title: Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis.
abstract: Randomized, controlled trials have demonstrated efficacy for second-generation antipsychotics in the treatment of acute mania in bipolar disorder. Despite depression being considered the hallmark of bipolar disorder, there are no published systematic reviews or meta-analyses to evaluate the efficacy of modern atypical antipsychotics in bipolar depression. We systematically reviewed published or registered randomized, double-blind, placebo-controlled trials (RCTs) of modern antipsychotics in adult bipolar I and/or II depressive patients (DSM-IV criteria). Efficacy outcomes were assessed based on changes in the Montgomery-Asberg Depression Rating Scale (MADRS) during an 8-wk period. Data were combined through meta-analysis using risk ratio as an effect size with a 95% confidence interval (95% CI) and with a level of statistical significance of 5% (p<0.05). We identified five RCTs; four involved antipsychotic monotherapy and one addressed both monotherapy and combination with an antidepressant. The two quetiapine trials analysed the safety and efficacy of two doses: 300 and 600 mg/d. The only olanzapine trial assessed olanzapine monotherapy within a range of 5-20 mg/d and olanzapine-fluoxetine combination within a range of 5-20 mg/d and 6-12 mg/d, respectively. The two aripiprazole placebo-controlled trials assessed doses of 5-30 mg/d. Quetiapine and olanzapine trials (3/5, 60%) demonstrated superiority over placebo (p<0.001). Only 2/5 (40%) (both aripiprazole trials) failed in the primary efficacy measure after the first 6 wk. Some modern antipsychotics (quetiapine and olanzapine) have demonstrated efficacy in bipolar depressive patients from week 1 onwards. Rapid onset of action seems to be a common feature of atypical antipsychotics in bipolar depression.
authors.affiliation: Bipolar Disorders Program, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Cruz
authors.forename: Jose
authors.initials: J
authors.lastname: Sanchez-Moreno
authors.forename: Ferran
authors.initials: F
authors.lastname: Torres
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Goikolea
authors.forename: Marc
authors.initials: M
authors.lastname: Valentí
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy*; D003987:Dibenzothiazepines / Q000627:therapeutic use; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005473:Fluoxetine / Q000627:therapeutic use; D006801:Humans; D000077152:Olanzapine; D010879:Piperazines / Q000627:therapeutic use; D010919:Placebos; D000069348:Quetiapine Fumarate; D015363:Quinolones / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D004338:Drug Combinations; D010879:Piperazines; D010919:Placebos; D015363:Quinolones; C492572:olanzapine-fluoxetine combination; D005473:Fluoxetine; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D000068180:Aripiprazole; D000077152:Olanzapine