New Derivatives or formulations of First line ASDs

Oxcarbazepine, Fosphenytoin and IV Valproate Sodium

Felbamate : It was first of the SGASDs approved by US FDA in 1993. It has a broad spectrum of activity in both partial and generalized seizures. It inhibits NMDA (N-Methyl D-Aspartate) and potentiates GABA (Gamma aminobutyric acid) and this dual action results in broad spectrum of action. It is approved in various countries worldwide for monotherapy and adjunctive treatment of partial seizures with or without generalization in patients 14 years and older, and as adjunctive therapy for partial and generalized seizures associated with Lennox-Gastaut syndrome in children 2 to 14 years of age (2). After its approval by the Food and Drug Administration in the United States, cases of aplastic anemia and hepatic failure were reported in significant numbers (3) hence its use is now restricted to patients with refractory epilepsy for whom benefits of treatment outweigh its risks. Interestingly aplastic anemia has not been observed in children below 13 years of age but hepatotoxicity remains a concern (4).

Gabapentin : It is an AED formed by the incorporating a cyclohexyl group to GABA, which allows this form of GABA to cross the blood-brain barrier (2). Gabapentin is characterized by excellent tolerability. It is not protein bound, has no appreciable hepatic metabolism and is excreted by the kidneys. Thus, Gabapentin is appropriate for use in patients who have multiple drug intolerances and who require relatively quick titration. It is approved for adjunctive use for treatment of partial seizures with or without secondary generalization in patients older than 12 years. Two randomized studies evaluated Gabapentin as adjunctive therapy in a pediatric population, the first in patients aged 3 to 12 years, where it was effective, and the second in patients aged 1 to 36 months, where only a trend was demonstrated (2,5). Thus, beyond 3 years it may be used as an effective adjunctive drug. Adverse effects are somnolence, ataxia and dizziness.

Lamotrigine : It has a broad spectrum of activity against multiple seizure types. It partly blocks the release of the excitatory neurotransmitter glutamate from nerve endings, and reduces the influx of sodium in the recipient neurons. Lamotrigine is found to be equally effective and better tolerated than Carbamazepine. It is completely absorbed after oral administration and metabolized primarily by glucuronidation. Its half life is about 36 hours on monotherapy but it is reduced to 15 hours if used in combination with Phenytoin or Carbamazepine. If used in combination, Valproate increases its concentration where as lamotrigine decreases Valproate levels by 25%. It has the best cognitive profile amongst all AEDs. Sedation is seen very rarely with this drug in monotherapy and it even has an "alerting" response in some patients. In children with Autism, ADHD and mental retardation and other behavior problems, where sedatives should be avoided, lamotrigine being a non sedative provides a good option. Another advantage of this drug is that, it doesn't reduce bone density with long term use (6,7). One idiosyncratic side effect of lamotrigine, which is similar to effects of older antiepileptic drugs is a rash. Infrequently (in less than 1 percent of cases), the rash can be serious and may progress to Stevens-Johnson syndrome, which can be life-threatening. Rashes are more common in children when lamotrigine is taken in association with Valproate Sodium and with rapid titration. Blurring of vision and ataxia are other adverse effects encountered with lamotrigine.

Lamotrigine is approved for adjunctive therapy in partial epilepsy, as well as for partial and generalized seizures associated with Lennox-Gastaut syndrome in children. It is also found to be efficacious in pharmacoresistant partial epilepsy as well as typical absence (8,9).