Prevalence trends and individual patterns of antiepileptic drug use in pregnancy 2006‐2016: A study in the five Nordic countries, United States, and Australia

Abstract

PurposeTo describe recent international trends in antiepileptic drug (AED) use during pregnancy and individual patterns of use including discontinuation and switching.MethodsWe studied pregnancies from 2006 to 2016 within linked population‐based registers for births and dispensed prescription drugs from Denmark, Finland, Iceland, Norway, Sweden, and New South Wales, Australia and claims data for public and private insurance enrollees in the United States. We examined the prevalence of AED use: the proportion of pregnancies with ≥1 prescription filled from 3 months before pregnancy until birth, and individual patterns of use by trimester.ResultsPrevalence of AED use in almost five million pregnancies was 15.3 per 1000 (n = 75 249) and varied from 6.4 in Sweden to 34.5 per 1000 in the publicly‐insured US population. AED use increased in all countries in 2006‐2012 ranging from an increase of 22% in Australia to 104% in Sweden, and continued to rise or stabilized in the countries in which more recent data were available. Lamotrigine, clonazepam, and valproate were the most commonly used AEDs in the Nordic countries, United States, and Australia, respectively. Among AED users, 31% only filled a prescription in the 3 months before pregnancy. Most filled a prescription in the first trimester (59%) but few filled prescriptions in every trimester (22%).ConclusionsUse of AEDs in pregnancy rose from 2006 to 2016. Trends and patterns of use of valproate and lamotrigine reflected the safety data available during this period. Many women discontinued AEDs during pregnancy while some switched to another AED.

Twenty-year trends in the use of anti-seizure medication among pregnant women in the Netherlands

“…General trends observed were also very similar to previous multinational studies: increases in the known safest ASMs lamotrigine and levetiracetam [11,13,23,24] as well as in ASMs with uncertain risk, often referred to as the ''second-generation" drugs [9,10,13]. Similar declining trends were observed for the higher risk medications, valproic acid and carbamazepine [9,11,24,25], with the exception of the newer topiramate [1,11,13]. In addition to other studies, we compared these trends with female reference populations.…”

“…Our estimate of overall ASM exposure during pregnancy was somewhat lower than observed in a study published in 2015 (3.6 vs. 4.3 per 1000) in which a broader ASM definition was applied [11]. General trends observed were also very similar to previous multinational studies: increases in the known safest ASMs lamotrigine and levetiracetam [11,13,23,24] as well as in ASMs with uncertain risk, often referred to as the ''second-generation" drugs [9,10,13]. Similar declining trends were observed for the higher risk medications, valproic acid and carbamazepine [9,11,24,25], with the exception of the newer topiramate [1,11,13].…”

“…In addition to other studies, we compared these trends with female reference populations. Few studies have been published on medication changes around pregnancy; how-ever, a multinational study concluded that patients switched mostly from valproate or topiramate [13]. We observed a higher tendency to switch from carbamazepine than from topiramate, potentially because overall use of topiramate was lower in our study.…”

“…Several international studies have been published assessing ASM exposure among pregnant women over time [9][10][11][12][13][14] and our study showed that valproic acid use remained common [14]. However, recent long-term population-based data on the full spectrum of ASMs are lacking.…”

Generating Real-World Evidence on the Quality Use, Benefits and Safety of Medicines in Australia: History, Challenges and a Roadmap for the Future

“…Importantly, Australian data have been used in six [38,[55][56][57][58][59] global studies investigating medicinerelated health outcomes, using novel statistical techniques that evaluate the sequence of medicines dispensed to identify medicine-adverse events. Another 26 have focused on utilisation patterns to benchmark medicine use in Australia against other countries, such as medicines for attention-deficit hyperactivity disorder (ADHD) [44], antipsychotics [60], and antiepileptics [61]. By international standards the number of individual-level medicine use and outcomes studies conducted in Australia is small [37] and certainly not delivering on its potential given the wealth of data available in this country.…”