Secular Trends in the Use of Valproate-Containing Medicines in Women of Childbearing Age in Europe: A Multinational DARWIN EU Network Study.
Bellas L., Català M., Burn E., Guo Y., Du M., Verhamme K., Fridgeirsson E., Duarte-Salles T., Kauko T., Kronqvist E., Brash JT., Seager S., Prieto-Alhambra D., Jödicke AM., Prats-Uribe A.
BACKGROUND: Valproate-containing medicines (VPA) are first-line treatments for epilepsy; however, they pose teratogenic risks, restricting their use in women of childbearing age. We aimed to estimate the secular trends in the use of VPA and alternative treatments in young women, and to characterise dose/strength, treatment duration, and indication in new VPA users. METHODS: We conducted a multi-national population-based cohort study using primary care records from the Netherlands, Spain, and the UK (IPCI, SIDIAP, CPRD GOLD), primary and outpatient specialist care records from Germany and Belgium (IQVIA DA Germany, IQVIA LPD Belgium), and hospital records from Finland (ACI VARHA), all mapped to the OMOP Common data model. All women present in the databases aged ≥ 12 and ≤ 55 years on the 1st of January of each year in the period 2010-2022 (or latest available), with at least 365 days of prior observation, were included. RESULTS: A total of 2 948 860 (CPRD GOLD), 718 835 (IPCI), 2 494 052 (SIDIAP), 157 361 (ACI VARHA), 218 250 (IQVIA LPD Belgium); and 5 152 752 (IQVIA DA Germany) women were included. Among those, 6416, 1241, 10 398, 1447, 945, and 4002 started treatments with VPA, respectively. Incidence and prevalence of VPA use in young women decreased between 2010 and 2021, while the prevalence of the alternative treatments pregabalin and gabapentin increased, especially in CPRD (it rises from 0.5% to 1.5%). Median age of new VPA users ranged between 40 and 43 years. Anxiety and depressive disorder were frequent comorbidities, and the use of hormonal contraceptives we were able to capture was low. Average treatment duration varied substantially across databases. CONCLUSION: Incidences and prevalence of use of VPA among young women declined since 2015. Conversely, alternative antiepileptics have increased in uptake, particularly gabapentinoids. The use of standardized federated analytics allowed for a rapid assessment of VPA utilization, supporting the regulatory agencies in their decision-making and improving patient safety across Europe.