title: Efficacy of second generation antipsychotics in treating acute mixed episodes in bipolar disorder: a meta-analysis of placebo-controlled trials.
abstract: BACKGROUND
  The literature on the treatment mixed episodes in Bipolar Disorder [BD] is sparse. Second generation antipsychotics [SGA] have documented efficacy in mania, but not mixed episodes. The objective of this meta-analysis was to ascertain the efficacy of SGA, either as mono- and/or adjunctive therapy, in the treatment of acute mixed episodes of BD, compared to placebo.
  
  
  METHODS
  A MEDLINE search for English language publications of randomized controlled trials [RCTs] comparing SGA with placebo in the treatment of an acute manic/mixed episode of BD, during the period 1990-2012, was performed using the terms 'atypical antipsychotics', 'SGA', 'mixed episodes', 'dysphoric mania' and each SGA independently. 9 RCTs reporting data on 1289 mixed episode patients treated with aripiprazole, asenapine, olanzapine, paliperidone-ER, risperidone, and ziprasidone, either as monotherapy or as adjunctive therapy, versus placebo, for 3-6 weeks, were included in the meta-analysis. We extracted data on the number of patients, SGA, duration of study and mean change in mania and depression scores from baseline to endpoint. Standardized mean difference between SGA and placebo for the mean baseline-to-endpoint change in mania and depression rating scores was calculated, with a 95% confidence limit.
  
  
  RESULTS
  SGA, either alone or in combination with mood stabilizers, had superior efficacy in treating manic symptoms of mixed episodes compared to placebo (-0.41, 95% CI -0.53, -0.30; overall effect p<0.00001). SGA were equally effective for manic symptoms in mixed episodes and pure mania (p=0.99). SGA had superior efficacy in treating depressive symptoms of mixed episodes (-0.30, 95% CI -0.47, -0.13; p<0.001) compared to placebo in two trials reporting this information.
  
  
  CONCLUSIONS
  Thirteen relevant studies could not be included as data for mixed-episodes were not presented separately.
  
  
  CONCLUSIONS
  SGA are effective in treating acute mixed episodes of BD, with predominant manic symptoms. Their efficacy in treating depressed mixed episodes remains unclear.
authors.affiliation: Mood Disorders Centre, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver BC Canada V6T2A1.
authors.forename: Kesavan
authors.initials: K
authors.lastname: Muralidharan
authors.forename: Mazen
authors.initials: M
authors.lastname: Ali
authors.forename: Leonardo E
authors.initials: LE
authors.lastname: Silveira
authors.forename: David J
authors.initials: DJ
authors.lastname: Bond
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Fountoulakis
authors.forename: Raymond W
authors.initials: RW
authors.lastname: Lam
authors.forename: Lakshmi N
authors.initials: LN
authors.lastname: Yatham
mesh_terms: D000208:Acute Disease; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic
chemical_list: D014150:Antipsychotic Agents
keywords: Bipolar disorders; Mania; Meta-analysis; Mixed episodes; Randomized controlled trials; Second generation antipsychotics