Modern management of epilepsy: Rational polytherapy

Although monotherapy is universally accepted for treating early epilepsy, as many as 40% of patients will continue to have seizures and develop intolerable adverse effects or most commonly, both. Once initial monotherapy has failed, the physician has the choice of either polytherapy by adding a second drug or of alternative monotherapy, that is, substitution of the first drug by another agent active for the same type(s) of seizures. No large randomized comparative trials exist although smaller studies indicate that polytherapy and alternative monotherapy may both achieve complete seizure control in up to 17% and further improvement in approximately 40% of cases. Polytherapy has the advantage of providing benefit in the small minority (15%) of patients who probably cannot be treated satisfactorily by alternative monotherapy, this often being achieved at the price of additional toxicity, undesirable drug interactions and the failure to identify the action of the individual drug. The real basis for rational choice of drugs in polytherapy are features such as efficacy, lack of interaction and low intrinsic toxicity. Theoretical and experimental considerations are of limited value until we know more about the basic mechanism(s) of specific seizures and epilepsy syndromes. At present, it is recommended that undue toxicity and inconvenient drug interactions should be avoided by lowering the dosage of the first drug as much as possible before a second drug is added. In most patients alternative monotherapy, that is, complete removal of the first drug, is a safe and effective option and polytherapy remains available when alternative monotherapy fails.