Randomized, double-blind, active-controlled Phase III study (n=139) in elderly participants with TRD testing intranasal esketamine (flexible 28–84 mg, twice weekly for 4 weeks) plus a new oral antidepressant versus intranasal placebo plus a new oral antidepressant.
This multicentre, randomized, double-blind, active-controlled trial evaluated efficacy, safety, and tolerability of flexible-dose intranasal esketamine administered twice weekly for 4 weeks in elderly participants (>=65 years) with treatment-resistant depression, each initiating a new oral antidepressant.
Participants started Day 1 with 28 mg intranasal esketamine; Day 4 dose was 28 or 56 mg and subsequent doses could be 28, 56 or 84 mg per investigator judgement. Oral antidepressant options (duloxetine, escitalopram, sertraline, venlafaxine XR) were started on Day 1 and continued through the double-blind induction phase.
Primary efficacy was change in MADRS total score at Week 4; safety monitoring included vital signs, labs, and protocol-specified cardiac and cognitive assessments.
Intranasal esketamine administered twice weekly for 4 weeks (flexible dosing) plus newly initiated oral antidepressant.
Day 1 = 28 mg; Day 4 = 28 or 56 mg; subsequent doses 28, 56 or 84 mg per investigator titration based on efficacy/tolerability.
New oral antidepressant initiated Day 1: duloxetine (min 60 mg/day), escitalopram (10 mg/day), sertraline (50–150 mg/day), or venlafaxine XR (75–150 mg/day).
Intranasal placebo administered twice weekly for 4 weeks plus newly initiated oral antidepressant.
Matching intranasal placebo using same titration schedule as esketamine.
New oral antidepressant initiated Day 1: duloxetine, escitalopram, sertraline, or venlafaxine XR (dosing per protocol).