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, I 2 =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. Plain Language Summary: Why was this study needed? Depression is common in children and teenagers, affecting about 3-6% of young people. It can seriously impact their school, friendships, and family life, and increase the risk of suicide. Doctors sometimes prescribe escitalopram (an antidepressant medication) for teenagers with depression, but we need clearer evidence about how well it works and whether it is safe. What did we do? We searched research databases for all high-quality studies that tested escitalopram in young people with depression. We found three studies involving 664 children and teenagers and combined their results to understand the overall benefits and risks. What did we find? Escitalopram showed a small and statistically borderline benefit for teenagers (ages 12-17) with depression compared to a placebo (sugar pill). For every 11 teenagers treated with escitalopram, one additional person improved because of the medication. Side effects were similar to those of the placebo. However, all three studies were funded by the drug manufacturer, and many teenagers improved even with placebo pills, which means we should interpret these results carefully. What does this mean? Escitalopram may help some teenagers with depression, particularly when other treatments like another antidepressant called fluoxetine are not suitable. However, the benefits are modest. Young people taking escitalopram should also receive counseling or therapy and be closely monitored by their doctor for side effects and suicidal thoughts. Keywords: escitalopram, major depressive disorder, adolescents, meta-analysis, GRADE, systematic review