Efficacy and safety of adjunctive therapy using esketamine or racemic ketamine for adult treatment-resistant depression: A randomized, double-blind, non-inferiority study
Efficacy and safety of adjunctive therapy using esketamine or racemic ketamine for adult treatment-resistant depression: A randomized, double-blind, non-inferiority study
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DOI：
10.1016/j.jad.2019.11.086
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发表时间：
2020-03-01
影响因子：
6.6
通讯作者：
Quarantini, Lucas C.
中科院分区：
文献类型：
--
作者：
Correia-Melo, Fernanda S.;Leal, Gustavo C.;Quarantini, Lucas C.
背景：氯胺酮及其对映体是治疗难治性抑郁症最有效的药物之一。然而，尚未直接比较外消旋氯胺酮和艾司氯胺酮。本研究的目的是评估艾司氯胺酮与氯胺酮相比在难治性抑郁症（TRD）患者中的疗效和安全性。方法：这是一项随机、双盲、活性对照、双中心、非劣效性临床试验，有两个平行组。受试者被随机分配接受氯胺酮0.5 mg/kg或艾司氯胺酮0.25 mg/kg 40分钟单次静脉输注。主要结局是使用蒙哥马利-艾斯伯格抑郁评定量表（MADRS）进行干预后24小时抑郁缓解率的差异，非劣效性界值为20%。结果：纳入并随机分配了63例受试者（29例接受氯胺酮治疗，34例接受艾司氯胺酮治疗）。24 h时，氯胺酮组24.1%的受试者和艾司氯胺酮组29.4%的受试者显示缓解，差异为5.3%（95% CILB-13.6%），证实了非劣效性。氯胺酮组的MADRS评分从33（SD 9.3）改善至16.2（SD 10.7），艾司氯胺酮组从33（SD 5.3）改善至17.5（SD 12.2），差异为-5.27%（95% CILB，-13.6）。两组均出现相似的轻度副作用。结论：艾司氯胺酮输注后24 h的TRD非劣效于氯胺酮。两种治疗均有效、安全且耐受性良好。
Background: Ketamine and its enantiomers have recently been highlighted as one of the most effective therapeutic options in refractory depression. However, racemic ketamine and esketamine have not been directly compared. The aim of this study is to assess the efficacy and safety of esketamine compared to ketamine in patients with treatment-resistant depression (TRD).Methods: This is a randomized, double-blind, active-controlled, bicentre, non-inferiority clinical trial, with two parallel groups. Participants were randomly assigned to a 40-min single intravenous infusion of ketamine 0.5 mg/kg or esketamine 0.25 mg/kg. The primary outcome was the difference in remission rates for depression 24 h following intervention using the Montgomery-Asberg Depression Rating Scale (MADRS), with a non-inferiority margin of 20%.Results: 63 subjects were included and randomly assigned (29 to receive ketamine and 34 to receive esketamine). At 24 h, 24.1% of participants in the ketamine group and 29.4% of participants in the esketamine group showed remission, with a difference of 5.3% (95% CILB -13.6%), confirming non-inferiority. MADRS scores improved from 33 (SD 9.3) to 16.2 (SD 10.7) in the ketamine group and from 33 (SD 5.3) to 17.5 (SD 12.2) in the esketamine one, with a difference of -5.27% (95% CILB, -13.6). Both groups presented similar mild side effects.Conclusions: Esketamine was non-inferior to ketamine for TRD 24 h following infusion. Both treatments were effective, safe, and well tolerated.