Placebo-controlled pharmacological trials in child and adolescents with bipolar disorder manic episode (BPD-ME): Systematic review, meta-analysis and a meta-regression on placebo response.

Randomized placebo controlled trials (RCT) are very important for testing efficacy and safety of a medical treatment. There is no too much RCT's in childhood bipolar disorder manic episode. In these trials, high placebo response poses a problem for the definition of real drug responses in practice. Therefore, analysis of predictors of drug and placebo response are important for conducting more reliable RCT's in the future. Comprehensive search conducted in PubMed, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL) and some other electronic databases. Studies including participants with Bipolar Disorder manic episode and associated symptoms (e.g ADHD, irritability) included. There was no restriction in terms of sex, ethnicity or initial severity. Participants over age 18 were excluded. Random effect size model was used for calculate effect sizes for placebo and drugs. A total of 1974 participants and 11 studies were included in the meta-analysis. Risperidone was highest effect size among drug arms. Number of the sites and number of the participants were associated with higher placebo response in meta-regression. We did not find any variable had an impact on drug response. There was no any publication bias in this meta-analysis. We found similar results as adult studies. Modifying number of the sites or ramdomized sample size may limit placebo response and could improve the efficacy of RCT's and enhance drugplacebo contrasts. [ABSTRACT FROM AUTHOR]