Intranasal esketamine in treatment resistant depression – a double-blind, randomized, efficacy and dose response study
Ella Daly, Jaskaran Singh, Maggie Fedgchin, Kimberly Cooper, Pilar Lim, Caroline Melman, Husseini Manji, Luc Van Nueten, Richard C. Shelton, Michael E. Thase, Maha Ahmad, Geert De Bruecker, Wayne C. Drevets
Study at a glance
AI-extracted from the abstract| Characteristics | Placebo-controlled, double-blind randomized trial (Panel A) Open-label |
|---|---|
| Sample size | 67 |
| Population | Patients with treatment-resistant depression |
| Interventions | Esketamine Placebo |
| Dose | 28 mg, 56 mg, or 84 mg twice-weekly |
| Duration | Two 1-week double-blind periods, 9-week optional open-label phase, 8-week posttreatment follow-up |
| Measures | Montgomery-Asberg Depression Rating Scale (MADRS) total score |
| Topics | Depression Esketamine Ketamine |
| Key findings | All three intranasal esketamine doses (28 mg, 56 mg, 84 mg) reduced MADRS total scores more than placebo in treatment-resistant depression, with the 28 mg dose showing a less durable effect. The authors report evidence suggesting sustained response after open-label dosing ceased, and no new safety findings. |
Abstract
Background: Intravenous ketamine and esketamine (ESK) produce rapid antidepressant action in treatment-resistant depression (TRD) patients, however dose response is not known. Study assessed efficacy, dose response and safety of intranasal ESK and ability to sustain response with gradual tapering of treatment frequency.
Methods: In the Panel A (conducted in USA and Belgium) of this placebo-controlled, double-blind study (Panel B: ongoing in Japan and not presented here), patients received study medication in two 1-week periods (Period 1: randomization [3:1:1:1] to placebo, ESK 28mg, 56mg, or 84mg [twice-weekly]; Period 2: non-responding placebo patients [moderate-to-severe symptoms] re-randomized [1:1:1:1] to one of above 4 treatments). After DB phase, patients entered 9-week optional open-label (OL) phase with tapered treatment frequency and 8-week posttreatment follow-up. Primary efficacy endpoint: change from baseline to day 8 (each period) in Montgomery-Asberg Depression Rating Scale (MADRS) total score (ANCOVA).
Results: Mean change in MADRS total score (DB phase, both periods combined; weighted combination test) in all 3 ESK groups was superior to placebo (ESK 28mg: p=0.021, 56mg: p=0.001, 84mg: p<0.001). 57 of 67 patients from DB phase entered OL phase. No new safety findings were noted.
Conclusions: All 3 doses of intranasal ESK were efficacious in TRD treatment; however, 28mg dose had less durable effect. There was evidence suggesting sustained response after cessation of OL dosing. All 3 doses were well-tolerated.
Comparable studies
Other randomized controlled trials on esketamine for depression, most cited first.