The Kimford J. Meador Research in Women with Epilepsy Award is awarded to provide support for ealy career clinician scientists who have made significant contributions to understanding and better care for women with epilepsy. This year’s recipient is Dr. Sally Mathias. Her research was on Efficacy, Safety and Need Change of Zonisamide During Pregnancy in Women with Epilepsy.
Efficacy, Safety and Need Change of Zonisamide During Pregnancy in Women with Epilepsy
Among the newer generation of anti-epileptic drugs (AEDs), the most commonly prescribed AEDs during pregnancy include lamotrigine and levetiracetam. There is insufficient data regarding the use of zonisamide during pregnancy. Zonisamide is FDA category C. For routine use of zonisamide during pregnancy, information is needed about the efficacy during pregnancy, tolerability, need for titration and safety for patient and the unborn fetus. This retrospective chart review aimed to answer these questions by including pregnant females aged 18-45 years old treated at the Kentucky Neuroscience Institute at University of Kentucky Epilepsy Clinic. Women with epilepsy prescribed zonisamide during pregnancy between 1/1/2013-5/24/2019 were included. We reviewed seizure frequency before and during pregnancy, analyzed zonisamide levels during pregnancy, investigated reported side effects and monitored for congenital malformations reported in children born to these subjects.
Two hundred seventy-eight pregnant women with epilepsy were evaluated and treated during this time period. Thirty-seven of these patients were treated with zonisamide during pregnancy. Fourteen of these patients met the inclusion criteria (inclusion criteria were starting zonisamide prior to conception or during the first trimester and having at least three serum zonisamide levels checked during pregnancy). Serum zonisamide levels for these subjects were analyzed by gestational age. We compared pre-pregnancy and pregnancy data regarding seizure frequency and found that the majority of subjects had no change in seizure frequency, some had reduction and that none had an increase in seizure frequency during pregnancy while prescribed zonisamide. Zonisamide was generally well tolerated with only one subject reporting side effects of dizziness and blurry vision. Outcomes of fetuses born to women with epilepsy treated with zonisamide revealed no congenital malformations and one reported intrauterine growth restriction in those with available data. Finally, fluctuations in zonisamide levels during pregnancy were studied through concentration/total daily dose (C/D) ratios by gestational age. The linear effect of gestational age was significant and negative indicating decreasing C/D ratios by gestational age. The quadratic effect of gestational age was significant and positive indicating that the rate of decline in C/D ratios slowed throughout gestation.
Our findings indicate that zonisamide levels decreased during pregnancy and majority require dose adjustments. The most rapid rates of decline are early on in gestation. Checking serum levels of zonisamide during pregnancy, preferably on a monthly basis is essential. Although our study is limited by a small sample size, it indicates that zonisamide may be an effective, well tolerated, and safe treatment for pregnant women with epilepsy.
Dr. Sally Mathias specializes in the care of adults and adolescents with epilepsy. Originally from India, she completed her neurology residency at University of Kentucky followed by a fellowship in Clinical Neurophysiology- epilepsy track at Vanderbilt University. After her fellowship, Dr. Mathias joined as Assistant Professor of Neurology and Epilepsy at University of Kentucky and the Veterans Affairs (VA) Medical Center in Lexington, Kentucky. She is also the Associate Program Director of the Adult Neurology Residency Program at University of Kentucky. Her clinical interests are women’s epilepsy- especially pregnancy and epilepsy, epilepsy surgery and status epilepticus.
Dr. Mathias is actively involved in clinical research in the topics pertaining to her clinical interests while also involving trainees in quality improvement projects. She has co-authored a book chapter on “seizures” in a maternal-fetal medicine text book, and another book chapter is underway. She is currently one of the collaborators on a Practice Improvement Project (PIP) for pre-pregnancy counseling/ folic acid use for the American Epilepsy Society (AES) practice management committee.