Comparative efficacy and tolerability of new-generation antidepressants for major depressive disorder in children and adolescents: protocol of an individual patient data meta-analysis.

Introduction Although previous conventional meta-analyses and network meta-analyses have provided some important findings about pharmacological treatments for children and adolescents with depressive disorders in the past decades, several questions still remain unsolved by the aggregate data from those meta-analyses. Individual participant data meta-analysis (IPD-MA) enables exploration of the impacts of individual characteristics on treatment effects, allowing matching of treatments to specific subgroups of patients. We will perform an IPD-MA to assess the efficacy and tolerability of new-generation antidepressants for major depressive disorder in children and adolescents. Methods and analysis We will systematically search for all double-blind randomised controlled trials (RCTs) that have compared any new-generation antidepressant with placebo for the acute treatment of major depressive disorder in children and adolescents, in the following databases: PubMed, EMBASE, the Cochrane Library, PsycINFO, Web of Science, CINAHL, LILACS and ProQuest Dissertations. We will contact all corresponding authors of included RCTs and ask for their cooperation in this project by providing individual participant data from the original trials. The primary outcomes will include efficacy, measured as the mean change of depression symptoms by Children’s Depression Rating Scale Revised (CDRS-R), and tolerability, measured as the proportion of patients who withdrew from the trials early due to adverse effects. The secondary outcomes will include response rates, remission rates, deterioration rate, all-cause discontinuation, suicidal-related outcomes and global functioning outcome. Using the raw de-identified study data, we will use mixed-effects logistic and linear regression models to perform the IPD-MAs. The risk of bias of included studies will be assessed using the Cochrane risk of bias tool. We will also detect the publication bias and effects of non-participation of eligible studies. Dissemination Ethical approval is not required given that informed consent has already been obtained from the patients by the trial investigators before the included trials were conducted. This study may have considerable implications for practice and help improve patient care.