Selecting Rational Drug Combinations in Epilepsy

Monotherapy remains the standard initial therapy of epilepsy, but when the first antiepileptic drug (AED) fails, combination therapy may be considered. The choice of combination therapy should take into consideration pharmacokinetic interactions, as well as pharmacodynamic interactions related to mechanism of action. There is evidence that an AED combination with different mechanisms of action is more likely to be successful than a combination with the same mechanisms. The combination of lamotrigine and valproate has been demonstrated to be synergistic in its efficacy. However, there are limited data to support other synergistic AED combinations.