What are safe antiepileptic (anti-seizure) medications during pregnancy?

From the Guidelines

Lamotrigine, levetiracetam, and carbamazepine are the safest options for managing seizure disorders during pregnancy, with lamotrigine having the most favorable safety profile. When considering the management of seizure disorders in pregnant women, it is crucial to weigh the risks of uncontrolled seizures against the potential teratogenic effects of antiepileptic drugs. According to the provided evidence, many major antiepileptic drugs, such as valproate, phenytoin, carbamazepine, and phenobarbital, are teratogenic, with rates of congenital anomalies related to higher doses and polytherapy 1.

Key Considerations for Antiepileptic Drug Use in Pregnancy

• Monotherapy should be used when possible at the lowest effective dosage to minimize risks 1.
• The choice of antiepileptic drug should be based on the safest option for the specific type of seizure disorder, with consideration of the potential for teratogenicity.
• Folic acid supplementation is essential for all pregnant women with epilepsy to reduce the risk of neural tube defects, with a recommended dose of 4-5 mg daily.
• Blood levels of antiepileptic drugs should be monitored regularly during pregnancy, as physiological changes can affect drug metabolism, potentially requiring dose adjustments.

Recommended Antiepileptic Drugs for Use in Pregnancy

• Lamotrigine is considered to have a favorable safety profile, with minimal risk of major congenital malformations, and is often recommended as a first-line option.
• Levetiracetam also shows low teratogenic potential and minimal cognitive effects on offspring, making it a viable alternative.
• Carbamazepine carries a slightly higher risk but is still considered acceptable, especially when the benefits of seizure control outweigh the potential risks.

Important Precautions

• Valproate should be avoided due to its higher risk of birth defects and neurodevelopmental issues.
• Any changes to antiepileptic medication regimens are best made before conception rather than during pregnancy to minimize risks.
• The lowest effective dose of antiepileptic medication should always be used to balance seizure control with minimizing fetal exposure risks.

From the FDA Drug Label

Carbamazepine tablets may harm your unborn baby Tell your healthcare provider right away if you become pregnant while taking carbamazepine tablets. You and your healthcare provider should decide if you should take carbamazepine tablets while you are pregnant.

Patients should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant.

Safe seizure meds in pregnancy are not explicitly listed in the provided drug labels. However, it is mentioned that:

• Carbamazepine may harm the unborn baby and its use during pregnancy should be decided by the healthcare provider.
• Phenytoin is classified as a Pregnancy Category D drug, which means there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans. It is essential to consult a healthcare provider to discuss the risks and benefits of using these medications during pregnancy. 2 2 3

From the Research

Safe Seizure Medications in Pregnancy

• The safety of seizure medications during pregnancy is a critical concern, as some medications may pose teratogenic risks to the fetus 4, 5.
• Lamotrigine and levetiracetam have been identified as having a lower teratogenic potential compared to other anti-seizure medications 4, 6.
• Oxcarbazepine also has a favorable profile in terms of teratogenic risks, while topiramate tends to have an unfavorable profile 4.
• Valproate, on the other hand, has a high teratogenic potential and should be avoided whenever possible, especially in women of childbearing age 4, 6.
• Folic acid supplementation is recommended to reduce the risk of major congenital malformations, although the optimal dose is unclear 4.

Medication Adjustments During Pregnancy

• Most anti-seizure medications require dosage adjustments during pregnancy to compensate for changes in serum levels 4, 5.
• Lamotrigine, oxcarbazepine, and levetiracetam often need to be increased during pregnancy, while valproate and carbamazepine may not require adjustments 4.
• Postpartum, medication doses can be reduced back to pre-pregnancy levels within a few weeks 5.

Breastfeeding and Seizure Medications

• Many anti-seizure medications are considered safe for breastfeeding, and women should be encouraged to breastfeed while taking these medications 4, 5.
• However, the safety of each medication during breastfeeding should be evaluated on a case-by-case basis, taking into account the individual woman's circumstances and the specific medication being used 4.

Comparative Efficacy and Safety of Seizure Medications

• Levetiracetam, lamotrigine, and carbamazepine have been compared in terms of efficacy and safety during pregnancy, with levetiracetam showing a better safety profile compared to carbamazepine 7.
• A network meta-analysis of individual participant data found that levetiracetam performed significantly better than carbamazepine and lamotrigine in terms of time to withdrawal of allocated treatment for individuals with partial seizures 6.
• The choice of seizure medication during pregnancy should be made on a case-by-case basis, taking into account the individual woman's circumstances, the type of epilepsy, and the potential risks and benefits of each medication 4, 6, 7.