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

Lamotrigine is an antiepileptic agent which blocks voltage-dependent sodium channels, thereby preventing excitatory neurotransmitter release. Clinical evidence indicates that lamotrigine is effective against partial and secondarily generalised tonic-clonic seizures, as well as idiopathic (primary) generalised epilepsy. As monotherapy, lamotrigine 100 to 300 mg/day has similar medium term (30 to 48 weeks efficacy to carbamazepine 300 to 1400 mg/day and phenytoin 300 mg/day against partial onset seizures and idiopathic generalised tonic-clonic seizures in adults with newly diagnosed epilepsy, and appears to be better tolerated than the older agents. As adjunctive therapy, lamotrigine (50 to 500 mg/day) has shown efficacy in short term (less than or equal to 6-month) placebo-controlled studies in adults with refractory partial epilepsy, reducing total seizure frequency (by less than or equal to 60%) and producing improvement (less than or equal to 50% reduction in seizure frequency) in less than or equal to 67% of patients. Both simple and complex partial seizures and secondarily generalised tonic-clonic seizures are reduced by lamotrigine, with generalised seizures (particularly absence seizures, atonic seizures and Lennox-Gastaut syndrome) tending to be more responsive than partial seizures. This reduction in seizure frequency is sustained on long term (less than or equal to 3 years) therapy and is reportedly accompanied by an improvement in psychological well-being. In children with refractory multiple seizure types, lamotrigine (less than or equal to 15 mg/kg/day; 400 mg/day) has proved effective as add-on therapy, with approximate to 40% of patients showing greater than or equal to 50% reductions in seizure frequency and approximate to 10% achieving abolition of seizures after 3 months' treatment. Generalised seizures, including atypical and typical absence seizures, atonic and tonic seizures and Lennox-Gastaut syndrome are most responsive. The most common adverse events associated with lamotrigine 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 treatment withdrawal. The risk of rash can, however be minimised through adoption of a low, slow dosage titration schedule on initiating therapy. As monotherapy, lamotrigine produces less drowsiness than carbamazepine or phenytoin, and less asthenia and ataxia than phenytoin. Clinical experience would therefore suggest that lamotrigine is a particularly effective and generally well tolerated broad-spectrum agent for adjunctive treatment of both partial epilepsy and idiopathic generalised epilepsy in adults and children. Initial indications point to the drug filling an increasingly important future role in the monotherapy of newly diagnosed epilepsy.