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 thos e before starting or after stopping the MSM. The 16 patients, (11 boys, fiv e 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 avai lable 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% (ran ge, 36-72%). Tn some patients this led to a deterioration in seizure contro l when MSM was added or an improvement in seizure control after MSM was sto pped. Conclusions: Although MSM is a valuable add-on, broad-spectrum drug when us ed in combination with LTG, adjustment of the LTG dose may be necessary whe n MSM is started or stopped, to allow for the fact that MSM lowers LTG bloo d levels.