Valproate effects on kinetics of lamotrigine in pregnancy and treatment with oral contraceptives

In eight women treated with lamotrigine monotherapy, the lamotrigine dose/plasma concentration (D/C) ratio increased by 295% from baseline outside pregnancy to midgestation, whereas in six women treated with lamotrigine in combination with valproate, the increase was only 60%. No difference in lamotrigine D/C ratio was found between users and nonusers of oral contraceptives comedicated with valproate. Valproate seems to reduce the induction of lamotrigine metabolism associated with pregnancy or use of contraceptives.