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.

在难治性抑郁症 （TRD） 患者中，ESCAPE-TRD 研究表明艾氯胺酮鼻喷雾剂优于喹硫平缓释剂。

确定 ESCAPE-TRD 结果的稳健性并确认艾氯胺酮鼻喷雾剂优于喹硫平缓释剂。

ESCAPE-TRD 是一项随机、开放标签、评分者盲法、主动对照的 IIIb 期试验。患者患有 TRD （即 在一次重度抑郁发作中对两种或多种抗抑郁治疗无反应）。患者以 1：1 的比例随机分配至灵活剂量的艾氯胺酮鼻喷雾剂或喹硫平缓释剂组，同时继续接受持续的选择性 5-羟色胺再摄取抑制剂/5-羟色胺去甲肾上腺素再摄取抑制剂。主要终点是在第 8 周达到 ≤10 的 Montgomery-Åsberg 抑郁量表评分，而关键的次要终点是在第 8 周达到缓解后，在第 32 周保持无复发。通过根据时间点、阈值和量表改变缓解的定义，对这些终点进行敏感性分析。

在 676 例患者中，336 例被随机分配到艾氯胺酮鼻喷雾剂组，340 例被随机分配到喹硫平缓释剂组。对主要和关键次要终点的所有敏感性分析都有利于艾氯胺酮鼻喷雾剂而不是喹硫平缓释剂，相对风险分别为 1.462 至 1.737 和 1.417 至 1.838 （均 p < 0.05）。艾氯胺酮鼻喷雾剂治疗缩短了首次缓解和确认缓解的时间（风险比：1.711 [95% 置信区间 1.402,2.087]，p < 0.001;1.658 [1.337,2.055]，p < 0.001）。

艾氯胺酮鼻喷雾剂在使用所有预先指定的缓解和复发定义时，始终显示出优于喹硫平缓释剂的显著优势。敏感性分析支持主要 ESCAPE-TRD 分析的结论，并证明了结果的稳健性。