Effects of polytherapy compared with monotherapy in antiepileptic drugs: An animal study

Although monotherapy in epilepsy treatment is frequently advocated, this is not based on studies with equal drug loads. This study was performed to in vestigate the experimental background of polytherapy with standardized drug loads. Dose-dependent effects on grip strength, accelerod performance, and spontaneous behavior of rats was used to study the effect of combining val proate and ethosuximide. The potency of the drugs (combination) was obtaine d by fitting the sigmoid E-max equation to the data. Drug interaction was a ssessed using the isobologram method and quantified by comparing equivalent drug loads with their 95% confidence intervals. We found that the effects of valproate and ethosuximide combine in a simple additive way in the grip strength experiment as well as in the accelerod experiment. In the behavior al studies, however, a higher drug load of the combination was needed to ob tain the same amount of sedation, signifying infra-additivity. Infra-additi vity of sedative effects is an important finding because this is by far the most frequent side effect mentioned in human studies. However, assessment of the therapeutic effect of the combination will have to be completed befo re a preference for mono- or polytherapy, based on the balance of adverse e ffects and efficacy, can be expressed.