依他佐辛鼻喷剂与喹硫平治疗难治性抑郁症的比较。
Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression.
机构信息
From the Department of Psychiatry, Psychosomatic Medicine, and Psychotherapy, University Hospital, Goethe University Frankfurt, and Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt (A.R.), Danuvius Klinik, Technische Universität München, Pfaffenhofen an der Ilm (T.M.), and Janssen Germany (K.C.) and Janssen EMEA (C.H.), Neuss - all in Germany; the Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary (I.B.); Janssen Pharmaceutica (J.B.) and Janssen EMEA (Y.K.) - both in Beerse, Belgium; the Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna (R.F.); Janssen Research and Development, New Jersey (D.-J.F.); Janssen EMEA, High Wycombe (T.I.), the Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, and South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Beckenham (A.H.Y.) - all in the United Kingdom; CHU Clermont-Ferrand, Department of Psychiatry, University of Clermont Auvergne, UMR 6602 Institut Pascal, Clermont-Ferrand (P.-M.L.), and Janssen EMEA, Paris (B.R.) - both in France; Champalimaud Research and Clinical Center, Champalimaud Foundation, and NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa - both in Lisbon, Portugal (A.J.O.-M.); Janssen EMEA, Dublin (S.M.-H.); and Janssen EMEA, Sofia, Bulgaria (Y.G.).
出版信息
N Engl J Med. 2023 Oct 5;389(14):1298-1309. doi: 10.1056/NEJMoa2304145.
BACKGROUND
In treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments during the current depressive episode, the percentage of patients with remission is low and the percentage with relapse is high. The efficacy and safety of esketamine nasal spray as compared with extended-release quetiapine augmentation therapy, both in combination with ongoing treatment with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI), in patients with treatment-resistant depression are unknown.
METHODS
In an open-label, single-blind (with raters unaware of group assignments), multicenter, phase 3b, randomized, active-controlled trial, we assigned patients, in a 1:1 ratio, to receive flexible doses (according to the summary of product characteristics) of esketamine nasal spray (esketamine group) or extended-release quetiapine (quetiapine group), both in combination with an SSRI or SNRI. The primary end point was remission, defined as a score of 10 or less on the Montgomery-Åsberg Depression Rating Scale (MADRS), at week 8 (scores range from 0 to 60, with higher scores indicating more severe depression). The key secondary end point was no relapse through week 32 after remission at week 8. All patients were included in the analysis; patients who discontinued the trial treatment were considered as having had an unfavorable outcome (i.e., they were grouped with patients who did not have remission or who had a relapse). Analyses of the primary and key secondary end points were adjusted for age and number of treatment failures.
RESULTS
Overall, 336 patients were assigned to the esketamine group and 340 to the quetiapine group. More patients in the esketamine group than in the quetiapine group had remission at week 8 (91 of 336 patients [27.1%] vs. 60 of 340 patients [17.6%]; P = 0.003) and had no relapse through week 32 after remission at week 8 (73 of 336 patients [21.7%] vs. 48 of 340 patients [14.1%]). Over 32 weeks of follow-up, the percentage of patients with remission, the percentage of patients with a treatment response, and the change in the MADRS score from baseline favored esketamine nasal spray. The adverse events were consistent with the established safety profiles of the trial treatments.
CONCLUSIONS
In patients with treatment-resistant depression, esketamine nasal spray plus an SSRI or SNRI was superior to extended-release quetiapine plus an SSRI or SNRI with respect to remission at week 8. (Funded by Janssen EMEA; ESCAPE-TRD ClinicalTrials.gov number, NCT04338321.).
背景
在治疗抵抗性抑郁症中，通常定义为在当前抑郁发作期间连续两次或两次以上治疗无反应，缓解率低，复发率高。在治疗抵抗性抑郁症患者中，与延长释放喹硫平增效治疗相比，艾司氯胺酮鼻喷雾剂的疗效和安全性尚不清楚，两者均与持续使用选择性 5-羟色胺再摄取抑制剂（SSRI）或 5-羟色胺-去甲肾上腺素再摄取抑制剂（SNRI）联合使用。
方法
在一项开放标签、单盲（评估者不知道分组情况）、多中心、3b 期、随机、活性对照试验中，我们以 1:1 的比例随机分配患者，分别接受灵活剂量（根据产品特性摘要）的艾司氯胺酮鼻喷雾剂（艾司氯胺酮组）或延长释放喹硫平（喹硫平组），两者均与 SSRI 或 SNRI 联合使用。主要终点是缓解，定义为蒙哥马利-Åsberg 抑郁评定量表（MADRS）评分在第 8 周时为 10 或更低（评分范围为 0 至 60，分数越高表示抑郁越严重）。关键次要终点是在第 8 周缓解后至第 32 周无复发。所有患者均纳入分析；退出试验治疗的患者被视为预后不良（即，他们被归入未缓解或复发的患者组）。对主要和关键次要终点的分析进行了年龄和治疗失败次数的调整。
结果
共有 336 例患者被分配到艾司氯胺酮组，340 例患者被分配到喹硫平组。与喹硫平组相比，艾司氯胺酮组在第 8 周时达到缓解的患者更多（336 例患者中有 91 例[27.1%] vs. 340 例患者中有 60 例[17.6%]；P=0.003），在第 8 周缓解后至第 32 周无复发的患者也更多（336 例患者中有 73 例[21.7%] vs. 340 例患者中有 48 例[14.1%]）。在 32 周的随访中，缓解率、治疗反应率以及从基线到 MADRS 评分的变化，均有利于艾司氯胺酮鼻喷雾剂。不良事件与试验治疗的既定安全性特征一致。
结论
在治疗抵抗性抑郁症患者中，与延长释放喹硫平联合 SSRI 或 SNRI 相比，艾司氯胺酮鼻喷雾剂联合 SSRI 或 SNRI 可在第 8 周时提高缓解率。（由 Janssen EMEA 资助；ESCAPE-TRD ClinicalTrials.gov 编号，NCT04338321。）
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