Correspondence

Initial Management of Epilepsy

N Engl J Med 2008; 359:2499-2500December 4, 2008

Article

To the Editor:

With regard to the article on the initial management of epilepsy, by French and Pedley (July 10 issue),1 there are about 1 million women of reproductive age who have epilepsy in the United States. Guidelines recommend highly effective contraception, since these women have a higher pregnancy-related risk than their healthy peers.2 Contraceptive decision making for women with epilepsy can be complex because of the increased clearance of contraceptive steroids associated with some antiepileptic drugs.

The authors recommend higher-dose oral contraceptives (50 μg of ethinyl estradiol). There are multiple forms of hormonal contraception that may be affected by coadministration with enzyme-inducing antiepileptic drugs. The recommendations for any hormonal contraceptive method in women using antiepileptic drugs remain theoretical, since the actual risk of pregnancy remains unknown. Nonhormonal, highly effective methods such as the intrauterine device (IUD) may be ideal for women with epilepsy, since the contraceptive mechanism of IUDs is unaffected by changes in hepatic enzyme activity.

Anne Davis, M.D., M.P.H.
Alison Pack, M.D.
Columbia University Medical Center, New York, NY 10032
ard4@columbia.edu

Dr. Davis reports serving on a speaker's bureau supported by a grant from Berlex (now Bayer) and receiving research support from Duramed. No other potential conflict of interest relevant to this letter was reported.

2 References

1
French JA, Pedley TA. Initial management of epilepsy. N Engl J Med 2008;359:166-176
Full Text | Web of Science | Medline

2
Practice parameter: management issues for women with epilepsy (summary statement): report of the Quality Standards Subcommittee of the American Academy of Neurology. Epilepsia 1998;39:1226-1231
CrossRef | Web of Science | Medline

To the Editor:

French and Pedley suggest levetiracetam as a potential initial therapy for the case described in the vignette. However, this drug was approved by the Food and Drug Administration (FDA) only as adjunctive therapy.1,2 Somnolence has been reported in 12 to 23% of patients using levetiracetam.3 In 2007, the FDA approved a revision of the safety labeling for levetiracetam, which included serious behavioral and mood disorders such as depression and suicidal ideation.3

Hussam Ammar, M.D.
Ashok Malani, M.D.
Heartland Regional Medical Center, St. Joseph, MO 64507
h_ammar68@yahoo.com

Sanjay Mughal, M.D.
University of Florida, Jacksonville, FL 32209

3 References

1
Keppra (levetiracetam): product report. Rockville, MD: Food and Drug Administration. (Accessed November 13, 2008, at http://www.fda.gov/cder/foi/label/2007/021035s057,021505s013lbl.pdf.)

2
French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 2004;62:1261-1273
Web of Science | Medline

3
Keppra (levetiracetam): safety report. Rockville, MD: Food and Drug Administration. (Accessed November 13, 2008, at http://www.fda.gov/medwatch/SAFETY/2007/Mar_PI/Keppra_PI.pdf.)

Author/Editor Response

Davis and Pack point out that an IUD would be an appropriate alternative to the use of oral contraceptives in patients with epilepsy who are receiving enzyme-inducing antiepileptic drugs. In our review, we state, “If the patient uses, or plans to use, an oral contraceptive pill, it would be preferable to avoid antiepileptic drugs that will increase the clearance of oral contraceptive pills.”

The use of a non–hormone-based therapy would circumvent any concern about increased clearance of steroid-based contraceptives. However, we have found that many women, although encouraged to consider such alternatives, are not willing to change their current method of contraception. Since oral contraceptives are still the most commonly used contraceptive method in the United States, we wished to provide advice regarding antiepileptic-drug selection for women who choose to continue their use.1

The FDA has elected to use only evidence from superiority trials to approve epilepsy drugs for monotherapy. This has substantially limited the number of antiepileptic drugs approved for initial monotherapy. In Europe, the regulatory agencies also accept data from large, active-control, noninferiority studies. Such a study demonstrated that levetiracetam was equally as effective as carbamazepine.2 We believe that these data support the use of levetiracetam as initial monotherapy.

Jacqueline A. French, M.D.
New York University School of Medicine, New York, NY 10016
jacqueline.french@nyumc.org

Timothy A. Pedley, M.D.
Columbia University School of Medicine, New York, NY 10032

2 References

1
Bensyl DM, Iuliano DA, Carter M, Santelli J, Gilbert BC. Contraceptive use -- United States and territories, Behavioral Risk Factor Surveillance System, 2002. MMWR Surveill Summ 2005;54:1-72[Erratum, MMWR Morb Mortal Wkly Rep 2005;54:1214.]
Medline

2
Brodie MJ, Perucca E, Ryvlin P, Ben-Menachem E, Meencke HJ. Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy. Neurology 2007;68:402-408
CrossRef | Web of Science | Medline

Citing Articles (1)