Abstracts

RATIONALE: At the end of this activity, the participant should be able to discuss the relationship between lamotrigine treatment and changes in homocysteine, folate and Vitamin B12 concentrations. Homocysteine is a thiol-containing amino acid that is formed by demethylation of methionine. Modest elevations in total plasma concentrations of homocysteine (tHcy) (15-30umol/l) appears to be an important, independent risk factor for both cardiac and cerebrovascular disease. Elevated tHcy concentrations may be associated with cognitive declines in neurodegenerative disorders. A role for elevated tHcy in teratogenicity has also been suggested. Data suggest that a deficiency in vitamin cofactors needed for Hcy metabolism (e.g., folate, vitamin B12) is associated with increased tHcy concentrations. Older, enzyme-inducing antiepileptic drugs (phenytoin, phenobarbital, carbamezapine) are associated with reduced folate and increased tHcy concentrations, with data derived mainly from cross-sectional studies. Little is known regarding the newer AEDs and changes in tHcy. We therefore investigated whether a non-inducing AED such as lamotrigine is associated with changes in tHcy plasma concentrations.
METHODS: Plasma tHcy, erythrocyte and plasma folate and serum vitamin B12 were analyzed as part of a multicenter evaluation of lamotrigine monotherapy in epilepsy. Blood samples were obtained prior to (baseline) and following, 32 weeks of monotherapy treatment with lamotrigine. Patients receiving other AEDs at baseline were excluded from analysis. Data are analyzed using Wilcoxan rank test with significance assigned at p[lt]0.05. All data presented as mean (SD). No attempt was made to control for, or intervene with patients dietary habits.
RESULTS: 11 patients (8 females) with newly diagnosed epilepsy were evaluated. Patients were not pregnant, nor had GI, hepatic or renal disease. Mean age & weight were 37.8 (13.8) years, 74.9 (19.9) kg. Mean lamotrigine dose during the maintenance period was 249.6 (73.7) mg/day. Mean tHcy, erythrocyte and plasma folate, as well as Vit. B12 concentrations did not significantly differ from pre-treatment values. No tHcy values exceeded 15umol/l. Data for all indicies are presented in the table below.
CONCLUSIONS: In contrast to previous reports with older enzyme inducing AEDs, these preliminary observations in a group of patients receiving initial monotherapy with lamotrigine for 32 weeks suggests that this agent is not associated with significant alterations in either folate, vitamin B12 or tHcy concentrations. Future studies directed toward confirming these observations as well as identifying the significance of elevations in tHcy in this population would be useful.[table1]
[Supported by: GlaxoSmithKline]; (Disclosure: Salary - Alain Vuong, Anne Hammer, Pamela Barrett: GSK, Grant - Barry E. Gidal: GSK, UCB-Pharma, PfizerRaj Sheth: GSK, IVAX, Consulting - Barry E. Gidal:GSK, UCB-Pharma, IVAXRaj Sheth: GSK, Honoraria - Barry E. Gidal: GSK, UCB-Pharma, PfizerRaj Sheth: GSK, Ortho-McNeil)