Anti-Seizure Medications During Pregnancy

Pregnant person speaking with doctor.

Epilepsy News From:

Tuesday, May 29, 2018

More than a million women with epilepsy are of childbearing age in the United States. Each year, 20,000 babies are born to women living with epilepsy. The fetus, or unborn baby, is exposed to anti-seizure medications in one of every 50 pregnancies.

What is the risk for seizures during pregnancy?

The best care for women with epilepsy during pregnancy aims at achieving complete seizure control while decreasing the fetus’ exposure to the potential harmful effects of anti-seizure medications. This is why the impact of pregnancy on medication levels and seizures is important to understand.

The following are results on a large study of women with epilepsy:

  • About two-thirds of the women were seizure free during their pregnancy
  • Seizure frequency is unchanged in the majority (70%) of the women during pregnancy
  • Approximately 12% have fewer seizures and a slightly higher percentage have more seizures during pregnancy

Women who have seizures a year before their pregnancy are more likely to continue to have seizures during their pregnancy than women with already fully-controlled seizures prior to pregnancy.

Why do seizures increase during pregnancy?

One of the reasons seizures increase during pregnancy is that blood levels of anti-seizure medications go down during pregnancy. Seizures are known to increase for some people when medication levels fall below one-third of the normal medication levels.

This is because the kidneys remove medications faster during pregnancy. Blood levels also may decrease because liver enzymes are triggered by pregnancy hormones. When this occurs, liver enzymes metabolize the medications faster. How fast a medication moves through the body is known as clearance.

  • Clearance of older medications (e.g., phenobarbital, phenytoin, carbamazepine, and valproic acid) increases during pregnancy by 10-55%.
  • Oxcarbazepine levels also tend to decrease during pregnancy however carbamazepine levels do not.
  • Of the new anti-seizure medications, lamotrigine and levetiracetam are the most widely used due to their known safety during pregnancy.
    • Clearance of lamotrigine and levetiracetam doubles during pregnancy compared to before pregnancy.
    • Lamotrigine levels tend to dramatically decrease during pregnancy, increasing the risk of seizures.
    • One study showed an increased seizure risk for women on lamotrigine when blood levels fell below two-thirds of the medication levels prior to pregnancy. This most often occurred in the second trimester.
    • Lamotrigine levels decrease differently from one pregnancy to another, even in the same person.

Are there guidelines?

Published guidelines recommend:

  • Monitoring anti-seizure medication levels at the beginning of each trimester and during the last month of pregnancy for women whose seizures are controlled.
  • Additional monitoring is recommended if seizures are not controlled or side effects occur.
  • Monitoring is also important in all cases to confirm medication adherence.
  • Free (unbound) concentrations should be measured for those anti-seizure medications that are highly bound to proteins in the blood, like phenytoin and valproic acid.

The frequency of drug-level monitoring needed during pregnancy depends on which anti-seizure medications are being used and whether seizures are controlled. Monitoring appears less important for drugs such as carbamazepine and valproic acid, where changes in drug levels are usually minor. Monitoring is more important for drugs with marked, but unpredictable, changes, such as lamotrigine, levetiracetam, oxcarbazepine, and possibly topiramate.

Summary

The following can help minimize seizure severity during pregnancy:

  • Understanding the impact of pregnancy on various seizure medications
  • Repetitive checking of antiseizure medication levels
  • Maintaining target pre-pregnancy medication levels

Related Links

References

  1. Yerby MS. Quality of life, epilepsy advances, and the evolving role of anticonvulsants in women with epilepsy. Neurology 55(2000):S21–31; S54 –58.
  2. Bobo WV, Davis RL, Toh S, et al. Trends in the use of antiepileptic drugs among pregnant women in the US, 2001-2007: a medication exposure in pregnancy risk evaluation program study. Paediatr Perinat Epidemiol 26(2012):578-588.
  3. Battino D, Tomson T, Bonizzoni E, Craig J, Lindhout D, Sabers A, et al. Seizure control and treatment changes in pregnancy: observations from the EURAP epilepsy pregnancy registry. Epilepsia 54(2013):1621–1627.
  4. Vajda FJE, O'Brien TJ, Graham JE, Hitchcock AA, Lander CM, Eadie MJ. Predicting epileptic seizure control during pregnancy. Epilepsy & Behavior 78 (2018): 91–95.
  5. Pennell PB. Antiepileptic drug pharmacokinetics during pregnancy and lactation. Neurology 61(2003): S35–S42.
  6. Pennell PB, Peng L, Newport DJ, Ritchie JC, Koganti A, Holley DK, et al. Lamotrigine in pregnancy: Clearance, therapeutic drug monitoring, and seizure frequency. Neurology 70(2008):2130–6.
  7. Reisinger TL, Newman M, Loring DW, Pennell PB, Meador KJ. Antiepileptic drug clearance and seizure frequency during pregnancy in women with epilepsy. Epilepsy & Behavior (2013):13-18.
  8. Harden C, Pennell P, Koppel B, Hovinga C, Gidal B, Meador K, et al. Management issues for women with epilepsy – focus on pregnancy (an evidence-based review): III. Vitamin K, folic acid, blood levels, and breast-feeding: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsia 50 (2009b):1247–1255.
  9. Tomson T, Landmark CJ, Battino D. Antiepileptic drug treatment in pregnancy: Changes in drug disposition and their clinical implications. Epilepsia 54(2013):405–414.
Authored by: Anumeha Sharma Sheth MD on 5/2018
Reviewed by: Joseph I. Sirven MD on 5/2018

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