SAN DIEGO—For patients with partial-onset seizures, combinations of antiepileptic drugs (AEDs) with different mechanisms of action may be associated with greater duration of treatment and fewer visits to hospitals and emergency rooms than combinations of AEDs with the same mechanism of action. Mechanism of action may correlate with variations in treatment persistence, risk of hospitalization, and risk of emergency room visit, according to research presented at the 65th Annual Meeting of the American Academy of Neurology.
Differences in patient demographics and comorbidities at baseline between patients taking various combinations of AEDs may result from physicians’ differential practice patterns for selecting the drugs, however. These demographic disparities may contribute to differences in outcome between patients taking various combinations of AEDs, said José E. Cavazos, MD, Professor of Neurology and Physiology at the University of Texas Health Science Center at San Antonio.
A Retrospective Analysis of AED Use
Dr. Cavazos and colleagues retrospectively analyzed data for 8,615 patients who submitted health insurance claims from July 2004 through March 2011. Eligible patients were 18 or older, had been diagnosed with epilepsy with partial seizures, and took two AEDs for 90 or more days. Subjects had a minimum of six months of continuous medical and prescription coverage before beginning combination therapy. Patients were followed until the end of their first combination therapy, the end of enrollment (which lasted a minimum of 12 months), or the end of available data.
The mechanisms of action under consideration included sodium channel blockers, gamma-aminobutyric acid analogs, synaptic vesicle protein 2A binders, and multiple mechanisms. The investigators grouped the patients into seven combinations of AED mechanisms of action (eg, sodium channel blocker and synaptic vesicle protein 2A binder, sodium channel blocker and sodium channel blocker, etc.).
Mechanism of Action Was Associated With Rate of Discontinuation
The mean ages differed between groups of patients receiving given combinations of AEDs. The mean age of patients taking a sodium channel blocker and an AED with a mixed mechanism of action was approximately 42, while the mean age of patients taking two gamma-aminobutyric acid analogs was about 48. Groups of patients receiving various AED combinations also differed significantly according to gender. Nearly 49% of patients taking a sodium channel blocker and a synaptic vesicle protein 2A binder were male, compared with 28% of patients who received two gamma-aminobutyric acid analogs.
Patients who received combinations of AEDs with different mechanisms of action had longer mean and median therapy durations than patients who received AEDs with the same mechanisms of action. Subjects who took two gamma-aminobutyric acid analogs remained on therapy for the shortest period. Patients who took a sodium channel blocker and a synaptic vesicle protein 2A binder had the longest mean and median therapy durations.
Combinations of AEDs with different mechanisms of action were associated with a lower likelihood of discontinuation, compared with combinations of AEDs with the same mechanism of action. Patients who took a sodium channel blocker and a synaptic vesicle protein 2A binder were less likely to discontinue therapy than patients who took two sodium channel blockers. Subjects who took two gamma-aminobutyric acid analogs or a gamma-aminobutyric acid analog and an AED with multiple mechanisms of action were more likely to discontinue treatment than patients who took two sodium channel blockers.
The combination of a sodium channel blocker and a synaptic vesicle protein 2A binder was associated with the lowest rate of hospitalization or emergency room visit. The combination of two gamma-aminobutyric acid analogs had the highest rate of hospitalization or emergency room visit. Patients who took two sodium channel blockers had a higher rate of emergency room visits than patients who took a sodium channel blocker and an AED with a different mechanism of action. Rates of in-patient admission were higher for patients who took two gamma-aminobutyric acid analogs than for patients who took a gamma-aminobutyric acid analog and an AED with a different mechanism of action.
AEDs’ Mechanisms of Action Are Debated
“Classifications of AEDs were based on their primary mechanism of action; however, there are differing opinions regarding the exact mechanisms of action attributed to particular AEDs,” said Dr. Cavazos. “Mechanism of action categories selected for this study may not have been sufficiently detailed to detect differences between AED combinations.” In addition, the study did not account for differences in clinical and safety profile between AEDs with the same mechanism of action. The researchers also assumed that the patients took their prescriptions consistently as directed.
“Further research is needed to more fully understand the role of mechanism of action in achieving optimal outcomes in AED combination therapy,” said Dr. Cavazos. Additional study could help identify other factors that may influence outcomes when managing partial-onset seizures with AEDs that have different mechanisms of action, he concluded.