title: Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis.
abstract: BACKGROUND
  Conventional meta-analyses have shown inconsistent results for efficacy of pharmacological treatments for acute mania. We did a multiple-treatments meta-analysis, which accounted for both direct and indirect comparisons, to assess the effects of all antimanic drugs.
  
  
  METHODS
  We systematically reviewed 68 randomised controlled trials (16,073 participants) from Jan 1, 1980, to Nov 25, 2010, which compared any of the following pharmacological drugs at therapeutic dose range for the treatment of acute mania in adults: aripiprazole, asenapine, carbamazepine, valproate, gabapentin, haloperidol, lamotrigine, lithium, olanzapine, quetiapine, risperidone, topiramate, and ziprasidone. The main outcomes were the mean change on mania rating scales and the number of patients who dropped out of the allocated treatment at 3 weeks. Analysis was done by intention to treat.
  
  
  RESULTS
  Haloperidol (standardised mean difference [SMD] -0·56 [95% CI -0·69 to -0·43]), risperidone (-0·50 [-0·63 to -0·38), olanzapine (-0·43 [-0·54 to -0·32], lithium (-0·37 [-0·63 to -0·11]), quetiapine (-0·37 [-0·51 to -0·23]), aripiprazole (-0·37 [-0·51 to -0·23]), carbamazepine (-0·36 [-0·60 to -0·11], asenapine (-0·30 [-0·53 to -0·07]), valproate (-0·20 [-0·37 to -0·04]), and ziprasidone (-0·20 [-0·37 to -0·03]) were significantly more effective than placebo, whereas gabapentin, lamotrigine, and topiramate were not. Haloperidol had the highest number of significant differences and was significantly more effective than lithium (SMD -0·19 [95% CI -0·36 to -0·01]), quetiapine (-0·19 [-0·37 to 0·01]), aripiprazole (-0·19 [-0·36 to -0·02]), carbamazepine (-0·20 [-0·36 to -0·01]), asenapine (-0·26 [-0·52 to 0·01]), valproate (-0·36 [-0·56 to -0·15]), ziprasidone -0·36 [-0·56 to -0·15]), lamotrigine (-0·48 [-0·77 to -0·19]), topiramate (-0·63 [-0·84 to -0·43]), and gabapentin (-0·88 [-1·40 to -0·36]). Risperidone and olanzapine had a very similar profile of comparative efficacy, being more effective than valproate, ziprasidone, lamotrigine, topiramate, and gabapentin. Olanzapine, risperidone, and quetiapine led to significantly fewer discontinuations than did lithium, lamotrigine, placebo, topiramate, and gabapentin.
  
  
  CONCLUSIONS
  Overall, antipsychotic drugs were significantly more effective than mood stabilisers. Risperidone, olanzapine, and haloperidol should be considered as among the best of the available options for the treatment of manic episodes. These results should be considered in the development of clinical practice guidelines.
  
  
  BACKGROUND
  None.
authors.affiliation: Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, University of Verona, Italy. andrea.cipriani@univr.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Cipriani
authors.forename: Corrado
authors.initials: C
authors.lastname: Barbui
authors.forename: Georgia
authors.initials: G
authors.lastname: Salanti
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rendell
authors.forename: Rachel
authors.initials: R
authors.lastname: Brown
authors.forename: Sarah
authors.initials: S
authors.lastname: Stockton
authors.forename: Marianna
authors.initials: M
authors.lastname: Purgato
authors.forename: Loukia M
authors.initials: LM
authors.lastname: Spineli
authors.forename: Guy M
authors.initials: GM
authors.lastname: Goodwin
authors.forename: John R
authors.initials: JR
authors.lastname: Geddes
mesh_terms: D018692:Antimanic Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D006801:Humans; D010352:Patient Dropouts; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
chemical_list: D018692:Antimanic Agents; D014150:Antipsychotic Agents