, survival analysis of sustained response, mixed-effects regression, and area-under-the-curve analysis.Traditional analysis showed significantly greater improvement in depression scores at week 1 for olanzapine/fluoxetine combination versus placebo (-9.55 versus -5.08, p < 0.001) and for olanzapine versus placebo (-8.31 versus -5.08, p < 0.001). Pattern analysis revealed olanzapine/fluoxetine combination had a significantly greater percentage of early persistent responders than placebo or olanzapine (32.4% versus 12.7%, p < 0.001; and 18.3%, p < 0.05, respectively). Survival analysis showed a significantly shorter time to sustained response for the combination versus placebo (p < 0.001), for olanzapine versus placebo (p = 0.04), and for the combination versus olanzapine (p = 0.03). Mixed-effects regression analysis revealed a significant therapy-by-time interaction (p < 0.001). Early area-under-the-curve analysis revealed a significantly greater percentage of improvement for the combination versus placebo (26.7% versus 13.9%, p < 0.001) and for olanzapine versus placebo (22.0% versus 13.9%, p < 0.001).Based on consistent results from related methods of measuring onset, olanzapine/fluoxetine combination demonstrated rapid onset of antidepressant effect (within 7 days) compared to placebo that was sustained over 8 weeks of treatment in a sample of BD patients. Using multiple statistical techniques may help profile a drug's onset of effect.

date/time value

  • September 2007

Digital Object Identifier (DOI)

  • 10.1111/j.1399-5618.2007.00491.x

PubMed Identifier

  • 17845277


  • 9


  • 6


  • Antipsychotic Agents
  • Benzodiazepines
  • Bipolar Disorder
  • Depressive Disorder
  • Drug Therapy, Combination
  • Female
  • Fluoxetine
  • Humans
  • Male
  • Randomized Controlled Trials as Topic
  • Regression Analysis
  • Survival Analysis
  • Treatment Outcome