The Effect of Valproic Acid on Gingival Overgrowth

Objectives: Gingival overgrowth is widely recognized as one of the side effects of phenytoin. Although most patients with epilepsy take multiple anti-epileptic drugs (AEDs), the effects of the other AEDs on gingival overgrowth are still unknown. In this study, we investigated the effects of valproic acid (VPA), a major AED, and its synergism with phenytoin, on gingival overgrowth. Methods: One hundred sixteen patients receiving AEDs therapy (73 males and 43 females; mean age: 13.5 years) were selected for this study. We evaluated the type of prescribed medicine, the degree of gingival overgrowth, and oral hygiene conditions. All patients were classified into 2 groups according to their prescription of phenytoin, then these 2 groups were further classified into the following subgroups according to their prescription of VPA; group 1a (phenytoin with VPA), group 1b (phenytoin without VPA), group 2a (AEDs except phenytoin with VPA), and group 2b (AEDs except phenytoin without VPA). Gingival overgrowth was scored at the location with the most aberrant overgrowth (0 to 4). The subjects' oral hygiene condition was also scored according to the state of dental plaques (0 to 2). Differences in these scores among the subgroups were statistically analyzed using the Kruskal-Wallis test and the Mann-Whitney U-test. Results: Sixty-three percent of the patients exhibited gingival overgrowth (group 1a: 87%, group 1b: 81%, group 2a: 40%, group 2b: 56%). No significant differences were seen in oral hygiene in the patients among the 4 groups. Significant differences were seen in the degrees of gingival overgrowth between group 1b and group 2a (p= 0.008), however the difference between group 1a and group 1b was not statistically significant. Conclusions: These results suggest that the use of VPA does not lead to an increase in gingival overgrowth, and its synergism with phenytoin also does not impact gingival overgrowth.