Blood levels of common antiepileptic drugs drop during pregnancy, causing breakthrough seizures

Blood levels of many commonly used antiepileptic drugs drop dramatically with the onset of pregnancy, report researchers from the University of Minnesota and the University of Pittsburgh today in JAMA Neurology.

The findings, collected as part of the multicenter study Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD), explain why many people with epilepsy start experiencing breakthrough seizures after conception, reinforcing the need to proactively increase doses of certain antiseizure medications and closely monitor blood levels over the course of pregnancy.

“When it comes to epilepsy, maintaining a fine-tuned medication regime is critical. Some people mistakenly believe that changes in the drugs’ blood concentration won’t occur until after 20 weeks of pregnancy, but our study shows how important it is to start monitoring and adjusting patients’ medication dosages early on,” said lead author Page Pennell, M.D., chair of neurology at the University of Pittsburgh and the principal investigator on the MONEAD trial. “Nearly half of all pregnancies in the United States are unplanned, so it is important to ensure that doctors have a clear picture of each patient’s baseline drug level even if they are not trying to conceive.”

Epilepsy is a life-altering neurological condition that affects children and adults alike, and two-thirds of cases do not have a known cause. In people with epilepsy, nerve cells in the brain are hyper-reactive, causing them to change the pattern of their electrical activity and become spontaneously active, millions of cells at a time. That synchronous activation is manifested in seizures, which can make a person become disoriented, lose consciousness and, in some cases, experience limb movements or rigidity.

Clinical management of epilepsy has had a fraught medical history, compounded by myths and stigma over the centuries. Many people with epilepsy go undiagnosed or under-treated. Even though epileptic seizures can often be successfully controlled with medications, the first-generation drugs had a slew of dangerous side effects and were contraindicated for people who are trying to conceive.

Since then, safer medications have entered the U.S. market and become widely available, but clinicians started noticing a new problem – patients whose epilepsy was successfully managed with medications started having seizures soon after becoming pregnant.

"Identifying which antiseizure medications may have changes in concentrations and at what point in pregnancy those changes occur is important for determining which patients may need to be monitored more closely during pregnancy and after delivery,” said senior author Angela Birnbaum, Ph.D., professor of experimental and clinical pharmacology at the University of Minnesota.

To get to the bottom of the mystery, Pennell and colleagues launched a study to analyze blood concentrations of 10 commonly used antiseizure drugs and compare them across different stages of pregnancy and after childbirth.

The study found that blood levels of seven out of 10 of the medications they examined dropped dramatically – from 29.7% for lacosamide, a commonly prescribed anticonvulsant, and up to 56.4% for lamotrigine.

In addition, the researchers noted that the drop in the drugs’ blood concentration occurred mere days after conception, long before most women have their first prenatal visit and before the pregnancy showed itself physically.

“Until now, we knew very little about how becoming pregnant impacted blood levels of most anti-epileptic medications,” said Vicky Whittemore, Ph.D., program director at the National Institute of Neurological Disorders and Stroke (NINDS). “This study lays the groundwork for a larger goal of the MONEAD study, which is to improve outcomes in women with epilepsy by better managing their medications over the course of pregnancy.”

This research was supported by NINDS and the National Institute of Child Health and Development (grants U01-NS038455, U01-NS050659, 2U01-NS038455) and University of Minnesota’s Doctoral Dissertation Fellowship.

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About the University of Minnesota College of Pharmacy

Founded in 1892, the University of Minnesota College of Pharmacy is the only pharmacy school in Minnesota, with campuses in the Twin Cities and in Duluth. The College of Pharmacy improves health through innovative education, pioneering research and interdisciplinary practice development that attends to the diverse needs of the people of Minnesota and the world.

About the University of Pittsburgh School of Medicine 

As one of the nation’s leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support. 

Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region’s economy. For more information about the School of Medicine, see www.medschool.pitt.edu.