Valproate and female patients: Prescribing attitudes of Italian epileptologists Loretta Giuliano a, ⁎, Angela La Neve b , Carlo Andrea Galimberti c , Umberto Aguglia d , Leonilda Bilo e , Caterina Ermio f , Giulia Monti g , Elena Zambrelli h , Corrado Zenesini g , Barbara Mostacci g a Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", Section of Neurosciences, University of Catania, Catania, Italy b Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Italy c Epilepsy Center, IRCCS Mondino Foundation, Pavia, Italy d Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Italy e Epilepsy Center, University “Federico II”, Naples, Italy f Department of Neuroscience, “S. Giovanni Paolo II” Hospital, Lamezia Terme, Catanzaro, Italy g IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy h Epilepsy Center, San Paolo Hospital, Milan, Italy abstract article info Article history: Received 27 March 2019 Revised 17 May 2019 Accepted 17 May 2019 Available online xxxx Introduction: After the European Medicines Agency (EMA) warning on the use of valproate (VPA) in female pa- tients, we explored the antiepileptic drug (AED) prescribing attitudes of Italian epileptologists with regard to sex and VPA use in patients with epilepsy. Material and methods: A specifically designed 30-item questionnaire was distributed at the annual multicenter meeting of the Italian League Against Epilepsy (LICE), held in Rome on January 2018. One hundred and sixty- nine physicians answered the questionnaire. Results: In females, VPA was significantly less prescribed as first-choice AED in childhood absence epilepsy (22% females vs 64% males, p b 0.001), Dravet syndrome (54% vs 71%, p = 0.01), juvenile myoclonic epilepsy (JME) (2% vs 74%, p b 0.001), and undetermined epilepsy (0% vs 32%, p b 0.001). Ninety-six percent of the respondents in- form teenage girls of the detrimental effects of intrauterine exposure to VPA; 74% recommend contraceptive measures when prescribing VPA. All the respondents stated that they were aware of the recommendations on VPA in female patients, and 64% claimed to have had difficulties in implementing them. Conclusions: The main challenges were represented by women with JME, who were seizure-free on VPA and failed to respond to levetiracetam and lamotrigine, and by little girls for whom VPA was considered the best choice. According to many Italian epileptologists, the decision to withdraw VPA should be shared with the patient. © 2019 Elsevier Inc. All rights reserved. Keywords: Epilepsy Valproate Women Female Practice patterns 1. Introduction Valproic acid (VPA) has been acknowledged over the last 30 years as the most teratogenic antiepileptic drug (AED), with an average dose- dependent risk of approximately 10% for major birth defects [1]. More- over, in the last decade, several studies showed a significant relation be- tween womb exposure to VPA and slightly impaired cognitive function in school and preschool children [2–14]. Behavioral disturbances and autism spectrum disorder were also found to be significantly increased after intrauterine exposure to VPA [3,10–12,14]. After the subsequent warning of the European Medicines Agency (EMA) [15–18], endorsed also by the Italian Drug Agency (Agenzia Italiana del farmaco; AIFA) [19], neurologists are currently prevented from prescribing valproate for epilepsy in girls and women of childbear- ing age unless other treatments are ineffective or not tolerated. Nevertheless, several Authors questioned the advisability of indis- criminately withholding VPA in this population, mainly because of its effectiveness in generalized epilepsies, where alternative options are scanty [20,21] and to the subsequent consideration that women should have the same rights as men to receive the most effective treatment for their disease [22]. Noteworthy, pregnancy might not be an option for several women. Little data exist on the impact of such evidence and recommenda- tions on practice patterns in women with epilepsy. Common trends in different countries are a reduced prescription of valproate overall and Epilepsy & Behavior 97 (2019) 182–186 ⁎ Corresponding author at: Department of Medical and Surgical Sciences and Advanced Technology “G.F. Ingrassia”, Section of Neurosciences, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy. E-mail address: giuliano.loretta@gmail.com (L. Giuliano). https://doi.org/10.1016/j.yebeh.2019.05.024 1525-5050/© 2019 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh