Department of Neuroscience Medical Affairs, Janssen Scientific Affairs, LLC, Titusville, New Jersey, USA.
Department of Statistics & Decision Sciences, Janssen Research & Development, LLC, Titusville, New Jersey, USA.
Depress Anxiety. 2021 Nov;38(11):1120-1130. doi: 10.1002/da.23193. Epub 2021 Jul 22.
Comorbid anxiety is generally associated with poorer response to antidepressant treatment. This post hoc analysis explored the efficacy of esketamine plus an antidepressant in patients with treatment-resistant depression (TRD) with or without comorbid anxiety.
TRANSFORM-2, a double-blind, flexible-dose, 4-week study (NCT02418585), randomized adults with TRD to placebo or esketamine nasal spray, each with a newly-initiated oral antidepressant. Comorbid anxiety was defined as clinically noteworthy anxiety symptoms (7-item Generalized Anxiety Disorder scale [GAD-7] score ≥10) at screening and baseline or comorbid anxiety disorder diagnosis at screening. Treatment effect based on change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score, and response and remission were examined by presence/absence of comorbid anxiety using analysis of covariance and logistic regression models.
Approximately 72% (162/223) of patients had baseline comorbid anxiety. Esketamine-treated patients with and without anxiety demonstrated significant reductions in MADRS (mean [SD] change from baseline at day 28: -21.0 [12.51] and -22.7 [11.98], respectively). Higher rates of response and remission, and a significantly greater decrease in MADRS score at day 28 were observed compared to antidepressant/placebo, regardless of comorbid anxiety (with anxiety: difference in LS means [95% CI] -4.2 [-8.1, -0.3]; without anxiety: -7.5 [-13.7, -1.3]). There was no significant interaction of treatment and comorbid anxiety (p = .371). Notably, in the antidepressant/placebo group improvement was similar in those with and without comorbid anxiety.
Post hoc data support efficacy of esketamine plus an oral antidepressant in patients with TRD, regardless of comorbid anxiety.
合并焦虑通常与抗抑郁治疗反应较差相关。本事后分析探讨了在伴有或不伴有合并焦虑的治疗抵抗性抑郁症（TRD）患者中，艾司氯胺酮联合抗抑郁药的疗效。
TRANSFORM-2 是一项双盲、剂量灵活、为期 4 周的研究（NCT02418585），将 TRD 成年患者随机分为安慰剂或 Esketamine 鼻喷雾剂组，每组均接受新起始的口服抗抑郁药治疗。合并焦虑的定义为筛查和基线时存在明显的焦虑症状（7 项广泛性焦虑障碍量表[GAD-7]评分≥10），或筛查时存在合并焦虑障碍诊断。采用协方差分析和逻辑回归模型，根据蒙哥马利-艾斯伯格抑郁评定量表（MADRS）总分的变化，以及反应和缓解情况，检查合并焦虑对疗效的影响。
约 72%（162/223）的患者基线时合并焦虑。有合并焦虑和无合并焦虑的 Esketamine 治疗患者的 MADRS 评分均显著降低（从基线到第 28 天的平均[标准差]变化：-21.0[12.51]和-22.7[11.98]）。与抗抑郁药/安慰剂相比，无论是否合并焦虑，反应和缓解率更高，MADRS 评分在第 28 天的降幅更大（有焦虑：LS 均值差值[-4.2[-8.1，-0.3]；无焦虑：-7.5[-13.7，-1.3]）。治疗与合并焦虑之间无显著交互作用（p=0.371）。值得注意的是，在抗抑郁药/安慰剂组中，有合并焦虑和无合并焦虑的患者的改善情况相似。
事后数据支持在伴有或不伴有合并焦虑的 TRD 患者中，艾司氯胺酮联合口服抗抑郁药的疗效。
