Dr. Bourgeois: Often in the treatment of epilepsy, when we are not successful with one drug, we attempt to combine two antiepileptic agents. Our purpose in doing so is to achieve a reduction in the number of seizures, but how do we think the two drugs will work together? Theoretically, there might be two reasons for combining two antiepileptic drugs. Perhaps we hope to achieve a wider antiepileptic spectrum with two or three agents than with one. If a patient, for instance, has more than one type of seizure and each type may respond to a different agent, then we may believe it better to administer two agents; or we may believe that different mechanisms may be involved in one specific seizure type and that two drugs are more likely to affect the different mechanisms; or we may believe that two drugs administered together will have an additive or enhancing effect.
Two drugs can demonstrate a combined action, or pharmacodynamic interaction, in three possible ways. If the combined action of two drugs is equal to the sum of their single actions, the interaction is additive. If the combined action is larger in quantity or degree (more than the expected sum of the two drugs added), the interaction is supra-additive (potentiation). If the combined action is less in quantity or degree than the sum of the individual drugs, it is infra-additive (antagonism).
Merely checking the anticonvulsant effect in order to measure the pharmacodynamic interactions of two antiepileptic drugs is not too. . .