Connors-BRI Symposium

Incorporating Sex as Biologic Variable to Advance Health

May 24, 2021 | 3-5PM

Virtual Event

Elizabeth Shashkova, BS

Brigham and Women’s Hospital


Objective: Postpartum tapering of antiseizure medications (ASMs) in women with epilepsy (WWE) has been long practiced in clinical settings, yet a standardized method has not been developed. ASM postpartum taper plans are individualized and require consideration of ASM-specific pharmacokinetics as well as patient’s ASM plasma concentrations and dose adjustments from preconception through late pregnancy. Lamotrigine (LTG) is the most widely used ASM for pregnant WWE. LTG clearance increases dramatically and requires frequent dose increases throughout pregnancy, but clearance drops rapidly during the early postpartum period, possibly leading to LTG toxicity if dose is not decreased. Conversely, rapid LTG dose decreases may increase the risk of seizure breakthrough. We reviewed patterns of postpartum tapers for LTG at our center to determine key factors for maintaining seizure stability and preventing clinical toxicity.

Methods: 54 WWE on LTG monotherapy were followed throughout pregnancy/postpartum in the Brigham and Women’s Hospital Epilepsy-Obstetrics program between 2012-2021. Clinical data on seizure types and frequency concurrent with therapeutic drug monitoring during pregnancy was collected in a longitudinal prospective database. A retrospective chart review was performed to confirm this information and corroborate with reports of toxicity symptoms to LTG (blurry vision, dizziness/balance problems) in the postpartum period. Dose changes were calculated as the difference between ASM dose on delivery day and end taper dose. Changes in seizure frequency were evaluated by comparing preconception seizure frequency to seizure frequency during first six weeks postpartum.

Results: Of the 54 patients analyzed, 7 (12.96%) experienced seizure worsening and 8 (14.81%) reported symptoms of toxicity in the six-week postpartum period, as compared to their preconception seizure frequency and symptoms. The average decrease in LTG dose during the postpartum taper was 46.18% (n=54). The average decrease in dose was similar (p>0.01) for patients with stable seizure frequency 45.35% (range, 0-85.7%, n=47) and patients with worsening seizure frequency 51.73% (range, 37.5-78.13%, n=7). The average decrease in dose was also similar (p>0.01) for patients with clinical toxicity 49.68% (range, 35.71-78.13%, n=8) and asymptomatic patients 45.57% (range, 0-85.7%, n=46).

Conclusions: There was not a significant difference in the total dose change between the stable and worsening seizure frequency groups or between the symptomatic and asymptomatic groups. The trend towards higher dose changes in the group with seizure worsening supports the need for larger studies. Further research is necessary to establish key factors for effective and safe postpartum tapers.


3PM – Welcome Remarks
3:05PM – Keynote Address
3:45PM – Featured Short Talks
4:20PM – Lightning Talks
4:50PM – Closing Remarks

Keynote Speaker

Janine Austin Clayton, MD

Janine Austin Clayton, M.D., Associate Director for Research on Women’s Health and Director of the Office of Research on Women’s Health (ORWH) at the National Institutes of Health (NIH), is the architect of the NIH policy requiring scientists to consider sex as a biological variable across the research spectrum. This policy is part of NIH’s initiative to enhance reproducibility through rigor and transparency. As co-chair of the NIH Working Group on Women in Biomedical Careers with NIH Director Dr. Francis Collins, Dr. Clayton also leads NIH’s efforts to advance women in science careers.

Prior to joining the ORWH, Dr. Clayton was the Deputy Clinical Director of the National Eye Institute (NEI) for seven years. A board-certified ophthalmologist, Dr. Clayton’s research interests include autoimmune ocular diseases and the role of sex and gender in health and disease. She is the author of more than 120 scientific publications, journal articles, and book chapters.
Dr. Clayton, a native Washingtonian, received her undergraduate degree with honors from Johns Hopkins University and her medical degree from Howard University College of Medicine. She completed a residency in ophthalmology at the Medical College of Virginia. Dr. Clayton completed fellowship training in cornea and external disease at the Wilmer Eye Institute at Johns Hopkins Hospital and in uveitis and ocular immunology at NEI.

Dr. Clayton has received numerous awards, including the Senior Achievement Award from the Board of Trustees of the American Academy of Ophthalmology in 2008 and the European Uveitis Patient Interest Association Clinical Uveitis Research Award in 2010. She was selected as a 2010 Silver Fellow by the Association for Research in Vision and Ophthalmology. In 2015, she was awarded the American Medical Women’s Association Lila A. Wallis Women’s Health Award and the Wenger Award for Excellence in Public Service. Dr. Clayton was granted the Bernadine Healy Award for Visionary Leadership in Women’s Health in 2016. She was also selected as an honoree for the Woman’s Day Red Dress Awards and the American Medical Association’s Dr. Nathan Davis Awards for Outstanding Government Service in 2017.