Broader is better

Until 1993, six antiepileptic drugs (phenytoin, phenobarbital, primidone, ethosuximide, carbamazepine, and valproate) accounted for the overwhelming majority of prescriptions written for the treatment of epilepsy. Among those, only valproate was truly a broad-spectrum drug, with some or good efficacy against all seizure types. Since 1993, felbamate, gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, zonisamide, and pregabalin were approved in the United States for the treatment of epilepsy. All were initially tested and approved as add-on treatment of partial-onset seizures, with or without secondary generalization. The era that began in 1993 was characterized not only by a new generation of antiepileptic drugs, but also by controlled trials in specific epileptic syndromes and in seizure types other than partial onset. From these trials, a gradually expanding pattern of a broader antiepileptic efficacy spectrum has emerged for several of the newer drugs, although some of them still retain a narrow spectrum, such as gabapentin, tiagabine, oxcarbazepine, and pregabalin (table).

The Lennox-Gastaut syndrome is a generalized epilepsy that is notoriously refractory to treatment. In a trial reported in 1993, felbamate was the first drug ever to be submitted to a controlled trial in this syndrome, and it was found to be superior to placebo, in particular against the most debilitating drop attacks.¹ Following this lead, subsequent similar placebo-controlled trials in this syndrome demonstrated the efficacy of lamotrigine² and then topiramate.³ Another generalized seizure type, absence seizures, was shown in a controlled trial to respond to lamotrigine.⁴

Generalized tonic-clonic seizures (GTCS) are …