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.

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.