Antiseizure medications consumption in 73 countries and regions from 2012 to 2022: a longitudinal trend study

Background: International trends in antiseizure medication use across countries from different geographical regions and income levels remain underexplored. Valproic acid (valproate) use has raised concerns due to its teratogenic risks, with World Health Organisation (WHO) guidelines recommending lamotrigine or levetiracetam as first-line therapy for epilepsy in women and girls of childbearing potential, advising against valproate use in this population. This study aimed to assess multinational trends in antiseizure medication (ASM) consumption from 2012 to 2022 in the context of evolving policy and regulatory actions. Methods: In this longitudinal trend study, we used pharmaceutical sales data of antiseizure medications from the IQVIA-Multinational Integrated Data Analysis System (MIDAS) between January 1, 2012 and December 31, 2022, covering 73 countries/regions. The list of ASMs included in this study was based on the Anatomical Therapeutic Chemical (ATC) Classification, N03A. We obtained the mid-year national/regional population estimates of each country from the United Nations Population Division and the total epilepsy (active idiopathic and secondary epilepsy) population from the Global Burden of Disease Collaborative Network. 41 high-income, 20 upper-middle income and 12 lower-middle-income countries/regions were included in this study. Antiseizure medication consumption rate was expressed as defined daily doses per 10,000 inhabitants per day (DDD/TID). Linear mixed models were used to estimate multinational, regional, and income-level trends in consumption over time. Findings: Multinational antiseizure medication consumption increased throughout the study period, with an average annual percentage change of +2·58% (95% CI +1·85% to +3·32%), rising from 40·96 DDD/TID (31·94-52·52) in 2012 to 52·87 DDD/TID (42·17-66·27) in 2022. The highest change in consumption was in South-eastern Asia (+5·20%, +3·41% to +7·03%), followed by Western Asia (+4·70%, +0·58% to +8·99%) and Southern Asia (+3·80%, +1·52% to +6·14%). Newer generation antiseizure medications such as levetiracetam (+21·72%, +13·86% to +30·11%) and lamotrigine (+7·48%, +6·34% to +8·63%) showed growth in consumption, while consumption of older medications such as phenobarbital (-2·85%, -9·50% to +4·29%), phenytoin (-11·19%, -17·58% to -4·30%), and carbamazepine (-1·09%, -1·95% to -0·23%) declined. In 2022, the consumption rate of high-income countries (88·36 DDD/TID, 71·69-108·90) was more than four times of lower-middle-income countries (15·63 DDD/TID, 8·75-27·91). Valproate remained the most widely used antiseizure medication globally (10·93 DDD/TID, 8·68-13·77) in 2022, with stronger growth observed in lower- (+4·24%, +1·73% to +6·81%) and upper-middle-income (+3·10%, +0·95% to +5·29%) countries, compared with high-income countries (+0·86%, -0·07% to +1·79%). Interpretation: Multinational antiseizure medication use increased between 2012 and 2022, particularly for newer medications like levetiracetam and lamotrigine. Disparities in access to antiseizure medications across countries of varying income levels persist, with valproate consumption remaining predominant. This underscores the urgent need to align prescribing practice with safety guidelines, in order to optimise patient outcomes. Since patient-level characteristics are not available in IQVIA-MIDAS, further research is warranted to examine consumption rates across different population groups. Funding: 4H) funded by AIR@InnoHK, administered by Innovation and Technology Commission of the Government of Hong Kong Special Administrative Region.