title: 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).
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: International Mood Disorders Research Centre, Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), Hospital Santiago Apóstol, University of the Basque Country, Vitoria, Spain. anamaria.gonzalez-pintoarrillaga@osakidetza.net
authors.forename: Ana
authors.initials: A
authors.lastname: Gonzalez-Pinto
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.forename: Catherine
authors.initials: C
authors.lastname: Reed
authors.forename: Diego
authors.initials: D
authors.lastname: Novick
authors.forename: Alessandra
authors.initials: A
authors.lastname: Barraco
authors.forename: Jaume
authors.initials: J
authors.lastname: Aguado
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Haro
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D000077152:Olanzapine; D016016:Proportional Hazards Models; D011569:Psychiatric Status Rating Scales; D055502:Secondary Prevention; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018692:Antimanic Agents; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine