Safe Antiepileptic Medications in Pregnancy
Levetiracetam is the safest first-line antiepileptic medication for pregnant women with epilepsy, showing no increased risks for major congenital malformations, long-term neurodevelopmental outcomes, psychiatric disorders, or growth impairment. 1
First-Line Medication Recommendation
- Levetiracetam should be the preferred choice based on large, well-controlled studies demonstrating excellent safety for both structural and neurodevelopmental outcomes 1
- Levetiracetam demonstrates better seizure control during pregnancy compared to lamotrigine, which experiences significant blood level drops requiring dose adjustments 2
- Lamotrigine is a reasonable alternative with relatively low malformation rates, though it requires careful monitoring as blood levels decline substantially during pregnancy, potentially leading to breakthrough seizures 2, 3, 4
Medications That Must Be Avoided
- Valproate must be completely avoided due to the highest teratogenic risk among all antiepileptics, causing major congenital malformations and severe neurodevelopmental impairment 1, 5, 4
- Phenytoin, carbamazepine, and phenobarbital should be avoided when possible due to associations with congenital anomalies 1, 6
- Topiramate and phenobarbital carry elevated risks of both congenital malformations and neurodevelopmental disorders, though lower than valproate 4
Practical Management Algorithm
Pre-Pregnancy Planning
- Achieve seizure control at the lowest effective dose before conception 1
- Switch from valproate or other high-risk medications to levetiracetam or lamotrigine at least 3-6 months before planned pregnancy 1, 3
- Initiate folic acid supplementation preconceptionally, though compliance remains challenging with only 12% of women taking it appropriately 2
During Pregnancy
- Use monotherapy whenever possible, as polytherapy increases malformation risk 3, 4
- Monitor drug concentrations regularly, particularly for lamotrigine and oxcarbazepine which show the most pronounced declines during pregnancy 3
- For lamotrigine users, expect dose increases of approximately 29% during pregnancy to maintain therapeutic levels 2, 7
- Prioritize preventing generalized tonic-clonic seizures, as these pose greater risk to mother and fetus than appropriate medication use 3
Important Caveats
- The primary goal is preventing tonic-clonic seizures, which are more dangerous to the fetus than appropriate antiepileptic medication use 3
- Newer antiepileptics (eslicarbazepine, perampanel, brivaracetam, cannabidiol, cenobamate) lack sufficient pregnancy data for safety conclusions 4
- Oxcarbazepine may cause birth control failure and requires alternative contraception methods; many patients allergic to carbamazepine are also allergic to oxcarbazepine 8
- Breastfeeding does not appear to add additional long-term risks to the child 4