The purpose of this study is to compare the efficacy and safety of switching treatment-resistant depression (TRD) subjects from a prior antidepressant treatment (to which they have not responded) to either intranasal esketamine plus a new oral antidepressant or switching to a new oral antidepressant plus intranasal placebo.
Randomized, double-blind, active-controlled, multicentre Phase III study in adults with treatment-resistant major depressive disorder comparing flexible-dose intranasal esketamine plus a new oral antidepressant versus intranasal placebo plus a new oral antidepressant.
Double-blind induction phase: 4 weeks with intranasal dosing twice weekly (start 56 mg, may increase to 84 mg per protocol) and initiation of one of four open-label oral antidepressants; safety and efficacy assessed acutely and during a 24-week follow-up for non-rollover participants.
Primary outcomes assess antidepressant efficacy in TRD; safety monitoring includes adverse events, vital signs, and tolerability with specified dose adjustments for tolerability through Day 15.
Intranasal esketamine (flexible 56 or 84 mg) twice weekly for 4 weeks plus a newly initiated oral antidepressant (duloxetine, escitalopram, sertraline, or venlafaxine XR).
Intranasal; start 56 mg Day 1; may increase to 84 mg on Day 4 and on Days 8/11; dose may be reduced for tolerability; stable after Day 15.
New oral antidepressant started Day 1 (duloxetine 60 mg/day minimum; escitalopram up to 20 mg/day, min 10 mg; sertraline up to 150 mg/day, min 50 mg; venlafaxine XR up to 225 mg/day, min 150 mg).
Matching intranasal placebo twice weekly for 4 weeks plus a newly initiated oral antidepressant (duloxetine, escitalopram, sertraline, or venlafaxine XR).
Matching intranasal placebo, administered on same schedule.
New oral antidepressant started Day 1 (duloxetine, escitalopram, sertraline, or venlafaxine XR) per investigator selection; titration per protocol.
This post-approval, double-blind, placebo-controlled study (n=223, TRANSFORM-2) finds that those with comorbid anxiety (72%) responded just as well as those without anxiety to esketamine (56-84mg, 4 weeks, combined with SSRI) treatment.