title: Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics.
abstract: BACKGROUND
  Optimal treatments for bipolar depression, and the relative value of specific drugs for that purpose, remain uncertain, including agents other than antidepressants.
  
  
  METHODS
  We searched for reports of placebo-controlled, monotherapy trials of mood-stabilizing anticonvulsants, second-generation antipsychotics, or lithium for acute major depressive episodes in patients diagnosed with type I or II bipolar disorder and applied random-effects meta-analysis to evaluate their efficacy, comparing outcomes based on standardized mean drug-placebo differences (SMD) in improvement, relative response rates (RR), and number-needed-to-treat (NNT).
  
  
  RESULTS
  We identified 24 trials of 10 treatments (lasting 7.5 weeks, with ≥ 50 collaborating sites/trial) that met eligibility criteria: lamotrigine (5 trials), quetiapine (5), valproate (4), 2 each for aripiprazole, olanzapine, ziprasidone, and 1 each for carbamazepine, lithium, lurasidone, and olanzapine-fluoxetine. Overall, pooled drug-over-placebo responder-rate superiority (RR) was moderate (29% [CI: 19-40%]), and NNT was 8.2 (CI: 6.4-11). By SMD, apparent efficacy ranked: olanzapine + fluoxetine ≥ valproate > quetiapine > lurasidone > olanzapine, aripiprazole, and carbamazepine; ziprasidone was ineffective, and lithium remains inadequately studied. Notably, drugs were superior to placebo in only 11/24 trials (5/5 with quetiapine, 2/4 with valproate), and only lamotrigine, quetiapine and valproate had > 2 trials. Treatment-associated mania-like reactions were uncommon (drugs: 3.7%; placebo: 4.7%).
  
  
  CONCLUSIONS
  Controlled trials of non-antidepressant treatments for bipolar depression remain scarce, but findings with olanzapine-fluoxetine, lurasidone, quetiapine, and perhaps carbamazepine and valproate were encouraging; lithium requires adequate testing.
authors.affiliation: International Consortium for Bipolar Disorder Research, McLean Hospital, Belmont, Massachusetts, USA.
authors.forename: V
authors.initials: V
authors.lastname: Selle
authors.affiliation: International Consortium for Bipolar Disorder Research, McLean Hospital, Belmont, Massachusetts, USA.
authors.forename: S
authors.initials: S
authors.lastname: Schalkwijk
authors.affiliation: International Consortium for Bipolar Disorder Research, McLean Hospital, Belmont, Massachusetts, USA.
authors.forename: G H
authors.initials: GH
authors.lastname: Vázquez
authors.affiliation: International Consortium for Bipolar Disorder Research, McLean Hospital, Belmont, Massachusetts, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Baldessarini
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D016208:Databases, Factual / Q000706:statistics & numerical data; D006801:Humans; D018021:Lithium Chloride / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D014150:Antipsychotic Agents; D018021:Lithium Chloride