EPIDEMIOLOGY AND HEALTH DATA INSIGHTS
Review Article
Nov 14, 2025 6 5

Antiepileptic Drugs and Parkinson's Disease: A Meta-Analysis of Existing Evidence

Ruslan Akhmedullin 1 * ,
Dina Kalinina 1,
Dinara Kazhaparova 1,
Antonio Sarria-Santamera 1,
Gaziz Kyrgyzbay 2,
Rauan Kaiyrzhanov 3
1 Department of Medicine, Nazarbayev University School of Medicine, Astana, Republic of Kazakhstan2 Epileptology Centre, Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan, Astana, Republic of Kazakhstan3 Department of Neuromuscular Disorders, University College London, London, UK* Corresponding Author
Epidemiology and Health Data Insights, 1(6), 2025, ehdi021, https://doi.org/10.63946/ehdi/17420
Publication date: Nov 14, 2025
Full Text (PDF)

ABSTRACT

Background. There is growing interest in the association between antiepileptic drugs (AEDs) exposure and subsequent Parkinson’s disease (PD).
Methods. We conducted a literature search in the PubMed, SCOPUS, and Web of Science databases. We identified studies using an observational design and performed a meta-analysis to evaluate the association between AEDs exposure and incident PD. We assessed the quality of the studies and identified the pooled odds ratio (OR) for those exposed to AEDs compared to those who were not.
Results. Of the 1,775 unique studies identified, 55 were selected for full-text review. Five studies (n = 127,324) were included. Quality assessment revealed moderate-to-high methodological quality in the studies included. The overall OR for a PD was 1.82 (95% CI: 1.35-2.45) in AEDs recipients. When considering each drug individually, the magnitude of association was highest for valproate (OR 3.94, 95% CI: 3.15-4.92) and lowest for carbamazepine (OR 1.32, 95% CI: 1.16-1.49). Further interaction tests revealed higher odds for lamotrigine than for carbamazepine and valproate than for carbamazepine and lamotrigine.
Conclusion. This study revealed potential associations between AEDs and incident PD. However, existing evidence remains insufficient, making it premature to draw inferences on this matter.

KEYWORDS

Antiepileptic Drugs AEDs Antiseizure Medications Epilepsy Parkinson’s Disease

CITATION (Vancouver)

Akhmedullin R, Kalinina D, Kazhaparova D, Sarria-Santamera A, Kyrgyzbay G, Kaiyrzhanov R. Antiepileptic Drugs and Parkinson's Disease: A Meta-Analysis of Existing Evidence. Epidemiology and Health Data Insights. 2025;1(6):ehdi021. https://doi.org/10.63946/ehdi/17420
APA
Akhmedullin, R., Kalinina, D., Kazhaparova, D., Sarria-Santamera, A., Kyrgyzbay, G., & Kaiyrzhanov, R. (2025). Antiepileptic Drugs and Parkinson's Disease: A Meta-Analysis of Existing Evidence. Epidemiology and Health Data Insights, 1(6), ehdi021. https://doi.org/10.63946/ehdi/17420
Harvard
Akhmedullin, R., Kalinina, D., Kazhaparova, D., Sarria-Santamera, A., Kyrgyzbay, G., and Kaiyrzhanov, R. (2025). Antiepileptic Drugs and Parkinson's Disease: A Meta-Analysis of Existing Evidence. Epidemiology and Health Data Insights, 1(6), ehdi021. https://doi.org/10.63946/ehdi/17420
AMA
Akhmedullin R, Kalinina D, Kazhaparova D, Sarria-Santamera A, Kyrgyzbay G, Kaiyrzhanov R. Antiepileptic Drugs and Parkinson's Disease: A Meta-Analysis of Existing Evidence. Epidemiology and Health Data Insights. 2025;1(6), ehdi021. https://doi.org/10.63946/ehdi/17420
Chicago
Akhmedullin, Ruslan, Dina Kalinina, Dinara Kazhaparova, Antonio Sarria-Santamera, Gaziz Kyrgyzbay, and Rauan Kaiyrzhanov. "Antiepileptic Drugs and Parkinson's Disease: A Meta-Analysis of Existing Evidence". Epidemiology and Health Data Insights 2025 1 no. 6 (2025): ehdi021. https://doi.org/10.63946/ehdi/17420
MLA
Akhmedullin, Ruslan et al. "Antiepileptic Drugs and Parkinson's Disease: A Meta-Analysis of Existing Evidence". Epidemiology and Health Data Insights, vol. 1, no. 6, 2025, ehdi021. https://doi.org/10.63946/ehdi/17420

