Mortality rates are higher in people with newly diagnosed and chronic epilepsy. Mortality risks should be discussed with patients with epilepsy, especially if anticonvulsant treatment is refused despite recurrent seizures.

Valproic acid (VPA) is a widely used anticonvulsant that is effective against most seizure types. Due to its teratogenic effects, its use should be avoided among females of childbearing age, unless other treatments are ineffective or not tolerated. This study aimed to determine the prevalence of VPA use in 2005-2018 in Estonia, with special attention to females of childbearing age. Methods: In this retrospective nationwide population-based cohort study, outpatient prescription data from the national health insurance provider were used. Annual sex-and age-specific prevalence rates were calculated, and changes therein during the study period were evaluated. Results: The annual rates of VPA use among females of childbearing age increased significantly in 2005-2014. After 2014, the increasing trend stopped; in 2014-2018, the prevalence rates declined slightly [prevalence rate ratio (PRR), 0.94; P = 0.136]. In males of the same age, the increasing trend continued (PRR, 1.08: P = 0.028). Among neurologists, the rate of VPA prescription to females aged < 15 and 15-44 years decreased during 2014-2018 (PRR, 0.74; P < 0.001 and PRR 0.72; P < 0.001, respectively); no change in prescription frequency was seen among psychiatrists during this period. Conclusions: The increasing trend in VPA usage among females of childbearing age in Estonia stopped after 2014, when the European Medicines Agency's strengthened restrictions on VPA use in females were communicated extensively in Estonia. The level of awareness of VPA's harmful effects during pregnancy is lower in the psychiatric community.

Although the overall risk of MS was similar in patients with epilepsy who were treated with VPA or CBZ, the distribution of MS components differed between treatment groups. Patients treated with CBZ or VPA less frequently had decreased high-density lipoprotein cholesterol levels or increased blood glucose concentrations, respectively. Females on VPA treatment could be at higher risk of MS than males.