Many Women of Childbearing Age Still Given Teratogenic Antiepileptic Drugs

Many women of childbearing age with epilepsy appear to receive valproate, topiramate, and phenytoin despite known teratogenic risks.

Many women of childbearing age who have epilepsy are treated with drugs that feature a high teratogenic risk, including valproate, topiramate, and phenytoin, according to study results published in JAMA Neurology.

Researchers retrospectively identified females with epilepsy age 15 to 44 years from a nationwide commercial database and supplemental Medicare and Medicaid insurance claims data (N=46,767). Patients were only included in the analysis if they had an International Classification of Diseases, Ninth Revision, Clinical Modification-coded epilepsy diagnosis with medical and pharmacy enrollment (n=38,764; mean [SD] age, 29.7 [9.0] years). Conversely, incident cases (n= 8003; mean [SD] age, 27.3 [9.4] years) needed a ≥2-year baseline  time without an epilepsy diagnosis or prescription for an antiepileptic drug (AED) prior to the index date. The primary outcome was the pattern of AED treatment based on type of seizure and comorbidity.

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The majority of incident epilepsy cases (98.6%; 3173 of 3219) who received AEDs for ≥90 days had received monotherapy as first-line treatment. The majority of prevalent cases (67.2%; 18,987 of 28,239) also received monotherapy.

Patients with general epilepsy were more likely to be treated with valproate (incident: 5.81%; prevalent: 13.1%) and phenytoin (incident: 5.48%; prevalent: 4.53%), whereas patients with focal epilepsy were more likely to be treated with oxcarbazepine (incident: 8.03%; prevalent: 9.89%).

For focal and generalized epilepsy patients, the most frequently prescribed AEDs included levetiracetam (incident: focal [40.5%]; generalized [45.0%]; prevalent: focal [20.3%]; generalized [22.2%]), lamotrigine (incident: focal [18.6%]; generalized, [17.6%]; prevalent: focal, [24.8%]; generalized [22.2%]), and topiramate (incident: focal [15.5%]; generalized [10.6%]; prevalent: focal [12.8%]; generalized [12.0%]).

Women with epilepsy were more likely to be prescribed valproate if they had comorbid headache or migraine (incident: 4.2%; prevalent: 10.4%), mood disorder (incident: 7.3%; prevalent: 15.9%), and anxiety and dissociative disorders (incident: 6.5%; prevalent: 13.5%).

Study limitations included the reliance on retrospective claims data and the possibility of inclusion of female participants who had nonepileptic events but received a prescription for an AED.

Findings from this study suggest “that physicians and women of childbearing age with epilepsy should be aware of and sensitive to teratogenicity risks of certain AEDs,” wrote the researchers.


Kim H, Faught E, Thurman DJ, Fishman J, Kalilani L. Antiepileptic drug treatment patterns in women of childbearing age with epilepsy [published online April 1, 2019]. JAMA Neurol. doi:10.1001/jamaneurol.2019.0447