Women with epilepsy experience lower antiseizure medicine concentration during pregnancy

Women with epilepsy experienced significant decreases in dose-normalized concentrations of antiseizure medications during pregnancy, according to a study published in JAMA Neurology.

“Management of epilepsy in pregnancy requires balancing risk of harm from suboptimal therapy and worsening maternal seizures with fetal risk from increased [antiseizure medication (ASM)] exposure due to unnecessary dose increases,” Page B. Pennell, MD, of the department of neurology at the University of Pittsburgh School of Medicine, and colleagues wrote.

Researchers sought to characterize pregnancy-associated concentration changes for several antiseizure medications in women with epilepsy, as lower blood concentrations of these therapeutic drugs may lead to adverse clinical outcomes.

Pennell and colleagues conducted a prospective, observational cohort study (Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs) , which enrolled participants from Dec. 19, 2012, to Feb. 11, 2016, at 20 U.S. locations. The study included 326 pregnant women with epilepsy and 104 nonpregnant control participants with epilepsy, aged 14 to 45 years, with an intelligence quotient greater than 70 and, for the pregnant cohort, a fetal gestational age younger than 20 weeks.

Researchers monitored the cohort of pregnant women until 9 months postpartum, with similar time points for the control group. They performed blood draws during four pregnancy study visits and three postpartum visits for the pregnant women and seven visits over 18 months for the control group. Dose-normalized concentrations were calculated as total or unbound plasma medication concentrations divided by total daily dose. Data were analyzed from May 1, 2014, to June 30, 2021.

According to study results, dose-normalized concentrations during pregnancy were decreased by up to 56.1% for lamotrigine, 36.8% for levetiracetam, 17.3% for carbamazepine, 32.6% for oxcarbazepine, 30.6% for unbound oxcarbazepine, 39.9% for lacosamide and 29.8% for zonisamide, compared with postpartum values. Conversely, no significant changes occurred for unbound carbamazepine, carbamazepine-10,11-epoxide and topiramate, although a decrease was observed for topiramate.

Data also showed that in comparison with dose-normalized concentrations from control participants, pregnancy dose-normalized median concentrations decreased significantly by week of gestational age for carbamazepine, carbamazepine unbound, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, oxcarbazepine unbound and zonisamide. Topiramate and carbamazepine-10,11-epoxide were the exception.

“Results of this cohort study suggest the need for higher doses of several ASMs during pregnancy and support therapeutic drug monitoring beginning early in pregnancy,” Pennell and colleagues wrote.