(ASPOT42) Antiseizure Medications Use And the Risk Of Parkinson’s Disease: A 15-year Population-based Study

Background: Recent studies have demonstrated the association between epilepsy and an increased risk of Parkinson’s disease (PD), however; there is limited evidence on the association with antiseizure medications (ASMs).

Objectives: To investigate the association between ASMs and incidence of PD in adults.

Methods: Using the provincial administrative health databases in Manitoba, Canada, we conducted a population-based cohort study including individuals aged >25 years from April 2008 to March 2022. We included all ASMs excluding clonazepam and safinamide, and examined individuals exposed to any ASM. We divided individuals into quartiles based on number of prescriptions issued, with those in first quartile with the fewest issued and those in fourth quartile with the most issued prescriptions. We examined the 7 most prescribed ASMs: valproic acid, lamotrigine, carbamazepine, gabapentin, pregabalin, topiramate, and levetiracetam. We defined PD diagnosis as individuals with either 1 hospitalization diagnosis code or 2 physician claims within 1 year using ICD-9-CM 332 or ICD-10-CM G20. We used logistic regression models, adjusting for age, sex, income, and epilepsy to calculate ORs and 95% CI. Sensitivity analysis was performed by excluding those diagnosed with PD within 1 year of being prescribed any ASM. Statistical analyses were performed using SAS software.

Results: During the study period, 63,286 individuals were exposed to ASMs and 883,667 were unexposed. Among the exposed group, 58.03% were female, 64.9% lived in urban regions, and 3.85% had epilepsy. We observed higher PD incidence among the exposed groups compared to the unexposed group (0.89% vs. 0.43%). Excluding gabapentin, the odds of PD incidence significantly increased with any ASM use (aOR=2.18 ,95%CI 1.99-2.39). Individuals in the fourth quartile, who filled more than 44 prescriptions, had higher odds of developing PD (aOR=3.64,95% CI 3.17-4.17) compared with individuals in quartile 1 (aOR=1.31, 95% CI 1.08-1.59). PD Incidence was significantly associated with the use of valproic acid (aOR=5.17,95% CI 4.33-6.17), levetiracetam (aOR=3.79,95% CI 2.99-4.80), lamotrigine (aOR=3.82;95% CI 2.9-5.04), and gabapentin (aOR=1.44,95% CI 1.34-1.56). Sensitivity analysis showed persistent results with primary analysis.

Conclusions: Over the 15-year study period, we found an association between ASMs and PD incidence. The use of lamotrigine, levetiracetam, valproic acid and gabapentin were associated with increased risk of PD development. Our findings provide insights into the potential risks and future research are warranted to understand the underlying mechanisms.