Sertraline blood concentrations and clinical efficacy in depression: a retrospective, exploratory determination of optimal therapeutic range

PURPOSE: To establish, in patients with depression, the baseline sertraline concentration range associated with optimal antidepressant response in clinical practice and compare it with previously proposed therapeutic ranges to improve interpretation of pharmacokinetic monitoring. METHODS: This retrospective naturalistic study analyzed inpatient serum sertraline concentrations paired with Hamilton Depression Rating Scale (HAMD) scores collected at admission and discharge. Concentration was the primary unit of analysis due to marked intra- and inter-individual variability. RESULTS: A total of 115 sertraline concentrations from 62 patients were obtained, each measured at any point during hospitalization and paired with HAMD scores at admission and discharge. Non-responders (< 50% HAMD improvement; n = 22) showed concentrations < 25 ng/mL, longer admissions, higher doses, and more adverse effects. Responders (≥ 50% HAMD improvement; n = 93) had a median of 39 ng/mL (IQR: 25-62). A subgroup with discharge-day measurements (n = 47) exhibited a median of 48 ng/mL (IQR: 35-65). Patients with psychotic depression (n = 19) had higher concentrations (median 67 ng/mL, IQR: 44-95) and greater clinical improvement. Responder concentrations aligned with literature HAMD and Brief Psychiatric Rating Scale (BPRS)-based studies. While the 10-150 ng/mL range proposed by guidelines encompasses most real-world values, concentrations < 25 ng/mL were associated with non-response. CONCLUSIONS: Therapeutic response to sertraline was achieved with concentrations > 25 ng/mL. Optimal response was associated with 35-65 ng/mL in the overall sample, and 45-95 ng/mL in patients with depressive and psychotic symptoms.