Pharmacology of antiepileptic drugs during pregnancy and lactation Page B. Pennell a, * , Barry E. Gidal b , Anne Sabers c , Jacki Gordon d , Emilio Perucca e , for the International AED Pharmacology Work Group for the Health Outcomes in Pregnancy and Epilepsy Forum a Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA b School of Pharmacy and Department of Neurology, University of Wisconsin, Madison, WI, USA c The Epilepsy Clinic, Glostrup University Hospital, Glostrup, Denmark d Epilepsy Therapy Development Project, Reston, VA, USA e Clinical Pharmacology Unit, University of Pavia, and Institute of Neurology IRCCS C Mondino Foundation, Pavia, Italy Received 22 August 2007; accepted 23 August 2007 Abstract Most women with epilepsy require continuous treatment during pregnancy, making antiepileptic drugs (AEDs) one of the most fre- quent chronic teratogen exposures. Therapeutic decisions should balance the risks to the developing fetus of AED exposure and of not treating or undertreating the epilepsy. The International AED Pharmacology Work Group of the Health Outcomes in Pregnancy and Epilepsy (HOPE) Forum identified four pharmacology topics critical to enhancing maternal and fetal outcomes for pregnancies exposed to AEDs: (1) hormonal therapies and endogenous changes: bidirectional interactions with AEDs; (2) pharmacokinetic alterations during pregnancy, the role of therapeutic drug monitoring, and the influence on seizure control and maternal and fetal outcomes; (3) multidrug transporters and their various roles during pregnancy; (4) breastfeeding in mothers taking AEDs. The report provides an overview of these key topics, highlights gaps in the current knowledge, and provides future directions for needed research. Ó 2007 Elsevier Inc. All rights reserved. Keywords: Epilepsy; Antiepileptic drugs; Pregnancy; Puerperium; Lactation; Drug treatment; Drug safety; Pharmacokinetics; Research; Breast milk 1. Introduction The Epilepsy Therapy Development Project estab- lished the Health Outcomes in Pregnancy and Epilepsy (HOPE) Forum with nine international working groups to address the critical need for further investigations to establish the optimal treatment of women with epilepsy during pregnancy and the postpartum period. The work group involved in preparing this article (International AED Pharmacology Work Group) approached the topic with consideration of the identified tasks of the HOPE Forum: to provide an overview of the current literature, to identify knowledge gaps, and to determine how future studies should be designed to better answer the relevant questions, all with the ultimate goal of an overall needs assessment that may be used to help guide future research priorities. Here we report on the findings and recommendations of the International AED Pharmacol- ogy Work Group. Investigation of several different pharmacology topics should be a priority to improve care of women during the childbearing years and to enhance maternal and fetal outcomes for all pregnancies exposed to AEDs. Given that in utero exposure to AEDs confers risks for both congeni- tal malformations and neurocognitive deficits, it is essential that studies that assess these risks take into account the degree of fetal exposure. At least as important as the assessment of dose effects is the assessment of maternal plasma AED concentrations and umbilical cord AED 1525-5050/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2007.08.018 * Corresponding author. Address: Emory Epilepsy Program, Depart- ment of Neurology, Woodruff Memorial Research Building, 101 Woodruff Circle, Suite 6000, Atlanta, GA 30322, USA. Fax: +1 404 712 8576. E-mail address: page.pennell@emoryhealthcare.org (P.B. Pennell). www.elsevier.com/locate/yebeh Available online at www.sciencedirect.com Epilepsy & Behavior 11 (2007) 263–269