Comparative efficacy of antidepressant medication for adolescent depression: a network meta-analysis and systematic review

Abstract

Purpose: To evaluate the success rate of different antidepressants in addressing depression among teenagers, while also offering substantiation for the efficacy and tolerability of these treatments in this demographic.

Methods: Participants were adolescents aged 6-18 years diagnosed with major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) , Chinese Classification of Mental Disorders (CCMD-3) or equivalent diagnostic criteria (e.g., Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition(DSM-4) , International Classification of Diseases, Tenth/Eleventh Revision(ICD10/11) ) . We conducted a systematic search of major databases (PubMed, Cochrane Library, and Web of Science) for randomized controlled trials (RCTs) published up to October 2024. The search strategy included the following keywords: "Depression," "Depressive Disorders," "Emotional Disorders," "adolescent," "young adult, " "minors," "fluoxetine," "sertraline," "paroxetine," "agomelatine," "vilazodone," "escitalopram," and "venlafaxine."

Results: Our network meta-analysis(NMA) included 15 RCTs involving 12,258 participants. The included studies were assessed using the Cochrane risk of bias tool. The majority of studies had low risk of bias in terms of randomization and allocation concealment, while some studies had unclear implementation of blinding or outcome assessment. The NMA results showed that in several major indicators Children's Depression Rating Scale-Revised (CDRS-R) , Clinical Global Impression-Severity (CGI-S) and Children's Global Assessment Scale (CGAS) , agomelatine (MD = -0.34, 95 % CI = -0.59, -0.09), fluoxetine (MD = -0.31, 95 % CI = -0.42, -0.21), sertraline (MD = -0.27, 95 % CI = -0.47, -0.06) were significantly better than placebo in improving CDRS-R. In terms of CGI-S, sertraline (MD = -4.39, 95 % CI = -4.77, -4.01) was more effective. In contrast to the placebo, escitalopram (MD = 2.08,95 % CI = 1.33,2.84) was more effective in CGAS; Surface Under the Cumulative Ranking Curve (SUCRA) values showed that escitalopram (96.1 % and 86.4 %) could achieve better therapeutic effects in CGAS and Clinical Global Impressions-Improvement (CGI-I) , and agomelatine (86.4 %) was more effective in improving CDRS-R scores than other drugs. Sertraline (100 %) appears to be the most likely strategy to decelerate the increase in CGI-I scores. The effectiveness of paroxetine (99.9%) in the management of Montgomery-Asberg Depression Rating Scale (MADRS) was significantly better than that of several other drugs.

Conclusion: For symptom severity scales, agomelatine (CDRS-R: SUCRA 86.4%) and paroxetine (MADRS: SUCRA 99.9%) demonstrated the greatest efficacy. For functional improvement, escitalopram ranked highest on CGAS (SUCRA 96.1%). Sertraline showed superiority in clinician-rated severity (CGI-S: SUCRA 100%) and improvement (CGI-I: SUCRA 80.2%). Clinical decisions should prioritize escitalopram for functional recovery and sertraline for severe cases requiring rapid symptom reduction.

Trial registration: PROSPERO registration number: CRD42024609880.

Keywords: Adolescents; Depression; Drug efficacy; Drug therapy; Network meta-analysis.

Fig. 1

Flow chart of literature screening for NMA

Fig. 2

Risk of bias graph and risk of bias summary

Fig. 3

Evidence relationship comparing the efficacy of fluoxetine, vilazodone, paroxetine, escitalopram, sertraline, venlafaxine, agomelatine, and placebo in the treatment of adolescent depression. A Children’s Depression Rating Scale-Revised (CDRS-R). B Clinical overall impression - Severity (CGI-S). C Global Assessment Scale for Children (CGAS). D Clinical Overall Impression Improvement Scale (CGI-I). E: Montgomery-Asberg Depression Rating Scale (MADRS)

Fig. 4

The SUCRA values of each treatment: A Children’s Depression Rating Scale-Revised (CDRS-R). B Clinical overall impression - Severity (CGI-S). C Global Assessment Scale for Children (CGAS). D Clinical Overall Impression Improvement Scale (CGI-I). E Montgomery-Asberg Depression Rating Scale (MADRS)

Fig. 5

Funnel plot of efficacy and safety results. A Children’s Depression Rating Scale-Revised (CDRS-R). B Clinical overall impression - Severity (CGI-S). C Global Assessment Scale for Children (CGAS). D Clinical Overall Impression Improvement Scale (CGI-I). E Montgomery-Asberg Depression Rating Scale (MADRS)