Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Plus a Newly Initiated Oral Antidepressant in Adult Patients with Treatment-Resistant Depression: A Randomized, Double-Blind, Multicenter, Active-Controlled Study Conducted in China and USA.
Xu Chen, Xuan Hou, Daisy Bai, Rosanne Lane, Chong Zhang, Carla Canuso, Gang Wang, Dong-Jing Fu
Neuropsychiatric Disease and Treatment March 31, 2023 DOI: 10.2147/ndt.s391096 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, active-controlled Phase 3 multicenter trial Peer reviewed |
|---|---|
| Sample size | 252 |
| Population | Primarily Chinese patients with treatment-resistant depression (single or recurrent episode), enrolled in China and the United States |
| Interventions | Intranasal esketamine escitalopram sertraline |
| Duration | Double-blind treatment phase with primary endpoint at Day 28 and assessment at 24 hours after first dose |
| Measures | Montgomery-Åsberg Depression Rating Scale (MADRS) |
| Topics | Depression Esketamine |
| Keywords | Intranasal Trd |
| Registration | NCT03434041 |
| Key findings | Esketamine plus a newly initiated oral antidepressant was not statistically superior to oral antidepressant plus placebo in reducing depressive symptoms at Day 28 (MADRS difference -2.0, 95% CI -4.64 to 0.55). Esketamine plus antidepressant did show a clinically meaningful reduction in depressive symptoms at 24 hours after the first dose in the overall and China sub-populations. No new safety signals were observed. |
Abstract
Purpose: This Phase 3, multicenter study (NCT03434041) was conducted in primarily Chinese patients with treatment-resistant depression (TRD) to support the registration of esketamine nasal spray in China. Patients and
Methods: This randomized, double-blind, active-controlled study was conducted in China and the United States (US) in patients with TRD (single or recurrent episode). Eligible patients were randomized 1:1 to receive intranasal esketamine or matching placebo, each in conjunction with a newly initiated oral antidepressant (AD; duloxetine, escitalopram, sertraline, and venlafaxine extended release) (ie, esketamine plus AD or AD plus placebo). The primary endpoint, change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Day 28, was analyzed using a mixed-effects model for repeated measures. Secondary endpoints including safety were also evaluated.
Results: Of 252 randomized patients (China, 224; US, 28), 214 completed the double-blind treatment phase. The difference between treatment groups at Day 28 was not statistically significant (difference in least-square means [95% CI]: -2.0 [-4.64, 0.55]; 2-sided p = 0.123). However, esketamine plus AD demonstrated a clinically meaningful treatment difference compared with AD plus placebo in MADRS total score at 24 hours after first dose for the study overall population and China sub-population (difference in least-square mean [95% CI]: -3.3 [-5.33, -1.33] and -2.6 [-4.64, -0.60], respectively). No new safety signals were observed.
Conclusion: Esketamine plus AD was not statistically superior to AD plus placebo in improving depressive symptoms in TRD patients at Day 28. Rapid reduction in depressive symptoms within 24 hours was observed for TRD patients treated with esketamine plus AD in the overall population and China sub-population. Safety was consistent with the established safety profile of esketamine.
Comparable studies
Other randomized controlled trials on esketamine for depression, most cited first.