Doing without valproate in women of childbearing potential with idiopathic generalized epilepsy: Implications on seizure outcome

Objective: Valproate (VPA) use in women with idiopathic generalized epilepsy (IGE) who are of reproductive age has been a matter of concern and debate, which eventually led to the recent restrictions by regulatory agencies. The aim of our study was to investigate the relationship between VPA avoidance/switch and seizure outcome in women of childbearing potential. Methods: We retrospectively reviewed data from female patients with IGE, 13-50 years of age, followed since 1980. We evaluated the prescription habits, and the rate of VPA switch for other antiepileptic drugs (AEDs) and its prognostic implications. Seizure remission (SR) was defined as the absence of any seizure type more than 18 months before the last medical observation. The main aim of the study was to assess (a) possible changes in seizure outcome related to VPA switch for other AEDs, especially in patients planning a pregnancy; and (b) possible differences in SR based on the presence/absence of VPA at last observation. Results: One hundred ninety-eight patients were included in the study. Overall SR at last medical observation was 62.7%. SR significantly differed between subjects taking and those not taking VPA (P <.001) at last visit. Multiple regression models showed that taking VPA at last medical observation was strongly associated with SR in both the general population (P <.001) and the juvenile myoclonic epilepsy (JME) group (P <.001). Thirty-six (70.6%) of 51 patients who switched from VPA during follow-up experienced a clinical worsening. Switching back to VPA was more frequently associated with SR at last observation (P <.001). In those patients who substituted VPA in view of a pregnancy, SR and drug burden (monotherapy vs polytherapy) differed significantly before and after the switch. Significance: Our study suggests that VPA avoidance/switch might be associated with unsatisfactory seizure control in women with IGE who are of childbearing potential. Our findings further highlight the complexity of the therapeutic management of female patients of reproductive age.