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 ( < or = 6-months) placebo-controlled studies in adults with refractory partial epilepsy, reducing total seizure frequency (by < or = 60%) and producing improvement ( > or = 50% reduction in seizure frequency) in < or = 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 ( < or = 3 years) therapy and is reportedly accompanied by an improvement in psychological well-being. In children with refractory multiple seizure types, lamotrigine ( < or = 15 mg/kg/day; 400 mg/day) has proved effective as add-on therapy, with approximately equal to 40% of patients showing > or = 50% reductions in seizure frequency and approximately equal 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 dermatological. Maculopapular or erythematous skin rash, occasionally severe, occurs in approximately equal 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.