Factors Associated With Dose-Corrected Active Moiety Concentrations of Venlafaxine: A Retrospective Therapeutic Drug Monitoring Study

Background: Interindividual variability in venlafaxine (VEN) exposure complicates the interpretation of therapeutic drug monitoring results. This study investigated factors associated with dose-corrected active moiety concentrations of VEN. Methods: This retrospective study included patients who received VEN treatment and underwent therapeutic drug monitoring at the Department of Psychiatry, Hangzhou Lin'an District Fifth People's Hospital, from October 2022 to September 2025. The active moiety concentration was defined as the sum of VEN and O-desmethylvenlafaxine (ODV) concentrations, and the dose-corrected concentration (C/D) was calculated as (VEN + ODV)/daily dose. Spearman correlation and linear regression analyses were used to evaluate the factors associated with the C/D. Exposure to cytochrome P450 2D6 inhibitors was evaluated in relation to the C/D. Results: A total of 251 patients were included in the study. The daily VEN dose was weakly positively correlated with VEN + ODV concentration (rho = 0.310, P < 0.001). Multivariate analysis showed that female sex, older than 60 years, renal impairment, and concomitant medication pattern were independently associated with a higher C/D (all P < 0.05). The C/D under antipsychotics only, antidepressants only, and antipsychotics plus antidepressants was 1.401-fold, 1.747-fold, and 1.880-fold higher than that under no treatment, respectively. Cytochrome P450 2D6 inhibitor exposure was independently associated with a higher C/D (exponential β = 1.483, 95% confidence interval: 1.191–1.845). Conclusions: Female sex, older than 60 years, renal impairment, and concomitant medication patterns were associated with higher concentrations of dose-corrected active VEN moiety.