Efficacy and Safety of Escitalopram for Major Depressive Disorder in Children and Adolescents: A Systematic Review and Meta-Analysis with Age-Specific Findings.

OBJECTIVE

To evaluate the efficacy, acceptability, and safety of escitalopram for pediatric major depressive disorder (MDD) through a systematic review and meta-analysis.

METHODS

We searched Cochrane CENTRAL, CINAHL, PubMed, ClinicalTrials.gov, and Scopus (January 2001- October 2025) for randomized controlled trials comparing escitalopram with placebo in children and adolescents (ages 6-17) with MDD. The primary outcome was the change in the Children's Depression Rating Scale-Revised (CDRS-R). Secondary outcomes included Clinical Global Impressions scores, response rates, and discontinuation rates. Two reviewers independently assessed the risk of bias using Cochrane tools. Random-effects meta-analysis was performed; certainty was evaluated using GRADE.

RESULTS

Three RCTs (664 participants) were identified: two acute trials (Wagner 2006, n=268; Emslie 2009, n=316) and one continuation trial (Saito 2023, n=80). Meta-analysis of acute trials included 572 participants (completion rates 81-82%). Escitalopram demonstrated small and borderline statistically significant improvements versus placebo: CDRS-R (weighted mean difference [WMD]=-2.46, 95% CI: -4.83 to -0.09, I2=0%; low certainty); CGI-Severity (WMD=-0.35, 95% CI: -0.57 to -0.12); CGAS (WMD=2.56, 95% CI: 0.37 to 4.75); non-response rates (relative risk=0.84, 95% CI: 0.72 to 0.98; number needed to treat=11). Overall discontinuation (RR=1.37, 95% CI: 0.97 to 1.93) and discontinuation due to adverse events (RR=1.88, 95% CI: 0.44 to 8.03) did not differ significantly (low to very low certainty). Continuation treatment did not significantly prevent relapse (p=0.051).

LIMITATIONS: Universal industry sponsorship, high placebo response (52-53% by CGI-I ≤2 in original publications), mixed trial results, limited evidence for children ages 6-11, and lack of independent replication.

CONCLUSION

Escitalopram demonstrates small and borderline statistically significant efficacy for adolescent MDD (aged 12-17 years). Short-term tolerability is acceptable; however, no definitive conclusion on long-term safety can be drawn, and evidence is insufficient to support use in children aged 6-11 years. It may be considered when fluoxetine is unsuitable, combined with psychosocial interventions and close monitoring. Further independent studies are needed.

REGISTRATION: PROSPERO CRD42019141268.