Pharmacological treatment of children and adolescents with depression.

INTRODUCTION: Despite an increasing number of studies, there is debate whether antidepressants have a favorable benefit/risk balance in depressed youth. Areas covered: A systematic search identified 23 systematic reviews and meta-analyses published between 2010-2016. More than 30 controlled clinical trials were conducted in adolescents, but only a few in pre-pubertal patients. About one-third of the trials were severely statistically underpowered. Most studies failed to detect differences from placebo, but a few found fluoxetine effective. Although no suicide occurred in these studies, antidepressants increased suicidality risk (including suicidal ideation and behavior) versus placebo (OR = 2.39). Only two placebo-controlled trials with acceptable statistical power were publicly funded: both showed efficacy of fluoxetine, and one found a higher incidence of suicidality (OR = 3.7, 95% C.I. 1.00-13.7). Expert opinion: In youth, antidepressants have, on average, a small therapeutic effect. The high placebo response is exacerbated by the large number of sites in many industry-funded studies. There is evidence that fluoxetine leads to greater and faster improvement than placebo or psychotherapy in adolescents. Considering both the high response to non-specific interventions and safety concerns, antidepressants should be used cautiously in youth, and limited to patients with moderate-to-severe depression for whom psychosocial interventions are either ineffective or not feasible.