Cognitive Behavioral Therapy vs. Antidepressants for Adolescent Major Depressive Disorder: A Network Meta-Analysis

Abstract

Introduction: Major depressive disorder (MDD) affects approximately 13% of adolescents, yet first-line treatment selection remains debated. Cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) are both recommended, but comparative efficacy and acceptability are uncertain. This network meta-analysis (NMA) aims to rank treatments for acute adolescent MDD.

Methods: We searched PubMed, PsycINFO, and Cochrane Central for randomized controlled trials (RCTs) comparing CBT, SSRIs (fluoxetine, escitalopram, sertraline), pill placebo, or treatment as usual in adolescents (12–18 years) with MDD. Primary outcomes: depression severity change (Children's Depression Rating Scale-Revised, CDRS-R) and all-cause discontinuation (acceptability). NMA used frequentist graph-theoretical methods. Risk of bias assessed with Cochrane RoB2.

Results: Twenty-two RCTs (n=3,847 adolescents) were included. Fluoxetine (standardized mean difference [SMD] –0.68, 95% CI –0.89 to –0.47) and combined CBT+fluoxetine (SMD –0.82, –1.04 to –0.60) were most efficacious versus placebo. CBT alone was superior to placebo (SMD –0.35, –0.52 to –0.18) but inferior to fluoxetine (p=0.02). Acceptability: CBT had lowest discontinuation (12%), followed by fluoxetine (19%), placebo (22%), sertraline (28%). No treatment differed significantly from placebo on suicidality risk. Heterogeneity was moderate (I²=38%).

Discussion: Fluoxetine monotherapy and combined treatment outperform CBT alone for symptom reduction, but CBT has superior acceptability. The absence of head-to-head comparisons between SSRIs limits ranking precision. Most trials excluded adolescents with active suicidality, limiting generalizability.

Conclusions: For moderate-to-severe adolescent MDD, fluoxetine (with or without CBT) is most efficacious. CBT alone is appropriate for mild depression or when families decline medication. Shared decision-making should weigh efficacy against side effect concerns.