Enhancing Methylphenidate’s Neurocognitive Effects in Pediatric ADHD with Adaptive Digital Therapy: A Randomized Controlled Trial

Xiaolu Chen,1 Sihan Wang,2 Xiaowen Yang,1 Chunmei Yu,1 Fang Ni,1 Jie Yang,1 Yu Tian,1 Jiucai Ye,1 Hao Liu,1 Xiang Chen,3 Rong Luo1 1Department of Pediatrics, West China Second University Hospital; Key Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Neuro Weave, Co., Ltd., Shanghai, 200001, People’s Republic of China; 3Fangcun Quanxiang (Beijing) Technology Co., Ltd, Beijing, 100010, People’s Republic of ChinaCorrespondence: Rong Luo, Department of Pediatrics, West China Second University Hospital; Key Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, Sichuan University, No. 20, Section 3, Renmin South Road, Chengdu, 610041, People’s Republic of China, Tel +86-13882050273, Email [email protected]: Digital therapeutics have emerged as promising adjuncts to pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), yet evidence from rigorously designed trials remains limited. This study aimed to evaluate the additive neurocognitive benefits of an adaptive digital therapy (Focus Pro) when combined with methylphenidate (MPH) in children with ADHD.Methods: In the present single-center, double-blind, randomized controlled trial, 85 children (6– 12 years old) diagnosed with ADHD were assigned to receive MPH plus Focus Pro (n=44) or MPH alone (n=41) over an eight-week treatment period, with follow-up assessments at week 12. The digital therapy consisted of daily 25-minute sessions that targeted attention and executive functioning. The primary outcomes included objective neurocognitive measures assessed by the Test of Variables of Attention (TOVA), alongside secondary outcomes based on parent-reported scales (Swanson, Nolan, and Pelham Rating Scale, Fourth Edition [SNAP-IV], Weiss Functional Impairment Rating Scale, and Clinical Global Impressions-Severity). The analysis employed mixed repeated-measures ANOVA under an intention-to-treat framework.Results: Although both groups exhibited comparable improvements on subjective measures, the combination group demonstrated significantly greater gains in objective neurocognitive performance, particularly on TOVA attention comparison scores, at week eight (p=0.006, Cohen’s d=0.809). Furthermore, a significant group effect was observed (F=8.478, p=0.005), with improvements sustained through post-intervention follow-up. Early symptom reduction was noted in both groups (week four, p< 0.001), but merely the combined therapy group maintained enhanced objective performance, revealing a divergence between subjective and objective outcomes.Conclusion: The integration of adaptive digital therapy with MPH can significantly enhance neurocognitive outcomes in pediatric ADHD, particularly in sustained attention and inhibitory control. These findings highlight the clinical potential of personalized digital tools, and underscore the importance of incorporating objective assessments when evaluating digital interventions.Keywords: attention deficit hyperactivity disorder, digital therapeutics, methylphenidate, randomized controlled trial, neuropsychological tests, executive function