TY - JOUR
T1 - How informative are open-label studies for youth with bipolar disorder? A meta-analysis comparing open-label versus randomized, placebo-controlled clinical trials
AU - Biederman, Joseph
AU - Petty, Carter R.
AU - Woodworth, K. Yvonne
AU - Lomedico, Alexandra
AU - O'Connor, Katherine B.
AU - Wozniak, Janet
AU - Faraone, Stephen V.
PY - 2012/3
Y1 - 2012/3
N2 - 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. Data Sources: 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. Study Selection: 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. Data Extraction: 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.
AB - 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. Data Sources: 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. Study Selection: 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. Data Extraction: 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.
UR - http://www.scopus.com/inward/record.url?scp=84859120551&partnerID=8YFLogxK
U2 - 10.4088/JCP.10m06490
DO - 10.4088/JCP.10m06490
M3 - Review article
AN - SCOPUS:84859120551
SN - 0160-6689
VL - 73
SP - 358
EP - 365
JO - Journal of Clinical Psychiatry
JF - Journal of Clinical Psychiatry
IS - 3
ER -