Why do some women with epilepsy use valproic acid despite current guidelines? A single-center cohort study

Current guidelines and regulations strongly discourage the use of valproic acid (VPA) in women of childbearing age because of the risk of congenital malformations and neurodevelopmental disability in children exposed to VPA in utero. Our goal was to establish the reasons for continued use of VPA in a cohort of women with epilepsy (WWE) and to characterize the subgroup of WWE who do not consent to withdraw VPA despite potential risks.

The study included consecutive adult premenopausal WWE who visited an outpatient epilepsy clinic between April 2017 and March 2018. Data on demographics (age, age at onset of epilepsy), characteristics of epilepsy (types and frequency of seizures), and its treatment were collected from medical records and seizure diaries. All WWE taking VPA were regularly informed about VPA-related risks and had the opportunity to discuss the withdrawal of VPA.

The study involved 353 WWE (mean age: 31.7 years). Focal epilepsy was diagnosed in 244 (69.1%) patients; 180 (51.0%) women had no seizures during last 12 months before the study visit, and 228 patients (64.6%) were on monotherapy. A total of 146 (41.3%) patients used VPA in the past, and 98 (27.8%) never used VPA. Of women who were currently on VPA (n = 109, 30.9%), 30 had concurrent severe disabilities that would make future pregnancy extremely unlikely, in further 15 patients, VPA was recommenced because of failure of alternative treatment and 64 women did not accept the plan of VPA withdrawal. Women currently on VPA were more likely to have genetic generalized epilepsy and to be on monotherapy (both p ≪ 0.001). Among 64 WWE who decided to continue therapy with VPA, 35 (55.5%) had generalized epilepsy and 35 (55.5%) were in remission, 27 (42.2%) had at least one child, 9 (14.1%) planned to have a child in the near future but only 15 (23.4%) used effective contraception.

Treatment with VPA is unavoidable in many WWE of childbearing age despite recent regulations. About 60% of WWE currently treated with VPA do not consent to withdraw VPA treatment after thorough consideration of potential risks and other 40% use VPA because pregnancy is highly unlikely and/or other treatments failed.