Summary Background Major depressive disorder is one of the most common mental disorders in children and adolescents. However, whether to use pharmacological interventions in this population and which ...drug should be preferred are still matters of controversy. Consequently, we aimed to compare and rank antidepressants and placebo for major depressive disorder in young people. Methods We did a network meta-analysis to identify both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LiLACS, regulatory agencies' websites, and international registers for published and unpublished, double-blind randomised controlled trials up to May 31, 2015, for the acute treatment of major depressive disorder in children and adolescents. We included trials of amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine. Trials recruiting participants with treatment-resistant depression, treatment duration of less than 4 weeks, or an overall sample size of less than ten patients were excluded. We extracted the relevant information from the published reports with a predefined data extraction sheet, and assessed the risk of bias with the Cochrane risk of bias tool. The primary outcomes were efficacy (change in depressive symptoms) and tolerability (discontinuations due to adverse events). We did pair-wise meta-analyses using the random-effects model and then did a random-effects network meta-analysis within a Bayesian framework. We assessed the quality of evidence contributing to each network estimate using the GRADE framework. This study is registered with PROSPERO, number CRD42015016023. Findings We deemed 34 trials eligible, including 5260 participants and 14 antidepressant treatments. The quality of evidence was rated as very low in most comparisons. For efficacy, only fluoxetine was statistically significantly more effective than placebo (standardised mean difference −0·51, 95% credible interval CrI −0·99 to −0·03). In terms of tolerability, fluoxetine was also better than duloxetine (odds ratio OR 0·31, 95% CrI 0·13 to 0·95) and imipramine (0·23, 0·04 to 0·78). Patients given imipramine, venlafaxine, and duloxetine had more discontinuations due to adverse events than did those given placebo (5·49, 1·96 to 20·86; 3·19, 1·01 to 18·70; and 2·80, 1·20 to 9·42, respectively). In terms of heterogeneity, the global I2 values were 33·21% for efficacy and 0% for tolerability. Interpretation When considering the risk–benefit profile of antidepressants in the acute treatment of major depressive disorder, these drugs do not seem to offer a clear advantage for children and adolescents. Fluoxetine is probably the best option to consider when a pharmacological treatment is indicated. Funding National Basic Research Program of China (973 Program).
Abstract Background Few meta-analyses have focused on the effect of cognitive behavioral therapy (CBT) for depression in children. Study Selection Randomized controlled trials comparing CBT with ...control conditions for depression in children (≤13 years old) were included. Data Sources Seven electronic databases (PubMed, Embase, CENTRAL, Web of Science, PsycINFO, CINAHL, and LiLACS) were searched from inception to September 2015. Data Extraction and Synthesis The primary efficacy was defined as mean change scores in depressive symptoms, and the second efficacy (remission) was a score below the threshold for a diagnosis of depression, both after treatment and at the end of follow-up. We also measured acceptability by the proportion of participants who discontinued treatment up to posttreatment. Results Nine studies with 306 participants were selected for this analysis. At posttreatment, CBT was significantly more effective than control conditions in terms of primary efficacy (standardized mean difference, −0.41; 95% confidence interval CI, −0.64 to −0.18) and secondary efficacy (odds ratio OR, 2.16; 95% CI, 1.24 to 3.78). At follow-up, the results were consistent with those of efficacy outcomes at posttreatment, with a standardized mean difference of −0.34 and an OR of 2.04. CBT had no statistical more all-cause discontinuations than the control group (OR, 0.69; 95% CI, 0.26 to 1.82). However, subgroup analyses found that CBT was only significantly more effective than nontreatment, while it was not better than wait list or psychological placebo. Conclusions CBT seems to be more beneficial in the treatment of depression in children than nontreatment; however, this finding is limited by the small size of the trials and low literature quality.
PDF
