Women with epilepsy have lower anticonvulsant drug concentration during pregnancy

February 18, 2022

1 minute read

Disclosures: Pennell reports research support from the NIH and the Karger Foundation, as well as financial relationships with Harvard Medical School, Harvard School of Public Health, American Epilepsy Society, American Academy of Neurology, and UpToDate Inc. Please consult the study for all other authors. relevant financial information.

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According to a study published in JAMA Neurology.

“The management of epilepsy during pregnancy requires balancing the risk of harm from suboptimal treatment and worsening of maternal seizures with the fetal risk of increased [antiseizure medication (ASM)] exposure due to unnecessary dose increases,” Page B. Pennell, MD, from the Department of Neurology at the University of Pittsburgh School of Medicine, and his colleagues wrote.

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Researchers sought to characterize pregnancy-associated concentration changes for several antiepileptic drugs 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 recruited participants from December 19, 2012, to February 11, 2016, at 20 sites in the United States. The study included 326 pregnant women with epilepsy and 104 non-pregnant control participants with epilepsy, ages 14 to 45, with an intelligence quotient greater than 70 and, for the pregnant cohort, a fetal gestational age less than 20 weeks.

The researchers followed the cohort of pregnant women up to 9 months postpartum, with similar timeframes for the control group. They took blood samples during four pregnancy study visits and three postpartum visits for pregnant women and seven visits over 18 months for the control group. Dose-normalized concentrations were calculated as total or unbound plasma concentrations divided by the total daily dose. Data was analyzed from May 1, 2014 to June 30, 2021.

According to the study results, dose-normalized concentrations during pregnancy decreased 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 lacosamide. zonisamide, compared to postpartum values. Conversely, no significant changes occurred for unbound carbamazepine, carbamazepine-10,11-epoxide and topiramate, although a decrease was observed for topiramate.

The data also showed that, compared to dose-normalized concentrations of control participants, median dose-normalized concentrations during pregnancy decreased significantly by week of gestational age for carbamazepine, carbamazepine unbound, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, unbound oxcarbazepine and zonisamide. Topiramate and carbamazepine-10,11-epoxide were the exception.

“The results of this cohort study suggest the need for higher doses of multiple ASMs during pregnancy and support therapeutic drug monitoring from early in pregnancy,” Pennell and colleagues wrote.

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