Antiepileptic drug utilization : need of sex-specific information and decision support

Abstract

Antiepileptic drugs are used for the treatment of epilepsy and for other neurological and psychiatric conditions, and therefore is prescribing of antiepileptic drugs a concern for physicians from many disciplines. The age and sex-specific prevalence, as well as the role of sex and gender aspects, vary between the conditions for which antiepileptic drugs are used. The overall aim of this thesis was to gain more understanding of the use of antiepileptic drugs on various diagnoses, focusing on sex/gender differences, and to explore physicians' perceptions of sex and gender in decision making on drug treatment.

The first two studies describe the antiepileptic drugs used in epilepsy and other conditions. Clear age and gender differences in the use of specific anti-epileptics were observed. The use of antiepileptic drugs in children and adolescents was mainly limited to epilepsy and the individual antiepileptic drugs prescribed appeared to be in accordance with approved indications and treatment guidelines. However, some antiepileptic drugs were used off-label in children and adolescents.

The third study evaluated the effect of a warning issued by the European Medicines Agency in November 2014 on restricted prescribing of valproic acid to girls and women of childbearing potential. The analyzes showed that the warning only affected the prescribing in girls and women with a psychiatric diagnosis. Prescribing to girls and women with epilepsy had decreased long before the warning was issued, which could indicate an increased awareness of the teratogenic risk of valproic acid among neurologists treating women with epilepsy.

The fourth study examined how primary care physicians perceive sex/gender and gender equality related to drug prescribing. The results showed that physicians experienced insufficient knowledge of sex/gender differences in drug treatment, although their expressed clinical experience indicated some awareness. The patient's sex was considered during diagnosing while drug prescribing decisions followed the regional recommendation lists because these were believed to be evidence-based and gender-neutral. Overall, physicians wanted more education and knowledge about sex and gender in drug treatment. However, finding reliable information about sex and gender aspects for individual drugs may be difficult. This can be facilitated by the web-based knowledge base Janusmed Sex and Gender, as described in the fifth study.

In summary, this thesis demonstrates sex differences in use of certain antiepileptic drugs, which probably reflect the different benefit and risk from these between men and women. Knowledge of how antiepileptic drugs are prescribed and used in women and men with different diagnoses may be useful in discussions on rational drug prescribing and to propose measures to improve prescribing behavior. As shown in this thesis, regulatory measures may be one approach to improve rational prescribing and to highlight the importance of the patient's sex. Another approach may be to get acquainted with sex and gender-related pharmacological information through the knowledge base Janusmed Sex and Gender.