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Cited by 297Attention Deficit Hyperactivity DisorderPharmacology and Obesity TreatmentPharmacovigilance and Adverse Drug Reactions

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ADHD Medications and Risk of Serious Cardiovascular Events in Young and Middle-aged Adults

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Habel, Laurel A., Cooper, William O., Sox, Colin M., Chan, K. Arnold, Fireman, Bruce H., Arbogast, Patrick G., Cheetham, T. Craig, Quinn, Virginia P., Dublin, Sascha, Boudreau, Denise M., Andrade, Susan E., Pawloski, Pamala A., Raebel, Marsha A., Smith, David H., Achacoso, Ninah, Uratsu, Connie, Go, Alan S., Sidney, Steve, Nguyen-Huynh, Mai N., Ray, Wayne A., Selby, Joe V.·2011·JAMA
DOI 10.1001/jama.2011.1830PMC PMC3350308
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Abstract

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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  1. [36]Cohen AL Jhung MA Budnitz DS Stimulant medications and attention deficithyperactivity disorder N Engl J Med 2006 354 21 2294 2295 16723627

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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
DOI
10.1001/jama.2011.1830
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
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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