Valproic Acid in Women of Reproductive Potential: Panacea or Pandora's Box

Valproic acid is a broad spectrum antiseizure medication used across epilepsy types. The association of valproic acid with teratogenicity, hepatoxicity, pancreatitis, female infertility, and more recently male infertility has resulted in recommendations and regulations that restrict its use, especially in women of reproductive potential. Large pregnancy registries indicate that valproic acid confers a teratogenicity risk of around 8 to 15%. Replacement of valproic acid with alternatives like levetiracetam and lamotrigine is associated with an approximately 20% risk of seizure recurrence or worsening. Factors like shorter duration of seizure remission before the switch, higher dose of valproic acid, multiple seizure types, and catamenial exacerbation of seizures could increase this risk. In this review, we focus on the role of valproic acid in epilepsy, with special emphasis on women in the reproductive age as well as the associated risks and the current regulations on its use. We also emphasize the importance of detailed communication and shared decision making in women of reproductive age who are considering a switch of medication from valproic acid to less teratogenic alternative.