Methsuximide reduces valproic acid serum levels.

The authors investigated whether methsuximide affects serum levels of valproic acid. Pre-morning-dose serum valproic acid levels were measured in 17 patients (12 male, 5 female; age range, 8-19; mean, 14.5 years) who either started or stopped taking methsuximide but whose dose of valproate and other medication remained unchanged. Four of these patients both started and stopped taking methsuximide. For the whole group the mean valproic acid level (+/- standard error) while not taking methsuximide was 81.9 +/- 5.3 mg/L and while taking methsuximide was 55.7 +/- 4.3 mg/L. The difference between the means was highly significant (paired t test, p < 0.001). The mean valproic acid serum level before taking methsuximide was 85.4 +/- 4.5 mg/L (14 patients), which decreased to 58.2 +/- 4.8 mg/L while taking methsuximide (difference highly significant, p < 0.001). In the eight patients who stopped taking methsuximide the mean serum level increased from 49.8 +/- 7.5 mg/L to 71.7 +/- 8.5 mg/L (difference significant p = 0.025). Because methsuximide reduces valproic acid serum levels, it may be necessary to increase the valproate dose when methsuximide is added or reduce the valproate dose when methsuximide therapy stops, to avoid loss of seizure control or valproate toxicity respectively.