Trends in valproate use in patients in Germany between 2009 and 2017
Introduction
Around one million people worldwide are taking valproate everyday [1]. Valproate, a γ-aminobutyric acid (GABA) agonist, was first approved in patients with epilepsy in France in the late 1960s, and its effectiveness in the context of severe epilepsy was documented in a randomized trial a few years later [2]. Currently, valproate is not only prescribed for epilepsy [3] but also for bipolar disorder [4] and migraine [5].
In recent years, there has been a growing evidence showing that valproate is a teratogenic drug and that the prescription of this molecule can have important deleterious effects in pregnant women [6]. A systematic review and meta-analysis found that the calculated incidence of births with congenital malformations was higher in women with epilepsy than in healthy women (7.08% versus 2.28%) and that the antiepileptic drug (AED) with the highest incidence was valproate (10.73%) [7]. Another meta-analysis of 29 cohort studies including 5100 infants and children exposed to AEDs in utero or during breastfeeding showed that the use of valproate was associated with cognitive developmental delays, autism, and psychomotor developmental delays [8]. The teratogenic effects of valproate are likely to be explained by increased levels of GABA in the brain, inhibition of voltage-gated sodium channels, and inhibition of histone deacetylases [9].
As a result of the growing concern about the safety of valproate, there has been a recent decrease in the prevalence of use of this drug in different countries [10], [11], [12], [13], [14]. However, data from Germany are scarce [14], and, since more than 15,700 people living in this country were prescribed valproate in 2009 [15], this scarcity of data is of particular concern. Therefore, the goal of this study was to analyze trends in valproate use in patients followed by neurologists and general practitioners in Germany between 2009 and 2017.
Section snippets
Database
This study was based on data from the Disease Analyzer database (IQVIA), which compiles drug prescriptions, diagnoses, and basic medical and demographic data obtained directly and in anonymous format from computer systems used in the practices of general practitioners and specialists [16]. Diagnoses (International Classification of Diseases, 10th revision [ICD-10]), prescriptions (Anatomical Therapeutic Chemical [ATC] Classification system), and the quality of reported data are being monitored
Results
Overall, 1,298,446 patients were followed in general and neurological practices in 2009, 1,358,160 in 2013, and 1,413,286 in 2017. The mean number of patients per practice with at least one prescription for valproate decreased in men (11.07 versus 9.92) and women aged 15–45 years (9.27 versus 5.88) followed in neurological practices between 2017 and 2009 while this number increased in men (12.07 versus 15.10) and women aged > 45 years (13.89 versus 15.91; Fig. 1). In general practices, there was
Discussion
To the best of our knowledge, this was the first study to analyze trends in valproate use among both men and women in Germany. The major finding of this retrospective study is that there was a decrease in the use of valproate among women of childbearing age. Interestingly, several authors have obtained similar results in other countries and settings. For example, Ackers and colleagues found in a 2009 population-based observational study conducted in the United Kingdom that the prevalence of
Author contributions
LJ contributed substantially to the conception of the study and the interpretation of the data, and drafted the manuscript. BS and JB contributed substantially to the conception of the study and the interpretation of the data, and revised the manuscript with a critical eye. KK contributed substantially to the conception of the study and the analysis of the data, and revised the manuscript with a critical eye. All authors gave the final approval of the version to be published.
Declaration of conflicts of interest
The authors declare that they have no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors have received no financial support for the research, authorship, and/or publication of this article.
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