Lamotrigine: an antiepileptic agent for the treatment of partial seizures

OBJECTIVE: To review the current literature on lamotrigine and its use as an antiepileptic drug (AED). DATA SOURCES: MEDLINE and bibliographic literature searches pertaining to lamotrigine were performed. Additionally, Burroughs Wellcome provided a comprehensive bibliography, data on file, and investigator's brochure. DATA SELECTION: The selection of reported data for this review includes both controlled and uncontrolled studies as well as case reports and unreported data from both European and US trials. DATA SYNTHESIS: Lamotrigine is effective as an adjunctive agent in the treatment of complex and simple partial seizures with or without secondary generalization. Anecdotal reports suggest that the spectrum of activity may include other seizure types, but controlled studies substantiating these reports are needed. Lamotrigine has a favorable pharmacokinetic profile, including a long half-life, low serum protein binding, and lack of mixed-function oxidase enzyme induction. It is likely that the drug induces metabolism through the glucuronidation pathway, although probably not to a clinically significant extent. Concurrent use of enzyme-inducing AEDs increase lamotrigine's clearance, whereas valproic acid decreases it. Adverse effects are primarily central nervous system-related, with dizziness, diplopia, ataxia, and somnolence reported in at least 10% of the patients treated. The incidence of these effects is higher in patients treated concomitantly with carbamazepine and may represent a pharmacodynamic interaction. The occurrence of rash may limit lamotrigine's use and was the most common cause for discontinuation in clinical trials (2.3%). The incidence of rash is higher in patients comedicated with valproic acid. CONCLUSIONS: Lamotrigine appears to be a safe and effective new AED for patients with refractory partial seizures when used as an adjunctive agent. It has a favorable pharmacokinetic profile allowing for once- or twice-daily dosing and adverse effects appear mild and transient. Additional studies are required to confirm efficacy in other seizure types.