Comparative efficacy, acceptability, and safety of medicinal, cognitive-behavioral therapy, and placebo treatments for acute major depressive disorder in children and adolescents: a multiple-treatments meta-analysis

New generation antidepressant therapies, including serotonin–norepinephrine reuptake inhibitor (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) were introduced in the late 1980s; however, few comprehensive studies compared the benefits and risks of various contemporary treatments for major depressive disorder (MDD) in pediatric patients. Multiple-treatments meta-analysis (MTM) was conducted to assess efficacy, acceptability, and safety of contemporary interventions in children and adolescents with MDD. Cochrane Library, AMED, CINAHL, EMBASE, LiLACS, MEDLINE, PSYCINFO, PSYNDEX, and Journal of Medicine and Pharmacy databases were searched for randomized controlled trials (RCTs) comparing medicinal interventions (citalopram, escitalopram, fluoxetine, mirtazapine, paroxetine, sertraline, venlafaxine), cognitive behavioral therapy (CBT), combined fluoxetine with CBT, and placebo treatment for acute MDD from January 1988 to March 2013. Treatment success, dropout rate, and suicidal ideation/attempt outcomes were measured. Bayesian methods were used to conduct a MTM including age and funding subgroups. A total of 21 RCTs (4969 participants) were identified. Combined fluoxetine/CBT exhibited the highest efficacy, with fluoxetine alone superior to CBT, paroxetine, sertraline, citalopram, escitalopram, and placebo treatment. Sertraline, paroxetine, escitalopram, and venlafaxine showed superior acceptability to fluoxetine and combined fluoxetine/CBT. Combined fluoxetine/CBT combination was less safe, though CBT was safer than fluoxetine alone. Combined fluoxetine/CBT, fluoxetine, and mirtazapine exhibited the highest efficacy; sertraline, escitalopram, venlafaxine, and paroxetine were the best tolerated; and mirtazapine and venlafaxine were the safest. Sertraline and mirtazapine exhibited optimally balanced efficacy, acceptability, and safety for first-line acute treatment of child and adolescent MDD.