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Improvements in functioning and workplace productivity with esketamine nasal spray versus quetiapine extended release in patients with treatment resistant depression: Findings from a 32-week randomised, open-label, rater-blinded phase IIIb study.

Eduard Vieta, Nahida Ahmed, Celso Arango, Anthony J. Cleare, Koen Demyttenaere, Markus Dold, Tetsuro Ito, Yerkebulan Kambarov, Stephanie Krüger, Pierre-Michel Llorca, Roger S McIntyre, Gabriele Sani, Christian von Holt, Benoit Rive

European Neuropsychopharmacology April 1, 2025 DOI: 10.1016/j.euroneuro.2024.12.013 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized, open-label, rater-blinded, active-controlled phase IIIb study Peer reviewed
Sample size 676
Population Patients with treatment resistant depression
Interventions Esketamine nasal spray Quetiapine extended release
Duration 32-week intervention
Topics Depression Esketamine
Keywords Functioning and productivity Quetiapine Treatment resistant depression Workplace productivity Depression treatment Workplace mental health Psychiatric medication Clinical research
Citations 12
Registration NCT04338321
Key points Esketamine nasal spray led to significantly more weeks of functional remission and greater reductions in work productivity loss compared to quetiapine extended release over 32 weeks.

Abstract

Patients with treatment resistant depression (TRD) experience a greater negative impact on their functioning and productivity at home and in the workplace versus treatment-responsive patients. Here, we report the effects of esketamine nasal spray (NS) versus quetiapine extended release (XR) on functioning, work productivity and activity impairment. ESCAPE‑TRD (NCT04338321) was a 32-week randomised, open‑label, rater‑blinded, active‑controlled phase IIIb study comparing the efficacy and safety of esketamine NS versus quetiapine XR, both alongside an ongoing selective serotonin reuptake inhibitor or serotonin norepinephrine reuptake inhibitor (SSRI/SNRI), in patients with TRD. Patient functioning was assessed via the Sheehan Disability Scale (SDS; functional remission ≤6). Absenteeism, presenteeism, work productivity loss and activity impairment over time were assessed using the Work Productivity and Activity Impairment: Depression (WPAI:D) questionnaire. Results were cumulated over the entire study duration. Esketamine NS-treated patients (N = 336) experienced 43.2 % more weeks with functional remission versus quetiapine XR-treated patients (N = 340) over the 32-week study period (difference: 2.0 weeks [95 % CI: 0.7, 3.3]; p = 0.0023 [ANCOVA models]). Up to Week 32, esketamine NS-treated patients experienced an 11.9 % reduction in productivity loss due to absenteeism (difference: -1.1 weeks [95 % CI: -2.9, 0.7]; p = 0.2285) and a 14.2 % reduction in overall work productivity loss (difference: -2.3 weeks, 95 % CI: [-3.9, -0.7] p = 0.0045) versus quetiapine XR-treated patients, based on mixed models for repeated measures. Patients receiving esketamine NS experienced greater improvements in functioning and productivity over 32 weeks versus quetiapine XR. These improvements demonstrate the clinical and functional benefit of treatment with esketamine NS for patients with TRD.

Comparable studies

Other randomized controlled trials on esketamine for depression, most cited first.

Study Year Design Participants
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68
Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) Adults with moderate-to-severe depression and nonresponse to at least two... 2019 Randomized controlled trial n = 346

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