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Neurology supplements are not peer-reviewed. Information contained in Neurology supplements represent the opinions of the authors and are not endorsed by nor do they reflect the views of the American Academy of Neurology, Editor-in-Chief, or Associate Editors of Neurology.

Optimizing therapy of seizures in women who use oral contraceptives

From the Comprehensive Epilepsy Center, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York (Dr. Harden), and Departments of Pharmacy and Neurology, University of Minnesota, MINCEP Epilepsy Care, Minneapolis, Minnesota (Dr. Leppik).

Address correspondence and reprint requests to Dr. Cynthia L. Harden, Comprehensive Epilepsy Center, Room K-615, 525 East 68th Street, Weill Cornell Medical Center, New York 10021, NY; e-mail: clharden{at}med.cornell.edu

There is no evidence that oral contraceptives (OCs) increase seizure activity, and OC use in the setting of antiepileptic drug (AED) treatment provides pregnancy prevention at among the highest rates of any available contraceptive method. One concern, however, is the increased risk for OC failure with the use of cytochrome P450 3A4 enzyme-inducing AEDs, such as phenobarbital, carbamazepine, phenytoin, felbamate, topiramate, and oxcarbazepine. Felbamate induces metabolism of only the progestogenic component, whereas topiramate induces metabolism of only the estrogenic component. There is preliminary evidence that lamotrigine induces the metabolism of a progestin, levonorgestrel. It is unclear whether the estrogenic or the progestogenic component is more clinically important in preventing pregnancy. To ensure maximal pregnancy prevention, it is therefore recommended that women taking enzyme-inducing AEDs should receive OCs containing at least 50 µg of ethinyl estradiol and that low-dose formulations in general should not be used. AEDs that do not induce cytochrome P450 3A4 enzymes, including valproic acid, gabapentin, levetiracetam, tiagabine, vigabatrin, zonisamide, and pregabalin, do not interact with OCs. There are no concerns regarding the treatment of seizures or increased pregnancy risk with the use of OCs and these non-enzyme-inducing AEDs. Lamotrigine levels, however, are reduced by 50% in the setting of OC use. Therefore, women with epilepsy taking lamotrigine need to be monitored carefully for seizures when OCs are started and for toxicity when OCs are discontinued. Dose adjustment to maintain clinical stability may be necessary in these settings. The placebo or pill-free week of the OC regimen may also be a period when clinical toxicity can occur. Even with the considerations discussed in this review, OCs are a reasonable contraceptive option for women with epilepsy taking AEDs.

This supplement has been supported through an unrestricted grant from UCB S.A., manufacturers of levetiracetam (Keppra®).

Disclosure: Dr. Harden reports the following: Speakers bureau: Novartis, UCB Pharma, Cyberonics, GlaxoSmithKline Research support: UCB Pharma, Medtronics, Neuropace, NINDS Consultant: GlaxoSmithKline, Cyberonics. Dr. Leppik reports the following: Speakers bureau and/or research support and/or consultancy: Abbott Laboratories, Elan Pharmaceuticals, GlaxoSmithKline, MedPointe, Medtronics, Novartis, OrthoMcNeil, Pfizer, Shire, UCB Pharma, Xcel Pharmaceuticals, NINDS.

Neurology supplements are not peer-reviewed. Information contained in Neurology supplements represents the opinions of the authors and is not endorsed by nor does it reflect the views of the American Academy of Neurology, Editorial Board, Editor-in-Chief, or Associate Editors of Neurology.