• Enzyme-inducing anti-seizure medications can increase how fast certain contraceptives leave the bloodstream.
• People with intellectual disabilities and people with drug-resistant epilepsy face greater risks.

Roughly one-third of people with epilepsy prescribed certain hormonal contraceptives were also prescribed anti-seizure medications that may reduce the effectiveness of the contraceptives, according to a study published in Neurology.

The research is important for several reasons, Laura Kirkpatrick, MD, pediatric neurologist with the University of Pittsburgh Medical Center, and colleagues wrote.

Many anti-seizure medications (ASMs) can induce hepatic enzymes, which can increase how fast systemic hormonal contraceptives clear from the bloodstream, they wrote.

“Many neurologists, in addition to primary care providers and OB/GYNs, lack awareness of these drug interactions,” Kirkpatrick told Healio. “I think a lot of it has to do with how siloed we are in our particular specialties, and no one is really thinking about the whole person across specialties.”

ASMs also carry an increased risk for congenital malformations and adverse neurodevelopment effects for children in utero, authors wrote. These risks are increased in people with epilepsy of child-bearing potential (PWECP) when the pregnancy is unplanned, as are risks for seizure and preterm birth.

Kirkpatrick and colleagues examined Medicaid claims for 110,976 PWECP aged 12 to 51 years (median age, 24 years; 54.8% white non-Hispanic) from 2016 to 2021.

Within that group, they identified 21,923 individuals who were prescribed a contraception method that was susceptible to hepatic enzyme induction.

By analyzing prescription fill dates and contraceptive procedure dates, they were able to determine that 32.6% of those PWECP had at least a 14-day period of overlap between the contraceptive and an enzyme-inducing anti-seizure medication (EIASM).

A total of 61.9% of those PWECP were prescribed the contraceptive first, while 38.1% were prescribed the ASM first.

The 14-day period is relevant because it has been used in similar research as the minimum threshold for reduced contraceptive effectiveness, according to the authors.

However, the median duration of overlap was 218 days, Kirkpatrick and colleagues wrote.

Kirkpatrick said she was surprised by the magnitude of people who had at least a 14-day period of overlap.

“I was both surprised and disappointed,” she said. “I thought it might be 10%, 20%, but it was nearly a third. People were potentially at risk of having their contraceptives affected by their seizure medicines for long enough that unintended or unwanted pregnancies might have occurred.”

Kirkpatrick and colleagues also found associations between patients with intellectual disability and any overlap (adjusted OR = 2.33; 95% CI, 2.19–2.48) and longer periods of overlap (aOR = 2.27; 95% CI, 2.05–2.53).

“I think, regarding people with intellectual disability, sometimes healthcare providers, both on the reproductive health side and on the neurology side, assume that those individuals aren’t going to be sexually active, and that therefore maybe the contraceptive drug interaction is less of a problem,” Kirkpatrick said. “But we also know that individuals with ID do become pregnant, are sexually active at times. It may be less often, but it does occur.”

Researchers also observed associations between drug-resistant epilepsy and any overlap (aOR = 1.73; 95% CI, 1.62–1.84) and longer overlap (aOR = 1.27; 95% CI, 1.14–1.41).

People with more severe epilepsy are more likely to be prescribed EIASMs to control symptoms, Kirkpatrick said.

“At the same time, individuals with really bad epilepsy would face even higher risks with an unplanned or unintended pregnancy,” she said.

Age also played a factor, researchers found. Compared with PWECP aged 19 to 34 years, PWECP who were aged 35 years and older had an aOR of 1.45 for any overlap (95% CI; 1.32–1.59) and an aOR of 1.51 for longer overlap (95% CI; 1.29–1.75).

Clinicians who work with PWECP should be more mindful of the intersections of neurology and reproductive health, Kirkpatrick said. She also advocated for the development of decision support tools that could help clinicians counsel patients about drug interactions and options.

Kirkpatrick and colleagues are conducting another study using the same data set looking at rates of pregnancy in the context of the interacting medications. In addition, they would like to conduct a study that seeks to identify more details about the context surrounding situations when PWECP are prescribed EIASMs and susceptible contraceptives.

The research could provide more information on the context of the drug interactions, including whether they can be tied to lack of awareness, a patient requesting the drugs even with counseling or a missed interaction all together.

“I can speculate that it’s because of poor recognition of the drug interactions, but until we hunt down the cases and investigate, we don’t really know,” Kirkpatrick told Healio.

Laura Kirkpatrick, MD, can be reached at neurology@healio.com.