Management of attention-deficit/hyperactivity disorder and co-occurring cardiovascular diseases

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that is usually identified during childhood, and more than half of affected individuals continue to experience symptoms into adulthood. ADHD medication can effectively reduce ADHD symptoms, but its benefits depend heavily on sustained treatment. Yet, patterns of medication discontinuation across age, sex, and country remain poorly understood. Although previous studies show that individuals with ADHD have higher likelihood of cardiovascular diseases and cardiometabolic risk factors, the associations of ADHD and ADHD medication with outcomes among individuals with cardiovascular disorders remain unclear. In Study I, we assessed the associations between ADHD and cardiometabolic risk factors, participation in non-pharmacological interventions, and adverse outcomes among individuals with myocardial infarction (MI). Clinical parameters and disease histories were largely similar across groups. Individuals with ADHD had higher rates of smoking and snus use, lower participation in follow-up evaluations, and lower risks of smoking cessation after MI. They also showed higher all-cause mortality after discharge, while recurrent cardiovascular events were similar between groups. In Study II, we described patterns of ADHD medication discontinuation in new users of ADHD medication across age groups, sex, and countries using a cross-country analysis. Discontinuation was least common in children and most frequent in young adults. One year after initiation, treatment continuation rates were observed in 65% of children, 47% of adolescents, 39% of young adults, and 48% of adults. The highest risk of discontinuation was observed during ages 18-19. When accounting for medication re-initiation, longer-term persistence increased; at five years, 50-60% of children and 30-40% of adolescents and adults remained covered by treatment in most countries. In Study III, we examined the associations of ADHD and ADHD medication use with adherence to antihypertensive medication. We found that individuals with ADHD showed higher rates of antihypertensive medication discontinuation over five years and higher odds of poor adherence after treatment initiation. Among those with ADHD, use of ADHD medication was linked to lower odds of poor adherence. In Study IV, we screened spontaneous reports from two major drug surveillance systems, EudraVigilance (December 2002-December 2024) and FAERS (January 2004-December 2024), to identify potential drug-drug interaction (DDI) signals. We identified 204 unique potential DDIs involving ADHD medications and cardiometabolic medications. The most frequently involved signals were combinations of methylphenidate with diabetes medications. Interactions with antithrombotic or lipid-modifying agents were not reported by any DDI checkers. Three signals, guanfacine with propranolol, guanfacine with metoprolol, and guanfacine with metformin, were consistently identified across both interaction checkers and product summary information. List of scientific papers I. Yao H, Brikell I, Larsson H, Li L, Du Rietz E, Hartman CA, Jernberg T, Andell P, Chang Z. Attention-deficit/hyperactivity disorder and cardiometabolic risk profile in patients with acute myocardial infarction: data from the SWEDEHEART registry. Eur J Prev Cardiol. 2025 Apr 11:zwaf151. https://doi.org/10.1093/eurjpc/zwaf151 II. Brikell I*, Yao H*, Li L*, Astrup A, Gao L, Gillies MB, Xie T, Zhang-James Y, Dalsgaard S, Engeland A, Faraone SV, Haavik J, Hartman C, Ip P, Jakobsdóttir Smári U, Larsson H, Man KK, de Oliveira Costa J, Pearson SA, Hostrup Nielsen NP, Snieder H, Wimberley T, Wong IC, Zhang L, Zoega H, Klungsøyr K, Chang Z. ADHD medication discontinuation and persistence across the lifespan: a retrospective observational study using population-based databases. Lancet Psychiatry. 2024 Jan;11(1):16-26. Epub 2023 Nov 27. https://doi.org/10.1016/s2215-0366(23)00332-2 III. Yao, H.*, Zhou, Y.*, Li, L.*, Gillies, M. B., Brikell, I., Gao, L., Wimberley, T., Xie, T., Zhang-James, Y., Astrup, A., Dalsgaard, S., Semark, B. D., Engeland, A., Faraone, S. V., Klungsøyr, K., Larsson, H., Man, K. K. C., Snieder, H., Wong, I. C. K., Yuen, A. S. C., Zoega, H., Hartman, C., & Chang, Z. ADHD and adherence to antihypertensive medication treatment: A multinational cohort study. BMC Medicine. Under review. [Submitted] IV. Yao, H., Dong, Z., Brikell, I., Du Rietz, E., Andell, P., Larsson, H., & Chang, Z. Drug-drug interactions between ADHD and cardiometabolic medications: A pharmacovigilance study. [Manuscript] * Equal contribution