L J Virta1, R Kälviäinen2, K Villikka3, T Keränen4,5. 1. Research Department, Social Insurance Institution of Finland, Turku. 2. Epilepsy Center, Neurocenter, School of Medicine, Institute of Clinical Medicine, Kuopio University Hospital and Faculty of Health Sciences, University of Eastern Finland, Kuopio. 3. Finnish Medicines Agency, Helsinki. 4. Department of Neurology, Kanta-Häme Central Hospital, Hämeenlinna. 5. Science Service Center, Kuopio University Hospital, Kuopio, Finland.
Abstract
BACKGROUND AND PURPOSE: Documented teratogenic effects of valproate (VPA) prompted restrictions of its use in females of childbearing age in 2014. We investigated possible annual changes in the outpatient use of VPA in Finland during 2008-2016 with a special focus on women. METHODS: We identified all outpatients with VPA purchases between 2008 and 2016 categorizing users due to epilepsy, bipolar disorder or miscellaneous indications. Temporal trends in the annual prevalence rates of VPA use were estimated using Poisson regression analyses. RESULTS: Between 2012 and 2016, the prevalence of VPA use among women aged 15-44 years decreased by 19%, from 50/10 000 to 40/10 000 (prevalence rate ratio, 0.81; 95% confidence intervals, 0.77-0.91; P < 0.001). The use of VPA due to epilepsy decreased significantly in females aged 15-24 and 25-34 years and that due to bipolar disorders decreased significantly in females aged 25-34 and 35-44 years. The use of VPA in the miscellaneous indication group decreased by 32% after 2014 in females aged 15-44 years and, most strikingly, by 56% among those aged 15-25 years. In women with epilepsy, the use of VPA increased among those over the age of 44 years. CONCLUSIONS: The rates of female VPA users with childbearing potential have decreased in all three major indication groups in Finland during recent years, especially after the European Medicines Agency restrictions were published in 2014. However, it still remains open to question as to whether the practice of VPA use follows current guidelines. A special concern is the relatively high prevalence of off-label use of VPA in fertile-aged females.
BACKGROUND AND PURPOSE: Documented teratogenic effects of valproate (VPA) prompted restrictions of its use in females of childbearing age in 2014. We investigated possible annual changes in the outpatient use of VPA in Finland during 2008-2016 with a special focus on women. METHODS: We identified all outpatients with VPA purchases between 2008 and 2016 categorizing users due to epilepsy, bipolar disorder or miscellaneous indications. Temporal trends in the annual prevalence rates of VPA use were estimated using Poisson regression analyses. RESULTS: Between 2012 and 2016, the prevalence of VPA use among women aged 15-44 years decreased by 19%, from 50/10 000 to 40/10 000 (prevalence rate ratio, 0.81; 95% confidence intervals, 0.77-0.91; P < 0.001). The use of VPA due to epilepsy decreased significantly in females aged 15-24 and 25-34 years and that due to bipolar disorders decreased significantly in females aged 25-34 and 35-44 years. The use of VPA in the miscellaneous indication group decreased by 32% after 2014 in females aged 15-44 years and, most strikingly, by 56% among those aged 15-25 years. In women with epilepsy, the use of VPA increased among those over the age of 44 years. CONCLUSIONS: The rates of female VPA users with childbearing potential have decreased in all three major indication groups in Finland during recent years, especially after the European Medicines Agency restrictions were published in 2014. However, it still remains open to question as to whether the practice of VPA use follows current guidelines. A special concern is the relatively high prevalence of off-label use of VPA in fertile-aged females.