Lamotrigine in absence and primary generalized epilepsies.
Although lamotrigine has been approved in the United States as adjunctive therapy for partial seizures in patients older than 12 years, there is increasing evidence that it is just as effective, if not more effective, in the treatment of generalized seizures. A large number of open-label studies and some single-blind data, all using lamotrigine as add-on therapy in patients with previously refractory generalized seizures, are available. Controlled studies, some on newly diagnosed, previously untreated patients with generalized seizures are ongoing. Investigations have demonstrated that patients with the following generalized seizure types improve with lamotrigine add-on therapy: Typical and atypical absence, atonic, generalized tonic-clonic, myoclonic, and clonic seizures. Response rates, defined as the percentage of patients with better than 50% reduction in seizure frequency, have been, depending on seizure type, in the range of 30% to 56%, with 0 to 33% of the patients becoming seizure free. The best responses have been noted in typical and atypical absences, and atonic seizures. Children and adults appear to have comparable responses. In addition, add-on studies in patients with specific, previously refractory, epilepsy syndromes have demonstrated that the best improvement in seizure control occurs in patients with petit mal epilepsy, "other symptomatic" generalized epilepsies, and in Lennox-Gastaut syndrome, followed by patients with other myoclonic epilepsies, myoclonic absence and West syndrome. Many previously refractory patients are able to achieve lamotrigine monotherapy. However, patients with nonprogressive myoclonic epilepsy have little, if any, response. Early data from ambulatory encephalographic (EEG) recordings in patients with previously refractory absence seizures, and from controlled studies on patients with newly diagnosed typical absence seizures, appear to confirm the efficacy of lamotrigine in those patients. Controlled studies are ongoing in patients with absence seizures, in patients with generalized tonic-clonic seizures, and in patients with Lennox-Gastaut syndrome. Dosing in generalized seizures is similar to that for partial seizures. Because of the shorter half-life of lamotrigine in children, as compared to adults, higher (mg/kg) doses are often needed in young patients. We conclude that lamotrigine is a promising drug for absence and primary generalized seizures in both children and adults.
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