Improvements in health-related quality of life with esketamine nasal spray versus quetiapine extended release.
Andreas Reif, Bernhard T Baune, Jozefien Buyze, Anthony J. Cleare, Shaun Johnson, Yerkebulan Kambarov, Nigel Olisa, Falk Schuster, Christian von Holt, Tamara Werner-Kiechle, Eduard Vieta
European psychiatry : the journal of the Association of European Psychiatrists October 14, 2025 DOI: 10.1192/j.eurpsy.2025.10123 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 676 |
| Population | Patients with treatment-resistant depression |
| Interventions | Esketamine nasal spray quetiapine extended release ongoing selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor |
| Duration | 32 weeks |
| Measures | Patient Health Questionnaire-9 (PHQ-9), 36-Item Short Form Survey (SF-36), Quality of Life in Depression Scale (QLDS), EuroQoL 5-Dimension 5-Level (EQ-5D-5L) |
| Topics | Depression Esketamine |
| Keywords | Clinical trial Quetiapine |
| Registration | NCT04338321 |
| Key findings | Esketamine nasal spray, added to an ongoing SSRI/SNRI, produced superior health-related quality-of-life and symptom improvements compared with quetiapine extended release in treatment-resistant depression. PHQ-9 remission by Week 32 was 34.5% with esketamine versus 18.2% with quetiapine (OR 2.39), and meaningful QLDS improvement occurred in 60.7% versus 41.8% (OR 2.16). |
Abstract
Clinical response and remission may not fully reflect patient priorities in treatment-resistant depression (TRD). Health-related quality-of-life (HRQoL) outcomes should be assessed to comprehensively capture treatment benefits. ESCAPE-TRD (NCT04338321) was a 32-week randomized, phase IIIb trial comparing esketamine nasal spray (NS) versus quetiapine extended release (XR), both alongside an ongoing selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor, in patients with TRD. Symptom and HRQoL improvements were assessed using the Patient Health Questionnaire-9 (PHQ-9), 36-Item Short Form Survey (SF-36), Quality of Life in Depression Scale (QLDS), and EuroQoL 5-Dimension 5-Level (EQ-5D-5L) measures. Esketamine NS-treated patients (N=336) reached PHQ-9 remission (score ≤4) quicker than quetiapine XR-treated patients (N=340), and more had remission by Week 32 (34.5% vs. 18.2%; odds ratio [OR]: 2.39 [1.67, 3.41], p<0.0001). "Role Emotional", "Mental Health", and "Social Functioning" SF-36 domains showed significantly greater improvements in esketamine NS-treated patients compared with quetiapine XR-treated patients at Week 32 (p<0.05), returning to levels close to general population norms. More esketamine NS-treated patients had a meaningful improvement in their QLDS score by Week 32 (60.7% vs. 41.8%; OR: 2.16 [1.59, 2.94], p<0.0001), and reached this improvement quicker than quetiapine XR-treated patients. Proportions of patients reporting an EQ-5D-5L score of 1 (no problems) were significantly higher across all domains with esketamine NS versus quetiapine XR at Week 32 (p<0.05). Esketamine NS produced superior improvements in HRQoL compared with quetiapine XR, indicating positive impacts on aspects of patients' lives that matter to them, alongside clinical symptoms of TRD.
Comparable studies
Other randomized controlled trials on esketamine for depression, most cited first.