{"title":"Methylphenidate and Long-Term Risk of Cardiovascular Diseases: A Nationwide Cohort Study.","authors":"Christelle Berthod, Thomas Loppinet, Marietou Ndiaye, Inesse Boussaha, Matthias Jacquet-Lagreze, Behrouz Kassaï-Koupai","doi":"10.1002/pds.70493","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Cardiovascular safety of methylphenidate remains a matter of debate.</p><p><strong>Methods: </strong>To evaluate the long-term cardiovascular risk associated with methylphenidate use, a cohort study was conducted using the French National Health Data System. New users were defined by a first methylphenidate dispensation (index date) between January 1, 2014, and December 31, 2023. Each new user was matched with three nonusers by sex and by month and year of birth. Individuals with prior cardiovascular disease or relevant cardiovascular comorbidities were excluded. The primary outcome was cardiovascular disease, defined by International Classification of Diseases codes or antihypertensive drug use. Cox proportional hazards models estimated adjusted hazard ratios (HRs), accounting for demographic and clinical covariates. Negative control outcomes were used to assess residual confounding, allowing the derivation of calibrated HRs and confidence intervals.</p><p><strong>Results: </strong>A total of 212 216 new users and 636 648 matching nonusers were included. Mean age was 13.7 years and 72% were males. Over a follow-up of ~4 years, 3858 cardiovascular diseases occurred (0.45%): 1960 in new users (9.2 per 1000) and 1898 in nonusers (3 per 1000). The adjusted HR was 2.37 (95% CI [2.21; 2.54]), with a calibrated HR of 1.85 (95% CI [1.55; 2.21]).</p><p><strong>Conclusions: </strong>The results suggest that methylphenidate use may be associated with an increased risk of cardiovascular diseases. Although the calibrated estimates indicate attenuation due to residual confounding, the association remained statistically significant. This supports recommendations for cardiovascular monitoring during treatment.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 10","pages":"e70493"},"PeriodicalIF":2.6000,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655642/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacoepidemiology and Drug Safety","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/pds.70493","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: Cardiovascular safety of methylphenidate remains a matter of debate.
Methods: To evaluate the long-term cardiovascular risk associated with methylphenidate use, a cohort study was conducted using the French National Health Data System. New users were defined by a first methylphenidate dispensation (index date) between January 1, 2014, and December 31, 2023. Each new user was matched with three nonusers by sex and by month and year of birth. Individuals with prior cardiovascular disease or relevant cardiovascular comorbidities were excluded. The primary outcome was cardiovascular disease, defined by International Classification of Diseases codes or antihypertensive drug use. Cox proportional hazards models estimated adjusted hazard ratios (HRs), accounting for demographic and clinical covariates. Negative control outcomes were used to assess residual confounding, allowing the derivation of calibrated HRs and confidence intervals.
Results: A total of 212 216 new users and 636 648 matching nonusers were included. Mean age was 13.7 years and 72% were males. Over a follow-up of ~4 years, 3858 cardiovascular diseases occurred (0.45%): 1960 in new users (9.2 per 1000) and 1898 in nonusers (3 per 1000). The adjusted HR was 2.37 (95% CI [2.21; 2.54]), with a calibrated HR of 1.85 (95% CI [1.55; 2.21]).
Conclusions: The results suggest that methylphenidate use may be associated with an increased risk of cardiovascular diseases. Although the calibrated estimates indicate attenuation due to residual confounding, the association remained statistically significant. This supports recommendations for cardiovascular monitoring during treatment.
期刊介绍：
The aim of Pharmacoepidemiology and Drug Safety is to provide an international forum for the communication and evaluation of data, methods and opinion in the discipline of pharmacoepidemiology. The Journal publishes peer-reviewed reports of original research, invited reviews and a variety of guest editorials and commentaries embracing scientific, medical, statistical, legal and economic aspects of pharmacoepidemiology and post-marketing surveillance of drug safety. Appropriate material in these categories may also be considered for publication as a Brief Report.
Particular areas of interest include:
design, analysis, results, and interpretation of studies looking at the benefit or safety of specific pharmaceuticals, biologics, or medical devices, including studies in pharmacovigilance, postmarketing surveillance, pharmacoeconomics, patient safety, molecular pharmacoepidemiology, or any other study within the broad field of pharmacoepidemiology;
comparative effectiveness research relating to pharmaceuticals, biologics, and medical devices. Comparative effectiveness research is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition, as these methods are truly used in the real world;
methodologic contributions of relevance to pharmacoepidemiology, whether original contributions, reviews of existing methods, or tutorials for how to apply the methods of pharmacoepidemiology;
assessments of harm versus benefit in drug therapy;
patterns of drug utilization;
relationships between pharmacoepidemiology and the formulation and interpretation of regulatory guidelines;
evaluations of risk management plans and programmes relating to pharmaceuticals, biologics and medical devices.
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