What Antiepileptics Have the Highest Risk of Parkinsonism? A Disproportionality Analysis in the World Health Organisation Pharmacovigilance Database.

BACKGROUND

The present study was performed to investigate which antiepileptic drug (AED) has the highest risk of drug-induced parkinsonism (DIP).

OBJECTIVE

The aim was to evaluate associations between AEDs and DIP reports in the World Health Organization pharmacovigilance database, Vigibase.

METHODS

Individual case safety reports (ICSRs) in patients ≥45 years registered between January 1, 2000 and June 31, 2024 with carbamazepine, lamotrigine, levetiracetam, or sodium valproate as "Parkinson-like events" (PLE) were extracted. Disproportionality analyses were performed, with cases being PLE and non-cases all other ICSRs. Results are shown as reporting odds ratios (ROR).

RESULTS

Among 16,174,796 ICSRs, 3339 reported PLE with the four AEDs, mainly in females between 45 and 64 years. The highest ROR value was with valproate sodium (3.09 [2.01-3.29]), followed by lamotrigine (2.14 [2.01-2.28]), levetiracetam (1.43 [1.32-1.55]), and carbamazepine (1.09 [1.01-1.17]). DIP risk increased with the number of associated AEDs.

CONCLUSIONS

Among AEDs, valproate sodium is associated with the higher risk of PLE and carbamazepine with the lowest.