(B-141) Increased Incidence of Parkinson's Disease Associated with Antiseizure Medication Use

Background: Recent studies linked epilepsy to an increased risk of Parkinson's disease (PD), but there is limited evidence regarding the role of antiseizure medications (ASMs).

Objectives: To investigate the association between ASM use and PD incidence in adults.

Methods: Using Manitoba administrative health databases, we conducted a population-based cohort study included individuals aged >25 years from April 2008 to March 2022. We included all ASMs and divided individuals into quartiles based on number of prescriptions, with the first quartile having the fewest and the fourth quartile with most prescriptions. We defined PD diagnosis as individuals with either 1 hospitalization diagnosis code or 2 physician claims within 1 year using ICD codes. We used Cox proportional hazards models, adjusting for demographic/clinical characteristics to calculate hazard ratio (HR) and 95% CI. Sensitivity analysis was performed by excluding those diagnosed with PD within 1 year of being prescribed any ASM.

Results: During the study period, 63,286 were exposed to ASMs and 883,667 were unexposed. Individuals exposed to ASMs had a higher incidence of PD compared with those not exposed, with rates approximately doubling from 0.43% (n=3,802) to 0.89% (n=562). Among the exposed group, 58.03% were female, 64.91% resided in urban areas, and 3.85% had epilepsy. Excluding gabapentin, PD incidence significantly increased with any ASM use (HR=2.59,95%CI2.26-2.97). Individuals in the fourth quartile who filled more than 44 prescriptions had higher odds of developing PD (HR=2.13,95%CI1.86-2.44) compared with individuals in quartile 1 (HR=1.14,95%CI0.94-1.38). PD Incidence was significantly associated with the use of polytherapy (HR=3.22=,95%CI 2.69-3.84). Incidence of PD was significantly associated with valproic acid (HR= 3.01, 95% CI 2.52-3.61), levetiracetam (HR=2.41, 95% CI 1.91 -3.04), lamotrigine (HR= 1.82; 95% CI 1.43-2.32), and gabapentin (HR= 1.04, 95% CI 0.96-1.13).

Conclusions: Over the 15-year study period, our findings show an association between ASMs and PD incidence. The use of any ASM, polytherapy, and a higher number of prescriptions were associated with an increased risk of PD. Future research is warranted to understand the underlying mechanisms.