Effect of a digital intervention on mental health symptoms in adults with chronic conditions: A three-arm randomized...

Anxiety, depression, and fatigue affect >50% of adults across a range of chronic medical conditions, leading to reductions in quality of life. Digital symptom management interventions may address this burden, but clinical trial evidence across diverse conditions is limited, and the added value of human support remains uncertain. This study aimed to determine whether a multicomponent digital intervention, delivered with or without human support, reduces anxiety and depression compared with usual care at 12 weeks in adults with chronic medical conditions, and whether human-supported delivery outperforms self-directed delivery.

A three-arm parallel-group open-label randomized controlled trial was conducted from February 2023 to December 2024, with online recruitment and delivery across 13 countries. 825 adults (≥18 years) with self-reported chronic medical conditions and internet access were allocated by computer-generated stratified block randomization (1:1:1) to: (i) waitlist control (n = 274); (ii) eMPower, a self-directed digital program integrating video-guided movement, breathwork, and meditation practices, a psychology-based coping skills curriculum, and disease education (n = 275); or (iii) eMPower + human support consisting of weekly telephone check-ins (≤15 min) from trained nonclinicians (n = 276). The primary outcome was change in Hospital Anxiety and Depression Scale (HADS) total score from baseline to 12 weeks in the eMPower + human support arm compared with the control arm, adjusted for baseline score, chronic condition type, age, and sex. Secondary outcomes included HADS anxiety and depression subscales, fatigue (Modified Fatigue Impact Scale [MFIS]), and health-related quality of life (Short Form-12 [SF-12] mental and physical component scores and EQ-5D-5L index score). Twelve-week assessments were completed by 695 participants (84.2%). Primary outcome data were available for 222 participants in the eMPower + human support arm, 214 in the self-directed eMPower arm, and 259 in the control arm. Analyses followed the intention-to-treat principle. In the prespecified primary comparison, eMPower + human support improved HADS total score by 2.9 points (95% CI [2.0, 3.8]; p < 0.001). In prespecified exploratory analyses, the self-directed eMPower arm also significantly improved HADS total score, compared with control (mean difference 2.6 points; 95% CI [1.8, 3.5]; p < 0.001). No significant differences were observed between intervention arms for any outcome (all p > 0.05). Both intervention arms were associated with improvements across prespecified secondary outcomes compared with control. No intervention-related adverse events were reported in any arm. Key limitations include the use of a waitlist control design, which does not control for nonspecific intervention effects; reliance on self-reported diagnoses for most participants; the 12-week follow-up period; and a predominantly female and highly educated sample, which may limit generalizability. Additional registered process-oriented secondary outcomes and exploratory outcomes will be reported in companion publications.

A multicomponent digital intervention with human support significantly reduced anxiety and depression symptoms compared with usual care in adults with chronic medical conditions. Comparable effects between self-directed and human-supported delivery in exploratory analyses highlight potential for scalable, low-resource implementation. Longer-term follow-up and cost-effectiveness analyses are warranted. Trial registration: ClinicalTrials.gov: NCT05786482.