What are the recommended anti-seizure (antiepileptic) medications for pregnant women?

Anti-Seizure Medications for Pregnancy

Lamotrigine and levetiracetam are the recommended first-line anti-seizure medications for pregnant women with epilepsy due to their lowest teratogenic potential, while valproate must be avoided whenever possible due to severe risks of congenital malformations and neurodevelopmental disorders. 1, 2

First-Line Medications

Lamotrigine and levetiracetam should be prioritized as first-line agents for women with epilepsy during pregnancy. 1, 2

• Both medications demonstrate the lowest teratogenic potential among anti-seizure medications 1
• Levetiracetam is associated with a low incidence of major congenital malformations based on pregnancy registry data 3
• These agents are relatively safe compared to older anti-seizure medications 2

Second-Line Options

Oxcarbazepine has favorable safety data and can be considered as an alternative option. 1

• Data on teratogenic risks are favorable for oxcarbazepine 1
• This medication may be appropriate when first-line agents are ineffective or not tolerated 1

Medications to Avoid or Use with Extreme Caution

Valproate must be avoided in pregnant women and women of childbearing potential whenever possible. 4, 5, 1

• Valproate increases the risk of neural tube defects to approximately 1-2%, compared to the general population risk of 0.14% 5
• The North American Antiepileptic Drug Pregnancy Registry reported a 10.7% congenital malformation rate with valproate monotherapy, representing a 4-fold increase compared to other anti-seizure medications 5
• Valproate causes negative impacts on neuropsychological development in children exposed in utero 1
• If valproate is absolutely necessary (when seizure freedom cannot be achieved with other medications), the patient must be fully informed of risks and folic acid supplementation is mandatory 4, 1

Topiramate and phenobarbital should be avoided due to elevated teratogenic risks. 1, 2

• Topiramate has an unfavorable teratogenic profile 1
• Both medications are associated with elevated risks of congenital malformations and neurodevelopmental disorders, though lower than valproate 2

Critical Dosing Considerations During Pregnancy

Most anti-seizure medications require dose increases during pregnancy to maintain therapeutic levels, with careful therapeutic drug monitoring essential. 1, 3, 6

Medications Requiring Dose Increases:

• Lamotrigine, oxcarbazepine, and levetiracetam need to be increased during pregnancy to compensate for declining serum levels 1
• Levetiracetam concentrations decrease significantly throughout most months of pregnancy 6
• For levetiracetam, maintain levels above 65% of preconceptional concentration in women who had seizures within 12 months before pregnancy 6
• Monthly therapeutic drug monitoring is recommended for levetiracetam during pregnancy 3, 6

Medications NOT Requiring Dose Increases:

• Valproate and carbamazepine are exceptions that typically do not require dose increases 1

Postpartum Management

After delivery, anti-seizure medication doses must be rapidly decreased to prevent toxicity. 1

• Baseline preconceptional levels are reached relatively quickly postpartum 1
• Down-titration should be performed empirically based on clinical response 1
• For levetiracetam specifically, changing from once-daily extended-release to twice-daily dosing at delivery may improve seizure control 3

Breastfeeding Recommendations

Women on anti-seizure medication monotherapy should be encouraged to breastfeed, as most medications are moderately safe. 4, 1

• Many anti-seizure medications in monotherapy are safe for breastfeeding 1
• Standard breastfeeding recommendations apply for phenobarbital, phenytoin, carbamazepine, and valproic acid 4
• The benefits of breastfeeding generally outweigh the minimal risks of medication exposure through breast milk 1

Essential Supplementation

Folic acid supplementation is mandatory for all women with epilepsy who are pregnant or planning pregnancy. 4, 1

• Folic acid reduces the risk of major congenital malformations 1
• For women on most anti-seizure medications, standard folic acid supplementation should be taken routinely 4
• Women with seizure disorders should receive 4 mg of folic acid daily, starting at least one month before conception and continuing through the first trimester 4

Key Clinical Pitfalls to Avoid

Do not discontinue anti-seizure medications abruptly in pregnant women, as this poses serious risks. 5

• Abrupt discontinuation can precipitate status epilepticus with attendant hypoxia and threat to life 5
• The severity and frequency of seizures must be weighed against medication risks 5
• Even minor seizures may pose hazards to the developing fetus 5

Do not rely solely on seizure-free status to guide monitoring intensity. 6

• Women who had seizures within 12 months before pregnancy require more careful monitoring as they are at higher risk for seizure frequency increase 6
• Low levetiracetam concentrations are significantly associated with increased seizure frequency in non-seizure-free patients 6

Do not assume newer anti-seizure medications are safe without adequate data. 2

• Insufficient data exist for eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate 2
• These medications should only be used when benefits clearly outweigh unknown risks 2