The pharmacodynamic basis of the association of anti-epileptic drugs

We analyze the factors which have lead from indiscriminate anti-epileptic polytherapy (inefficient and poorly tolerated) to a tendency towards the use of monotherapy, the limits of this monotherapy and the need for rational polytherapy. We indicate the factors on which rational polytherapy should be based. Pharmacodynamic factors which affect efficacy (spectrum and mode of action) are considered as are toxicity (dose-dependant, idiosyncratic and teratogenous). We review experimental and clinical studies of associations of anti-epileptic drugs. Aspects of the methodologies used for this are emphasized It is concluded that polytherapy may be necessary in 40% of all epileptic patients, and may be beneficial in 10-15%. Polytherapy should be based on the relationship between benefit and risk. Controlled studies are necessary to Establish this relationship in clinical practice.