Antidepressant treatment of depression in children and adolescents: a systematic review and dose-response meta-analysis

Pediatric major depressive disorder (MDD) often leads to recurrent depression in adulthood. The efficacy, safety and dose dependency of pharmacological effect is unclear. We conducted a systematic review and dose-response meta-analysis comprising of 22 double-blind randomized controlled trials, the majority of which had short trial durations ranging from 6 to 12 weeks. Studies were identified from PubMed, Ovid Embase, Ovid Medline, Ovid PsycInfo, Wanfang, ClinicalTrial.gov and CENTRAL until July 31, 2023. Doses of all antidepressants were converted to fluoxetine equivalents. Outcomes including treatment response, remission, suicidality, tolerability and acceptability were assessed. Sensitivity analysis, funnel plot and the trim-and fill method are used to assess and adjust for publication bias. Findings revealed that antidepressants were marginally more effective than placebos in terms of treatment response, but significantly increased the risk of adverse effects. No significant differences were observed in remission, suicidality, or overall dropout rates. Dose-response analysis indicated a relatively flat increase in response probability with higher fluoxetine equivalent doses, but also a sharp increase risk of discontinuation due to side effects. This study suggests that antidepressants for pediatric MDD may be less effective in adults, emphasizing the need to balance treatment benefits with potential adverse effects when considering interventions for this population.