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Treatment of Juvenile Myoclonic Epilepsy in Patients of Child-Bearing Potential

  • Anna Serafini
  • Elizabeth Gerard
  • Pierre Genton
  • Arielle Crespel
  • Philippe GelisseEmail author
Current Opinion

Abstract

Juvenile myoclonic epilepsy (JME) is both a frequent and a very characteristic epileptic syndrome with female preponderance. Treatment of JME in women of childbearing potential must consider multiple factors such as desire for pregnancy, use of contraception, seizure control and previously used antiepileptic drugs (AEDs). Approximately 85% of cases are well controlled with valproate, which remains the reference AED in JME but is nowadays considered unsafe for the expecting mother and her fetus. The prescription of valproate is now severely restricted in women of childbearing potential but may still be considered, at the lowest possible dose and when pregnancies can be reliably planned, with temporary alternatives to valproate prescribed before fertilization. Alternatives have emerged, especially lamotrigine and levetiracetam, but also topiramate, zonisamide, and recently perampanel, but none of these AEDs can be considered fully safe in the context of pregnancy. In special settings, benzodiazepines and barbiturates may be useful. In some cases, combination therapy, especially lamotrigine and levetiracetam, may be useful or even required. However, lamotrigine may have the potential to aggravate JME, with promyoclonic effects. Carbamazepine, oxcarbazepine and phenytoin must be avoided. Valproate, levetiracetam, zonisamide, topiramate if the daily dose is ≤ 200 mg and perampanel if the daily dose is ≤ 10 mg do not affect combined hormonal contraception. Lamotrigine ≥ 300 mg/day has been shown to decrease levonorgestrel levels by 20% but does not compromise combined hormonal contraception. Patients with JME taking oral contraceptive should be counselled on the fact that the estrogenic component can reduce concentrations of lamotrigine by over 50%, putting patients at risk of increased seizures. Pregnancy is a therapeutic challenge, and the risk/benefit ratio for the mother and fetus must be considered when choosing the appropriate drug. Lamotrigine (< 325 mg daily in the European Registry of Antiepileptic Drugs in Pregnancy) and levetiracetam seem to be comparatively safer in pregnancy than other AEDs, especially topiramate and valproate. Plasma concentration of lamotrigine and levetiracetam decreases significantly during pregnancy, and dosage adjustments may be necessary. With persisting generalized tonic–clonic seizures, the combination of lamotrigine and levetiracetam offer the chance of seizure control and lesser risks of major congenital malformations. The risk of malformation increases when valproate or topiramate are included in the drug combination. In one study, the relative risk of autism and autism spectrum disorders (ASD) in children born to women with epilepsy (WWE) treated with valproate were, respectively, 5.2 for autism and 2.9 for ASD versus 2.12 for autism and 1.6 for ASD in WWE not treated with valproate. More studies are needed to assess the risk of autism with AEDs other than valproate. The current knowledge is that the risk appears to be double that in the general population. In patients with JME, valproate remains an essential and life-changing agent. The consequences of a lifetime of poorly controlled epilepsy need to be balanced against the teratogenic risks of valproate during limited times in a woman’s life. The management of JME in WWE should include lifestyle interventions, with avoidance of sleep deprivation, and planned pregnancy.

Notes

Compliance with Ethical Standards

Funding

No sources of funding were used to prepare this manuscript.

Conflicts of interest

Dr. Serafini has no conflicts of interest related to this article. Pr. Gerard has received speaker honoraria from UCB-China. She served as site principal investigator (PI) for industry-sponsored research (SAGE pharmaceuticals, Sunovion). She also serves as site PI for the MONEAD trial (U01NS038455). Dr. Genton has received speaker honoraria from Sanofi-Aventis, UCB, and Eisai. Dr. Crespel has received support from pharmaceutical companies for teaching programs (Sanofi-Aventis, UCB). Dr. Crespel served as a board member for Eisai-France. Dr. Gelisse has received support from pharmaceutical companies for teaching programs (Sanofi-Aventis, UCB, Psicofarma). He received a research grant from the French League Against Epilepsy and the Janssen-Cilag company. He was a paid consultant for Eisai-France in 2011.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Anna Serafini
    • 1
  • Elizabeth Gerard
    • 2
  • Pierre Genton
    • 3
  • Arielle Crespel
    • 4
  • Philippe Gelisse
    • 4
    Email author
  1. 1.Department of Neurology and RehabilitationUniversity of Illinois at ChicagoChicagoUSA
  2. 2.Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  3. 3.Centre Saint Paul-Henri Gastaut HospitalMarseilleFrance
  4. 4.Epilepsy UnitHôpital Gui de ChauliacMontpellier Cedex 05France

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