JAMA: Anticonvulsant concentration monitoring in Pregnant women with Epilepsy

A new study has found that there was a need for higher doses of several antiseizure medications during pregnancy to prevent seizure worsening.Therefore early in pregnancy, therapeutic medication monitoring should begin, and increased dosages of these anticonvulsants may be required throughout the pregnancy. The findings of this study were in the Journal of American Medical Association.

Lower blood concentrations of antiseizure medicines in pregnant women with epilepsy can have negative clinical implications. Page B. Pennell and colleagues set out to characterize pregnancy-related variations in the concentrations of multiple antiseizure medicines in women with epilepsy in this investigation.

From December 19, 2012, to February 11, 2016, 20 US sites enrolled in the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) prospective observational cohort research. Pregnant women with epilepsy and non-pregnant control participants with epilepsy were included in the study. Women between the ages of 14 and 45 were eligible, as were those with an IQ of at least 70 points and, in the case of pregnant women, a fetus gestational age of less than 20 weeks. A total of 1087 women were screened for eligibility, with 397 being rejected and 230 opting out. From May 1, 2014, through June 30, 2021, data was evaluated.

The plasma concentrations of drugs in women on monotherapy or in combination with non interfering medications were studied. The pregnant women's cohort was followed for 9 months after delivery, with control individuals being followed at similar intervals. Total or unbound plasma drug concentrations were divided by total daily dose to get dose-normalized concentrations. Phlebotomy was done on pregnant women during four pregnancy study visits and three postpartum visits, and on control participants during seven visits over 18 months. The major hypothesis was to compare nonpregnant postpartum dose-normalized concentrations to those of control subjects during pregnancy.

The key findings are as follow:

1. 326 pregnant women and 104 control participants satisfied the eligibility criteria for this study out of 351 pregnant women and 109 control participants registered in MONEAD.

2. Dose-normalized concentrations during pregnancy were reduced 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 when compared to postpartum values.

3. Unbound carbamazepine, carbamazepine-10,11-epoxide, and topiramate showed no significant alterations, however topiramate showed a decrease.

In conclusion, the findings of this cohort study show that greater dosages of various ASMs may be required during pregnancy, and that therapeutic medication monitoring should begin early in the pregnancy. The study's purpose was to develop a tailored treatment plan for pregnant women with epilepsy that included ASM dose adjustments to prevent seizure worsening and to achieve the best possible balance of maternal and child outcomes.

Reference:

Pennell PB, Karanam A, Meador KJ, et al. Antiseizure Medication Concentrations During Pregnancy: Results From the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) Study. JAMA Neurol. Published online February 14, 2022. doi:10.1001/jamaneurol.2021.5487