SUPPLEMENTARY FILES

Supplementary Files

REFERENCES

  1. Feigin VL, Vos T, Nichols E, Owolabi MO, Carroll WM, Dichgans M, et al. The global burden of neurological disorders: translating evidence into policy. Lancet Neurol. 2020;19(3):255-65. doi: 10.1016/S1474-4422(19)30411-9
  2. Dorsey ER, Sherer T, Okun MS, Bloem BR. The Emerging Evidence of the Parkinson Pandemic. J Parkinsons Dis. 2018;8(s1):S3-s8. doi: 10.3233/JPD-181474
  3. Ding C, Wu Y, Chen X, Chen Y, Wu Z, Lin Z, et al. Global, regional, and national burden and attributable risk factors of neurological disorders: The Global Burden of Disease study 1990-2019. Front Public Health. 2022;10:952161. doi: 10.3389/fpubh.2022.952161
  4. Sumadewi KT, Harkitasari S, Tjandra DC. Biomolecular mechanisms of epileptic seizures and epilepsy: a review. Acta Epileptologica. 2023;5(1):28. doi: 10.1186/s42494-023-00141-4
  5. Müller-Nedebock AC, Dekker MCJ, Farrer MJ, Hattori N, Lim SY, Mellick GD, et al. Different pieces of the same puzzle: a multifaceted perspective on the complex biological basis of Parkinson's disease. NPJ Parkinsons Dis. 2023;9(1):110. doi: 10.1038/s41531-023-00526-9
  6. Anttila V, Bulik-Sullivan B, Finucane HK, Walters RK, Bras J, Duncan L, et al. Analysis of shared heritability in common disorders of the brain. Science. 2018;360(6395). doi: 10.1126/science.aap8757
  7. Soliman Y, Mouffokes A. Parkinson's disease and epilepsy: A bidirectional relationship and potential risks of antiepileptic drugs - a meta-analysis. Journal of the Neurological Sciences. 2023;455. doi: 10.1016/j.jns.2023.120787
  8. Cano A, Fonseca E, Ettcheto M, Sanchez-Lopez E, de Rojas I, Alonso-Lana S, et al. Epilepsy in Neurodegenerative Diseases: Related Drugs and Molecular Pathways. PHARMACEUTICALS. 2021;14. doi: 10.3390/ph14111057
  9. Simonet C, Bestwick J, Jitlal M, Waters S, Ben-Joseph A, Marshall CR, et al. Assessment of Risk Factors and Early Presentations of Parkinson Disease in Primary Care in a Diverse UK Population. JAMA Neurol. 2022;79(4):359-69. doi: 10.1001/jamaneurol.2021.4996
  10. Jacobs BM, Belete D, Bestwick J, Blauwendraat C, Bandres-Ciga S, Heilbron K, et al. Parkinson's disease determinants, prediction and gene-environment interactions in the UK Biobank. J Neurol Neurosurg Psychiatry. 2020;91(10):1046-54. doi: 10.1136/jnnp-2019-322646
  11. Spina E, Perugi G. Antiepileptic drugs: indications other than epilepsy. Epileptic Disord. 2004;6(2):57-75.
  12. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71
  13. Hwang YS, Kang MG, Yeom SW, Jeong CY, Shin BS, Koh J, et al. Increasing incidence of Parkinson's disease in patients with epilepsy: A Nationwide cohort study. J Neurol Sci. 2024;458:122891. doi: 10.1016/j.jns.2024.122891
  14. Belete D, Jacobs BM, Simonet C, Bestwick JP, Waters S, Marshall CR, et al. Association Between Antiepileptic Drugs and Incident Parkinson Disease. JAMA Neurol. 2023;80(2):183-7. doi: 10.1001/jamaneurol.2022.4199
  15. Kostev K, Doege C, Jacob L, Smith L, Koyanagi A, Gollop C, et al. Association between Antiepileptic Drugs and Incident Parkinson's Disease among Patients Followed in German Primary Care Practices. Brain Sci. 2023;13(3). doi: 10.3390/brainsci13030415
  16. Zhang Q, Bestwick J, Dobson R, Marshall C, Noyce A. Association between Antiepileptic Drugs and Subsequent Parkinson's Disease in East London. MOVEMENT DISORDERS. 2023;38:S276-S7.
