What Are the Consequences of Changing Antiepileptic Drug Regimens as Part of Pregnancy Planning?

WASHINGTON, DC—Women with epilepsy of reproductive age have a high likelihood of successfully changing their antiepileptic drug (AED) regimen to lower teratogenic risks during future pregnancies, according to a retrospective study presented at the 71st Annual Meeting of the American Epilepsy Society. If an initial AED regimen change fails, further alterations may prove successful, the researchers said.

Mitigating Risk to Offspring

Studies have found that certain AEDs increase the risk of structural and neurodevelopmental teratogenicity. “Women with epilepsy of childbearing age require careful reconsideration of their AED type and dose, given that the maternal benefits of treatment during potential future pregnancies should be weighed against adverse effects on the developing fetus,” said P. Emanuela Voinescu, MD, PhD, and colleagues. “Too often, not switching AEDs leads to exposing future offspring to undue risk.” Neurologists may be hesitant to change an AED regimen due to concerns about worsening seizures, however, and data to predict the risk of seizure worsening with an AED regimen change are lacking, the researchers said. Dr. Voinescu is an Instructor in Neurology at Harvard University and a neurologist at Brigham and Woman’s Hospital in Boston.

P. Emanuela Voinescu, MD, PhD

Dr. Voinescu and colleagues conducted a retrospective study to quantify the risk of failure when altering an AED regimen for reproductive safety, and to identify the causes of failure. The study included 40 women with epilepsy between ages 16 and 45 who had been on a stable AED regimen for more than six months and whose AED regimen was changed to improve the outcome of a future pregnancy. Changes included AED switch, AED dose reduction, AED number reduction, and complete discontinuation of AEDs.

The researchers excluded patients with psychogenic nonepileptic seizures, history of substance abuse, history of nonadherence to medications or scheduled visits, progressive cerebral disease or lesion, or other major medical illness. The patients’ AED regimen changes occurred between 2005 and 2017.

The investigators conducted a retrospective chart review for seizure frequency during the six months prior to the AED regimen change, during the transition interval, and in the six months after achieving the final regimen. They also collected demographic and epilepsy history details and reviewed patients’ most recent neurology clinic notes to assess long-term prognosis.

An AED regimen change was considered successful if the new regimen was continued without additional alterations. Otherwise, the change was considered a failure, and researchers documented the reason for continued alterations and the final outcome.

Most Changes Were Successful

The initial AED regimen change was successful for 75% of patients (n = 30). After taking into account patients whose regimens underwent a second change, 90% of patients (n = 36) had a successful change.

“A failed first change is not a predictor of failure for a subsequent alteration,” the researchers said. Half of the failed first changes occurred because of medication side effects. In those cases, a trial of another medication or complete AED discontinuation were successful strategies. Seven out of nine patients (78%) who initially were on valproic acid discontinued it successfully.

Persistent seizure worsening occurred in two patients with medically refractory epilepsy. Patients rarely and only transiently lost seizure-free status. Potential covariates (eg, epilepsy and seizure types, seizure freedom status, AED type, and type of alteration) did not seem to significantly affect outcomes.

To further study AED regimen changes for reproductive safety, the researchers are conducting a prospective, observational, parallel-group, switch-control study.

—Jake Remaly