Efficacy of esketamine nasal spray over quetiapine extended release over the short and long term: sensitivity analyses of ESCAPE-TRD, a randomised phase IIIb clinical trial.

In people with treatment-resistant depression, esketamine nasal spray outperformed quetiapine extended release across multiple measures. Sensitivity analyses using different definitions of remission and relapse consistently favored esketamine, with relative risks for the primary endpoint ranging from 1.462 to 1.737 and for the key secondary endpoint from 1.417 to 1.838. Esketamine also shortened time to first remission by 71% and confirmed remission by 66%. The robustness of the original ESCAPE-TRD trial findings was confirmed.

Study at a glance

Abstract

In patients with treatment resistant depression (TRD), the ESCAPE-TRD study showed esketamine nasal spray was superior to quetiapine extended release. To determine the robustness of the ESCAPE-TRD results and confirm the superiority of esketamine nasal spray over quetiapine extended release. ESCAPE-TRD was a randomised, open-label, rater-blinded, active-controlled phase IIIb trial. Patients had TRD (i.e. non-response to two or more antidepressive treatments within a major depressive episode). Patients were randomised 1:1 to flexibly dosed esketamine nasal spray or quetiapine extended release, while continuing an ongoing selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor. The primary end-point was achieving a Montgomery-Åsberg Depression Rating Scale score of ≤10 at Week 8, while the key secondary end-point was remaining relapse free through Week 32 after achieving remission at Week 8. Sensitivity analyses were performed on these end-points by varying the definition of remission based on timepoint, threshold and scale. Of 676 patients, 336 were randomised to esketamine nasal spray and 340 to quetiapine extended release. All sensitivity analyses on the primary and key secondary end-point favoured esketamine nasal spray over quetiapine extended release, with relative risks ranging from 1.462 to 1.737 and from 1.417 to 1.838, respectively (all p < 0.05). Treatment with esketamine nasal spray shortened time to first and confirmed remission (hazard ratio: 1.711 [95% confidence interval 1.402, 2.087], p < 0.001; 1.658 [1.337, 2.055], p < 0.001). Esketamine nasal spray consistently demonstrated significant superiority over quetiapine extended release using all pre-specified definitions for remission and relapse. Sensitivity analyses supported the conclusions of the primary ESCAPE-TRD analysis and demonstrated robustness of the results.