Unintended Pregnancy in Epilepsy May Be Linked to Contraceptive, AED Combo

Patients taking enzyme-inducing antiepileptic drugs and hormonal contraceptives face a greater risk of unintended pregnancy.

Women with epilepsy frequently report unintended pregnancy, which may be associated with the type of hormonal contraception and anti-epileptic drug(s) (AEDs) being used, according to study results published in Neurology.1

Data from the Epilepsy Birth Control Registry (EBCR) published in 2016 showed that about 46.6% of women with epilepsy (WWE) at risk for unintended pregnancy used hormonal contraception.2

“Epilepsy practice guidelines suggest that WWE achieve optimal seizure control on the minimum effective dosage of AED and take recommended dosages of folic acid supplement before conception in order to minimize their significantly increased risk of having offspring with major congenital malformations.  The timing of conception, therefore, involves planning,” Andrew Herzog, MD, professor of neurology at Harvard Medical School in Boston, Massachusetts, and lead investigator of the study, told Neurology Advisor.

In the general population, the researchers noted, hormonal contraception is considered highly effective. However, the efficacy of hormonal contraceptives may be compromised in WWE who take AEDs associated with enzyme-inducing effects.

In the current study, Dr Herzog and colleagues analyzed retrospective data from the EBCR to examine associations between AED and contraceptive combinations used with rates of unintended pregnancy in WWE.

The EBCR contained data on 1144 WWE age 18 to 47 that provided information on demographics, contraceptive and AED use, epilepsy, and pregnancy on a web-based survey. The investigators categorized AEDs based on enzyme-inducing potential and contraceptives as hormonal or non-hormonal.

In total, 345 participants reported at least 1 unintended pregnancy (345/437, 78.9%), and 65% of all pregnancies were unintended (523/804). Participants age 38 to 47 had the lowest rate of unintended pregnancy (relative risk [RR]: 1.48), whereas participants younger than 18 or age 18 to 27 had higher rates of unintended pregnancy (RR: 2.03 and 1.63, respectively, P <.0001 for both). The rate of unintended pregnancy was higher in minority and Hispanic participants compared with whites and non-Hispanics (RR: 1.22, P =.005 and RR: 1.24, P =.002, respectively).

Hormonal contraception had a relative risk for unintended pregnancy of 4.94 (P <.0001) compared with intrauterine devices, which had the lowest rate (3.1%). Oral forms of hormonal contraception had a higher risk compared with non-oral forms (RR: 2.89, P <.0001), and combined oral contraceptives had a higher risk compared with implanted progestin (RR: 7.34, P =.04).

When data were analyzed based on the AED-contraceptive combination, the combination of enzyme-inducing AEDs with hormonal contraception had the highest relative risk of unintended pregnancy (RR: 2.35, P =.01). Further, WWE taking enzyme-inducing AEDs accounted for 60.7% of all unintended pregnancies in participants on hormonal contraception.

“In view of the important consequences of unintended pregnancy on pregnancy outcomes, healthcare providers should be familiar with the reciprocal interactions that exist between a number of antiepileptic drugs and hormonal contraception and, in particular, that the risk of unintended pregnancy may double when combining hormonal contraception with enzyme-inducing antiepileptic drugs,” Dr Herzog said.

In an accompanying editorial, Kimford J. Meador, MD, of the Stanford Neuroscience Health Center in Palo Alto, California and Dick Lindhout, MD, PhD, of the University Medical Center Utrecht and Stichting Epilepsie Instellingen Nederland, in The Netherlands, wrote that despite the study’s limitations, including the use of retrospective data and self-reported outcomes, the results were “striking.”3

“Given their high risk for unintended pregnancies, WWE need to be informed of issues related to differential AED risks of teratogenesis when the AED is first prescribed rather than waiting until the woman is considering pregnancy,” they wrote.

Disclosures: The study was funded by the Epilepsy Foundation and Lundbeck. Drs Mandle and Cahill report receiving salary support from Lundbeck. Dr Meador reports receiving support from the National Institutes of Health and Sunovion Pharmaceuticals, and travel support from UCB Pharma. Dr Meador serves as a research consultant for Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, UCB Pharma, and Vivus Pharmaceuticals. Dr Lindhout is a member of the Central Project Commission of EURAP, which reports receiving financial support from Bial, Eisai, GlaxoSmithKline, Janssen-Cilag, Novartis, Pfizer, Sanofi-Aventis, and UCB Pharma.


  1. Herzog AG, Mandle HB, Cahill KE, Fowler KM, Hauser WA. Predictors of unintended pregnancy in women with epilepsy. Neurology. 2017;88(8):728-733.
  2. Herzog AG, Mandle HB, Cahill KE, Fowler KM, Hauser WA, Davis AR. Contraceptive practices of women with epilepsy: Findings of the epilepsy birth control registry. Epilepsia. 2016;57(4):630-637.
  3. Meador KJ, Lindhout D. Epilepsy and unintended pregnancies. Neurology. 2017;88(8):724-725.