Managing Antiseizure Medications in Pregnancy

Background and Objective Medication management in pregnant women with epilepsy (PWWE) poses challenges, and understanding the effects of metabolic changes on antiseizure medications (ASMs) is important in planning care for PWWE. The possible teratogenic effects and risks of poorly controlled seizures have to be weighed. There are data in the literature on clinical management of ASMs including the effects of drug levels on seizures and factors that predict seizure frequency, but timing and frequency of monitoring and dose adjustment paradigms have not been well studied.

Methods This retrospective study was approved by the Institutional Review Board at Johns Hopkins University. We retrospectively identified adult PWWE evaluated during pregnancy at the Johns Hopkins Bayview Medical Center epilepsy clinic, between January 1, 2007, and January 1, 2021. We reviewed charts for information regarding demographics, medical and epilepsy history, medications, serum drug levels, and dosing paradigms. We assessed risk factors for breakthrough seizures with a focus on frequency and timing of laboratory testing. We calculated the dose-normalized concentration (DNC) for analysis with levetiracetam and lamotrigine, assessing changes in DNC over time by half trimesters, and analyzed DNC and effects on seizures in pregnancy. We also compared preemptive vs clinically based lamotrigine dose adjustments in managing epilepsy in pregnancy.

Results A total of 45 pregnancies in 39 patients were included in this study, 8 generalized, 28 focal epilepsy, and 3 unclassified. 31 PWWE (36 pregnancies) were on lamotrigine and/or levetiracetam, and 14 of these pregnancies experienced breakthrough seizures, 77% in the first trimester. Seizures led to the diagnosis of pregnancy in 5 patients. The DNC for levetiracetam decreased significantly compared with prepregnancy levels by the second half of the first trimester and demonstrated variable but frequently significant or near significant reduction throughout pregnancy. DNC for lamotrigine decreased significantly in the first half of the first trimester and remained significant throughout pregnancy. Age of mother at conception, week of first ASM serum level and number of levels obtained during pregnancy, and epilepsy type were not associated with breakthrough/increase in seizures. The history of drug resistance (p = 0.038) was associated with a higher odds of seizures. In those on lamotrigine, preemptive dose adjustments demonstrated similar results regarding seizure control when compared with clinical-based or laboratory-based dose management (p = 0.531).

Discussion This study demonstrates that frequency and timing of ASM level monitoring may not affect overall seizure outcomes during pregnancy in those on lamotrigine or levetiracetam. Furthermore, one can consider preemptive dose adjustments or a laboratory-based/clinical-based approach in managing lamotrigine as both seem safe and feasible. However, in those with drug-resistant epilepsy before pregnancy, earlier and closer monitoring is warranted given the risk of seizures early during pregnancy. Larger prospective studies are needed to confirm these results.