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Cited by 119Attention Deficit Hyperactivity DisorderPharmaceutical studies and practicesPharmacovigilance and Adverse Drug Reactions

Cardiac Safety of Central Nervous System Stimulants in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder

Winterstein, Almut G., Gerhard, Tobias, Shuster, Jonathan, Johnson, Michael, Zito, Julie M., Saidi, Arwa·2007·Pediatrics
DOI 10.1542/peds.2007-0675
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Abstract

OBJECTIVES. Case reports have raised concerns about the risk of cardiac events associated with central nervous system stimulants for the treatment of attention-deficit/hyperactivity disorder. PATIENTS AND METHODS. This was a retrospective cohort study that used 10 years (July 1994 to June 2004) of Florida Medicaid claims data cross-linked to Vital Statistics Death Registry data. The cohort was composed of all youth 3 to 20 years old who were newly diagnosed with attention-deficit/hyperactivity disorder. Each month of follow-up was classified according to stimulant claims (methylphenidate, amphetamines, and pemoline) as current use (active stimulant claim), former use (time after periods of current use), or nonuse (time preceding the first stimulant claim, including follow-up of youth who were never exposed to stimulants). The study's end points were (1) cardiac death, (2) first hospital admission for cardiac causes or (3) first emergency department visit for cardiac causes. Risks were compared with time-dependent Cox regression analysis adjusting for various cardiac risk factors. RESULTS. During 124932 person-years of observation (n = 55383), 73 youth died, 5 because of cardiac causes. No cardiac death occurred during 42612 person-years of stimulant use. Hospital admissions for cardiac cause occurred for 27 children (8 during stimulant use, 11 during 35671 person-years of former use, and 8 during 46649 person-years of nonuse); and 1091 children visited the emergency department for cardiac causes (8.7 per 1000 person-years). Current stimulant use was associated with a 20% increase in the hazard for emergency department visits when compared with nonuse. No increased risk was found for periods of former use when compared with nonuse. CONCLUSIONS. Incidence rates of cardiac events requiring hospitalization were small and similar to national background rates. Stimulants were associated with an increase in cardiac emergency department visits. More evidence is needed that addresses the long-term risk/benefit of the various treatment options and the effect of other cardiac risk factors and comedications.

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Authors
Winterstein, A. G., Gerhard, T., Shuster, J., Johnson, M., Zito, J. M., & Saidi, A.
Affiliations
  • Department of Healthcare Administration, College of Pharmacy
  • Department of Epidemiology, Biostatistics, and Health Policy, General Clinical Research Center
  • Gainesville Mental Health Partners, Gainesville, Florida
  • University of Maryland, Baltimore (US)
  • University of Florida (US)
ORCID
Venue
Pediatrics
Publisher
American Academy of Pediatrics (AAP)
Published
2007-12-01
Volume
120
Issue
6
Pages
e1494-e1501
ISSN
  • 0031-4005 (ISSN-L)
  • 1098-4275
DOI
10.1542/peds.2007-0675
OpenAlex
W2136389780
Cited by
119
References
32
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 11 · 2014: 7 · 2013: 4 · 2012: 21
FWCI
5.23
Type
journal article
Language
en
Open access
closed
Locations
  • PEDIATRICS (publishedVersion)
  • PubMed (publishedVersion)
Funders
Agency for Healthcare Research and Quality (U18HS016097)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
Keywords
attention deficit hyperactivity disorder, psychostimulants, cardiac safety, methylphenidate, amphetamine, pemoline, cardiovascular mortality, emergency department visits, children and adolescents, stimulant use
MeSH terms
Adolescent, Adult, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, Female, Heart Diseases, Humans, Male, Retrospective Studies, Risk Factors, Cohort Studies

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