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

Xinyu Zhou, Andrea Cipriani, Toshi A. Furukawa, Pim Cuijpers, Yuqing Zhang, Sarah E. Hetrick, Juncai Pu, Shuai Yuan, Cinzia Del Giovane, Peng Xie*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article numbere018357
Pages (from-to)1-7
Number of pages7
JournalBMJ Open
Volume8
Issue number1
Early online date24 Jan 2018
DOIs
Publication statusPublished - Jan 2018

Funding

This protocol is registered in PROSPERO at the National Health Service Centre for Reviews and Dissemination at the University of York (registration number: CRD42016051657). No ethics review is required for this IPD-MA, since informed consent has already been obtained from the patients by the trial investigators before the trial was conducted. We will publish the results in a peer-reviewed journal. 1Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 2Department of Psychiatry, University of Oxford, Oxford, UK 3Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK 4Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine and School of Public Health, Kyoto, Japan 5Department of Clinical Psychology, Neuro and Developmental Psychology, Amsterdam Public Health Research Institute, VU University Amsterdam, Amsterdam, The Netherlands 6Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 7Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China 8Orygen, The National Centre of Excellence in Youth Mental Health and the Centre of Youth Mental Health, University of Melbourne, Melbourne, Australia 9Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland Acknowledgements AC is supported by the National Institute for Health Research Oxford Cognitive Health Clinical Research Facility. Funding This work is supported by the National Basic Research Program of China (973 Program) (Grant No. 2009CB918300). expert witness for a patent issue about quetiapine extended release. TAF has received lecture fees from Eli Lilly, Janssen, Meiji, MSD, Otsuka, Pfizer and Tanabe-Mitsubishi and consultancy fees from Sekisui Chemicals and Takeda Science Foundation. He has received royalties from Igaku-Shoin and Nihon Bunka Kagaku-sha publishers. He has received research support from Mochida and Tanabe-Mitsubishi. SEH is an editor of the Cochrane Common Mental Disorders Group, an author of the Cochrane systematic review of newer generation antidepressants for depression in children and adolescents and an author (senior) on the Cochrane review of psychological, pharmacological and their combination for child/adolescent depression. XZ, PC, YZ, JP, SY, CDG and PX declare no competing interests.

FundersFunder number
Centre of Youth Mental Health
Collaborative Innovation Center for Brain Science
National Centre of Excellence in Youth Mental Health
National Institute for Health Research Oxford Cognitive Health Clinical Research Facility
Universität Bern
University of Melbourne
Chongqing Medical University
National Key Research and Development Program of China2009CB918300

    Keywords

    • adolescent
    • antidepressant
    • child
    • individual patient data meta-analysis
    • systematic review

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