Methsuximide lowers lamotrigine blood levels: A pharmacokinetic antiepileptic drug interaction

Purpose: To determine whether methsuximide (MSM) affects lamotrigine (LTG) blood levels and whether any change is of clinical significance. Methods: LTG serum levels in 16 patients taking MSM were compared with those before starting or after stopping the MSM. The 16 patients, (11 boys, five girls) were young people (mean age, 15.5 years; range, 9-19 years) with a variety of seizure types and syndromes. In six cases, LTG levels were available both before MSM was started and after it was stopped. Results: The mean LTG serum concentration before starting or after stopping MSM was 13.4 mg/L, and the mean level while taking MSM was 6.3 mg/L. This difference was highly significant (p < 0.0005, paired r test). MSM lowered the LTG serum concentration in every case, with a mean decrease of 53% (range, 36-72%). Tn some patients this led to a deterioration in seizure control when MSM was added or an improvement in seizure control after MSM was stopped. Conclusions: Although MSM is a valuable add-on, broad-spectrum drug when used in combination with LTG, adjustment of the LTG dose may be necessary when MSM is started or stopped, to allow for the fact that MSM lowers LTG blood levels.