Abstracts

Rationale: Avoiding unplanned pregnancies is crucial for women with epilepsy (WWE) given the potential risks of pregnancy and the structural teratogenic and neurodevelopmental risks of some anti-epileptic drugs (AEDs). However, there are complex bi-directional interactions between hormonal contraception and AEDs, which can limit contraceptive efficacy or impact AED levels. Contraceptive guidelines recommend intramuscular depot medroxyprogesterone acetate (DMPA) as an effective contraceptive though pharmacokinetic studies of DMPA efficacy in the setting of AED use are needed. In addition, progestin therapy may be effective in some WWE to prevent or reduce seizures. We assessed reasons for DMPA use and reported seizure effects among WWE participating in a study to investigate DMPA concentrations with co-administered AEDs.  Methods: We enrolled 17 WWE on AEDs and receiving DMPA for clinical indications in a multi-site pilot study with the primary aim of comparing MPA serum levels in WWE to MPA serum levels in control women. This report is of the secondary aim to assess the clinical characteristics, reasons for use, and experiences of WWE prescribed DMPA. At enrollment, study staff administered questionnaires regarding the participant's clinical reasons for DMPA use and any perceived effect on their seizures retrospectively. Medication use was verified in the electronic medical record.  Results: We recruited participants from neurology and gynecology practices between July 2017 and May 2019. The mean age of the participants was 33 years (range 18-49), and mean BMI = 29 kg/m2 (range 19-71). Participants described themselves as White (n=10), Black or African American (3), Asian or Asian American (1), American Indian or Native Alaskan (1), and Hispanic (2). Eight WWE reported use of enzyme-inducing AEDs (eiAEDs) and 9 WWE reported reported non-eiAEDs ) (Table 1.) Seven of 17 WWE reported DMPA use for contraception, 7 for management of menstrual cramps or bleeding, and 4 reported other reasons including endometriosis, polycystic ovarian syndrome and pelvic pain. DMPA use was first recommended by their neurologist (8/17), gynecologist (7/17), or primary care provider (2/13). In addition to the gynecologic indications, 14/17 (82%) reported DMPA use for its potential effects on seizures. Of the 17 WWE, 7 reported improvement in seizure frequency, and 6 of these 7 also reported improvement in seizure severity attributed to DMPA use. None perceived any worsening in seizure frequency or severity. Overall, 13/17 (76%) reported they were somewhat or very satisfied with DMPA use. Four of the 8 WWE using eiAEDs reported use of DMPA more frequently than the recommended 12-week dosing interval (range = 4-10 weeks.)  Conclusions: In this study of WWE receiving DMPA, 41% perceived that use of DMPA reduced either their seizure frequency or severity, and 35% described improvement in both frequency and severity. 82% reported that a reason for their DMPA use was the potential effect on their seizures. Most WWE reported DMPA use additionally for treatment of menstrual cramps or bleeding and/or for contraception. Further investigation is needed to confirm and quantify the impact of progestins or combined hormonal contraceptive therapies on seizures, and our larger study will describe the impact of AEDs on serum levels of MPA.  Funding: Dr. Dutton received funding from the Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston MA and from Harvard Catalyst: National Institute of Health (NIH) Clinical and Translational Science Award (CTSA): UL1TR001102.Dr. Davis received support from the Society of Family Planning Mid-career Mentorship grant.