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The clinical efficacy of lamotrigine as an antiepileptic drug

Product license applications for lamotrigine have been filed or approved in more than 50 countries throughout the world. In preclinical models, this drug demonstrates activity against both maximal electroshock and pentylenetetrazol seizures. The primary action of lamotrigine is, most likely, blockade of sodium channels, with resultant inhibition of glutamate and aspartate release. As would be expected from this spectrum of activity, the drug has shown clinical efficacy in both partial and generalized seizures and in a variety of epilepsy syndromes. Particularly promising results have been demonstrated in difficult-to-control epilepsy syndromes with mixed seizures. Half-life of lamotrigine in adults receiving monotherapy is approximately 24 hours. Its half-life is decreased by approximately 50% when it is used in combination with enzyme-inducing antiepileptic drugs, such as phenobarbital, carbamazepine, and phenytoin; in contrast, valproate extends the half-life of lamotrigine by two- to three-fold. Its administration has no effect on the metabolism of other antiepileptic drugs, with the exception of a possible minor increase in the proportion of carbamazepine-10, 11-epoxide. The usual maintenance dosage of lamotrigine is 200 to 500 mg daily given in two divided doses. In US open studies of adult patients with treatment-refractory partial epilepsy, increased seizure control was demonstrated with higher dosages. Extension studies have shown even better efficacy with daily doses of approximately 700 mg. Multiple studies and clinical usage have shown lamotrigine to be well tolerated, with patients reporting a sense of well-being during drug therapy. The most frequently reported adverse events are CNS-associated side effects and rash. Lamotrigine is a major addition to the currently available armamentarium ofx antiepileptic drugs.