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Chapter 4: Antiepileptic Drugs: Second-Generation/Newer Agents

KERI S. KIM; JEFFREY J. MUCKSAVAGE; GRETCHEN M. BROPHY

RREVIEW OF SECOND-GENERATION/NEWER AGENTS

PLACE IN THERAPY

The advent of the second-generation antiepileptic drugs ushered in a period of improved management of patients with epilepsy. The introduction of these agents began in 1993 and greatly expanded the available epilepsy treatment options. Currently, 11 second-generation antiepileptic drugs (AEDs) are approved for use in the United States. Table 4-1 provides a summary of the available second-generation AEDs. Due to the regulations of the Food and Drug Administration (FDA) with respect to studying AEDs in the United States, many of these agents are initially approved as adjunctive agents. In essence, they are added to an established therapeutic regimen of patients being managed primarily with a first-generation AED (i.e., carbamazepine, phenobarbital, phenytoin, or valproic acid). Most of them are approved for use as adjunctive therapy in the management of partial seizures with or without secondary generalization, primary generalized tonic-clonic seizures, or myoclonic seizures. As more data emerge, monotherapy approval for these agents may be pursued and the use of these agents will inevitably be expanded in clinical practice. At times, these agents may also be used for nonepileptic purposes. For example, gabapentin and pregabalin, while initially used for seizure management, are used almost exclusively today for the management of neuropathic pain and other pain syndromes.

TABLE 4-1Summary of Second-Generation Antiepileptic Drugs
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TABLE 4-1 Summary of Second-Generation Antiepileptic Drugs
AED/Year of FDA Approval Felbamate Felbatol®68 1993 Gabapentin Neurontin®12 1994 Lamotrigine Lamictal®69 1994 Topiramate Topamax®70 1996 Tiagabine Gabitril®26 1997 Levetiracetam Keppra®28,29 1999 Oxcarbazepine Trileptal®39 2000 Zonisamide Zonegran®51 2000 Pregabalin Lyrica®11 2004 Lacosamide Vimpat®61 2008 Ezogabine71 Potiga® 2011
FDA Indication Alternative agent as monotherapy or adjunctive therapy for partial seizure with and without secondary generalization in adults (>14 yrs) Adjunctive therapy for partial seizures with and without secondary generalization (>12 yrs) Adjunctive therapy for partial seizures, primary generalized TC seizures, generalized seizures of Lennox-Gastaut syndrome (>2 yrs) Monotherapy (>10 yrs) or adjunctive (2–16 yrs) for partial onset or primary generalized TC seizures Adjunctive therapy for partial seizures in adults and children (>12 yrs) Adjunctive therapy for partial onset seizures (>4 yrs), myoclonic seizures (>12 yrs), primary generalized TC seizures (>6 yrs) Monotherapy or adjunctive therapy for partial seizures in adults Adjunctive therapy for partial seizures in adults (>16 yrs) Adjunctive therapy for partial onset seizures in adults Adjunctive therapy for partial-onset seizures (>17 yrs) Add-on treatment for partial onset seizures (>18 yrs)
Alternative agent as adjunctive therapy for partial and generalized seizures associated with Lennox-Gastaut syndrome in children (2–14 yrs) Adjunctive therapy for partial seizures in children (3–12 yrs) Monotherapy for partial seizures (conversion to monotherapy from CBZ, PB, PHT, VPA, PRM (>16 yrs) Lennox-Gastaut syndrome (>2 yrs) Monotherapy for partial seizures in children (>4 yrs) Adjunctive ...

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