Newer Antiepileptic Drugs & GABA Modulators

Introduction & scope

• Antiseizure medications (ASMs) — the preferred current term over "antiepileptic drug (AED)" — the drugs suppress seizures, not the epilepsy; pharmacotherapy is symptomatic, providing neither prophylaxis nor cure, and no antiepileptogenic agent yet exists.
• "Newer" = second- & third-generation — agents introduced from the 1990s onward — lamotrigine, gabapentin, topiramate, tiagabine, levetiracetam, then the still-newer brivaracetam, lacosamide, perampanel, eslicarbazepine, rufinamide, stiripentol, cenobamate, cannabidiol, fenfluramine, ganaxolone and retigabine.
• Why newer agents — older drugs fail to control ~⅓ of patients, carry dose-limiting toxicity, and the enzyme-inducers (phenytoin, carbamazepine, phenobarbital) cause broad CYP/UGT interactions; newer agents are generally less sedating, cleaner kinetically, and lower-interaction — though less extensively studied.
• Rational basis — seizures reflect an imbalance favouring excitation over inhibition (excess glutamate, deficient GABA); newer ASMs were rationally designed against four molecular target families — voltage-gated ion channels, GABA enhancement, synaptic-release machinery, and ionotropic glutamate receptors.