Advances in the pharmacotherapy of epilepsy

Three new antiepileptic drugs (AEDs) are likely to be approved in the United States by the Food and Drug Administration in the near future. In general, all three have good safety profiles, causing only mild, well-tolerated side effects. Felbamate (FBM) is effective in the treatment of partial seizures and Lennox-Gastaut epilepsy. FBM appears to have a broader spectrum of antiepileptic activity than carbamazepine (CBZ) or phenytoin (PHT). Gabapentin (GBP) was designed to be a structured analogue of gamma-aminobutyric acid (GABA). GBP is most effective in the maximal electroshock model of seizures but may have a different mechanism of action than CBZ and PHT. Unique pharmacokinetic properties (no hepatic metabolism and no protein binding) may make GBP especially useful for certain patients, such as those with hepatic disease and elderly patients who are receiving multiple medications. The overall profile of activity of lamotrigine (LTG) is similar to that of PHT and may act on voltage-sensitive sodium channels to stabilize neuronal membranes. LTG is effective in partial seizures, and there is some indication that LTG may be helpful in primary generalized seizures. The long half-life and lack of effect on other AEDs will make LTG easy to dose and add to a patient's existing regimen. These new agents will provide physicians with more effective medications from which to choose in the treatment of the patient with epilepsy.