title: Effects of asenapine in bipolar I patients meeting proxy criteria for moderate-to-severe mixed major depressive episodes: a post hoc analysis.
abstract: OBJECTIVE
  Depression is the predominant psychosocial and suicide burden in bipolar disorder, yet there is a paucity of evidence-based treatments for bipolar depression.
  
  
  METHODS
  This post hoc subgroup analysis of data pooled from two 3-week, randomized, placebo- and olanzapine-controlled trials (December 2004-April 2006, N = 489 and November 2004-April 2006, N = 488) examined a subgroup of patients meeting criteria for moderate-to-severe mixed major depressive episodes, defined using DSM-IV-TR criteria for mixed episodes (mania and major depression simultaneously) with a baseline Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥ 20.
  
  
  RESULTS
  Decreases in MADRS scores (least squares mean [SE]), the a priori primary outcome, were significantly greater in the asenapine group than in the placebo group from baseline to day 7 (-11.02 [1.82] vs -4.78 [1.89]; P = .0195), day 21 (-14.03 [2.01] vs -7.43 [2.09]; P = .0264), and endpoint (-10.71 [1.76] vs -5.19 [1.98]; P = .039). Decreases in MADRS scores with asenapine were significantly greater than with olanzapine from baseline to day 7 (-6.26 [1.47]; P = .0436). Decreases in Young Mania Rating Scale mean total score were greater with asenapine than with placebo or olanzapine at all time points assessed. A significantly greater reduction from baseline to day 21 in the Short Form-36 mental component summary score was observed with asenapine, but not olanzapine, compared with placebo (16.57 vs 5.97; P = .0093). Asenapine was generally well tolerated.
  
  
  CONCLUSIONS
  These data provide support for the potential efficacy of asenapine in mixed major depressive episodes; however, these data cannot be linearly extrapolated to nonmixed major depression.
authors.affiliation: School of Medicine, Deakin University, 1 Gheringhap St, Geelong, VIC 3220, Australia mikebe@barwonhealth.org.au.
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.forename: John W G
authors.initials: JW
authors.lastname: Tiller
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Lakshmi N
authors.initials: LN
authors.lastname: Yatham
authors.forename: Gin S
authors.initials: GS
authors.lastname: Malhi
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Weiller
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000150:complications* / Q000188:drug therapy*; D003865:Major Depressive Disorder / Q000150:complications* / Q000188:drug therapy*; D003986:Dibenzocycloheptenes; D004311:Double-Blind Method; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D000077152:Olanzapine; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings; D001569:Benzodiazepines; C522667:asenapine; D000077152:Olanzapine