Preconception drug levels and RTC-guided monitoring as predictors of seizure control during pregnancy

Background Pregnancy-related pharmacokinetic changes may reduce antiseizure medication (ASM) exposure and compromise seizure control in pregnant women with epilepsy (PWWE). However, there is scant literature to guide how to adjust ASM dosing. Objectives To examine associations of preconception trough concentrations with preconception seizure freedom and of ratio-to-target concentration (RTC) with seizure worsening during pregnancy. Design A retrospective longitudinal cohort study. Methods PWWE receiving lamotrigine (LTG) or levetiracetam (LEV) monotherapy were included. Trough concentrations, concentration-to-dose ratios (CDRs), and RTCs were assessed from preconception through postpartum. Logistic regression evaluated clinical predictors of seizure worsening. Receiver operating characteristic analyses identified exposure cut-offs, and generalized estimating equations assessed associations between repeated RTC measurements and seizure worsening. Results We analyzed 296 samples from 76 women (LEV, n=37; LTG, n=39). Lack of seizure freedom during the 9 months before conception was independently associated with seizure worsening (adjusted odds ratio, 15.591; 95% confidence interval, 4.522–53.759). Higher preconception trough concentrations were associated with preconception seizure freedom. Concentrations of 13.62 μg/mL for LEV and 5.28 μg/mL for LTG discriminated preconception seizure freedom, with areas under the curve (AUCs) of 0.751 and 0.680, respectively. Concentrations and CDRs declined during pregnancy. Among women who were not seizure-free before conception, lower RTC values were associated with seizure worsening; RTC cut-offs were 0.54 for LEV and 0.71 for LTG, with AUCs of 0.792 and 0.859, respectively. Conclusion Preconception seizure status and drug exposure may identify women at increased risk of seizure worsening. Risk-stratified RTC monitoring may support individualized therapeutic drug monitoring, particularly among women without preconception seizure control, although these thresholds require prospective validation.