Improvements in Functioning with Esketamine Nasal Spray versus Quetiapine Extended Release in Patients with Treatment Resistant Depression

Introduction In the ESCAPE-TRD study, esketamine nasal spray (ESK-NS) significantly increased chance of remission at Week 8 versus (vs) quetiapine extended release (Q-XR) in patients (pts) with treatment resistant depression (TRD; Reif et al . NEJM 2023; 389:1298–309). Changes in disability and functional impairment due to depressive symptoms assessed with the Sheehan Disability Scale (SDS) are reported. Objectives To assess the effect of ESK-NS vs Q-XR on pts’ daily functioning using SDS, considering their symptom evolution. Methods ESCAPE‑TRD was a randomised phase IIIb trial comparing the efficacy of ESK-NS vs Q-XR, both alongside an ongoing selective serotonin/serotonin-norepinephrine reuptake inhibitor, in pts with TRD. Clinical response (CRes) was defined as ≥50% improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline or total score ≤10, clinical remission (CRem) was defined as total MADRS score of ≤10, and functional remission (FRem) was defined as SDS total score ≤6. The Kaplan-Meier method was used for time to event analyses, and hazard ratios (HRs) were estimated using Cox regression models. Time in each state was estimated by treatment arm and compared between arms using analysis of covariance. Results 336 and 340 pts were randomised to ESK-NS and Q-XR, respectively. Significantly more ESK-NS treated pts achieved CRes, CRem and FRem (HRs: 1.848, 1.711 and 1.819, respectively; all p<0.001), and achieved these faster, compared to Q-XR ( Figure 1 ). In each arm and at each time point, more pts reached CRes than CRem, and more reached CRem than FRem, illustrating that FRem is more difficult to achieve ( Figure 1 ). Total time in CRes was 5.4 weeks greater for ESK-NS compared with Q-XR; total time in CRem was 3.7 weeks greater and in FRem 2.0 weeks greater for ESK-NS vs Q-XR, respectively ( Table 1 ). Image 1: Image 2: Conclusions These data support a temporal cascade of events from CRes to CRem to FRem; ESK-NS improved time to, and in, each outcome vs Q-XR. Treatments that reduce clinical symptoms better and faster provide the best chance of improving functional impairment. Disclosure of Interest None Declared