Abstract

The Second Generation Anti Seizure Drugs (SGASD) have been traditionally known as "Newer Antiepileptic Drugs" since 1993. Now after 16 years of use in clinical practice the term "Second Generation Anti Seizure Drugs" should replace this term. Felbamate, the first of the SGASDs is approved for monotherapy and adjunctive treatment of partial seizures with or without generalization in patients 14 years and older, and in Lennox-Gastaut syndrome in children 2 to 14 years of age. Lamotrigine and Topiramate are broad spectrum Anti seizure drugs (ASD) for monotherapy in partial epilepsy and add-on for partial and generalized seizures associated with Lennox-Gastaut syndrome and typical absences. In children with Autism, ADHD and mental retardation, Lamotrigine is useful. Tiagabine, Gabapentin and Zonisamide are approved partial seizures in adults and adolescents. Vigabatrin is used in patients with refractory partial epilepsy when other appropriate drugs have failed, and in children with infantile spasms. Levetiracetam, a very exciting drug is unique among ASDs because it is effective starting with the initial dose. It is effective against refractory partial seizures. Oxcarbazepine, better tolerated derivative of carbamazepine is as effective as its parent drug. Fosphenytoin is better suited than Phenytoin in control of seizure in status epilepticus. Retigabine, a potassium channel opener and Lacosamide are under development. While choosing an add-on drug, co-morbid conditions, safety and it's mechanism of action should be taken into consideration as well, for the best results. If the initial drug is working on sodium channel the second one should be working through GABA (Gamma aminobutyric acid) and vice versa.

Key words- Seizures, Anti seizure drugs, Refractory Epilepsy, Adjunctive therapy, Levetiracetam, Lamotrigine, Retigabine

Introduction

The Second Generation Anti Seizure Drugs (SGASDs) have been traditionally known as "Newer Antiepileptic Drugs". "Newer Antiepileptic Drugs" has been used in the literature for Felbamate, Lamotrigine, Vigabatrin and Gabapentin. Now some more drugs have been added to this group but the name "Newer Antiepileptics" is still used even after 16 years of use in clinical practice. However not all the seizure episodes are epilepsy and not all the anti seizure drugs (ASD) are used as anti epileptics (AED) (for e.g. Fosphenytoin is available only as IV formulation, hence this anti seizure drug cannot be termed as anti-epileptic.) Hence, now the term "Second Generation Anti seizure Drugs" can and should replace this term.

The first-line anticonvulsants came into existence after discovery of Phenytoin in 1930s and continued till 1978 when last of this series and the most versatile one, the Sodium Valproate was marketed. Then there was a lull in the development of new drugs for seizure control. In US the 1990s were declared as "Decade of Brain" by President George Bush (Sr.) by Presidential Proclamation 6158, signed on July 17th 1990, hence in 1990s the emphasis again shifted towards discovery of newer molecules for seizure control. Eventually in 1993, after a hiatus of 15 years Felbamate was marketed, marking the beginning of the "Second Generation Anti Seizure Drugs" and which was followed by a flurry of new discoveries which is still continuing. Availability of a plethora of choices makes a physician's choice more challenging too.

This review article aims to evaluate the Second Generation Anti Seizure drugs on the basis of their pharmacological properties, uses and their efficacy in management of Pediatric Seizure Disorders.

Most of the new ASDs are approved only as adjunctive therapy for partial seizures, however now a huge amount of data is available supporting their efficacy as initial monotherapy also. Thus, indications for these drugs are gradually broadening for e.g. oxcarbazepine, lamotrigine, topiramate and levetiracetam are now considered appropriate for monotherapy in partial seizures and topiramate for treatment of primary generalized seizures.

The choice of the most suitable ASD should take into account its spectrum of efficacy and special pharmacological properties as well as patient's co-morbid conditions and special needs, although the first consideration should be effectiveness of the drug against a particular seizure type. Equivalence in efficacy with better tolerability and lesser adverse effects may be considered as superiority. (1)

Second Generation Anti Seizure Drugs: The drugs are
depicted in Table 1.


1: Second generation anti-seizure drugs:

Felbamate
Gabapentin
Lamotrigine
Vigabatrin
Topiramate
Tiagabine
Levetiracetam
Zonisamide