The Need & Importance of Switching ASMs Preconception

Research shows that certain anti-seizure medications (ASMs) are more suitable for pregnancy than others. If a patient taking ASM(s) that pose higher risks is considering pregnancy, their clinician should help them understand why switching medications may be most conducive to a safe and healthy pregnancy and work with them to make the switch before they get pregnant.

When switching ASMs or adjusting dosages, the goal is to identify the lowest effective ASM dosage that will pose the least teratogenic risk to the fetus while maintaining the patient’s seizure control. This transition should start well in advance of pregnancy — for those who will undergo major changes in their ASM regimen, this could be as much as 12 months before the patient attempts to become pregnant. 

If a patient takes a high-risk ASM, it is important to talk to them about the potential risks of switching medications, including an impact on other existing health conditions and an increased risk of seizures.

Topics covered on this page include:

Evaluating ASM Options

When considering switching a patient’s ASMs, work with a neurologist to carefully assess the patient’s epilepsy-specific factors. Shared decision-making plays a crucial role in this process. Before making the switch, evaluate the patient's prescription history. Reintroducing a medication that failed to adequately control seizures or had intolerable side effects may not be effective if the reasons for discontinuing it still apply. 

Consider why the previous medication was ineffective and explore how factors could have impacted its efficacy and side effect profile. These factors could include: 

  • Triggers
  • Non-compliance
  • Substance use
  • Poor sleep hygiene 
  • External factors, such as mood or anxiety at the time of the epilepsy diagnosis

Exploring the patient’s history will help the clinician make a more informed decision about switching the patient’s ASMs. In some cases, it’s worth considering combining two lower-risk drugs, such as levetiracetam and lamotrigine, if one didn’t work well as monotherapy previously.

Advise patients to use contraception when switching or adjusting medications to defer pregnancy until their regimen is optimized. 

Switching ASMs During Pregnancy

Ideally, patients should attempt medication switches well before becoming pregnant. This advanced planning helps avoid exposing the fetus to multiple medications and increasing the risk of patient seizures. In cases of unplanned pregnancy, medication switching should not be attempted unless the patient is taking a medication of high risk throughout pregnancy (e.g., valproic acid). In this case, the clinician should evaluate whether the dose can be lowered or removed. 

Strategies for Handling Valproic Acid Prior to Pregnancy

Deciding to remove or lower valproic acid requires careful consideration of the patient’s epilepsy, seizure types, and medication trials. Trained specialists should do this in consultation with the patient. The patient’s healthcare providers may need to collaborate to schedule an appointment quickly. 

If quickly removing valproic acid (likely switching to levetiracetam), consider in-patient admission and consult a neurologist/epilepsy specialist for electroencephalogram (EEG) monitoring to ensure no excessive seizure activity is seen, then titrate dose accordingly.

The window for increased risk for major congenital malformations due to valproic acid exposure is generally complete by 13 weeks of pregnancy. If it is not possible to lower or remove valproic acid from a pregnant patient’s medication regimen before this point, it is not urgent to do so after. However, stopping continued exposure to valproic acid is likely to reduce the fetus’s risk of adverse neurodevelopmental outcomes. It’s vital to consider reducing or removing valproic acid regardless of how far along the patient’s pregnancy is.

NOTE: Lamotrigine is difficult to titrate once a patient is pregnant, given increased metabolism in pregnancy, and rarely should be started during pregnancy. Additionally, adding lamotrigine to valproic acid during a cross-over carries a high risk of rash.

For patients who require valproic acid to maintain seizure control, minimizing a patient’s valproic acid dose can lower teratogenic risk. Data suggests that valproic acid dosage can also drive polytherapy-related risks, so adding a second low-risk medication to lower valproic acid doses may be beneficial. A common approach to transitioning off valproic acid prior to pregnancy is:

  • Add levetiracetam to the patient's regimen and then gradually withdraw valproic acid over a period of four to six weeks. 
  • If levetiracetam is not completely effective, add lamotrigine to levetiracetam.
  • When adding lamotrigine to levetiracetam while the patient is not taking valproic acid, the standard titration of lamotrigine can be used. 
  • However, if the patient is still on valproic acid, a slower titration of lamotrigine at half the usual speed is an option. As an example:
    • Step 1: 25 mg every other day for two weeks
    • Step 2: 25 mg a day for two weeks
    • Step 3: 50 mg a day for two weeks 
    • Step 4: 100 mg a day, etc.
  • If levetiracetam is not tolerated, switching to lamotrigine is an option.

When possible, avoid switching directly from valproic acid to lamotrigine due to potential drug-drug interactions and the increased risk of allergic reactions such as Stevens-Johnson syndrome (SJS). However, if necessary (e.g., contraindication to levetiracetam):

  • The titration of lamotrigine should be adjusted accordingly to half as fast as usual (see above example). 
  • When withdrawing valproic acid, the levels of lamotrigine will decrease, which may require further dosage adjustments.

In idiopathic generalized epilepsies, consider an ambulatory EEG to rule out absence seizures and assess the response to new medications. 

If none of these approaches works, recommendations become less clear:

  • For generalized epilepsy, zonisamide (some favorable data supporting low rates of major congenital malformations, but there is limited cognitive data available) followed by lacosamide (no significant data available on risk of malformations or neurodevelopmental outcomes) may be considered. 
  • In cases of focal epilepsy, oxcarbazepine or carbamazepine followed by lacosamide may be a potential option.

With any transition of ASMs, it is important to obtain blood levels of the new medication approximately one week after the target dose and steady-state is achieved. Further dosage adjustments may be needed if the blood levels are particularly low or if seizures are not as well controlled as desired. The blood level will also help to establish the target concentration during pregnancy for therapeutic drug monitoring and dosage adjustments in pregnancy to accommodate the enhanced clearance of the new ASM.

Guide Your Patients

As clinicians, it is essential to guide and support our patients through the process of switching ASMs. The process can be overwhelming and stressful, particularly if they have a history of prior ASM treatments that were ineffective. Clearly communicate so patients understand why different ASMs are being considered. You should position the ASM switch as part of the larger pregnancy plan, keeping the long-term goal of a safe and successful pregnancy at the forefront. When tapering ASMs, such as valproic acid, provide clear directions to ensure a smooth transition. 

For patients facing an unplanned pregnancy, acknowledge the emotional impact it may have and respond with patience and understanding. Counsel your patient on the risks of pregnancy as you would any other patient but take their medication into account (see Anti-seizure Medications and Pregnancy & Suitability page).

Reviewed by: Page Pennell, MD FAES, August 2023