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

Date:
February 14, 2022
Source:
University of Pittsburgh
Summary:
Blood levels of many commonly used antiepileptic drugs drop
dramatically with the onset of pregnancy, report researchers.



FULL STORY ========================================================================== Blood levels of many commonly used antiepileptic drugs drop dramatically
with the onset of pregnancy, report researchers from the University of Pittsburgh and the University of Minnesota 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 Pitt 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. In people
with epilepsy, 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."
Additional authors of this study are Ashwin Karanam, Ph.D., of the
University of Minnesota; Kimford Meador, M.D., of Stanford University; Elizabeth Gerard, M.D., of Northwestern University; Laura Kalayjian,
M.D., of the University of Southern California; Patricia Penovich,
M.D., of the Minnesota Epilepsy Group; Abigail Matthews, Ph.D., of the
Emmes Company; and Thomas McElrath, M.D., Ph.D., of Brigham and Women's Hospital and Harvard University.

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.

========================================================================== Story Source: Materials provided by University_of_Pittsburgh. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Page B. Pennell, Ashwin Karanam, Kimford J. Meador, Elizabeth
Gerard,
Laura Kalayjian, Patricia Penovich, Abigail Matthews, Thomas
M. McElrath, Angela K. Birnbaum, Morris Cohen, Maurice Druzin,
Richard Finnell, Gregory Holmes, Lorene Nelson, Zachary Stowe,
Linda Van Marter, Peter Wells, Mark Yerby, Eugene Moore, Ryan May,
Dominic Ippolito, Carrie Brown, Chelsea Robalino, Julia Skinner,
Lisa Davis, Nilay Shah, Brenda Leung, Mark Friedman, Hayley Loblein,
Traci Sheer, Suzanne Strickland, Erin Latif, Yong Park, Delmaris
Acosta-Cotte, Patty Ray, Alison Pack, Kirsten Cleary, Joyce Echo,
Annette Zygmunt, Camilla Casadei, Evan Gedzelman, Mary Dolan, Kim
Ono, Donald Bearden, Christine Ghilian, Diane Teagarden, Melanee
Newman, Paul McCabe, Michael Paglia, Cora Taylor, Rosemarie
Delucca, Kristina Blessing, Paula Emanuela Voinescu, Katrina
Boyer, Ellen Hanson, Amy Young, Paige Hickey, Jolie Strauss, Hayley
Madeiros, Li Chen, Stephanie Allien, Yvonne Sheldon, Taylor Weinau,
Gregory L Barkley, Marianna Spanaki-Varelas, Andrea Thomas, Jules
Constantinou, Nazin Mahmood, Vibhangini Wasade, Shailaja Gaddam,
Andrew Zillgitt, Taimur Anwar, Carla Sandles, Theresa Holmes,
Emily Johnson, Gregory Krauss, Shari Lawson, Alison Pritchard,
Matthew Ryan, Pam Coe, Julie Hanna, Katie Reger, Jenny Pohlman,
Alisha Olson, Jacqueline French, William Schweizer, Chris Morrison,
William MacAllister, Tobi Clements, Sean Hwang, Hima Bindu Tam,
Yael Cukier, Erica Meltzer, Jacqueline Helcer, Connie Lau, William
Grobman, Joseph Coda, Emily Miller, Irena Bellinski, Elizabeth
Bachman, Casey Krueger, Jordan Seliger, Jennifer DeWolfe, John
Owen, Matthew Thompson, Cheryl Hall, David Labiner, James Maciulla,
Jennifer Moon, Kayla Darris, Jannifer Cavitt, Michael Privitera,
Kellie Flood-Schaffer, George Jewell, Lucy Mendoza, Enrique Serrano,
Yasin Salih, Christin Bermudez, Michelle Miranda, Naymee Velez-
Ruiz, Pedro Figueredo, Anto Bagic, Alexandra Urban, Satya Gedela,
Christina Patterson, Arundhathi Jeyabalan, Krestin Radonovich,
Melissa Sutcliffe, Susan Beers, Carrie Wiles, Sandra Alhaj, Alice
Stek, Sonia Perez, Rachel Sierra, Jeffrey Tsai, John W Miller,
Jennie Mao, Vaishali Phatak, Michelle Kim, Andrea Cheng-Hakimian,
Gina DeNoble, Maria Sam, Lamar Parker, Melissa Morris, Jessica
Dimos, Danielle Miller. Antiseizure Medication Concentrations During
Pregnancy. JAMA Neurology, 2022; DOI: 10.1001/jamaneurol.2021.5487 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220214111749.htm

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