Randomised Controlled Trials Of SNRIs In Treating Major Depressive Disorder In Children And Adolescents:a Meta-Analysis Of Efficacy And Acceptability

Background:New generation antidepressant therapies, including serotonin-norepinephrine reuptake inhibitor (SNRIs) were introduced in the late 1980s; however, few comprehensive studies have compared the benefits and risks of various contemporary treatments for major depressive disorder (MDD) in young patients.Methods:A comprehensive literature search of the PubMed, Cochrane, Embase, Web of Science, and PsycINFO databases was conducted from 1970 to October 2014. Only clinical trials that randomly assigned one SNRI or placebo to patients aged 7 to 18 years who met the diagnostic criteria for major depressive disorder (MDD) were included. Treatment success, dropout rate, and suicidal ideation/attempt outcomes were measured. Primary efficacy was determined by pooling the risk ratios (RRs) of response and remission. Acceptability was determined by pooling the RRs of dropouts for all reasons and for adverse effects as well as suicide-risk outcomes.Results:Six trials with a total of 973 patients were considered to be eligible for inclusion. SNRIs were not significantly more effective than placebo in primary efficacy (response rate:RR=1.09,95% CI:0.97-1.22, z=1.49, p=0.14; remission rate:RR= 1.45,95% CI:1.01-2.09, z=2.02, p=0.04). On an individual SNRI basis, with regard to response, no significant difference was found in either comparison. The OR of duloxetine to placebo was 1.13 (95% CI:0.99 to 1.28), and the OR of venlafaxine to placebo was 1.03 (95% CI:0.83 to 1.27). Significantly more patients taking SNRIs discontinued treatment due to adverse effects than those taking placebo (8.8% vs 3.0%; RR=2.92,95% CI,1.67 to 5.09, p=0.0002).Conclusions:SNRI therapy does not display a superior efficacy and is not better tolerated compared to placebo in these young patients.