Anticonvulsant drugs. An update

A considerable amount of information is now available concerning the clinical pharmacology of the anticonvulsant drugs. Some of the more important data are reviewed in this article. In recent years, valproic acid (or sodium valproate) has found a place as a major anticonvulsant agent, while older drugs such as troxidone and sulthiame seem to be disappearing from use. Although much information is available, the essential mechanisms of action of the anticonvulsant drugs are still not understood, either at a molecular or at an electrophysiological level. The pharmacokinetics of the anticonvulsants in common use are now reasonably well documented, though some minor questions are still to be answered. Numerous interactions between anticonvulsants and endogenous substances or other drugs administered concurrently (including other anticonvulsants) have been recorded, but much work still needs to be done to elucidate the frequency and mechanisms of the various interactions. Many adverse effects of the anticonvulsants are known, but further unwanted effects of long-established drugs continue to emerge from time to time, including the still somewhat controversial matter of anticonvulsant-related dysmorphogenesis. The use of valproic acid and its sodium salt has been associated with a worrying incidence of serious liver and pancreatic toxicity. Adequate basic data are now available to put the clinical use of anticonvulsants on a rational basis, but much work remains to be done in this area. In particular, the question of ‘therapeutic ranges’ of plasma concentrations of the various drugs needs to be reinvestigated in a rigorous statistical fashion, and in relation to different clinical types of epilepsy. The usefulness of monitoring free rather than total drug concentrations also needs further investigation. The ultimate test of the validity of all background scientific pharmacological information about anticonvulsants is its usefulness in the treatment of patients with epilepsy.