Dose Monitoring of Lamotrigine Monotherapy in Pregnancy: Are Pregnant Women with Epilepsy Currently Optimally Managed? A Systematic Review

Abstract

BACKGROUND: Lamotrigine monotherapy is the first-line treatment for epilepsy in pregnant women. However, altered pharmacokinetics during pregnancy can lead to suboptimal drug levels and increased seizure risk. This systematic review aimed to evaluate current therapeutic drug monitoring (TDM) strategies for lamotrigine monotherapy in pregnant women with epilepsy and provide guidance for monitoring and dose adjustments. METHODS: A systematic search was performed using the Ovid-MEDLINE, Ovid-EMBASE, and Ovid-Cochrane Central Register of Controlled Trials databases. Studies were included if data on lamotrigine dosing, concentration, TDM strategies, efficacy, or safety were available. RESULTS: Eleven studies were analyzed, revealing heterogeneity in outcomes with selective reporting of TDM strategies; however, clear similarities were observed. Blood samples were collected every 1-3 months during pregnancy to maintain prepregnancy baseline drug levels. Lamotrigine's apparent and relative clearance increased across trimesters, particularly in the second and third trimesters, coinciding with a period of increased seizure frequency and required dose adjustments. Details on dose adjustments were limited. Some studies have proposed using the threshold of the ratio to the target concentration to predict increased seizure risk. No distinct association was observed between adverse newborn outcomes and lamotrigine dose or serum concentration. Few maternal adverse effects have been reported after delivery, confirming the necessity of empirical postpartum tapering. CONCLUSIONS: Further studies are required to establish evidence-based standardized protocols encompassing all aspects of TDM. Early interventions, such as empirical dose increases during pregnancy and postpartum tapering, and routine monitoring from preconception to the postpartum period may enhance seizure control, reducing the risk of breakthrough seizures for the mother and unborn child. Copyright 2024 Wolters Kluwer Health, Inc. All rights reserved.