Lamotrigine. A review of its use in childhood epilepsy

Lamotrigine is an antiepileptic agent that blocks use-dependent voltage-sensitive sodium channels, thereby preventing excitatory neurotransmitter release. However, this mechanism does not explain the broad range of clinical efficacy of this agent. In noncomparative trials, adjunctive lamotrigine (< or = 15 mg/kg/day) improved seizure control in children and adolescents with various refractory seizure types, with about 29 to 90% of patients showing a > or = 50% reduction in seizure frequency after > or = 3 months' treatment. Lamotrigine was particularly effective in generalised seizures, especially absence seizures and those related to the Lennox-Gastaut syndrome. In one placebo-controlled study, 33% of children and young adults (aged 3 to 25 years) with refractory Lennox-Gastaut syndrome had a reduction in seizure frequency of > or = 50% after 16 weeks of adjunctive lamotrigine treatment, compared with 16% of placebo recipients (p = 0.01). Significant reductions in seizure frequency when compared with placebo were also observed in patients with refractory generalised and partial seizures. The use of lamotrigine has also been associated with beneficial effects on cognition and behaviour. Adverse events associated with lamotrigine are primarily neurological, gastrointestinal and dermatological and are typically mild or moderate and transient with the exception of a potentially serious rash. Maculopapular or erythematous skin rash occurred in approximately 12% of paediatric patients (aged < 16 years) treated with lamotrigine and was the most common reason for treatment discontinuation. More severe forms of rash, including Stevens-Johnson syndrome, occasionally occurred, with a 3-fold higher incidence in children (approximately 1%) than adults (approximately 0.3%). However, lamotrigine treatment in paediatric trials was generally given at higher initial doses and faster dose escalations than recently revised recommendations. These factors, as well as concomitant use of valproic acid (valproate sodium), are associated with an increased risk of rash. Although published clinical evidence is still limited in paediatric populations, lamotrigine is an effective and generally well tolerated broad-spectrum agent for adjunctive treatment of refractory seizures in children, most notably in those with Lennox-Gastaut syndrome. Results of direct comparisons with other antiepileptic agents are needed to determine more clearly the place of lamotrigine, particularly relative