  17. Skow A, Douglas I, Smeeth L. The association between Parkinson's disease and anti-epilepsy drug carbamazepine: a case-control study using the UK General Practice Research Database. Br J Clin Pharmacol. 2013;76(5):816-22. doi: 10.1111/bcp.12109
  18. Zadikoff C, Munhoz RP, Asante AN, Politzer N, Wennberg R, Carlen P, et al. Movement disorders in patients taking anticonvulsants. J Neurol Neurosurg Psychiatry. 2007;78(2):147-51. doi: 10.1136/jnnp.2006.100222
  19. Hidvegi T, Ewing M, Hale P, Dippold C, Beckett C, Kemp C, et al. An autophagy-enhancing drug promotes degradation of mutant alpha1-antitrypsin Z and reduces hepatic fibrosis. Science. 2010;329(5988):229-32. doi: 10.1126/science.1190354
  20. Rizzo G, Copetti M, Arcuti S, Martino D, Fontana A, Logroscino G. Accuracy of clinical diagnosis of Parkinson disease: A systematic review and meta-analysis. Neurology. 2016;86(6):566-76. doi: 10.1212/WNL.0000000000002350
  21. Basselin M, Chang L, Chen M, Bell JM, Rapoport SI. Chronic carbamazepine administration attenuates dopamine D2-like receptor-initiated signaling via arachidonic acid in rat brain. Neurochem Res. 2008;33(7):1373-83. doi: 10.1007/s11064-008-9595-y
  22. López-Sendón J, Mena MA, de Yébenes JG. Drug-induced parkinsonism. Expert Opin Drug Saf. 2013;12(4):487-96. doi: 10.1517/14740338.2013.787065
  23. Johannessen CU, Johannessen SI. Valproate: past, present, and future. CNS Drug Rev. 2003;9(2):199-216. doi: 10.1111/j.1527-3458.2003.tb00249.x
  24. van Nuland AJM, den Ouden HEM, Zach H, Dirkx MFM, van Asten JJA, Scheenen TWJ, et al. GABAergic changes in the thalamocortical circuit in Parkinson's disease. Hum Brain Mapp. 2020;41(4):1017-29. doi: 10.1002/hbm.24857
  25. Cook L, Verbrugge J, Schwantes-An TH, Schulze J, Foroud T, Hall A, et al. Parkinson's disease variant detection and disclosure: PD GENEration, a North American study. Brain. 2024;147(8):2668-79. doi: 10.1093/brain/awae177
  26. Sharma A, Osato N, Liu H, Asthana S, Dakal TC, Ambrosini G, et al. Common genetic variants associated with Parkinson's disease display widespread signature of epigenetic plasticity. Sci Rep. 2019;9(1):18464. doi: 10.1038/s41598-019-54865-w
  27. Song H, Chen J, Huang J, Sun P, Liu Y, Xu L, et al. Epigenetic modification in Parkinson's disease. Front Cell Dev Biol. 2023;11:1123621. doi: 10.3389/fcell.2023.1123621
  28. Cavalli G, Heard E. Advances in epigenetics link genetics to the environment and disease. Nature. 2019;571(7766):489-99. doi: 10.1038/s41586-019-1411-0
  29. Toth M. Epigenetic Neuropharmacology: Drugs Affecting the Epigenome in the Brain. Annu Rev Pharmacol Toxicol. 2021;61:181-201. doi: 10.1146/annurev-pharmtox-030220-023841
  30. Myrianthopoulos NC, Kurland AA, Kurland LT. Hereditary predisposition in drug-induced parkinsonism. Arch Neurol. 1962;6:5-9. doi: 10.1001/archneur.1962.00450210007001
  31. Schapira AH. Neurobiology and treatment of Parkinson's disease. Trends Pharmacol Sci. 2009;30(1):41-7. doi: 10.1016/j.tips.2008.10.005
  32. Willmore LJ. Antiepileptic drugs and neuroprotection: Current status and future roles. Epilepsy & Behavior. 2005;7:25-8. doi: 10.1016/j.yebeh.2005.04.007

LICENSE

Creative Commons License
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.