The impact of pregnancy-related hormonal and physiological changes on antiseizure medications: expert perspective

ABSTRACT

Introduction

Epilepsy is a disorder of recurrent, unprovoked seizures affecting approximately 15 million individuals of childbearing potential worldwide. Patients with epilepsy rely on regular daily therapy with antiseizure medications (ASMs). Furthermore, ASMs are also prescribed for other neuropsychiatric indications (e.g. bipolar disorder, pain, migraines) with over 2% of the pregnancies in the United States involving prenatal exposure to ASMs.

Areas covered

ASM concentrations are affected by hormonal and physiological changes in pregnancy, including increases in renal and hepatic blood flow, decreased protein binding, and changes in enzyme activity. Clearance changes typically reverse within a few weeks after delivery. During pregnancy, many ASMs, such as lamotrigine, levetiracetam, and oxcarbazepine, should have serum concentrations monitored and doses increased to maintain the individualized target range for seizure control. ASMs metabolized via glucuronidation, primarily lamotrigine, undergo marked increases in clearance throughout pregnancy, requiring about 3-fold the pre-pregnancy daily dose by delivery. Postpartum, ASM doses are usually decreased over several weeks to prevent drug toxicity.

Expert opinion

In the future, the development of a physiologically-based pharmacokinetic model for various ASMs may enable empiric dose adjustments in pregnancy without the difficulties of frequent therapeutic drug monitoring.

KEYWORDS:

• Antiseizure medications
• epilepsy
• hormones
• pregnancy
• postpartum

Article highlights

• Antiseizure medications (ASMs) are commonly used among individuals of childbearing potential

• During pregnancy, the rise in estrogen and several physiological changes are responsible for increased clearance of several ASMs

• The postpartum period is characterized by a rapid decrease in ASM clearance back to non-pregnant baselines

• ASM levels should be monitored closely in pregnancy and doses adjusted to prevent a decrease in blood concentrations and worsening of seizure control

• In the future, personalized ASM dosage adjustments in pregnancy may be easier and more accessible with the establishment of physiologically-based pharmacokinetic models and identification of personal variables affecting gestational-induced drug clearance, such as genotype, epigenetics, and the gut microbiome

Declaration of interest

PB Pennell receives royalties from UpToDate, research support from the National Institutes of Health, and honoraria/travel reimbursements from the American Epilepsy Society, National Institutes of Health, Epilepsy Foundation, International League Against Epilepsy, and academic medical centers. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.