Comparative efficacy of combination drug therapy in refractory epilepsy

We retrospectively examined treatment records of developmentally disabled adults with highly refractory epilepsy to determine whether any combinations of 8 of the most commonly used antiepileptic drugs (AEDs) possessed superior efficacy.

We obtained the treatment records from 148 developmentally disabled adults with refractory epilepsy cared for in 2 state-run institutions. These records charted monthly convulsive seizure occurrence and AED regimen over 30 years. We studied the effects of 8 commonly used AEDs alone and in combination on seizure frequency in within-patient comparisons.

Out of the 32 most frequently used AED combinations, we found that only the combination of lamotrigine and valproate had superior efficacy, measured against both an aggregate measure of other AED regimens to which patients were exposed, and in head-to-head comparisons with other AED combinations. We also found that while use of 2 concurrent AEDs provided improved efficacy over monotherapy, use of 3 AEDs at a time provided no further benefit over two.

These results suggest that at least one AED regimen provides significantly better efficacy in refractory convulsive epilepsy, and that AEDs should be used no more than 2 at a time. Limitations of the study include its retrospective design, lack of randomization, and small sample sizes for some drug combinations. Future prospective trials are needed in this challenging clinical population.