Comparison of Weight-Based Valproic Acid Dosing in Treatment of Mental Illness Among Obese and Nonobese Patients.

Abstract

A weight-based dosing approach of 20-30 mg/kg per day of valproic acid (VPA) has been shown to achieve rapid attainment of mood symptom control. Due to interindividual pharmacokinetic variability, therapeutic drug monitoring may be a useful tool to avoid VPA toxicity. Limited research exists on the impact of patient body weight on VPA pharmacokinetic profiles. This analysis aims to explore the correlation between steady-state serum levels of VPA and weight-based dosing strategies, including total body weight (TBW), ideal body weight (IBW), and adjusted body weight (AdjBW), between obese and nonobese patients. This single-center, retrospective, observational cohort analysis evaluated weight-based dosing of VPA in obese and nonobese patients admitted to inpatient psychiatry at a large academic medical center between July 1, 2017, and July 1, 2022. This analysis included 93 obese and 93 nonobese patients. No significant difference in median VPA serum concentrations was observed between groups (P = 0.82). However, the obese group received a lower median weight-based dose (15.6 mg/kg) compared with the nonobese group (19.5 mg/kg, P < 0.001). A stronger correlation was found between VPA dose and therapeutic serum levels in the obese group compared with the nonobese group regardless of weight-based dosing strategy. Dosing with AdjBW in obese patients most closely approximated dosing with TBW in nonobese patients. In obese patients, our analysis suggests dosing VPA using AdjBW may be considered as the preferred dosing strategy over IBW or TBW to minimize toxicity risk. Further research is needed with larger sample sizes and diverse patient populations to confirm these findings.