Correlation between levetiracetam plasma concentration and adverse effects and efficacy in patients with epilepsy

Abstract

ABSTRACT

Background Therapeutic drug monitoring of levetiracetam is often done in clinical practice, for example in patients with persisting seizures or possible adverse effects. However, evidence of the correlation between levetiracetam plasma concentration and adverse effects and efficacy is scarce and the true optimal reference range for levetiracetam has not yet been established.

Methods This double-center, retrospective observational study included real-world data from cases where levetiracetam plasma concentrations were measured in patients with epilepsy between January 2019 and September 2024. Data was derived from medical health records. The correlation between levetiracetam plasma concentration and adverse effects and efficacy were assessed.

Results Overall, 273 patients were included. 261 Patients were included in the adverse effects analyses, of which 35.7% experienced adverse effects. Patients with adverse effects had a higher levetiracetam plasma concentration compared to patients without adverse effects (p = 0.009). Patients with levetiracetam concentrations above 25 mg/L experienced more adverse effects compared to patients with lower plasma concentrations (p = 0.006). Multivariate analysis showed that adverse effects were more common in patients with supra-therapeutic plasma concentrations (25-45 mg/L) compared to those with therapeutic plasma concentrations (5-25 mg/L) (adjusted OR 1.95 (1.04 – 3.64)). No correlation was found between levetiracetam plasma concentration and efficacy.

Conclusions Levetiracetam plasma concentration was found to be correlated with the occurrence of adverse effects but not with treatment efficacy in patients with epilepsy. Therefore, therapeutic drug monitoring of levetiracetam is useful when adverse effects are suspected, but it does not seem to assist in predicting the efficacy of levetiracetam treatment.