Efficacy of Electronic Cognitive Behavioral Therapy Alone and Combined With Pharmacotherapy for Depression and Anxiety in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Electronic cognitive behavioral therapy (e-CBT) is a scalable intervention for anxiety and depressive disorders.While its efficacy against inactive controls is well documented, its comparative effectiveness against first-line pharmacotherapy remains critically underexplored.We conducted a systematic review and meta-analysis (International Prospective Register of Systematic Reviews (PROSPERO): CRD420261413686) of randomized controlled trials (RCTs) comparing e-CBT with waitlist, active psychotherapy, usual care, or medication in adults with anxiety and depression.Effect sizes were pooled using random-effects models with restricted maximum likelihood (REML) and Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustments.Outcomes were assessed using Hedges' g and risk ratios (RR), and evidence certainty was evaluated via the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.Twenty-two RCTs were included in the analysis.Compared to waitlist/attention controls (k, number of independent contrasts = 11), e-CBT demonstrated a large, statistically significant reduction in depression severity (Hedges' g, standardized mean difference = 0.91; 95% CI: 0.63 to 1.18).However, re-expression onto the Patient Health Questionnaire-9 (PHQ-9) scale yielded an absolute reduction (3.86 points) that fell below the pre-specified minimally important difference (MID) of 5 points.No clear difference was found between e-CBT and active face-to-face or bibliotherapy CBT (k = 3; g = 0.08; 95% CI: -0.59 to 0.75); the wide interval means equivalence could not be established.Adding e-CBT to usual care gave an imprecise, non-significant estimate (k = 3; g = 0.32; 95% CI: -1.41 to 2.05; p = 0.511) that neither confirms nor excludes a benefit.The network geometry revealed zero head-to-head RCTs comparing e-CBT monotherapy directly with antidepressant medication.Nineteen of the 22 trials (86%) were at high overall risk of bias, and funnel-plot asymmetry (Egger's test; p = 0.0056) suggested small-study effects, possibly including publication bias; most GRADE certainty ratings were very low.e-CBT is a scalable option that showed no clear difference from faceto-face CBT in a small number of trials, but its efficacy against inactive controls may be overestimated because of small-study effects and methodological limitations.A critical evidence gap exists regarding its comparative efficacy against pharmacotherapy, necessitating rigorous blinded head-to-head non-inferiority trials.