Comparative efficacy of unique antiepileptic drug regimens in focal epilepsy: An exploratory study

To compare efficacy of unique antiepileptic drug (AED) polytherapy regimens among patients with focal epilepsy.

From a longitudinal study of AED treatment, we identified patients with active focal epilepsy who had attempted at least two unique AED regimens (mono-, duo-, or tri-therapy). Efficacy was defined as the presence of at least one six-month period of continuous seizure freedom during exposure to a regimen. To control for individual variations in response and epilepsy severity, we used within-patient comparison approaches, in which we: 1) compared head-to-head unique regimens tried within the same patients; 2) compared one regimen versus aggregate of other regimens attempted in that patient; and 3) compared aggregated monotherapy versus polytherapy regimens.

757 patients met our criteria and had collectively attempted 170 unique regimens. In the head-to-head analysis, lamotrigine monotherapy was more effective than phenytoin monotherapy. Two regimens were more effective than the aggregate of other regimens attempted: levetiracetam/lamotrigine duotherapy and lamotrigine monotherapy. Two other regimens exhibited slightly better efficacy but did not reach statistical significance: clobazam/levetiracetam/lamotrigine and levetriacetam/oxcarbazepine. Patients who previously attempted at least four regimens had slightly better outcomes on polytherapy than monotherapy, though this was not significant.

We identified two unique regimens more likely to be associated with ≥6 months of seizure freedom: levetiracetam/lamotrigine duotherapy and lamotrigine monotherapy. Polytherapy may be an effective alternative to monotherapy for patients with focal epilepsy and persistent seizures.