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Cited by 128Attention Deficit Hyperactivity DisorderPharmacovigilance and Adverse Drug ReactionsPharmaceutical studies and practices

Mortality Associated with Attention-Deficit Hyperactivity Disorder (ADHD) Drug Treatment: A Retrospective Cohort Study of Children, Adolescents and Young Adults Using the General Practice Research Database

McCarthy, Suzanne, Cranswick, Noel, Potts, Laura, Taylor, Eric, Wong, Ian C.K.·2009·Drug Safety
DOI 10.2165/11317630-000000000-00000
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Abstract

Background Following reports of sudden death in patients taking medication to treat attention-deficit hyperactivity disorder (ADHD), this study aimed to identify cases of death in patients prescribed stimulants and atomoxetine and to determine any association between these and sudden death.Method The UK General Practice Research Database (GPRD) was used to identify patients aged 2-21 years from 1 January 1993 to 30 June 2006 with a prescription for methylphenidate, dexamfetamine or atomoxetine. Patients were followed from the date of first prescription until whichever came first: date of death, transferred-out date, age >21 years or end of the study period.Results From a cohort of 18 637 patient-years, seven patients died. Cause of death was obtained for six of the patients. None were deemed to be cases of sudden death. Compared with a general population rate of sudden death in the literature, the worst-case scenario of one case of sudden death gave an incident rate ratio of 1.63 (95% CI 0.04, 9.71). Although it was not the primary outcome of the study, following reports of suicide in the cohort the standardized mortality ratio (SMR) of suicide was calculated. Due to differences in the definition of suicide used for children and adults, patients were categorized into two age groups: 11-14 years and 15-21 years. The SMR for suicide for patients aged 11-14 years was 161.91 (95% CI 19.61, 584.88). The SMR for suicide for patients aged 15-21 years was 1.84 (95% CI 0.05, 10.25).Conclusion This study demonstrated no increase in the risk of sudden death associated with stimulants or atomoxetine. However, an increased risk of suicide was seen. Although we cannot exclude that the medications may contribute to the increased risk of suicide, there are other factors such as depression and antisocial behaviour that frequently co-exist with ADHD, which can also predispose to teenage suicide. Clinicians should identify patients at increased risk of cardiovascular events and identify those patients at increased risk of suicide, particularly males with co-morbid conditions, and monitor them appropriately.

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  • Stimulant medications have not been shown to increase the risk of sudden death beyond that observed in children not receiving stimulants.

    “In fact, stimulant medications have not been shown to increase the risk of sudden death beyond that observed in children who are not receiving stimulants.114–118”

    From Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents (2019) · cites this paper as [115]

  • In another study, the incidence of sudden death in children prescribed ADHD drugs was not found to be statistically different to that in the general population, but the study was limited by its sample size.

    “In another study the incidence of sudden death in children prescribed ADHD drugs was not found to be statistically different to that in the general population; but this study was limited by its sample size [91].”

    From European guidelines on managing adverse effects of medication for ADHD (2011) · cites this paper as [91]

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Authors
McCarthy, S., Cranswick, N., Potts, L., Taylor, E., & Wong, I. C. K.
Affiliations
  • UCL School of Pharmacy (GB)
  • Royal Children's Hospital (AU)
  • King's College London (GB)
Corresponding author
Wong, Ian C.K.
ORCID
Venue
Drug Safety
Publisher
Springer Science and Business Media LLC
Published
2009-11
Volume
32
Issue
11
Pages
1089-1096
ISSN
0114-5916 (ISSN-L)
DOI
10.2165/11317630-000000000-00000
OpenAlex
W2111812421
Cited by
128
References
36
Citations by year
2026: 1 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 6 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 9 · 2016: 10 · 2015: 5 · 2014: 15 · 2013: 9 · 2012: 19
FWCI
8.84
Type
journal article
Language
en
Open access
closed
Locations
  • Drug Safety (publishedVersion)
  • PubMed (publishedVersion)
  • The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
Funders
American Heart Association
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
Keywords
attention deficit hyperactivity disorder, ADHD medication, sudden death, stimulants, methylphenidate, d-amphetamine, atomoxetine, suicide, standardized mortality ratio, children and adolescents, cardiovascular risk
MeSH terms
Atomoxetine Hydrochloride, Adolescent, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Cause of Death, Child, Child, Preschool, Death, Sudden, Dextroamphetamine, Female, United Kingdom, Humans, Male, Methylphenidate, Propylamines, Retrospective Studies, Risk Factors, Suicide, Cohort Studies, Databases, Factual, Adrenergic Uptake Inhibitors, Young Adult

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