Rational Regimens: How to Combine Drugs in Treating Epilepsy

Andrew N. Wilner, MD; Jose E. Cavazos, MD, PhD


June 03, 2013

Which Combination Is Best?

We found that rational combination therapy (2 drugs with different mechanisms of action) was better. An irrational combination (eg, combining 2 sodium-channel blockers, or 2 GABA analogs) was inferior to a rational combination. We were able to demonstrate that on the basis of mechanism of action, the combination of 2 sodium-channel blockers was inferior to the combination of a sodium-channel blocker plus an SV2-A binding drug. We did the same for GABA drugs.

The study has limitations. All patients were adults and insured, so individuals who were on Medicaid or who were uninsured were not included. Still, we can learn some information from these data. There seems to be a signal that combining medications with different mechanisms of action is superior to combining medications with similar mechanisms of action.

Dr. Wilner: One of your findings was that the combination of a sodium-channel blocker and an SV2-A binding drug was associated with the lowest percentage of patients with either a hospitalization or emergency department visit. Could you just remind us what those drugs would be?

Dr. Cavazos: The only SV2-A binding drug that is approved in the United States is levetiracetam. The sodium-channel blockers are carbamazepine, phenytoin, lacosamide, lamotrigine, or oxcarbazepine. The idea is that combining one of those with levetiracetam was superior to combing 2 medications from the sodium-channel group.

Dr. Wilner: How are findings going to affect your practice in the future?

Dr. Cavazos: We demonstrated that the combination that appears to be most effective for first use, which gives patients the best chance of success, is a sodium-channel blocker and levetiracetam. This study suggests that if I have a patient with first monotherapy failure, switching to combination therapy with levetiracetam plus a sodium-channel blocker is the next logical step.

Dr. Wilner: Dr. Cavazos, thank you very much for sharing the results of your research with us today.


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