Research Department, Social Insurance Institution of Finland, Turku.
Epilepsy Center, Neurocenter, School of Medicine, Institute of Clinical Medicine, Kuopio University Hospital and Faculty of Health Sciences, University of Eastern Finland, Kuopio.
Eur J Neurol. 2018 Jun;25(6):869-874. doi: 10.1111/ene.13610. Epub 2018 Mar 31.
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.
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.
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.
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.
有文献报道丙戊酸（VPA）具有致畸作用，因此在 2014 年限制其在育龄女性中的使用。我们调查了 2008-2016 年期间芬兰门诊 VPA 使用的可能年度变化，特别关注女性。
我们确定了 2008 年至 2016 年期间所有使用 VPA 的门诊患者，根据癫痫、双相情感障碍或其他指征对患者进行分类。使用泊松回归分析估计 VPA 使用的年度患病率趋势。
2012-2016 年期间，15-44 岁女性 VPA 使用的患病率下降了 19%，从 50/10000 降至 40/10000（患病率比，0.81；95%置信区间，0.77-0.91；P<0.001）。15-24 岁和 25-34 岁女性因癫痫使用 VPA 显著减少，25-34 岁和 35-44 岁女性因双相情感障碍使用 VPA 显著减少。15-44 岁女性中，杂项指征组的 VPA 使用量在 2014 年后下降了 32%，15-25 岁女性中下降了 56%，最为显著。在癫痫女性中，44 岁以上女性使用 VPA 的比例增加。
近年来，芬兰所有三个主要指征组具有生育能力的女性 VPA 用户比例均有所下降，尤其是在 2014 年欧洲药品管理局发布限制使用 VPA 的规定后。然而，VPA 的使用是否符合当前指南仍存在疑问。一个特别令人关注的问题是，在有生育能力的女性中，VPA 的标签外使用相对较高。
