Pharmacological principles as a basis for polytherapy

Most patients with newly diagnosed epilepsy can be optimally controlled by prescribing a single anti-epilepsy drug, selected on the basis of its efficacy and safety profile. In about one-third of patients, however, seizures persist during monotherapy, despite the intake of the maximally tolerated drug dose. In such cases, substantial therapeutic benefit may be achieved by prescribing appropriate drug combinations. Safe use of multiple drug therapy requires a good knowledge of clinical pharmacology, particularly an awareness of potentially adverse drug interactions. As many older anti-epilepsy drugs have similar modes of action, their interaction may not always be of clinical benefit, because drug side-effects may also be additive. There is, however, evidence that specific combinations may be particularly advantageous; for example, valproate and ethosuximide in the management of refractory absence seizures. Compared with older drugs, some of the recently developed agents 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 of their pharmacological effect being 'complementary' to that of concurrently used agents.