Despite known teratogenicity risks, many women of childbearing age with epilepsy are prescribed valproate, topiramate, and phenytoin.
Hyunmi Kim, MD, PhD, MPH
In a retrospective cohort study, researchers found that many women of childbearing age with epilepsy were treated with valproate, topiramate, and phenytoin despite known teratogenicity risks; risk awareness should be increased among this patient population to improve current practice.
Researchers discovered that of women of childbearing age with epilepsy, valproate sodium (incident: 5.81% [n=35]; prevalent: 13.1% [n=514]) and phenytoin sodium (incident: 5.48% [n=33]; prevalent: 4.53% [n=178]) were more commonly prescribed for generalized epilepsy, and oxcarbazepine (incident: 8.03% [n=53]; prevalent: 9.89% [n=386]) for focal epilepsy. Valproate and topiramate were more likely prescribed for comorbid headache or migraine; valproate was more often prescribed for psychiatric comorbidities.
“This population-based longitudinal cohort study suggests that a noticeable proportion of women were treated with valproate and topiramate despite known teratogenicity risks,” the corresponding author Hyunmi Kim, MD, PhD, MPH, Clinical Professor of Neurology at Stanford University, and colleagues wrote.1 “Comorbidities may be likely to affect selecting certain antiepileptic drug (AEDs) despite their teratogenicity risks. This finding suggests that physicians and women of childbearing age with epilepsy should be aware of and sensitive to teratogenicity risks of certain AEDs. In addition, efforts to raise awareness of current American Academy of Neurology quality measures on the counseling of teratogenicity risk may assist in ensuring that the risk-benefit profiles of treatments are evaluated by both clinicians and patients.”
In this population-based, observational, longitudinal study, researchers sought to examine AED treatment patterns during 180 or more days of follow-up after the index date to identify if differences in selection of AEDs were more associated comorbidities or epilepsy types among women of childbearing age (15—44) with epilepsy.
Researchers used a nationally representative claims database to identify a total of 46,767 women enrolled between Jan. 1, 2009, and Dec. 31, 2013, in the Truven Health MarketScan commercial and supplemental Medicare (CCMC) and Medicaid insurance claims databases. Women were then distributed grouped according to 3 intervals of follow-up: 180 to 364 days, 365 to 729 days, and 730 days or longer.
There were 8003 incident cases classified and the mean age was 27.3 years; 75.4% (n=6038 women) were enrolled for CCMC benefits. Researchers reported that the epilepsy diagnosis was classified as focal (19.8% [n=1587]), generalized (25.4% ), and undefined (54.8% ). The most common comorbidity reported was headache or migraine (27% ) and the most common psychiatric comorbidities were anxiety and dissociative disorder (19.6% ) and mood disorders (18.4% ).
A total of 38,764 prevalent cases were identified, with a mean age of 29.7 years; 64.6% (n=25,038 women) were enrolled for CCMC benefits. Similarly, to incident cases, epilepsy diagnosis was classified as focal (20.8 ), generalized (23.5 ), and undefined (55.6% [21,555]). Headache or migraine was reported as the most common comorbidity (31.4% [12,180]), and anxiety and dissociative disorder (23.4% ) and mood disorders were the most common psychiatric comorbidities.
Among the 3219 women in the incident cases who received AEDs for 90 days or more, 98.6% (n=3173) received monotherapy as first-line treatment; among 28,239 treated prevalent cases, 67.2% (n=18,987) received monotherapy. AED treatment was not documented during the 180 days or more of follow-up after diagnosis in 44.3% (n=3544) of incident cases and 24.5% (n=9480) of prevalent cases.
The most commonly prescribed AEDs for both focal and generalized epilepsy were levetiracetam (incident: focal, 40.5% ; generalized, 45% ; prevalent: focal, 20.3% ; generalized, 22.2% ), lamotrigine (incident: focal, 18.6% [n=123]; generalized, 17.6% [n=106]; prevalent: focal, 24.8% [n=968]; generalized, 22.2% [n=871]), and topiramate (incident: focal, 15.5% [n=102]; generalized, 10.6% [n=64]; prevalent: focal, 12.8% [n=499]; generalized, 12% [n=470]).
Valproate was more often prescribed for 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%]); and topiramate was more commonly prescribed for those with comorbid headache or migraine (incident: 335 of 1251 [26.8%]; prevalent: 2322 of 8046 [28.9%]).
“Many women appear to be treated with valproate and topiramate despite known teratogenicity risks,” the researchers concluded. “Comorbidities may affect selecting certain AEDs despite their teratogenicity risks.”
To improve current practice, the researchers recommend disseminating knowledge of teratogenicity of certain AEDs to increase risk awareness.
1. Kim H, Faught E, Thurman D, et al. Antiepileptic Drug Treatment Patterns in Women of Childbearing Age With Epilepsy. JAMA Neurol. 2019.