Therapeutic Monitoring of Antiseizure Drugs Should Begin Early in Pregnancy

In pregnant women with epilepsy, blood levels of common antiseizure medications (ASMs) dropped during pregnancy. Therapeutic drug monitoring should be initiated early in pregnancy, with increasing doses of antiseizure medications (ASMs) possibly needed throughout the pregnancy, a study published in JAMA Neurology suggests.

In the US, safer ASMs are available on the market, however, clinicians have noticed patients successfully treated with ASMs were starting to have seizures after becoming pregnant. This prompted researchers to assess the ASMs that may have blood concentration changes and when these changes occur in pregnancy in order to identify patients that need therapeutic drug monitoring during and after pregnancy. The objective of the current study was to describe pregnancy-related blood concentration changes in a number of ASMs used among women with epilepsy.

The prospective, observational, 20-site Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) cohort study was conducted in the United States. Study enrollment occurred between December 19, 2012, and February 11, 2016. The study population comprised pregnant women with epilepsy and nonpregnant control participants with epilepsy. Study inclusion criteria were age 14 to 45 years, intelligence quotient >70 points, and a fetal gestational age (GA) of <20 weeks in the pregnant cohort.

Among 1087 women with epilepsy who were evaluated for eligibility, 305 pregnant women (median age, 29 years; range, 19 to 43 years) and 109 control participants (median age 29 years; range, 16 to 43 years) were enrolled in MONEAD. The eligible women were taking either ASM monotherapy or polytherapy with noninteracting ASMs. Plasma concentrations of all ASMs were assessed. Monitoring in the pregnant cohort continued through 9 months postpartum, with similar time points established for the control cohort.

Dose-normalized concentrations of the ASMs were calculated as measured or unbound plasma concentrations of medication divided by the total daily dose. The ASMs being taken by the women included lamotrigine, levetiracetam, lacosamide, oxcarbazepine, zonisamide, topiramate, and carbamazepine. Compared with postpartum values, dose-normalized concentrations during pregnancy were decreased significantly by up to 56.1% with lamotrigine (P <.001), 36.8% with levetiracetam (P <.001), 17.3% with carbamazepine (P =.03), 32.6% with oxcarbazepine (P <.001), 30.6% with unbound oxcarbazepine (P <.001), 39.9% with lacosamide (P <.001), and 29.8% with zonisamide (P <.001). Although no significant changes were reported with unbound carbamazepine, carbamazepine-10-11-epoxide, and topiramate, a decrease was reported with topiramate (P =.18).

Further, compared with dose-normalized concentrations from the cohort arm, pregnancy dose-normalized median concentrations decreased significantly by week of GA with carbamazepine (P =.02), carbamazepine unbound (P =.01), lacosamide (P <.001), lamotrigine (P <.001), levetiracetam (P= .01), oxcarbazepine (P <.001), oxcarbazepine unbound (P <.001), and zonisamide (P <.001), but not with topiramate or carbamazepine-10-11-epoxide.

A study limitation included the small number of women taking ASMs other than lamotrigine and levetiracetam, although the study itself had on of the largest ASM pharmacokinetic information for pregnant and control individuals, the researchers explained.

The study’s findings offer a personalized treatment approach for women with epilepsy during pregnancy. The researchers concluded, “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.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference  

Pennell PB, Karanam A, Meador KJ, et al; MONEAD Study Group. 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