Wearable-derived cardiovascular and autonomic changes associated with ADHD stimulant medication: A remote monitoring study of adults with ADHD (Preprint)

BACKGROUND Adults with ADHD commonly receive treatment with stimulant medications. While clinical trials have documented cardiovascular associations of these medications, real-world continuous monitoring data capturing medication-related physiological patterns in naturalistic settings remain limited. Understanding such patterns through remote monitoring technologies could provide valuable insights for treatment optimization and safety monitoring. OBJECTIVE This study aimed to examine differences in autonomic and cardiovascular function between off-medication and on-medication phases in adults with ADHD using continuous wearable monitoring, while adjusting for lifestyle exposure (alcohol consumption, smoking) and time-of-day patterns. METHODS We conducted a within-individual observational cohort study with 12-month remote monitoring via wearable technology and mobile-health platform. The multi-center study was conducted at King's College London, United Kingdom, and Vall d'Hebron Research Institute, Spain. Participants were adults aged 18-60 with DSM-5 confirmed ADHD, recruited from adult ADHD clinic waiting lists before treatment initiation. Data were available from 199 participants who had reached the stable medication phase, of whom 104 met eligibility criteria with valid baseline (off-medication) and stable on-medication data (≥7 days of adequate wearable data per phase). The primary analysis examined changes in daytime (07:00-22:00) physiological measures between off-medication baseline and stable on-medication phases (28-day windows). The wearable device provided minute-level processed biomarkers including pulse rate, pulse rate variability, respiratory rate, electrodermal activity and skin temperature. Participant data were collected via the RADAR-base platform. Generalized linear mixed-effects models assessed medication associations, adjusting for age, site, alcohol use frequency and smoking status. RESULTS Analysis of 4,104 participant-days showed stimulant medication was associated with modest cardiovascular changes during daytime hours: mean daytime pulse increased 2.46 bpm (95% CI, 1.99-2.93; P<.001), respiratory rate 0.39 breaths/minute (95% CI, 0.21-0.56; P<.001), and maximum pulse rate variability 7.41 ms (95% CI, 3.15-11.65; P=.01). Electrodermal activity and skin temperature showed no consistent medication-related differences. Frequent alcohol consumption (≥4 times/week) was associated with higher pulse rate (+2.78 bpm; 95% CI, 0.80-4.77; P=.024), lower pulse rate variability (-11.88 ms; 95% CI, -19.86 to -3.90; P=.017), and elevated electrodermal activity (+0.90 µS; 95% CI, 0.25-1.56; P=.027). Current smoking was associated with higher pulse rate (+2.67 bpm; 95% CI, 0.73-4.60; P=.027) and respiratory rate (+1.66 breaths/minute; 95% CI, 0.83-2.49; P<.001). CONCLUSIONS Real-world continuous monitoring demonstrates that stimulant medications for adult ADHD are associated with time-specific, modest cardiovascular changes. Frequent alcohol consumption and current smoking showed associations with cardiovascular parameters, highlighting the importance of comprehensive assessment in ADHD treatment. These findings support the value of digital health technologies and continuous physiological monitoring for understanding medication associations in naturalistic settings, with potential to inform personalized treatment approaches and safety monitoring protocols. INTERNATIONAL REGISTERED REPORT RR2-https://doi.org/10.1186/s12888-022-04429-6