Janssen Research & Development, LLC, Titusville, New Jersey.
Corresponding author: Ibrahim Turkoz, PhD, Department of Statistics & Decision Sciences, Janssen Research & Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ 08560 (
J Clin Psychiatry. 2021 Jul 20;82(4):20m13800. doi: 10.4088/JCP.20m13800.
To evaluate response to esketamine nasal spray plus an oral antidepressant (ESK + AD) at day 28 in patients with major depressive disorder () and treatment-resistant depression (TRD) who did not meet response criteria within the first week of treatment. The current study is a pooled post hoc analysis of two phase 3, double-blind, active-controlled studies, conducted between August 2015 and February 2018, comparing ESK + AD with an oral antidepressant plus placebo (AD + PBO). Early treatment response was defined as a ≥ 50% decrease in Montgomery-Åsberg Depression Rating Scale total score at day 2 or days 2 and 8. Response rates at day 28 were determined among those not meeting early response criteria. 518 patients in the analysis had day 28 observations (ESK + AD, n = 310; AD + PBO, n = 208). A greater percentage of patients treated with ESK + AD versus AD + PBO met response criteria beginning at day 2 (17.3% [55/318] vs 9.4% [19/203]) and at all subsequent timepoints, including day 28 (58.7% [182/310] vs 45.2% [94/208]). In day 2 nonresponders, 54.9% vs 44.3% (ESK + AD vs AD + PBO, respectively) achieved response at day 28 ( < .01). Similarly, among day 2 and 8 nonresponders, 52.1% vs 42.4% achieved response by day 28 ( = .01). In nonresponders at day 2 and at days 2 and 8, the odds ratio for a response at day 28 was 1.61 (95% CI, 1.09-2.40) with ESK + AD versus 1.56 (95% CI, 1.04-2.35) with AD + PBO. Patients with TRD without a demonstrated response within the first week of treatment may still derive benefit from a full 4-week induction course of esketamine nasal spray. ClinicalTrials.gov identifiers NCT02417064 and NCT02418585.
评估在不符合治疗第 1 周应答标准的重度抑郁症（MDD）和治疗抵抗性抑郁症（TRD）患者中，使用依他佐辛鼻喷剂联合口服抗抑郁药（ESK+AD）治疗在第 28 天的应答情况。本研究是两项为期 3 期、双盲、活性对照研究的事后汇总分析，于 2015 年 8 月至 2018 年 2 月进行，比较了 ESK+AD 与口服抗抑郁药联合安慰剂（AD+PBO）。早期治疗应答定义为在第 2 天或第 2 天和第 8 天，蒙哥马利-阿斯伯格抑郁评定量表总分至少降低 50%。在不符合早期应答标准的患者中确定第 28 天的应答率。分析中有 518 例患者具有第 28 天观察值（ESK+AD，n=310；AD+PBO，n=208）。与 AD+PBO 相比，更多接受 ESK+AD 治疗的患者从第 2 天开始（17.3%[55/318]比 9.4%[19/203]）和随后所有时间点开始（包括第 28 天）满足应答标准（58.7%[182/310]比 45.2%[94/208]）。在第 2 天无应答者中，54.9%比 44.3%（ESK+AD 比 AD+PBO）在第 28 天应答（ < .01）。同样，在第 2 天和第 8 天无应答者中，52.1%比 42.4%在第 28 天应答（ = .01）。在第 2 天和第 2 天和第 8 天无应答者中，ESK+AD 治疗的第 28 天应答的优势比为 1.61（95%CI，1.09-2.40），AD+PBO 为 1.56（95%CI，1.04-2.35）。在治疗第 1 周内未显示应答的 TRD 患者仍可能从依他佐辛鼻喷剂的完整 4 周诱导疗程中获益。临床试验.gov 标识符 NCT02417064 和 NCT02418585。
