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. 2023 Feb 1;80(2):183-187.
doi: 10.1001/jamaneurol.2022.4699.

Association Between Antiepileptic Drugs and Incident Parkinson Disease

Daniel Belete  1 , Benjamin M Jacobs  1   2 , Cristina Simonet  1 , Jonathan P Bestwick  1 , Sheena Waters  1 , Charles R Marshall  1   2 , Ruth Dobson  1   2 , Alastair J Noyce  1   2
Affiliations

Association Between Antiepileptic Drugs and Incident Parkinson Disease

Daniel Belete et al. JAMA Neurol. .

Erratum in

  • Error in Title.
    [No authors listed] [No authors listed] JAMA Neurol. 2023 Feb 1;80(2):216. doi: 10.1001/jamaneurol.2022.5503. JAMA Neurol. 2023. PMID: 36779984 Free PMC article. No abstract available.

Abstract

Importance: Recent studies have highlighted an association between epilepsy and Parkinson disease (PD). The role of antiepileptic drugs (AEDs) has not been explored.

Objective: To investigate the association between AEDs and incident PD.

Design, setting, and participants: This nested case-control study started collecting data from the UK Biobank (UKB) in 2006, and data were extracted on June 30, 2021. Individuals with linked primary care prescription data were included. Cases were defined as individuals with a Hospital Episode Statistics (HES)-coded diagnosis of PD. Controls were matched 6:1 for age, sex, race and ethnicity, and socioeconomic status. Prescription records were searched for AEDs prescribed prior to diagnosis of PD. The UKB is a longitudinal cohort study with more than 500 000 participants; 45% of individuals in the UKB have linked primary care prescription data. Participants living in the UK aged between 40 and 69 years were recruited to the UKB between 2006 and 2010. All participants with UKB-linked primary care prescription data (n = 222 106) were eligible for enrollment in the study. Individuals with only a self-reported PD diagnosis or missing data for the matching variables were excluded. In total, 1477 individuals were excluded; 49 were excluded due to having only self-reported PD, and 1428 were excluded due to missing data.

Exposures: Exposure to AEDs (carbamazepine, lamotrigine, levetiracetam, and sodium valproate) was defined using routinely collected prescription data derived from primary care.

Main outcomes and measures: Odds ratios and 95% CIs were calculated using adjusted logistic regression models for individuals prescribed AEDs before the first date of HES-coded diagnosis of PD.

Results: In this case-control study, there were 1433 individuals with an HES-coded PD diagnosis (cases) and 8598 controls in the analysis. Of the 1433 individuals, 873 (60.9%) were male, 1397 (97.5%) had their race and ethnicity recorded as White, and their median age was 71 years (IQR, 65-75 years). An association was found between AED prescriptions and incident PD (odds ratio, 1.80; 95% CI, 1.35-2.40). There was a trend for a greater number of prescription issues and multiple AEDs being associated with a greater risk of PD.

Conclusions and relevance: This study, the first to systematically look at PD risk in individuals prescribed the most common AEDs, to our knowledge, found evidence of an association between AEDs and incident PD. With the recent literature demonstrating an association between epilepsy and PD, this study provides further insights.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Waters reported receiving grants from UK Research and Innovation. The Innovate UK grant was received by his supervisor and funded his Research Associate position during the conduct of the study. Dr Marshall reported receiving grants from Tom and Sheila Springer Charity and grants from Barts Charity during the conduct of the study; grants from the National Institute for Health and Care Research (NIHR), grants from Innovate UK, grants from the Michael J. Fox Foundation, and grants from Alzheimer’s Research UK outside the submitted work. Dr Dobson reported grants from the Multiple Sclerosis Society of Great Britain and Northern Ireland, grants from the National Multiple Sclerosis Society, grants from the BMA Foundation, grants from the Horne Family Charitable Trust, grants from the Medical Research Council, grants from the NIHR, grants from Biogen, grants from Merck, grants from Celgene (now Bristol Myers Squibb), and personal fees from Novartis, Janssen Biogen, Merck, Teva, and Roche. Dr Noyce reported receiving grants from Barts Charity, Parkinson’s UK, Cure Parkinson’s, the Michael J. Fox Foundation, Innovate UK, Solvemed, and Alchemab and personal fees from AstraZeneca, AbbVie, Zambon, BIAL, uMedeor, Alchemab, Britannia, and Charco Neurotech outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Forest Plot of Odds Ratios (ORs) of Number of Different Antiepileptic Drugs (AEDs) and Number of AEDs Issues for Parkinson Disease (PD)
See this image and copyright information in PMC

Comment in

References

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