Therapeutic drug monitoring of sertraline and symptom change in major depressive disorder: a naturalistic outpatient study

Background: Therapeutic drug monitoring (TDM) has been proposed to address interindividual variability in antidepressant exposure and to support concentration–response informed dosing. However, evidence linking sertraline serum concentrations to clinical response remains inconsistent. This study examined whether steady-state serum concentrations of sertraline (SCS) are associated with symptom improvement in major depressive disorder (MDD). Methods: In this study, adult outpatients with MDD receiving sertraline monotherapy were assessed at baseline (t0), 1 month (t1) and 3 months (t2) using the 21-item Hamilton Depression Rating Scale (HAMD-21). Morning steady-state SCS were quantified by LC–MS/MS. Regression models tested associations between SCS and percentage symptom change (delta) at t1 and t2. An exploratory analysis evaluated the association between baseline HAMD-21 severity and delta at 3 months. Results: The sample included 52 patients. No association was observed between SCS and symptom change. In the exploratory analysis, baseline HAMD-21 scores were associated with delta at 3 months. Conclusions: In our study, steady-state sertraline concentrations were not associated with symptom improvement over 3 months in linear models. Baseline symptom severity emerged as a key determinant of change, suggesting that limited baseline severity in part of the sample may have reduced sensitivity to detect concentration–response relationships.