title: Comparative efficacy and acceptability of combined antipsychotics and mood stabilizers versus individual drug classes for acute mania: Network meta-analysis.
abstract: OBJECTIVE
  Recent network meta-analyses of drug treatments for acute mania have only evaluated the efficacy and acceptability of individual drug treatments. The relative efficacy and acceptability of combined drug treatment has not been assessed.
  
  
  METHODS
  Double-blind drug trials in acute mania were identified using a systematic search strategy. We recorded numbers of patients enrolled, endpoints for efficacy (changes in mania rating scales, numbers of responders) and acceptability (numbers of dropouts) and treatment administered (categorized as antipsychotic, mood stabilizer, combined antipsychotic/mood stabilizer or placebo). Data were analyzed using a random effects frequentist network meta-analysis.
  
  
  RESULTS
  All three drug categories were more effective than placebo. Antipsychotics and combined antipsychotic/mood stabilizer were significantly more effective than mood stabilizers for changes in mania rating scales. Combined antipsychotic/mood stabilizer was significantly more effective than mood stabilizers and antipsychotics for responder rate. Dropout rates were significantly lower for antipsychotics compared with placebo and mood stabilizers. Combined antipsychotic/mood stabilizer had the highest probability of being the best treatment based on change in mania rating scales (96.1% for all mania scales; 85.5% for Young Mania Rating Scale), and 99.3% for being the best treatment for responders. Antipsychotics had 82.0% probability as the best treatment to minimize dropouts.
  
  
  CONCLUSIONS
  Combined antipsychotic/mood stabilizer appears to have efficacy advantages over antipsychotic or mood stabilizer monotherapy in acute mania, and should be considered as first line therapy.
authors.affiliation: Department of Psychological Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand paul.glue@otago.ac.nz.
authors.forename: Paul
authors.initials: P
authors.lastname: Glue
authors.affiliation: Department of Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Peter
authors.initials: P
authors.lastname: Herbison
mesh_terms: D000208:Acute Disease; D018692:Antimanic Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D002220:Carbamazepine / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D018020:Lithium Compounds / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D018692:Antimanic Agents; D014150:Antipsychotic Agents; D018020:Lithium Compounds; D002220:Carbamazepine; D014635:Valproic Acid
keywords: Acute mania; antipsychotics; combination treatment; mood stabilizers; network meta-analysis; systematic review