LAMOTRIGINE - AN UPDATE OF ITS PHARMACOLOGY AND THERAPEUTIC USE IN EPILEPSY

Lamotrigine is an antiepileptic agent which blocks voltage-dependent s odium channels, thereby preventing excitatory neurotransmitter release . Clinical evidence indicates that lamotrigine is effective against pa rtial and secondarily generalised tonic-clonic seizures, as well as id iopathic (primary) generalised epilepsy. As monotherapy, lamotrigine 1 00 to 300 mg/day has similar medium term (30 to 48 weeks efficacy to c arbamazepine 300 to 1400 mg/day and phenytoin 300 mg/day against parti al onset seizures and idiopathic generalised tonic-clonic seizures in adults with newly diagnosed epilepsy, and appears to be better tolerat ed than the older agents. As adjunctive therapy, lamotrigine (50 to 50 0 mg/day) has shown efficacy in short term (less than or equal to 6-mo nth) placebo-controlled studies in adults with refractory partial epil epsy, reducing total seizure frequency (by less than or equal to 60%) and producing improvement (less than or equal to 50% reduction in seiz ure frequency) in less than or equal to 67% of patients. Both simple a nd complex partial seizures and secondarily generalised tonic-clonic s eizures are reduced by lamotrigine, with generalised seizures (particu larly absence seizures, atonic seizures and Lennox-Gastaut syndrome) t ending to be more responsive than partial seizures. This reduction in seizure frequency is sustained on long term (less than or equal to 3 y ears) therapy and is reportedly accompanied by an improvement in psych ological well-being. In children with refractory multiple seizure type s, lamotrigine (less than or equal to 15 mg/kg/day; 400 mg/day) has pr oved effective as add-on therapy, with approximate to 40% of patients showing greater than or equal to 50% reductions in seizure frequency a nd approximate to 10% achieving abolition of seizures after 3 months' treatment. Generalised seizures, including atypical and typical absenc e seizures, atonic and tonic seizures and Lennox-Gastaut syndrome are most responsive. The most common adverse events associated with lamotr igine are primarily neurological, gastrointestinal and dermatalogical. Maculopapular or erythematous skin rash, occasionally severe, occurs in approximate to 10% of patients and is the most common cause of trea tment withdrawal. The risk of rash can, however be minimised through a doption of a low, slow dosage titration schedule on initiating therapy . As monotherapy, lamotrigine produces less drowsiness than carbamazep ine or phenytoin, and less asthenia and ataxia than phenytoin. Clinica l experience would therefore suggest that lamotrigine is a particularl y effective and generally well tolerated broad-spectrum agent for adju nctive treatment of both partial epilepsy and idiopathic generalised e pilepsy in adults and children. Initial indications point to the drug filling an increasingly important future role in the monotherapy of ne wly diagnosed epilepsy.