Valproic acid improves psychotic agitation without influencing plasma risperidone levels in schizophrenic patients.

OBJECTIVE To investigate the effect of valproic acid on plasma levels of risperidone and its active metabolite, 9-hydroxyrisperidone under steady state conditions in 12 schizophrenic patients. METHODS The efficacy and tolerability for the combination treatment of valproic acid and risperidone were examined. RESULTS The addition of valproic acid to risperidone significantly reduced total scores of PANSS positive symptoms, especially excitement and hostility scores, but did not change SAS scores. Addition of valproic acid did not alter plasma concentrations of risperidone or 9-hydroxyrisperidone or active moiety, and the risperidone/9-hydroxyrisperidone ratio. The combination of valproic acid with risperidone decreased plasma levels of HVA, but not those of MHPG; additionally, treatment with this combination was found to reduce dopaminergic activity. CONCLUSION These results suggest that the addition of valproic acid to risperidone is both effective and well tolerated for treating excitement and impulsiveness in schizophrenic patients without influencing the metabolism of risperidone, and treatment with valproic acid and risperidone.