Effectiveness of olanzapine monotherapy and olanzapine combination treatment in the long term following acute mania--results of a two year observational study in bipolar disorder (EMBLEM)

J Affect Disord. 2011 Jun;131(1-3):320-9. doi: 10.1016/j.jad.2010.11.037. Epub 2010 Dec 31.

Abstract

Background: This study compared the 2-year outcomes of patients with a manic/mixed episode of bipolar disorder taking olanzapine monotherapy or olanzapine in combination with other agents.

Methods: EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 2-year, prospective, observational study of clinical and functional outcomes of bipolar patients with an index manic/mixed episode. The study consisted of two phases: acute (12 weeks) and maintenance (follow-up over 2 years). The longitudinal outcome measure was the Clinical Global Impression-Bipolar Disorder scale. Cox regression models compared outcomes of both therapy groups using intention-to-treat and switching medication analysis. Treatment-emergent adverse events were also assessed.

Results: 1076 patients were included in this analysis. 29% took olanzapine as monotherapy (n = 313) and 71% as combination (n = 763) at 12-weeks post-baseline (end of study acute phase). After adjusting for patient characteristics using switching medication analysis, only relapse rates differed (p = 0.01) in favour of monotherapy-treated patients. There was no significant difference in rates of improvement, remission, and recovery. Patients treated with combination therapy reported more tremor (OR 2.37, 95%CI 1.44-3.89) and polyuria (OR 3.08, 95%CI 1.45-6.54) treatment-emergent events than monotherapy, although weight change was greater in the monotherapy group.

Limitations: Unknown confounding and potential selection bias may differentially impact treatment outcomes.

Conclusions: EMBLEM patients benefitted from the selected therapy to a similar extent. Differences in patient characteristics between those prescribed monotherapy and combination therapy appear to be clinically relevant in the treatment decision. Physicians must balance the benefits and risks when determining appropriate treatment for individual patients.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antimanic Agents / administration & dosage
  • Antimanic Agents / therapeutic use
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines / administration & dosage
  • Benzodiazepines / therapeutic use*
  • Bipolar Disorder / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Olanzapine
  • Proportional Hazards Models
  • Psychiatric Status Rating Scales
  • Secondary Prevention
  • Time Factors
  • Treatment Outcome

Substances

  • Antimanic Agents
  • Antipsychotic Agents
  • Benzodiazepines
  • Olanzapine