Impact of valproate discontinuation on seizure control in women of reproductive age

OBJECTIVE: To evaluate seizure control in women of reproductive age treated with valproic acid and to compare seizure outcomes between those who continued valproic acid and those who were switched to other anti-seizure medications. METHODS: Data of women with epilepsy were analyzed from prospectively maintained electronic medical records between 2013 and 2022 at a tertiary epilepsy referral center. Women aged 18 to 45 years with generalized or focal epilepsy who were well controlled on valproic acid were included. Clinical characteristics, anti-seizure medication use, seizure control during valproic acid treatment and after switching to other anti-seizure medications, adverse effects, and pregnancy-related complications were analyzed. RESULTS: Sixty-nine women with epilepsy who were seizure-free for at least one year on valproic acid were included. Of these, 28 had juvenile myoclonic epilepsy, 30 had other idiopathic generalized epilepsy subtypes, and 11 had focal epilepsy. Only 26 patients (37.68%) required a valproic acid dose greater than 800 milligrams per day for seizure control. Eighteen patients were switched from valproic acid to other anti-seizure medications, of whom 10 (55.55%) experienced seizure recurrence at 12-month follow-up. Among patients who continued valproic acid, teratogenicity occurred in three patients (5.88%), with a mean daily dose of 1133 milligrams. The requirement for polytherapy was higher in the switch group compared to the valproic acid continuation group (44.44% versus 11.80%). SIGNIFICANCE: In women with epilepsy who are well controlled on low-dose valproic acid, switching to alternative anti-seizure medications is associated with a high risk of seizure recurrence and increased need for polytherapy. Decisions regarding withdrawal of valproic acid should be individualized, planned well in advance of pregnancy, and made after detailed discussion with the patient, balancing the risks of losing seizure control against potential teratogenic effects.