Epilepsy drugs may quietly undermine hormonal birth control, study finds

A large analysis of U.S. Medicaid claims has revealed a striking gap between what is known about drug interactions and what actually happens in clinical practice. Nearly one-third of people with epilepsy who were prescribed hormonal contraceptives vulnerable to drug interactions also received antiseizure medications that can render those contraceptives less effective, according to a University of Pittsburgh-led study published in Neurology, the medical journal of the American Academy of Neurology. The finding matters because some epilepsy medications carry known risks to a developing fetus, which makes reliable contraception a cornerstone of safe care for many patients with epilepsy of childbearing potential.

The pharmacological problem at the heart of the study is well established but often underappreciated. A subset of antiseizure medications act as enzyme inducers, meaning they ramp up the activity of hepatic cytochrome P450 enzymes and other metabolic pathways responsible for clearing steroid hormones from the body. When these enzyme-inducing drugs are taken alongside hormonal contraceptives that rely on sustained blood levels of estrogen or progestin, the contraceptive hormones are broken down faster, lowering circulating concentrations and potentially weakening the contraceptive effect. The result can be a silent reduction in protection against unplanned pregnancy, with no obvious warning sign for the patient.

To quantify how often this risky combination occurs, the researchers turned to U.S. Medicaid claims data, identifying 110,976 people with epilepsy of childbearing potential who were receiving antiseizure medications. Nearly one in five had received a hormonal contraceptive that could be affected by enzyme-inducing antiseizure medications between 2018 and 2021. The affected contraceptive methods included combined and progestin-only pills, contraceptive patches, vaginal rings and subdermal implants, all of which depend on systemic hormone levels that enzyme induction can erode.

The overlaps were not fleeting. Among the individuals who received both a susceptible contraceptive and an enzyme-inducing antiseizure medication, nearly one-third experienced at least one period of 14 days or longer when the two prescriptions overlapped. The median duration of overlap was 218 days, just over seven months. That is a substantial window during which a patient may have been relying on contraception whose effectiveness was potentially compromised, often without knowing it.

“These were not simply brief or isolated prescription overlaps,” said corresponding author Laura Kirkpatrick, M.D., M.S., assistant professor of pediatrics and neurology at the University of Pittsburgh School of Medicine. “For many people, the overlap continued for months. Clinicians should routinely consider potential drug interactions and make sure patients understand their options, including contraceptive methods that are not affected by enzyme-inducing antiseizure medications.”

The study also identified groups at heightened risk. People with intellectual disability had more than twice the odds of experiencing an overlapping prescription period compared with people without intellectual disability, a disparity that underscores how patients with complex communication or care-coordination needs may be especially vulnerable to missed interactions. Those with drug-resistant epilepsy and those aged 35 or older also had higher odds of overlap and longer stretches of concurrent prescriptions, patterns that may reflect more intensive medication regimens and longer treatment histories.

The stakes are particularly high in epilepsy care because pregnancy itself requires careful planning. Some antiseizure medications have been associated with risks to a developing fetus, and uncontrolled seizures pose their own dangers during pregnancy. An unplanned pregnancy can leave less opportunity to transition a patient to medications with better-established safety profiles for both mother and child. Effective, reliable contraception is therefore not a peripheral concern in epilepsy management; it is intertwined with medication choices, seizure control and reproductive goals.

Importantly, the researchers stress that not all contraceptive methods are equally susceptible. Intrauterine devices, including both hormonal and copper devices, are not affected by enzyme-inducing antiseizure medications and may be appropriate options when consistent with a patient’s preferences. The authors also note that co-use of an interacting combination may sometimes be reasonable, provided the patient understands the potential risks and benefits and makes an informed choice. The goal is not to prohibit specific prescriptions but to ensure that decisions are made deliberately rather than by default.

“Pregnancy planning is especially important for people with epilepsy, but patients may not realize that some antiseizure medications can interact with some forms of hormonal contraception,” said senior author Page B. Pennell, M.D., chair of the Department of Neurology at Pitt’s School of Medicine. “This study highlights an opportunity for neurologists, reproductive health clinicians, pharmacists and patients to have more coordinated conversations about medications, contraception and reproductive goals.”

Looking ahead, the research team plans to examine pregnancy rates among people who received overlapping prescriptions, a step that will help determine whether the pharmacological concern translates into measurable contraceptive failure at the population level. The authors also call for research into practical interventions, including electronic health record alerts, pharmacist review and education aimed at both patients and clinicians, to raise awareness of these interactions and support shared decision-making. Additional authors of the study included Elizabeth I. Harrison of the University of Virginia, Caryn Dutton of Beth Israel Deaconess Medical Center and Harvard University, Wesley T. Kerr and Scott D. Rothenberger of Pitt, and Samuel W. Terman of the University of Michigan. The work received support from the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the American Epilepsy Society, the Epilepsy Foundation, the American Academy of Neurology, the American Brain Foundation, the Epilepsy Study Consortium and the UPMC Competitive Medical Research Fund. For the roughly one in five patients whose prescriptions fall into this vulnerable category, the study’s message is clear: the interaction between seizure control and contraception deserves a place in every treatment conversation.

Subject of Research: Co-prescription of enzyme-inducing antiseizure medications and hormonal contraceptives in people with epilepsy

Article Title: Common epilepsy medication and birth control combinations may reduce contraceptive effectiveness

Article References: Common epilepsy medication and birth control combinations may reduce contraceptive effectiveness. (n.d.). Original publication

Image Credits: AI Generated

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Keywords: epilepsy, hormonal contraceptives, antiseizure medications, drug interactions, enzyme-inducing drugs, Medicaid, unplanned pregnancy, Neurology journal, reproductive health, pharmacokinetics, contraceptive effectiveness, shared decision-making