Prescribing antiepileptic drugs to women of reproductive age

Abstract

The notion that use of antiepileptic drugs by pregnant women increases the risk for major congenital malformations is not new, but the oversimplification of grouping all antiepileptic drugs together into the same risk category is outdated. Data have accumulated to show the differential risks for major congenital malformations, with the highest risk consistently associated with in-utero valproate exposure. 1 Hernandez-Diaz S Smith CR Shen A et al. Comparative safety of antiepileptic drugs during pregnancy. Neurology. 2012; 78: 1692-1699 Crossref PubMed Scopus (399) Google Scholar The Neurodevelopmental Effects of Antiepileptic Drugs study also concluded that the highest risk for impaired cognitive function at 6 years of age occurs in the children of women who took valproate during pregnancy compared with other antiepileptic drug monotherapies. 2 Meador KJ Baker GA Browning N et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol. 2013; 12: 244-252 Summary Full Text Full Text PDF PubMed Scopus (526) Google Scholar Reports from pregnancy registries have also revealed that the teratogenic risk for valproate is dose dependent, 3 Harden CL Meador KJ Pennell PB et al. Practice parameter update: management issues for women with epilepsy—focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology. 2009; 73: 133-141 Crossref PubMed Scopus (274) Google Scholar and it was tempting for physicians to not worry about the level of the so-called safe antiepileptic drugs, such as lamotrigine. However, a landmark paper in 2011 by the investigators of the EURAP international registry, 4 Tomson T Battino D Bonizzoni E et al. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. Lancet Neurol. 2011; 10: 609-617 Summary Full Text Full Text PDF PubMed Scopus (549) Google Scholar reporting on 3909 pregnancies exposed to the four most common antiepileptic drug monotherapies (carbamazepine, valproate, lamotrigine, and phenobarbital), showed that not only did the antiepileptic drug choice matter in determining the relative risk of major congenital malformations, but also the dose at conception, even for lamotrigine despite having the lowest risk. Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registryDifferent antiepileptic drugs and dosages have different teratogenic risks. Risks of major congenital malformation associated with lamotrigine, levetiracetam, and oxcarbazepine were within the range reported in the literature for offspring unexposed to antiepileptic drugs. These findings facilitate rational selection of these drugs, taking into account comparative risks associated with treatment alternatives. Data for topiramate and phenytoin should be interpreted cautiously because of the small number of exposures in this study. Full-Text PDF