Background: Depression and anxiety are major public health concerns among adolescents. Computerized cognitive behavioral therapy (cCBT) has emerged as a potential intervention, but its efficacy in adolescents remains unestablished. Objective: This review aimed to systematically review and meta-analyze findings on the efficacy of cCBT for the treatment of adolescent depression and anxiety. Methods: Embase, PsycINFO, and Ovid MEDLINE were systematically searched for randomized controlled trials in English, which investigated the efficacy of cCBT for reducing self-reported depression or anxiety in adolescents aged 11 to 19 years. Titles, abstracts, and full texts were screened for eligibility by 2 independent researchers (TB and LC). A random-effects meta-analysis was conducted to pool the effects of cCBT on depression and anxiety symptom scores compared with the control groups. Study quality was assessed using the Cochrane Collaboration Risk of Bias tool. Results: A total of 16 randomized controlled trials were eligible for inclusion in this review, of which 13 (81%) were included in the meta-analysis. The quality of the studies was mixed, with 5 (31%) studies rated as good overall, 2 (13%) rated as fair, and 9 (56%) rated as poor. Small but statistically significant effects of cCBT were detected, with cCBT conditions showing lower symptom scores at follow-up compared with control conditions for both anxiety (standardized mean difference −0.21, 95% CI −0.33 to −0.09; I2=36.2%) and depression (standardized mean difference −0.23, 95% CI −0.39 to −0.07; I2=59.5%). Secondary analyses suggested that cCBT may be comparable with alternative, active interventions (such as face-to-face therapy or treatment as usual). Conclusions: This meta-analysis reinforces the efficacy of cCBT for the treatment of anxiety and depression and is the first to examine this exclusively in adolescents. Future research could aim to identify the active components of these interventions toward optimizing their development and increasing the feasibility and acceptability of cCBT in this age group. Trial Registration: PROSPERO CRD42019141941; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=141941
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