Metabolic Differentiation in Manic Episode of Bipolar Disorder Compared to Substance-Induced Psychosis and Substance Use Disorder Based on Serum Valproate Level

Abstract

Aim: Valproic acid (VPA) is primarily used in the treatment of epilepsy but also has uses in the treatment of manic episodes in bipolar disorder and substance use disorders. Manic episodes and psychosis may also affect hepatic clearance and drug distribution volume. The aim of this study was to assess the effect of mania and psychosis compared to substance use on VPA pharmacokinetics, specifically changes in total and unbound clearance. Material and Methods: Fifty patients with a manic episode of bipolar disorder, and 51 patients with substance use disorder, 38 of whom were considered as substance-induced psychosis, were included in this retrospective study. All patients received a constant dose of 1000 mg VPA daily for at least five days, and serum VPA concentrations were measured. Results: The mean serum levels of VPA were 59.2±17.4 μg/ml in the substance use disorder group, 60.9±13.5 μg/ml in the substance-induced psychosis group, and 61.8±13.7 μg/ml in the manic episode of bipolar disorder group. No significant difference was found between the groups (p=0.840). When considering substance use disorder and substance-induced psychosis as one group, the mean VPA level of 60.5±14.4 μg/ml in this group showed no significant difference compared to 61.8±13.7 μg/ml in the manic episode of bipolar disorder (p=0.630). Conclusion: After reaching steady-state plasma levels, no significant difference in serum VPA levels was observed between the three groups. This suggests that manic episodes do not lead to a significant increase in VPA metabolism compared to substance use disorder or substance-induced psychosis.