How is levetiracetam monotherapy currently monitored in pregnancy? A systematic review

Abstract

BACKGROUND: Levetiracetam is commonly used as antiepileptic drug during pregnancy and has a well-established safety profile in that setting. Pregnancy-related pharmacokinetic changes may result in decreased levetiracetam levels and increased seizure frequency during pregnancy. Therapeutic drug monitoring (TDM) of levetiracetam levels may facilitate dose adjustment. Although levetiracetam TDM is widely used in pregnancy, robust guidelines are still lacking, resulting in heterogeneous use of TDM. OBJECTIVES: The aim of this review was to provide insight into levetiracetam TDM strategies utilised during pregnancy. METHODS: A systematic search up to 17 April 2025 was carried out using MEDLINE, Embase, APA PsycINFO, and Cochrane Central Register of Controlled Trials through Ovid. Studies were eligible for inclusion if data on levetiracetam dosing, concentrations, monitoring, efficacy, or safety during pregnancy were available. All articles were assessed for the risk of bias, and relevant data were extracted. RESULTS: The ten studies included revealed significant variability in epilepsy monitoring during pregnancy, TDM strategies, and dose adjustments. An increase in seizure frequency during pregnancy was described. However, data on levetiracetam maternal and foetal safety were limited. CONCLUSIONS: This review highlights the heterogeneity in levetiracetam TDM strategies in pregnancy. The pharmacokinetic changes during pregnancy require dose adjustments to maintain seizure control, but no standardised TDM protocol is available. Future research should focus on standardizing TDM strategies, validating target concentration thresholds, and assessing long-term maternal and foetal safety.