PHARMACOLOGICAL PRINCIPLES AS A BASIS FOR POLYTHERAPY

Most patients with newly diagnosed epilepsy can be optimally controlle d by prescribing a single anti-epilepsy drug, selected on the basis of its efficacy and safety profile. In about one-third of patients, howe ver, seizures persist during monotherapy, despite the intake of the ma ximally tolerated drug dose. In such cases, substantial therapeutic be nefit may be achieved by prescribing appropriate drug combinations. Sa fe use of multiple drug therapy requires a good knowledge of clinical pharmacology, particularly an awareness of potentially adverse drug in teractions. As many older anti-epilepsy drugs have similar modes of ac tion, their interaction may not always be of clinical benefit, because drug side-effects may also be additive. There is, however, evidence t hat specific combinations may be particularly advantageous; for exampl e, valproate and ethosuximide in the management of refractory absence seizures. Compared with older drugs, some of the recently developed ag ents possess different and more selective mechanisms of action, which may result in enhanced therapeutic benefit when specific combinations are used. Preliminary observations do suggest that, in some cases, the efficacy exhibited by certain new drugs could be explained in terms o f their pharmacological effect being 'complementary' to that of concur rently used agents.