In this review study, second-generation
antiepileptic drugs (AEDs) (
levetiracetam,
gabapentin,
topiramate,
lamotrigine,
zonisamide,
oxcarbazepine,
vigabatrin,
pregabalin,
rufinamide,
tiagabine,
lacosamide, and
felbamate) and
injectable AEDs (
levetiracetam,
lacosamide,
fosphenytoin,
lorazepam, and
valproic acid) available in North America were compared with those available in Japan. Three second-generation AEDs (
gabapentin,
topiramate, and
lamotrigine) were recently approved in Japan.
Levetiracetam is currently under review for approval by the Japanese regulatory agency. An ideal AED would have a broad-spectrum activity to control multiple types of
seizures, favorable safety profile, limited potential for
drug-drug interaction, many bioequivalent formulations, long half life to allow infrequent administration, and antiepileptogenic effects that may provide a fundamental cure of epileptic patients by suppressing the development of epileptogenic network and neutralizing previously established epileptogenic foci in the brain. The second-generation AEDs have been developed to possess some of these ideal properties. All the second-generation AEDs are efficacious for the treatment of patients with
partial seizures. In addition,
levetiracetam,
topiramate,
lamotrigine, and
zonisamide are effective for the treatment of patients with
generalized tonic-clonic seizures, absences,
myoclonic seizures,
Lennox-Gastaut syndrome, and
West syndrome; however,
lamotrigine is not effective for the treatment of patients with
myoclonic seizures.
Rufinamide and
felbamate are useful for the treatment of patients with
Lennox-Gastaut syndrome; however owing to its serious adverse effects, including
aplastic anemia and
hepatic failure,
felbamate is used as the last resort for the treatment of patients with intractable
seizures.
Vigabatrin is particularly effective for the treatment of patients with
West syndrome; however, the patients need to be regularly monitored for the development of peripheral visual field defect.
Gabapentin,
oxcarbazepine,
vigabatrin, and
tiagabine are ineffective for the treatment of patients with absences and/or
myoclonic seizures and may aggravate these conditions. Treatment with
levetiracetam or
topiramate (
off-label use) is the new option for patients with refractory
status epilepticus, which is characterized by downregulation of the inhibitory
gamma-aminobutyric acid system, because these drugs act via different mechanisms and are rapidly titratable, especially intravenous
levetiracetam. The pharmacokinetic profiles of
levetiracetam,
gabapentin, and
pregabalin are favorable: these drugs exhibit minimal protein binding, do not undergo hepatic metabolism, are not involved in any clinically relevant drug interactions, and rarely lead to the development of serious adverse effects. In general,
levetiracetam is probably the closest to being the ideal AED because of its broad-spectrum favorable pharmacokinetic profile and safety profile as well as because of the availability of its parenteral formulation. Among the
injectable AEDs,
fosphenytoin is a water-soluble
prodrug and is used to treat patients with
status epilepticus. Systemic and local side effects of this
drug are fewer than those of
phenytoin.
Lorazepam, a
benzodiazepine is used as the first-line AED for the treatment of patients with
status epilepticus. The effects of this
drug are more prolonged than those of
diazepam.
Intravenous administration of
valproic acid is regarded as a new treatment option for patients with
status epilepticus, because
sedative and negative effects on the cardiorespiratory system of this
drug are lesser than those of the traditional
injectable AEDs. These novel medications will aid the improvement of the quality of life of epileptic patients through improved seizure control and reduced adverse effects.