What are the recommendations for managing seizure medications during pregnancy?

Managing Seizure Medications During Pregnancy

Women with epilepsy who are pregnant or planning pregnancy should be transitioned to levetiracetam or lamotrigine monotherapy at the lowest effective dose, while avoiding valproate due to its high teratogenic risk, and should receive high-dose folic acid (4-5 mg daily) starting before conception. 1, 2

Preconception Planning and Counseling

Women with epilepsy should receive nondirective counseling about pregnancy risks, including the fact that approximately one-third will experience increased seizures during pregnancy, and that congenital anomaly risk is elevated regardless of medication status 1. The goal is to optimize medication regimen before conception occurs 1, 3.

Key Counseling Points:

• Maintaining control of tonic-clonic seizures is critical for both maternal and fetal health 4
• Uncontrolled seizures pose greater risks than most antiepileptic medications 1
• The likelihood of having a healthy baby remains very high with appropriate management 3

Medication Selection and Optimization

Preferred Medications:

Levetiracetam and lamotrigine have emerged as the safest options during pregnancy based on current evidence 1, 5, 6. Recent clinical experience suggests levetiracetam may maintain better seizure control during pregnancy than lamotrigine, which experiences significant blood level drops due to pregnancy-related pharmacokinetic changes 6.

Medications to Avoid:

• Valproate must be avoided due to elevated risk of fetal malformations, particularly at doses above 800 mg/day 2, 4, 6
• Phenytoin, carbamazepine, and phenobarbital are teratogenic and should be avoided when equally effective alternatives exist 2
• Topiramate should be avoided due to teratogenic concerns 5

Monotherapy vs. Polytherapy:

Aim for monotherapy at the lowest effective dose whenever possible, as polytherapy increases teratogenic risk 1, 2. However, not all polytherapy combinations are equally harmful—the key is avoiding valproate and topiramate in combinations 5.

Folic Acid Supplementation

High-dose folic acid (4-5 mg daily) should be started at least one month before conception and continued through the first trimester to reduce neural tube defect risk 1, 2, 3. This is substantially higher than standard prenatal supplementation 1.

A common pitfall: Only 12% of women planning pregnancy in one tertiary center were taking folic acid, indicating this recommendation is frequently missed 6.

Medication Adjustments During Pregnancy

Monitoring Strategy:

• Frequent monitoring of serum drug levels throughout pregnancy is essential due to physiological changes affecting drug metabolism 1, 4
• Lamotrigine levels can drop significantly during pregnancy, requiring dose adjustments 6
• Levetiracetam pharmacokinetics are also affected, though it appears more stable than lamotrigine 6

Dosing Principles:

• Use the lowest dosage that maintains seizure control 3
• Consider more frequent dosing intervals to minimize peak drug concentrations 7
• Never abruptly discontinue antiepileptic medications during pregnancy, as breakthrough seizures can be catastrophic 1, 8

Prenatal Care and Monitoring

Specialized Care Coordination:

Arrange consultation with maternal-fetal medicine specialists and neurologists for coordinated care 1. Schedule more frequent prenatal visits to monitor both seizure control and pregnancy progression 1.

Fetal Monitoring:

• High-resolution ultrasonography before week 20 of gestation 3
• Serum alpha-fetoprotein measurement 3
• Amniocentesis is not routinely indicated 3

Specific Medication Considerations

Levetiracetam:

The FDA label indicates levetiracetam is Pregnancy Category C, with animal studies showing developmental toxicity at doses similar to or greater than human therapeutic doses 9. However, clinical evidence supports it as one of the safest options available 1, 5, 6. Levetiracetam is excreted in breast milk, requiring individualized decisions about breastfeeding 9.

Oxcarbazepine:

If a patient is on oxcarbazepine, consider transitioning to levetiracetam or lamotrigine, as oxcarbazepine requires consideration for alternative therapy during pregnancy 8. Serum level monitoring is recommended if oxcarbazepine is continued 10.

Labor, Delivery, and Postpartum

Emergency Preparedness:

Activate emergency medical services for pregnant individuals experiencing seizures, as this represents a critical medical emergency 2. Seizures lasting >5 minutes require immediate intervention 2.

Breastfeeding:

Breastfeeding should be encouraged in women taking lamotrigine or levetiracetam, with monitoring of the infant for possible adverse effects 10, 3. The benefits of breastfeeding generally outweigh theoretical risks of antiepileptic drug exposure through breast milk 3.

Common Pitfalls to Avoid

• Never stop antiepileptic medications abruptly due to pregnancy concerns—this can precipitate status epilepticus 1, 8
• Don't fail to adjust medication doses in response to pregnancy-related pharmacokinetic changes 1
• Avoid switching medications during pregnancy if possible—medication changes should be attempted before conception 4
• Don't overlook the psychological impact of managing chronic epilepsy during pregnancy 1
• Recognize that pregnancy generally has little effect on overall seizure control, though individual variation exists 4

Registry Enrollment

Encourage enrollment in the North American Antiepileptic Drug (NAAED) pregnancy registry by calling 1-888-233-2334 to contribute to safety data collection 9.