Elsevier

Epilepsy & Behavior

Volume 92, March 2019, Pages 26-30
Epilepsy & Behavior

Trends in valproate use in patients in Germany between 2009 and 2017

https://doi.org/10.1016/j.yebeh.2018.12.002Get rights and content

Highlights

  • In total, more than 1,000,000 patients were included in the study.

  • The use of valproate strongly decreased from 2009 to 2017 in young women.

  • The use of valproate also strongly decreased from 2009 to 2017 in young men.

  • There was a substantial decrease in the share of physicians prescribing valproate.

Abstract

Objective

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.

Methods

This study included all patients aged ≥ 15 years followed in 2009, 2013, and 2017 in neurological (N = 99) and general (N = 499) practices in Germany. Trends in valproate use were estimated based on the mean number of patients per practice who were prescribed valproate and the proportion of physicians prescribing it. Covariables included gender, age, and physician. This cross-sectional study uses descriptive statistics only.

Results

In total, 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 aged 15–45 years per practice with at least one valproate prescription decreased in neurological (men: 11.07 versus 9.92; women: 9.27 versus 5.88) and general practices (men: 0.82 versus 0.75; women: 0.60 versus 0.37) between 2009 and 2017. Moreover, the proportion of neurologists prescribing valproate in women between 15 and 45 years of age decreased over time (94% in 2009 versus 86% in 2017), and there was also a substantial decrease in the share of general practitioners prescribing valproate in men (47% versus 41%) and women between 15 and 45 years of age (37% versus 22%).

Conclusion

The proportion of men and women between 15 and 45 years of age receiving valproate decreased in neurological and general practices 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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