Valproate for Seizure Control Still Prescribed to Women of Reproductive Age

Among women of reproductive age and pregnant women with epilepsy, valproate remains the most commonly prescribed antiseizure medication (ASM) in Poland. Current prescription patterns of ASMs, like valproate, expose newborns to structural and neurobehavioral teratogenic effects. These are the findings of a study published in the journal Seizure.

Valproate during pregnancy is associated with major malformations at birth, cognitive and behavioral dysfunction, and autism spectrum disorder (ASD). Both national and European health organizations have advised against the use of older ASM drugs such as valproate and carbamazepine. Prescription patterns of these early-generation drugs have decreased, in favor of drugs such as lamotrigine, levetiracetam, and oxcarbazepine. However, subsequent research in women of reproductive age, both in Poland and in other countries worldwide, indicates that many with epilepsy still receive prescriptions for valproate. It remains unclear whether prescribing practices in Poland have changed to keep pace with public health advisories.

In a nationwide, population-based cohort study, researchers assessed the treatment patterns of ASMs in women of reproductive age and pregnant women with epilepsy in Poland. The researchers collected data from Poland’s National Health Fund, Poland’s publicly funded health care system, from 2019 through 2022. They analyzed medical records for 36,784 patients for 2019, and 32,304 patients for 2022. The women were between ages 15 and 49, diagnosed with epilepsy, and had filled a prescription for at least 1 antiseizure medication.

The researchers determined that in 2019, valproate was prescribed for 38% of women; it was the most-often prescribed drug for epilepsy, followed by levetiracetam and lamotrigine.

By 2022, however, only 32% of patients filled valproate prescriptions. Levetiracetam instead was most frequently prescribed (40%), followed by lamotrigine (33%; P <.001 for all comparisons over time). Carbamazepine was the least frequently used epilepsy drug throughout the study period.

Women aged 19 to 34 used valproate the least often, with only 28% receiving prescriptions by 2022. By contrast, girls aged 15 to 18 received valproate most frequently, and constituted nearly half of valproate users in the study. By 2022, they, too, filled valproate prescriptions less often (38%; P <.001).

Pregnant women most often received monotherapy other than valproate. Nevertheless, nearly 25% filled valproate prescriptions in 2019; this proportion fell to 16% by 2022. They more often received levetiracetam and lamotrigine. Far fewer women used other drugs such as topiramate or phenytoin for seizure control.

Study limitations included lack of information on any diagnoses beyond epilepsy corresponding to the ASM prescriptions, such as for psychiatric conditions; and on drug dosages, which may be relevant to neonatal outcomes. Also, pregnancies ending in abortions were not included in the analysis.

The researchers suggested that regulatory restrictions on prescribing valproate should be tightened to protect newborns. In particular, they warned, “It is of concern that valproate is the most commonly prescribed ASM in girls aged 15–18, with 38% of them still being treated with VPA [valproate] in 2022 in Poland. The rate of unplanned pregnancies may be high in this age group, not mentioning the risk of polycystic ovary syndrome related to valproate.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the authors’ disclosures.