Background – Why?
In the early 2000’s, results from several antiepileptic drug (AED) pregnancy registries revealed that valproate the highest risks of AEDs for congenital malformations. In addition around the same time, researchers from the NIH NEAD study examined the short and long-term outcomes in babies exposed to four different AEDs during pregnancy. From the NEAD study, we know that valproate also has the highest risks for cognitive and behavioral impairments. In May 2018, a continuation of the NEAD study was published. This time, researchers were curious to learn if the prescribing habits of AEDs in pregnant women had changed since the publication of the NEAD study. Below is a summary of the most recent findings from this MONEAD study.
Research Methods – How?
The purpose of the MONEAD study is to examine a variety of maternal and child outcomes for presently used AEDs, and is the first study to examine the effects of AED blood levels. The first publication from the MONEAD study sought to demonstrate what AEDs are now being prescribed to pregnant women with epilepsy. Researchers selected different groups of patients to compare the AEDs. These groups were 1) pregnant women with epilepsy, 2) pregnant women without epilepsy, and 3) non-pregnant women with epilepsy. The pregnant women without epilepsy and the non-pregnant women with epilepsy served as “controls.” These groups were considered the standards that the pregnant women with epilepsy were compared against. This type of research design – using control groups – helps to verify that results are statistically significant rather than just left up to chance. Women that participated in this study were from 20 epilepsy centers across the country. Data was collected from December 2012 to January 2016.
Research Results – What?
Below are some common prescribing trends that researchers identified when analyzing their data:
- 74% of pregnant women with epilepsy were taking only one AED
- The most commonly used AEDs were lamotrigine and levetiracetam
- If a combination of AEDs was used, the most likely combination was lamotrigine and levetiracetam
- These trends were consistent regardless of the type of epilepsy, geographic region, or date of enrollment into the study
- Note: lamotrigine and levetiracetam have been previously shown to have lower risks for the baby with respect to congenital malformations and cognitive impairment
Impact of the Research – So what? and Now what?
The results of this research were encouraging – it appears that over the time since the NEAD and other study results were published showing the higher risk of valproate in pregnant patients, there has been a notable decrease in the prescribing of valproate. Lamotrigine and levetiracetam appear to be favorites of prescribers, likely because we have data supporting their lower risk in pregnancy.
You may be asking, “What about other epilepsy medications?” Well, right now we only have pregnancy risk data on 9 of approximately 30 medications used to treat epilepsy. This research study highlights the need for additional research on AEDs. Now, we need healthcare practitioners and researchers alike to continue to explore the safety of AEDs in pregnant women. Consider asking your provider if you can participate in a clinical trial.
Doctor of Pharmacy Candidate
P4 Student – Class of 2019
The Ohio State University College of Pharmacy
Jim McAuely, RPh, PhD
Professor of Pharmacy Practice & Science and Neurology
Associate Dean for Academic Affairs
The Ohio State University
Kimford J. Meador, MD
Professor of Neurology and Neurological Sciences
Director of the SHC Epilepsy Monitoring Unit
Meador, et al. Changes in Antiepileptic Drug-Prescribing Patterns in Pregnant Women with Epilepsy. Epilepsy Behav. Epub 2018 May 3. doi: 10.1016/j.yebeh.2018.04.009.
Victoria Williams is a fourth-year PharmD student at The Ohio State University in Columbus, Ohio. Next month she will be completing a clinical rotation at The Ohio State University Wexner Medical Center on a Neurology unit of the hospital. She earned her undergraduate degree in the Pharmaceutical Sciences from Ohio State in 2015. Upon graduation from the Doctor of Pharmacy program in May, Ms. Williams hopes to pursue a clinical pharmacy practice residency at a large academic medical center or tertiary teaching hospital. Ms. Williams has a passion for education and hopes to one day teach as a faculty member at a college of pharmacy.