Effectiveness and safety of escitalopram treatment personalized based on therapeutic drug monitoring of drug plasma concentration: a prospective cohort study.

This is the first prospective study aiming to quantify the effectiveness and safety of escitalopram monotherapy initiation where therapeutic drug monitoring (TDM) was used to achieve the therapeutic reference range (TRR) of plasma concentration. PsyCise-E (NCT05210140) was a hospital-based study conducted in Belgrade, Serbia, involving 92 outpatients with a baseline Hamilton Rating Scale for Depression (HAM-D) score higher than 13. The primary endpoint was the relative reduction in HAM-D score from baseline to week eight, with dose personalization based on TDM four weeks after treatment initiation. Patients were categorized into groups: (1) unadjusted (they achieved TRR at 10 mg/day), (2) adjusted (their dose was adjusted to achieve TRR) and (3) inadequate (they did not reach TRR). Safety was assessed by the occurrence of adverse drug reactions (ADRs) and QTc interval prolongation. Most patients required a dose escalation beyond 10 mg/day (71/92), and most patients achieved TRR after eight weeks (79/92). The 55% (95% CI: 47-64) reduction in HAM-D scores did not correlate with escitalopram plasma concentrations and did not differ between groups; however, response and remission rates were significantly higher in patients who achieved TRR by week four. The incidence of ADRs (47/92) increased by 3.2% (0.1-6.3) per ng/ml escitalopram, with no significant differences between the groups. QTc prolongation of 5.5 ms (1.8-9.3) did not correlate with plasma concentration and did not differ between groups. While TDM-guided dosing likely only marginally improved escitalopram effectiveness, it increased treatment safety as TDM-guided dose escalation did not lead to ADRs or QTc prolongation.