What are safe medication options for seizure prophylaxis and suppression in pregnancy?

From the Guidelines

Lamotrigine, levetiracetam, and carbamazepine are the safest medication options for seizure prophylaxis and suppression in pregnancy, with lamotrigine being the preferred choice due to its favorable safety profile and minimal association with birth defects. When considering medication options for seizure prophylaxis and suppression in pregnancy, it is essential to weigh the risks and benefits of each medication, as both the disease and its treatments can adversely affect pregnancy 1. Some key points to consider when selecting a medication include:

• Lamotrigine (starting at 25mg daily, gradually increasing to 100-400mg daily in divided doses) is often preferred due to its favorable safety profile and minimal association with birth defects.
• Levetiracetam (500-1500mg twice daily) is another excellent choice with limited evidence of teratogenicity.
• Carbamazepine (200-400mg twice daily) is also reasonable but carries a slightly higher risk of neural tube defects.
• All pregnant women taking antiepileptic medications should take high-dose folic acid (4mg daily) starting before conception and continuing throughout pregnancy to reduce neural tube defect risk, as recommended by guidelines for preconception counseling and care 1.
• Blood levels of these medications should be monitored regularly during pregnancy as physiological changes can alter drug metabolism, often requiring dose adjustments.
• Valproate should be avoided if possible due to its higher risk of birth defects and potential impact on the child's cognitive development.
• The goal is to control seizures with the lowest effective dose of the safest medication, as uncontrolled seizures pose significant risks to both mother and fetus.
• Any medication changes ideally should occur before conception rather than during pregnancy.

From the FDA Drug Label

Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy Patients should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry if they become pregnant. Valproic Acid Oral Solution, USP may harm your unborn baby. If you take Valproic Acid Oral Solution, USP during pregnancy for any medical condition, your baby is at risk for serious birth defects that affect the brain and spinal cord and are called spina bifida or neural tube defects.

Safe medication options for seizure prophylaxis and suppression in pregnancy are limited.

• Levetiracetam may be considered, but patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy.
• Valproate is not recommended due to the high risk of birth defects. It is essential to weigh the benefits and risks of each medication and consider alternative options when possible 2, 3.

From the Research

Safe Medication Options for Seizure Prophylaxis and Suppression in Pregnancy

The following medications are considered safe for seizure prophylaxis and suppression in pregnancy:

• Levetiracetam: often used as a less teratogenic agent 4
• Lamotrigine: often used as a less teratogenic agent, however, its disposition may change during pregnancy, reflected in declining plasma drug concentrations 5, 4
• Oxcarbazepine: its disposition may change during pregnancy, reflected in declining plasma drug concentrations 5
• Other antiepileptic drugs (AEDs) with low teratogenic risk: should be used at the lowest dose necessary to control seizures 4

Medications to Avoid in Pregnancy

• Valproic acid: should be avoided unless indispensable due to its high teratogenic risk, particularly at dosage levels >1000 mg/day 5, 6, 4
• Polytherapy: involving treatment with more than one AED, seems to be associated with an increased risk of birth defects compared with monotherapy 5

General Principles for Managing Epilepsy in Pregnancy

• Seizure control must not be neglected in a pregnant woman with epilepsy since seizures are associated with harm to the fetus as well as the mother 6
• The common treatment strategy has been to use the appropriate AED for the woman's seizure disorder as monotherapy in the lowest effective dosage throughout pregnancy 5
• Regular monitoring of drug concentrations is recommended during pregnancy, in particular for lamotrigine and oxcarbazepine 5, 7
• Folic acid supplementation is recommended for women with epilepsy, at dosage levels recommended for the general population of women of childbearing age 6