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Cited by 68Attention Deficit Hyperactivity DisorderEpilepsy research and treatmentPharmacovigilance and Adverse Drug Reactions

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Association between methylphenidate treatment and risk of seizure: a population-based, self-controlled case-series study.

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Man, Kenneth K C, Lau, Wallis C Y, Coghill, David, Besag, Frank M C, Cross, J Helen, Ip, Patrick, Wong, Ian C K·2020·The Lancet Child & Adolescent Health
DOI 10.1016/s2352-4642(20)30100-0
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Abstract

Background Individuals with attention-deficit hyperactivity disorder (ADHD) are at increased risk of seizures. Stimulant medications such as methylphenidate are the most commonly prescribed treatment for ADHD, but the association between their therapeutic use and the risk of seizures is unclear. We aimed to investigate the association between methylphenidate treatment and the risk of seizure. Methods For this population-based observational study, we used the electronic medical record database of the Hong Kong Clinical Data Analysis And Reporting System to identify individuals aged 6-25 years who received at least one methylphenidate prescription during the study period. Individuals with records of seizure or epilepsy before the study period were excluded. Individuals treated with methylphenidate who had seizures during the study period were included in the subsequent analyses, and a self-controlled case-series design was used to control for time-invariant individual characteristics. We did additional analyses using skin infection as a negative control outcome. We compared relative incidence of seizure during periods when individuals were exposed to methylphenidate with that during non-exposed periods. Findings Of 29 604 individuals prescribed methylphenidate between Jan 1, 2001, and Dec 31, 2017, 269 (199 males and 70 females) had incident seizures. The mean age at baseline was 6·66 years (SD 2·01) and the median age at the incident seizure was 9·69 years (IQR 7·62-12·99). The overall incidence of seizure during methylphenidate treatment was 4·4 per 10 000 patient-years. We detected an increased risk of seizure during the first 30 days of methylphenidate treatment compared with that during non-exposed periods, with an incidence rate ratio of 4·01 (95% CI 2·09-7·68). No increase in risk was identified during the following 31-180 days of treatment (1·13, 0·56-2·25) or during subsequent treatment (1·38, 0·92-2·07). We did not identify an increased risk in any risk window for the negative control outcome analysis. No individuals died because of a seizure during the study period. Interpretation The incidence of seizures was higher in the period immediately after the start of methylphenidate treatment than in the non-exposed period. No increased risk was observed during continuation of methylphenidate treatment. The association between methylphenidate treatment and seizures immediately after initiation of medication can be seen as a potential safety signal. Monitoring of neurological outcomes in individuals with ADHD is recommended when they first start methylphenidate treatment. Funding Hong Kong Research Grants Council.

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Metadata

Authors
Man, K. K. C., Lau, W. C. Y., Coghill, D., Besag, F. M. C., Cross, J. H., Ip, P., & Wong, I. C. K.
Affiliations
  • UCL School of Pharmacy (GB)
  • The University of Melbourne (AU)
  • King's College London (GB)
  • Great Ormond Street Hospital (GB)
  • University of Hong Kong (HK)
Corresponding author
Ip, Patrick
ORCID
Venue
The Lancet Child & Adolescent Health
Publisher
Elsevier BV
Published
2020-06
Volume
4
Issue
6
Pages
435-443
ISSN
2352-4642 (ISSN-L)
DOI
10.1016/s2352-4642(20)30100-0
OpenAlex
W3027866619
Cited by
68
References
10
Citations by year
2026: 6 · 2025: 8 · 2024: 8 · 2023: 21 · 2022: 9 · 2021: 11 · 2020: 5
FWCI
7.66
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet Child & Adolescent Health (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Discovery Research Portal (University of Dundee) (submittedVersion)
Funders
Hong Kong Research Grants Council General Research Fund (17108717)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
Keywords
methylphenidate, seizures, attention deficit hyperactivity disorder, stimulant medication, adverse drug reactions, seizure risk, pediatric and adolescent patients, drug safety, self-controlled case series, incidence rate ratio
MeSH terms
Adolescent, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Child, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Follow-Up Studies, Hong Kong, Humans, Male, Methylphenidate, Monitoring, Physiologic, Retrospective Studies, Seizures, Cohort Studies, Incidence, Poisson Distribution, Databases, Factual, Age Distribution, Sex Distribution, Risk Assessment, Young Adult

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