Comparative efficacy and tolerability of first-generation and newer-generation antidepressant medications for depressive disorders in children and adolescents: study protocol for a systematic review and network meta-analysis.
BACKGROUND
Depressive disorders are among the most common psychiatric disorders in children and adolescents, and have adverse effects on their psychosocial functioning. Questions concerning the efficacy and safety of antidepressant medications in the treatment of depression in children and adolescents, led us to integrate the direct and indirect evidence using network meta-analysis to create hierarchies of these drugs.


METHODS
Seven databases with PubMed, EMBASE, the Cochrane Library, Web of Science, CINAHL, LiLACS and PsycINFO will be searched from 1966 to December 2013 (updated to May, 2015). There are no restrictions on language or type of publication. Randomised clinical trials assessing first-generation and newer-generation antidepressant medications against active comparator or placebo as acute treatment for depressive disorders in children and adolescents (under 18 years of age) will be included. The primary outcome for efficacy will be mean improvement in depressive symptoms, as measured by the mean change score of a depression rating scale from baseline to post-treatment. The tolerability of treatment will be defined as side effect discontinuation, as defined by the proportion of patients who discontinued treatment due to adverse events during the trial. We will also assess the secondary outcome for efficacy (response rate), acceptability (all-cause discontinuation) and suicide-related outcomes. We will perform the Bayesian network meta-analyses for all relative outcome measures. Subgroup analyses and sensitivity analyses will be conducted to assess the robustness of the findings.


RESULTS
The network meta-analysis will provide useful information on antidepressant treatment for child and adolescent depression. The results will be disseminated through peer-reviewed publication or conference presentations.


BACKGROUND
PROSPERO CRD42015016023.
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xinyu
X
Zhou
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Bin
B
Qin
Research Department of Clinical, Educational and Health Psychology, University College London, London, UK.
Craig
C
Whittington
Department of Child and Adolescent Psychiatry, AP-HP, Hôpital Pitié-Salpétrière, Institut des Systèmes Intelligents et de Robotiques (ISIR), Centre National pour la Recherche Scientifique, Université Pierre et Marie Curie, Paris, France.
David
D
Cohen
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Yiyun
Y
Liu
Department of Diagnostic, Clinical, and Public Health Medicine, University of Modena and Reggio, Emilia, Modena, Italy.
Cinzia
C
Del Giovane
Department of Psychology, Appalachian State University, Boone, North Carolina, USA.
Kurt D
KD
Michael
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Yuqing
Y
Zhang
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Peng
P
Xie
D000293:Adolescent; D000928:Antidepressive Agents / Q000627:therapeutic use*; D002648:Child; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy*; D004361:Drug Tolerance; D006801:Humans; D011569:Psychiatric Status Rating Scales; D000078202:Systematic Reviews as Topic; D016896:Treatment Outcome; D015201:Meta-Analysis as Topic
D000928:Antidepressive Agents
CLINICAL PHARMACOLOGY