Association Between Antiepileptic Drugs and Incident Parkinson Disease

Abstract

ImportanceRecent studies have highlighted an association between epilepsy and Parkinson disease (PD). The role of antiepileptic drugs (AEDs) has not been explored.ObjectiveTo investigate the association between AEDs and incident PD.Design, Setting, and ParticipantsThis 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.ExposuresExposure to AEDs (carbamazepine, lamotrigine, levetiracetam, and sodium valproate) was defined using routinely collected prescription data derived from primary care.Main Outcomes and MeasuresOdd 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.ResultsIn 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 RelevanceThis 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.

Association between Antiepileptic Drugs and Incident Parkinson’s Disease among Patients Followed in German Primary Care Practices

“…Overall, our results confirm the findings of Belete et al [ 5 ], with similar ORs for any AED, sodium valproate, and carbamazepine in both studies. Although Belete et al also found significant positive associations for lamotrigine and levetiracetam, we did not find a significant association for either drug in the multivariate analysis.…”

“…Although the association between prescription medications and subsequent diagnosis of PD is of particular clinical relevance, it has not been comprehensively studied. Recently, Belete and colleagues reported that prescriptions of several antiepileptic drugs (AED) are significantly associated with an increased incidence of PD in the UK [ 5 ]. However, the association differed depending on the type of AED, being strongest for valproate (OR: 3.82; 95% CI: 2.41–6.05) and weakest (and statistically non-significant) for carbamazepine (OR: 1.43; 95% CI: 0.97–2.11).…”

“…However, the association differed depending on the type of AED, being strongest for valproate (OR: 3.82; 95% CI: 2.41–6.05) and weakest (and statistically non-significant) for carbamazepine (OR: 1.43; 95% CI: 0.97–2.11). The authors also conducted analyses in a hospital setting and studied the four most commonly prescribed AEDs in the UK, but these findings may not be generalizable to other AEDs or other countries [ 5 ]. Therefore, we examined whether these associations can be replicated in German primary care practices.…”

Association Between Use of Any of the Drugs Prescribed in Norway and the Subsequent Risk of Parkinson Disease

“…We found an association between antiepileptics (N03) and increased risk of PD, which was also recently reported in a UK Biobank substudy. 35 The antiepileptic valproic acid is linked to drug-induced tremors, 36 which might lead to either misdiagnosis of PD or an earlier diagnosis of true PD, because of better health monitoring. Moreover, the HR in our time-lagged results decreased quickly toward 1 (no effect) already 5 years before PD diagnosis, arguing for a reverse causal explanation of this association.…”

Error in Title

“…In the Original Investigation “Association Between Antiepileptic Drugs and Incident Parkinson Disease in the UK Biobank,” published online December 27, 2022, the title was incorrect and should have appeared as “Association Between Antiepileptic Drugs and Incident Parkinson Disease.” This article has been corrected online.…”