Pittsburgh, PA—In some cases, expectant mothers might need higher doses of antiseizure medications and increased therapeutic drug monitoring beginning early in pregnancy, according to a new study.

A report in JAMA Neurology points out that blood levels of many commonly used antiepileptic drugs drop significantly with the onset of pregnancy.

Researchers from the University of Pittsburgh and colleagues recently revealed the findings, which were collected as part of the multicenter study Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD).

The authors note that those changes help explain why many women with epilepsy start having breakthrough seizures after conception. They urge that clinicians consider increasing doses of certain antiseizure medications and carefully tracking blood levels over the course of pregnancy.

“When it comes to epilepsy, maintaining a fine-tuned medication regime is critical. Some people mistakenly believe that changes in the drugs' blood concentration won't occur until after 20 weeks of pregnancy, but our study shows how important it is to start monitoring and adjusting patients' medication dosages early on,” said lead author Page Pennell, MD, chair of neurology at Pitt and the principal investigator on the MONEAD trial. “Nearly half of all pregnancies in the United States are unplanned, so it is important to ensure that doctors have a clear picture of each patient's baseline drug level even if they are not trying to conceive.”

Noting that lower blood concentrations of antiseizure medications during pregnancy can have adverse clinical consequences, the study team sought to characterize pregnancy-associated concentration changes for several antiseizure medications among female epilepsy patients.

Conducted at 20 U.S. sites, MONEAD reported data on 351 pregnant women and 109 control participants from December 19, 2012, to February 11, 2016. Researchers monitored medication plasma concentrations in women taking monotherapy or in combination with noninteracting medications and followed pregnant participants through 9 months postpartum, with similar time points for control participants.

Results indicate that, compared with postpartum values, dose-normalized concentrations during pregnancy were decreased by up to:

• 56.1% for lamotrigine (15.60 μg/L/mg to 6.85 μg/L/mg; P <.001)

• 36.8% for levetiracetam (11.33 μg/L/mg to 7.16 μg/L/mg; P <.001),

• 17.3% for carbamazepine (11.56 μg/L/mg to 7.97 μg/L/mg; P = .03), 32.6% for oxcarbazepine (11.55 μg/L/mg to 7.79 μg/L/mg; P <.001),

• 30.6% for unbound oxcarbazepine (6.15 g/L/mg to 4.27 g/L/mg; P <.001), 39.9% for lacosamide (26.14 g/L/mg to 15.71 g/L/mg; P <.001), and

• 29.8% for zonisamide (40.12 g/L/mg to 28.15 μg/L/mg; P <.001).

On the other hand, researchers report, no significant changes occurred for unbound carbamazepine, carbamazepine-10,11-epoxide, and topiramate, although a decrease was observed for topiramate (29.83 μg/L/mg to 13.77 μg/L/mg; P = .18).

“Additionally, compared with dose-normalized concentrations from control participants, pregnancy dose-normalized median (SE) concentrations decreased significantly by week of gestational age: carbamazepine, -0.14 (0.06) μg/L/mg (P = .02); carbamazepine unbound, -0.04 (0.01) μg/L/mg (P = .01); lacosamide, -0.23 (0.07) μg/L/mg (P < .001); lamotrigine, -0.20 (0.02) μg/L/mg (P < .001); levetiracetam, -0.06 (0.03) μg/L/mg (P = .01); oxcarbazepine, -0.14 (0.04) μg/L/mg (< .001); oxcarbazepine unbound, -0.11 (0.03) μg/L/mg (P < .001); and zonisamide, -0.53 (0.14) μg/L/mg (P <.001) except for topiramate (-0.35 [0.20] μg/L/mg per week) and carbamazepine-10,11-epoxide (0.02 [0.01] μg/L/mg),” according to the report.

“Study results suggest that therapeutic drug monitoring should begin early in pregnancy and that increasing doses of these anticonvulsants may be needed throughout the course of pregnancy,” the authors write.

“Identifying which antiseizure medications may have changes in concentrations and at what point in pregnancy those changes occur is important for determining which patients may need to be monitored more closely during pregnancy and after delivery,” added senior author Angela Birnbaum, PhD, professor of experimental and clinical pharmacology at the University of Minnesota.

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