Clinical opinion: Earlier employment of polytherapy in sequential pharmacotherapy of epilepsy

Abstract

Modern pharmacotherapy for epilepsy consists of orderly, sequential drug trials, in which antiepileptic drugs (AEDs) are chosen under the concept of individual patient-oriented (or - tailored) pharmacotherapy. Although monotherapy has been established as the preferred mode of AEDs therapy in both newly diagnosed and drug resistant epilepsies, there are still lack of evidence to favor either monotherapy or polytherapy in epilepsy, which has generated continuing controversies on the preferred mode of pharmacotherapy. However, each mode of pharmacotherapy may have both advantages and disadvantages, which are different and variable related to individual case scenario. We conducted a brief comparative overview between monotherapy and polytherapy to provide clues for earlier employment of polytherapy in each steps of sequential drug trials. Previous claims about the advantages of monotherapy over polytherapy are not supported but gradually losing its ground by the introduction of a large number of drugs carrying pharmacological advantages for combination therapy. Current evidence stresses the importance of combining drugs having synergistic interactions for better outcome of polytherapy, which has not been considered in previous clinical investigations comparing monotherapy and polytherapy. It is likely that a significant improvement in the outcome of current AEDs therapy is feasible by earlier employment of polytherapy as well as identification of combination drug regimens carrying synergistic interactions. At present, lamotrigine(LTG) and valproate(VPA) combination regimen is the only well documented synergistic regimen, but there are a long-list of candidate regimens requiring future trials in appropriate designs.

Keywords: Maximally tolerable dose (MTD); Monotherapy; Polytherapy; Sequential pharmacotherapy; Total drug load (TDL).