Therapeutic options provided by new antiepileptic drugs

Abstract The introduction on the French market of vigabatrin, gabapentin and lamotrigine has considerably diversified our conventional therapeutical schemes in epilepsies, as will be as amplified by the arrivals of topiramate, tiagabine and oxcarbazepine. Compared to the conventional drugs, these new products present more favorable pharmacokinetics, no or very weak interactions and a better tolerability, specially regarding the cognitive field. They should be used according to their spectrum of activity, function of their modes of action. In add-on trials on partial epilepsy patients all these new products have shown efficacy on partial and secondarily generalized seizures. Seizure frequency is reduced by at least 50 p. 100 in 30 to 50 p. 100 of the patients. A substantial number of patients can be rendered seizure-free with vigabatrin. Lamotrigine has a broader spectrum, as it is also efficacious on the different seizure types of generalized, symptomatic or idiopathic epilepsies. Main adverse events are non-specific central nervous system disturbances such as dizziness, drowsiness, ataxia, tremor or diplopia. More specifically, vigabatrin may induce weight gain and requires closer supervision in case of psychiatric history; lamotrigine which has also probable antidepressant properties, may induce skin rashs, rarely severe. Further data are needed for gabapentin which is now used at daily dosages which are two to three times those used in the initial studies. Gabamimetic agents may be worsening in some cases of generalized epilepsies, more specially on absence and myoclonic seizures. The most obvious benefits, some patients becoming seizure-free, are obtained in cases of intermediate severity, with a bitherapy including one of these new drugs. Developments in children are often delayed. Nevertheless the prognosis, including cognitive outcome, is considerably improved in infantile spasms with vigabatrin and in Lennox-Gastaut syndrome with lamotrigine and felbamate, the latter being highly toxic. For the moment in France, authorities have limited the use of all these new antiepileptic drugs to adjunctive therapy in epilepsies resisting to conventional drugs. But recent monotherapy data show similar efficacy with better tolerability. Once the pivotal, controlled studies have enabled to obtain regulatory approval, all these compounds must undergo a large-scale evaluation phase in order to better define dosages, long-term tolerability, indications and eventual contra-indications in the various epileptic syndromes, including children.