Efficacy and safety of interactive digital therapeutics with cognitive behavioral therapy for depressive symptoms in patients with major depressive disorder: A multicenter, randomized, assessor-blinded trial versus an active mood diary control.

INTRODUCTION

Digital cognitive behavioral therapy (CBT) is effective for major depressive disorder, but many interventions use static, non-interactive content. Interactive digital therapeutics with CBT (iDT-CBT) provides adaptive, dialogue-based interventions.

METHODS

We conducted an 8-week randomized, assessor-blinded trial comparing iDT-CBT with an active mood diary control in 110 adults with major depressive disorder. The primary outcome was change in BDI-II score at Week 8. Secondary outcomes included PHQ-9, MADRS, and BAI. Analyses included all randomized participants, using analysis of covariance adjusted for baseline score and sex.

RESULTS

BDI-II improvement was greater with iDT-CBT than with the active mood diary (13.34 vs. 6.54 points; adjusted p = 0.0003). PHQ-9, MADRS, and BAI improvements also favored iDT-CBT. Week 8 remission proportions were higher with iDT-CBT for BDI-II (30.4% vs. 9.3%), PHQ-9 (62.5% vs. 44.4%), MADRS (23.2% vs. 5.6%), and BAI (50.0% vs. 20.4%). In logistic regression adjusted for baseline score and sex, the conditional odds of remission favored iDT-CBT for all four outcomes (p = 0.011, 0.039, 0.014, and 0.002, respectively), although the unadjusted risk-difference confidence interval for PHQ-9 included zero. However, the BDI-II effect was attenuated in the site-adjusted mixed model for repeated measures (MMRM), and BDI-II and PHQ-9 effects were not significant in MMRM, multiple-imputation, or observed-case analyses. MADRS and BAI remained significant. No adverse-event-related discontinuations or intervention-related serious adverse events occurred.

DISCUSSION: iDT-CBT showed promising short-term efficacy, although effects on self-reported depressive symptoms were sensitive to the analytical method. Longer-term studies are needed.

CLINICAL TRIAL REGISTRATION: Clinical Research Information Service identifier: KCT0010758 (https://cris.nih.go.kr/cris/search/detailSearch.do?seq=30575).