title: How informative are open-label studies for youth with bipolar disorder? A meta-analysis comparing open-label versus randomized, placebo-controlled clinical trials.
abstract: OBJECTIVE
  To examine the informativeness of open-label trials toward predicting results in subsequent randomized, placebo-controlled clinical trials of psychopharmacologic treatments for pediatric bipolar disorder.
  
  
  METHODS
  We searched journal articles through PubMed at the National Library of Medicine using bipolar disorder, mania, pharmacotherapy, treatment and clinical trial as keywords. This search was supplemented with scientific presentations at national and international scientific meetings and submitted manuscripts from our group.
  
  
  METHODS
  Selection criteria included (1) enrollment of children diagnosed with DSM-IV bipolar disorder; (2) prospective assessment of at least 3 weeks; (3) monotherapy of a pharmacologic treatment for bipolar disorder; (4) use of a randomized placebo-controlled design or an open-label design for the same therapeutic compound; and (5) repeated use of the Young Mania Rating Scale (YMRS) as an outcome.
  
  
  METHODS
  The following information and data were extracted from 14 studies: study design, name of medication, class of medication, dose of medication, sample size, age, sex, trial length, and YMRS mean and standard deviation baseline and follow-up scores.
  
  
  RESULTS
  For both study designs, the pooled effect size was statistically significant (open-label studies, z = 8.88, P < .001; randomized placebo-controlled studies, z = 13.75, P < .001), indicating a reduction in the YMRS from baseline to endpoint in both study designs. In a meta-analysis regression, study design was not a significant predictor of mean change in the YMRS.
  
  
  CONCLUSIONS
  We found similarities in the treatment effects between open-label and randomized placebo-controlled studies in youth with bipolar disorder indicating that open-label studies are useful predictors of the potential safety and efficacy of a given compound in the treatment of pediatric bipolar disorder.
authors.affiliation: Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, MA 02114, USA. jbiederman@partners.org
authors.forename: Joseph
authors.initials: J
authors.lastname: Biederman
authors.forename: Carter R
authors.initials: CR
authors.lastname: Petty
authors.forename: K Yvonne
authors.initials: KY
authors.lastname: Woodworth
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lomedico
authors.forename: Katherine B
authors.initials: KB
authors.lastname: O'Connor
authors.forename: Janet
authors.initials: J
authors.lastname: Wozniak
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
mesh_terms: D001714:Bipolar Disorder / Q000188:drug therapy*; D002648:Child; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D006801:Humans; D011619:Psychotropic Drugs / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012107:Research Design / Q000706:statistics & numerical data
chemical_list: D011619:Psychotropic Drugs