Young Allan H, Llorca Pierre-Michel, Fagiolini Andrea, Falkai Peter, Cardoner Narcís, Nielsen René E, Blomqvist Ola, Godinov Yordan, Rive Benoît, Diels Joris, Mulhern-Haughey Siobhán, Reif Andreas
Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Bethlem Royal Hospital, South London and Maudsley NHS Foundation Trust, London, UK.
Br J Psychiatry. 2025 Feb;226(2):72-78. doi: 10.1192/bjp.2024.124. Epub 2024 Dec 2.
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 < 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], < 0.001; 1.658 [1.337, 2.055], < 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片。
确定ESCAPE - TRD研究结果的稳健性，并证实艾氯胺酮鼻喷雾剂优于喹硫平缓释片。
ESCAPE - TRD是一项随机、开放标签、评估者盲法、活性对照的IIIb期试验。患者患有TRD（即重度抑郁发作期间对两种或更多种抗抑郁治疗无反应）。患者按1:1随机分配至灵活给药的艾氯胺酮鼻喷雾剂或喹硫平缓释片组，同时继续使用正在进行的选择性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周时蒙哥马利-阿斯伯格抑郁评定量表评分≤10，而关键次要终点是在第8周达到缓解后至第32周无复发。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。
676例患者中，336例随机分配至艾氯胺酮鼻喷雾剂组，340例随机分配至喹硫平缓释片组。对主要和关键次要终点的所有敏感性分析均显示艾氯胺酮鼻喷雾剂优于喹硫平缓释片，相对风险分别为1.462至1.737和1.417至1.838（均<0.05）。使用艾氯胺酮鼻喷雾剂治疗缩短了首次缓解和确诊缓解的时间（风险比：1.711 [95%置信区间1.402, 2.087]，<0.001；1.658 [1.337, 2.055]，<0.001）。
使用所有预先指定的缓解和复发定义，艾氯胺酮鼻喷雾剂始终显示出优于喹硫平缓释片的显著优势。敏感性分析支持了ESCAPE - TRD主要分析的结论，并证明了结果的稳健性。
