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ADHD Medications and Risk of Serious Cardiovascular Events in Young and Middle-aged Adults
Open accessAbstract
CONTEXT: More than 1.5 million US adults use stimulants and other medications labeled for treatment of attention-deficit/hyperactivity disorder (ADHD). These agents can increase heart rate and blood pressure, raising concerns about their cardiovascular safety. OBJECTIVE: To examine whether current use of medications prescribed primarily to treat ADHD is associated with increased risk of serious cardiovascular events in young and middle-aged adults. DESIGN, SETTING, AND PARTICIPANTS: Retrospective, population-based cohort study using electronic health care records from 4 study sites (OptumInsight Epidemiology, Tennessee Medicaid, Kaiser Permanente California, and the HMO Research Network), starting in 1986 at 1 site and ending in 2005 at all sites, with additional covariate assessment using 2007 survey data. Participants were adults aged 25 through 64 years with dispensed prescriptions for methylphenidate, amphetamine, or atomoxetine at baseline. Each medication user (n = 150,359) was matched to 2 nonusers on study site, birth year, sex, and calendar year (443,198 total users and nonusers). MAIN OUTCOME MEASURES: Serious cardiovascular events, including myocardial infarction (MI), sudden cardiac death (SCD), or stroke, with comparison between current or new users and remote users to account for potential healthy-user bias. RESULTS: During 806,182 person-years of follow-up (median, 1.3 years per person), 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use (median, 0.33 years), with a crude incidence per 1000 person-years of 1.34 (95% CI, 1.14-1.57) for MI, 0.30 (95% CI, 0.20-0.42) for SCD, and 0.56 (95% CI, 0.43-0.72) for stroke. The multivariable-adjusted rate ratio (RR) of serious cardiovascular events for current use vs nonuse of ADHD medications was 0.83 (95% CI, 0.72-0.96). Among new users of ADHD medications, the adjusted RR was 0.77 (95% CI, 0.63-0.94). The adjusted RR for current use vs remote use was 1.03 (95% CI, 0.86-1.24); for new use vs remote use, the adjusted RR was 1.02 (95% CI, 0.82-1.28); the upper limit of 1.28 corresponds to an additional 0.19 events per 1000 person-years at ages 25-44 years and 0.77 events per 1000 person-years at ages 45-64 years. CONCLUSIONS: Among young and middle-aged adults, current or new use of ADHD medications, compared with nonuse or remote use, was not associated with an increased risk of serious cardiovascular events. Apparent protective associations likely represent healthy-user bias.
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“However, these findings should be considered in light of data from 2 large studies that reported no significant increase in risk for cardiovascular events in current users of ADHD medications compared with nonusers (262, 263).”
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Evaluating medication effects outside of clinical trials: new-user designs
Ray, W. A. (2003) · American Journal of Epidemiology · doi:10.1093/aje/kwg231 · Cited by 1,646
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Methylphenidate: Its Pharmacology and Uses
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Glynn, R. J., Schneeweiss, S., & Stürmer, T. (2006) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/j.1742-7843.2006.pto_293.x · Cited by 541
Guidelines for the Pharmacologic Treatment of Neurobehavioral Sequelae of Traumatic Brain Injury
Warden, D. L., Gordon, B., McAllister, T. W., Silver, J., Barth, J. T., Bruns, J. J., Drake, A., Gentry, T., Jagoda, A. S., Katz, D. I., et al. (2006) · Journal of Neurotrauma · doi:10.1089/neu.2006.23.1468 · Cited by 438
ADHD Drugs and Serious Cardiovascular Events in Children and Young Adults
Cooper, W. O., Habel, L. A., Sox, C. M., Chan, K. A., Arbogast, P. G., Cheetham, T. C., Murray, K. T., Quinn, V. P., Stein, C. M., Callahan, S. T., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1110212 · Cited by 411
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Kooij, J. J. S., Bijlenga, D., Salerno, L., Jaeschke, R., Bitter, I., Balázs, J., Thome, J., Dom, G., Kasper, S., Nunes Filipe, C., et al. (2019) · European Psychiatry · doi:10.1016/j.eurpsy.2018.11.001 · Cited by 686
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Metadata
- Authors
- Habel, L. A., Cooper, W. O., Sox, C. M., Chan, K. A., Fireman, B. H., Arbogast, P. G., Cheetham, T. C., Quinn, V. P., Dublin, S., Boudreau, D. M., Andrade, S. E., Pawloski, P. A., Raebel, M. A., Smith, D. H., Achacoso, N., Uratsu, C., Go, A. S., Sidney, S., Nguyen-Huynh, M. N., Ray, W. A., & Selby, J. V.
- Affiliations
- Kaiser Permanente (US)
- Boston University (US)
- Regions Hospital (US)
- University of California, San Francisco (US)
- Corresponding author
- Habel, Laurel A.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2011-12-28
- Volume
- 306
- Issue
- 24
- Pages
- 2673
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC3350308
- OpenAlex
- W2122411644
- Cited by
- 297
- References
- 40
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 14 · 2023: 17 · 2022: 16 · 2021: 18 · 2020: 19 · 2019: 16 · 2018: 15 · 2017: 17 · 2016: 15 · 2015: 23 · 2014: 24 · 2013: 29 · 2012: 49
- FWCI
- 22.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- U.S. Public Health Service (223-2005-10100C, 223-2005-10012C, HHSA290-2005-0033, 223-2005-20006C, HHSA290-2005-0042, 223-2005-10012)
- National Institute on Aging (K23AG028954)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Keywords
- attention deficit hyperactivity disorder, ADHD medication, cardiovascular events, myocardial infarction, sudden cardiac death, stroke, methylphenidate, amphetamine, atomoxetine, stimulants, cardiovascular safety, young and middle-aged adults, healthy user bias, heart rate, blood pressure, medication dispensing, Medicaid, Kaiser Permanente
- MeSH terms
- Adult, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Cardiovascular Diseases, Female, Humans, Male, Middle Aged, Myocardial Infarction, Retrospective Studies, Risk, Cohort Studies, Death, Sudden, Cardiac, Stroke, Electronic Health Records
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