Anticonvulsant Agents: Lamotrigine

Abstract

Lamotrigine [3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine] is one of the more recently developed antiepileptic drugs used around the world with FDA approval since 1994. Its primary anticonvulsant effect is exerted by stabilizing presynaptic neuronal membranes by inhibiting voltage-sensitive sodium channels and modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate), with additional activity on voltage-sensitive calcium channels. Clinical evidence indicates that lamotrigine is effective against focal and secondarily generalized tonic-clonic seizures, as well as idiopathic (primary) generalized seizures, both in adjunctive and monotherapy. Interindividual variability in lamotrigine disposition is prominent and influenced by comedication, pregnancy, age, and disease status. As metabolization is primarily through hepatic glucuronic acid conjugation, elimination half-life and clearance may vary depending on concomitant medication and other antiepileptic drugs. Target dosing of lamotrigine ranges from 50 to 500 mg/day, depending on co-administered drugs. The most common adverse events associated with lamotrigine are primarily neurological, gastrointestinal, and dermatological. Lamotrigine-associated skin rash, occurring in about 3–10% of patients and the most common cause of treatment withdrawal, typically appears within the first 4 weeks of treatment; its likelihood can be diminished by starting with a low dose and escalating slowly. Lamotrigine is often suggested as an ideal anticonvulsant drug during pregnancy, seen its effectiveness and lower risk of fetal malformations, this despite the need for slow introduction to prevent toxicity and risk of decreased effectiveness due to increased clearance, necessitating continuous dose adjustments.