Combination of valproate and ethosuximide: antiepileptic and neurotoxic interaction.

The combination of ethosuximide and valproate has been advocated, particularly in patients with atypical and myoclonic absences. This drug combination has been assessed experimentally in mice by studying the effect of the pharmacodynamic interactions between the two drugs on the efficacy vs. toxicity ratio. All results were expressed in terms of brain concentrations. A purely additive anticonvulsant interaction was found. However, due to a less than additive neurotoxic interaction, the combination had a better efficacy vs. toxicity score than either drug alone. These results, although not representative for all drug combinations, provide evidence that the dissociation between the anticonvulsant and the neurotoxic interaction of two antiepileptic drugs can result in a better protective index for certain combinations of antiepileptic drugs.