New research provides medication-specific guidance for safely increasing antiseizure medication (ASM) doses during pregnancy, delivering real-world evidence the neurology community has long needed to inform care for pregnant women with epilepsy.
Earlier studies have shown that pregnancy profoundly alters the metabolism of ASMs, often necessitating dose increases two or three times over baseline pre-pregnancy levels to maintain therapeutic blood concentrations. Maintaining these levels is essential, as allowing them to fall below roughly 65 percent of baseline sharply increases the risk of breakthrough seizures.
Until recently, however, clinicians have relied largely on anecdotal experience to guide ASM dose adjustments during pregnancy. Findings from this new multicenter, prospective trial—published online Dec. 29 in Neurology—provide much-needed data to inform dosing strategies and support more systematic, evidence-based clinical decision-making, however.
This latest research was driven by a very simple question, said Page B. Pennell, MD, FAAN, chair of neurology at the University of Pittsburgh School of Medicine and the study's senior author: “How do we take what we know about drug clearance in pregnant women with epilepsy and provide guidance on medication dose adjustments based on real-world evidence that clinicians everywhere can actually adopt?”...
Frequent drug level monitoring proved essential in capturing the dynamic changes of pregnancy. Based on observed practice patterns, the study supports checking ASM levels approximately every four to six weeks, a schedule that may be more intensive than what many clinicians currently employ.
“This paper really reinforces that less-frequent monitoring, once per trimester, or only early and late in pregnancy, is probably insufficient,” Dr. Maturu said. “It gives us a much clearer sense of how often we should be checking levels and making adjustments.”
Importantly, metabolic changes begin early. Although women in MONEAD were enrolled up to 20 weeks' gestation, prior work by Dr. Pennell and colleagues has shown significant clearance changes as early as five weeks—prompting her to advise patients to contact their neurologist immediately after a positive pregnancy test...
The postpartum period has emerged as one of the most critical, and underappreciated, phases of ASM management. As pregnancy-related metabolic changes rapidly normalize, serum drug levels can rebound within days.
“In this study, the average time to dose reduction was about three days after delivery,” Dr. Maturu noted. “That's a very practical signal that we need to reassess medications almost immediately after childbirth.”
Dr. Pennell added that while doses often need to be reduced quickly, they may still remain slightly higher than pre-pregnancy levels to account for sleep deprivation, stress, and seizure vulnerability during early parenthood.
A key takeaway for Dr. Hopp was that monitoring must continue soon after birth, when ASM pharmacokinetics begin reverting toward baseline...
Both Drs. Pennell and Maturu stressed that these findings reinforce the need for routine, proactive pregnancy counseling for all patients of childbearing potential.
“About half of pregnancies in women with epilepsy are unplanned,” Dr. Maturu said. “That means these conversations can't wait until someone says they're trying to conceive.”
Preconception counseling should include establishing baseline ASM levels, explaining the likelihood of dose increases, and outlining a postpartum adjustment plan. Clear expectations improve adherence and reduce anxiety when changes become necessary, Dr. Pennell emphasized.
Dr. Hopp noted that counseling should help patients understand the rationale behind frequent monitoring and dose adjustments...
Data were also strongest for a limited number of commonly used ASMs, leaving many newer or less frequently prescribed agents understudied.
“Out of more than 30 antiseizure medications available, we have robust pregnancy safety data for only a handful of drug options,” Dr. Pennell said
https://neurologytoday.aan.com/doi/full/10.1097/01.wnt.0001189220.34776.35
Pennell PB, Li D, Kerr WT, Pack AM, French J, Gerard E, Birnbaum AK, McFarlane KN, Meador KJ; MONEAD Study Group. Antiseizure Medication Dosing Strategy During Pregnancy and Early Postpartum in Women With Epilepsy in MONEAD. Neurology. 2026 Jan 27;106(2):e214483. doi: 10.1212/WNL.0000000000214483. Epub 2025 Dec 29. PMID: 41461064.
Abstract
Background and objectives: Antiseizure medications (ASMs) undergo marked pharmacokinetic alterations during pregnancy and postpartum. Suboptimal ASM management can lead to adverse maternal and child outcomes. However, there is scant literature to guide how to adjust ASM dosing. This study analyzed how ASMs were dosed in a large observational cohort study of pregnant women with epilepsy (PWWE) who had favorable seizure outcomes.
Methods: Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) was a prospective, observational cohort study that enrolled PWWE 2012-2016 across 20 US epilepsy centers. Inclusion criteria were PWWE, ages 14-45 years, and <20 weeks' gestational age. Seizures and ASM type(s) and doses were documented in a daily diary. Our analysis included ASM doses in pregnancy through early postpartum (6 weeks post-delivery). For each ASM, we analyzed percent participants who underwent ≥1 dose change in pregnancy and postpartum, time of first dose change after enrollment, time to subsequent changes, amount of each dose adjustment, and percent of conception dose at delivery and 6-week postpartum.
Results: A total of 299 participants (median 31 [range 17-46] years) were eligible for analysis. Median enrollment was 14-weeks gestation. Dose increases were made in 246/363 (67.8%) of ASMs during pregnancy beginning median 32 days post-enrollment; dose decreases were made within 6 weeks post-delivery for 171/357 (47.9%) of ASMs beginning median 3 days postpartum. For lamotrigine, 128/146 (87.7%) participants had doses increased, by 100 mg/d (median), reaching 191% of conception dose (mean) by delivery. Postpartum, 103/146 (70.5%) had dose tapers, by 100 mg/d (median), to 116% of conception dose (mean) by 6 weeks. For levetiracetam, 70/125 (56.0%) participants had doses increased, by 500 mg/d (median), reaching 177% of conception dose (mean) by delivery. Postpartum, 43/125 (34.4%) had dose tapers, by 500 mg/d (median), to 136% of conception dose (mean) by 6 weeks. For other ASMs, 10/14 had doses increased in pregnancy and 8/14 were tapered early postpartum.
Discussion: Previous MONEAD analyses showed no difference in seizure control between pregnant and nonpregnant women with epilepsy. We detail how ASMs were managed in pregnancy and early postpartum to achieve this favorable outcome. These findings can be useful for the management of PWWE. Limitations of this study include limited data in the first trimester, enrollment from epilepsy centers, and limited number of participants on a wider variety of ASMs.
Maturu S, Long L. Navigating the Storm-A New Horizon: An Updated Guide for Managing Antiseizure Medications During Pregnancy and the Postpartum Period. Neurology. 2026 Jan 27;106(2):e214585. doi: 10.1212/WNL.0000000000214585. Epub 2025 Dec 29. PMID: 41461062.
Excerpt
This study by Pennell et al. offers a roadmap of guidance on increasing and decreasing ASMs during pregnancy and the postpartum period, respectively. This is particularly important considering new and updated national practice guidelines. As we move forward, it is important to confirm the benefit of medication adjustments during conception and the postpartum period and how we can use the pharmacokinetics and pharmacodynamics of all ASMs to improve outcomes for patients. Specifically, do patients that are pregnant who undergo ASM changes have better seizure control compared with those who maintain preconception doses? Is there a need to adjust ASMs in the first trimester, and if so, does earlier adjustment impact clinical outcomes? And finally, does a slightly higher dosing of ASMs in the postpartum period help with seizure burden?
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