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Original Investigation
April 1, 2019

Antiepileptic Drug Treatment Patterns in Women of Childbearing Age With Epilepsy

Author Affiliations
  • 1Department of Neurology, Stanford University School of Medicine, Palo Alto, California
  • 2Department of Neurology, Emory University School of Medicine, Atlanta, Georgia
  • 3UCB Pharma, Smyrna, Georgia
  • 4UCB Pharma, Raleigh, North Carolina
JAMA Neurol. 2019;76(7):783-790. doi:10.1001/jamaneurol.2019.0447
Key Points

Question  Are comorbidities or epilepsy types associated with the selection of antiepileptic drugs in women with epilepsy of childbearing age?

Findings  In a cohort study of 46 767 women of childbearing age with epilepsy, valproate sodium and phenytoin sodium were more commonly used for generalized epilepsy; oxcarbazepine was more often used for focal epilepsy. Valproate and topiramate were more likely prescribed in women with comorbid headache or migraine; valproate was more likely prescribed in women with comorbid psychiatric comorbidities.

Meaning  Many women appear to receive valproate, topiramate, and phenytoin despite known teratogenicity risks; to improve current practice, teratogenicity risk awareness should be increased among women of childbearing age with epilepsy and other medical conditions, and among physicians.

Abstract

Importance  Limited population-based data are available on antiepileptic drug (AED) treatment patterns in women of childbearing age with epilepsy; the current population risk is not clear.

Objectives  To examine the AED treatment patterns and identify differences in use of valproate sodium and topiramate by comorbidities among women of childbearing age with epilepsy.

Design, Setting, and Participants  A retrospective cohort study used a nationwide commercial database and supplemental Medicare as well as Medicaid insurance claims data to identify 46 767 women with epilepsy aged 15 to 44 years. The eligible study cohort was enrolled between January 1, 2009, and December 31, 2013. Data analysis was conducted from January 1, 2017, to February 22, 2018.

Exposures  Cases required an International Classification of Diseases, Ninth Revision, Clinical Modification–coded epilepsy diagnosis with continuous medical and pharmacy enrollment. Incident cases required a baseline of 2 or more years without an epilepsy diagnosis or AED prescription before the index date. For both incident and prevalent cases, focal and generalized epilepsy cohorts were matched by age, payer type, and enrollment period and then compared.

Main Outcomes and Measures  Antiepileptic drug treatment pattern according to seizure type and comorbidities.

Results  Of the 46 767 patients identified, there were 8003 incident cases (mean [SD] age, 27.3 [9.4] years) and 38 764 prevalent cases (mean [SD] age, 29.7 [9.0] years). Among 3219 women in the incident epilepsy group who received AEDs for 90 days or more, 3173 (98.6%) received monotherapy as first-line treatment; among 28 239 treated prevalent cases, 18 987 (67.2%) received monotherapy. In 3544 (44.3%) incident cases and 9480 (24.5%) prevalent cases, AED treatment was not documented during 180 days or more of follow-up after diagnosis. Valproate (incident: 35 [5.81%]; prevalent: 514 [13.1%]) and phenytoin (incident: 33 [5.48%]; prevalent: 178 [4.53%]) were more commonly used for generalized epilepsy and oxcarbazepine (incident: 53 [8.03%]; prevalent: 386 [9.89%]) was more often used for focal epilepsy. Levetiracetam (incident: focal, 267 [40.5%]; generalized, 271 [45.0%]; prevalent: focal, 794 [20.3%]; generalized, 871 [22.2%]), lamotrigine (incident: focal, 123 [18.6%]; generalized, 106 [17.6%]; prevalent: focal, 968 [24.8%]; generalized, 871 [22.2%]), and topiramate (incident: focal, 102 [15.5%]; generalized, 64 [10.6%]; prevalent: focal, 499 [12.8%]; generalized, 470 [12.0%]) were leading AEDs prescribed for both focal and generalized epilepsy. Valproate was more commonly prescribed for women with comorbid headache or migraine (incident: 53 of 1251 [4.2%]; prevalent: 839 of 8046 [10.4%]), mood disorder (incident: 63 of 860 [7.3%]; prevalent: 1110 of 6995 [15.9%]), and anxiety and dissociative disorders (incident: 57 of 881 [6.5%]; prevalent: 798 of 5912 [13.5%]). Topiramate was more likely prescribed for those with comorbid headache or migraine (incident: 335 of 1251 [26.8%]; prevalent: 2322 of 8046 [28.9%]).

Conclusions and Relevance  Many women appear to be treated with valproate and topiramate despite known teratogenicity risks. Comorbidities may affect selecting certain AEDs despite their teratogenicity risks.

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