Cost-effectiveness of a neurocognitive training video-game intervention for major depressive disorder: a health-economic analysis of a randomized clinical trial

Background: Major depressive disorder (MDD) produces substantial healthcare and productivity costs. Neurocognitive dysfunction in MDD is a primary mediator of functional impairment, disability, and lost productivity, driving workplace presenteeism, stalling psychosocial recovery, and persisting in remitted patients. It further inflates healthcare costs by suppressing treatment efficacy and promoting relapse, while current MDD treatments yield only small-to-modest improvements in neurocognitive functioning. Meliora is a video game therapeutic addressing this unmet need by delivering personalized closed-loop executive-functions training (EFT) as an adjunct to treatment as usual (TAU). Objective: This study estimated the 52-week cost-effectiveness of Meliora compared with TAU alone using data from a randomized controlled trial. Methods: We conducted a post hoc trial-based modeled economic evaluation using data from the Meliora randomized controlled trial (NCT05426265). The primary analysis included 343 participants in a modified intention-to-treat cohort (Meliora, n=180; TAU, n=163). Health utilities were estimated by mapping Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scores to EuroQol 5-Dimension 5-Level utilities. Direct healthcare costs were estimated from depression severity, and productivity costs were estimated from Sheehan Disability Scale (SDS) absenteeism and presenteeism items. Trial-derived outcomes were integrated and extrapolated over a 52-week horizon. Uncertainty was evaluated using multiple imputation and stratified bootstrap resampling. Results: Compared with TAU alone, Meliora was associated with lower productivity costs (–\\$5,640; 5th–95th percentile interval –\\$9,178 to –\\$2,049), lower direct healthcare costs (–\\$907; –\\$1,274 to –\\$536), lower total costs (–\\$6,248; –\\$9,814 to –\\$2,614), and higher QALYs (0.0329; 0.0221 to 0.0434). Meliora was economically dominant in the base-case model, with a net monetary benefit of \\$9,538 at a willingness-to-pay threshold of \\$100,000/QALY. Meliora also reduced absenteeism by 0.82 days/week and presenteeism by 1.17 days/week relative to TAU. Conclusions: Adjunctive Meliora was associated with higher QALYs, lower modeled healthcare and productivity costs, and improved work functioning over 52 weeks. This analysis extends health-economic evaluations in MDD to a neurocognition-targeting digital intervention and provides a basis for prospective payer and real-world economic evaluation.