Women & Epilepsy

There’s more to it than simply avoiding valproic acid in pregnancy. A lot more. From menses to menopause, women who suffer from epilepsy are at increased risk of a number of complications from their neurologic disease–and from their treatment.

In this week’s BrainWaves episode, Dr. Danielle Becker reviews some of the major issues faced by women with seizure disorders, and the doctors who treat them. Starting with puberty, the fluctuating levels of estrogen and progesterone may significantly impact the frequency of epileptic events. For reasons that are described in better detail in the episode this week, Estrogen is often considered an “Exacerbater” of epilepsy, whereas Progesterone is “Protective.”

The introduction of estrogen-containing oral contraceptives to control acne and prevent pregnancy simultaneously will also introduce a dramatic alteration of the hepatic

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Shades of Orange. From https://www.flickr.com/photos/armydre2008/3152160402/ under a Creative Commons license.

machinery involved in anti-epileptic drug (AED) metabolism. For example, lamotrigine (which is often a drug of choice in women of childbearing age) levels may be cut in half after only a few days of estrogen-containing oral contraceptive use, significantly increasing the risk of seizure in these patients. Not surprisingly, if lamotrigine dosing is increased to compensate for this heightened hepatic metabolism, this drug level may become toxic at twice the normal levels during a patient’s “pill-free week.” Prior to initiating an oral contraceptive in patients on any hepatically-metabolized AED, it is imperative that you as the provider discuss these drug-drug interactions and address any complications they may risk.

Later in a woman’s life, should she desire pregnancy, there are a number of steps you must take as her neurologist. Besides the risk of neural tube defects, which any medical student can describe, women with epilepsy are also at significantly greater risk of the following:

  • Non-neural tube defect congenital malformations
  • Increased clearance of medications (lower serum levels) of lamotrigine, phenytoin, and carbamazepine
  • Increased risk of premature contractions or delivery (among smokers)
  • Lower life satisfaction
  • Lower partner satisfaction
  • Separation or divorce
  • Losing their jobs in the post-partum period

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But there was NO consistently observed increase in risk of seizure during pregnancy according to the American Epilepsy Society. That being said, given the increased clearance of drugs like lamotrigine, phenytoin, carbamazepine (and probably also levetiracetam and oxcarbazepine), the levels of these drugs should be monitored regularly and adjusted when appropriate. While it is NOT the objective of BrainWaves to provide medical advice, it is worth knowing that experts recommend checking these drug levels throughout pregnancy and reducing the dose by as much as one-half (particularly for lamotrigine) immediately following delivery in order to prevent neurotoxicity. And after delivery, the fluctuation of serum protein levels and unprecedented sleep deprivation are more than enough reason to encourage you as the provider to attend to these patients’ needs in extreme detail.

So take a listen to our episode this week, and be sensitive to these critical issues in the management of women with epilepsy.

 

[Jim Siegler]


The content in this episode was vetted and approved by Danielle Becker.

REFERENCES

Meador K, Reynolds MW, Crean S, Fahrbach K and Probst C. Pregnancy outcomes in women with epilepsy: a systematic review and meta-analysis of published pregnancy registries and cohorts. Epilepsy Res. 2008;81:1-13.

Meador KJ, Baker GA, Browning N, Cohen MJ, Bromley RL, Clayton-Smith J, Kalayjian LA, Kanner A, Liporace JD, Pennell PB, Privitera M, Loring DW and Neurodevelopmental Effects of Antiepileptic Drugs Study G. Breastfeeding in children of women taking antiepileptic drugs: cognitive outcomes at age 6 years. JAMA Pediatr. 2014;168:729-36.

Veliskova J and Desantis KA. Sex and hormonal influences on seizures and epilepsy. Horm Behav. 2013;63:267-77.

Herzog AG, Fowler KM, Smithson SD, Kalayjian LA, Heck CN, Sperling MR, Liporace JD, Harden CL, Dworetzky BA, Pennell PB, Massaro JM and Progesterone Trial Study G. Progesterone vs placebo therapy for women with epilepsy: A randomized clinical trial. Neurology. 2012;78:1959-66.

Tauboll E, Sveberg L and Svalheim S. Interactions between hormones and epilepsy. Seizure. 2015;28:3-11.

Crawford P. Best practice guidelines for the management of women with epilepsy. Epilepsia. 2005;46 Suppl 9:117-24.

Reiter SF, Bjork MH, Daltveit AK, Veiby G, Kolstad E, Engelsen BA and Gilhus NE. Life satisfaction in women with epilepsy during and after pregnancy. Epilepsy Behav. 2016;62:251-257.

Harden CL, Hopp J, Ting TY, Pennell PB, French JA, Hauser WA, Wiebe S, Gronseth GS, Thurman D, Meador KJ, Koppel BS, Kaplan PW, Robinson JN, Gidal B, Hovinga CA, Wilner AN, Vazquez B, Holmes L, Krumholz A, Finnell R, Le Guen C, American Academy of N and American Epilepsy S. Practice parameter update: management issues for women with epilepsy–focus on pregnancy (an evidence-based review): obstetrical complications and change in seizure frequency: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology. 2009;73:126-32.

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