Center for Depression Research and Clinical Care, University of Texas Southwestern Medical Center, Dallas, TX, USA; Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Janssen Scientific Affairs, LLC, Titusville, NJ, USA.
J Affect Disord. 2023 Jan 15;321:153-160. doi: 10.1016/j.jad.2022.10.020. Epub 2022 Oct 20.
To evaluate the impact of baseline irritability on clinical outcomes in adults with treatment-resistant depression (TRD) treated with fixed or flexible doses of esketamine nasal spray plus a newly initiated oral antidepressant (ESK+AD) and to explore whether treatment with ESK affects irritability symptoms over time.
This was a post hoc analysis of pooled data from two 4-week, double-blind, phase 3 studies: TRANSFORM-1 (NCT02417064) and TRANSFORM-2 (NCT02418585). Adults with TRD (n = 560) were randomly assigned to ESK+AD or placebo nasal spray plus oral antidepressant (AD+PBO). Irritability was assessed with Item 6 of the 7-item Generalized Anxiety Disorder scale at screening and baseline. Changes in depression severity (Montgomery-Åsberg Depression Rating Scale [MADRS] total score) were evaluated by analysis of covariance (ANCOVA) models. Rates of MADRS response (≥50 % decrease from baseline total score) and remission (total score ≤ 12) were examined using multiple logistic regression models.
Of 560 participants with TRD, 52.9 %, 23.2 %, and 23.9 % had high, low, and varying levels of irritability, respectively. No significant interaction between baseline irritability and treatment group was observed for change in MADRS total score, treatment response, or remission at day 28; numerically greater improvement was observed on all outcomes with ESK+AD versus AD+PBO at day 28 regardless of baseline irritability level. Percentages of patients reporting adverse events were similar across the three baseline irritability groups.
TRANSFORM-1 and TRANSFORM-2 were not designed to prospectively evaluate predetermined irritability outcomes.
These post hoc results support efficacy of ESK+AD in patients with TRD, regardless of baseline irritability.
ClinicalTrials.gov identifiers: NCT02417064 (TRANSFORM-1), NCT02418585 (TRANSFORM-2).
评估基线激惹性对接受固定或灵活剂量 Esketamine 鼻喷雾剂联合新起始口服抗抑郁药（ESK+AD）治疗的难治性抑郁症（TRD）成人临床结局的影响，并探讨 Esketamine 治疗是否会随时间推移影响激惹性症状。
这是两项为期 4 周、双盲、3 期研究（TRANSFORM-1[NCT02417064]和 TRANSFORM-2[NCT02418585]）的汇总数据的事后分析。TRD 成人（n=560）被随机分配到 ESK+AD 或安慰剂鼻喷雾剂联合口服抗抑郁药（AD+PBO）。在筛查和基线时使用 7 项广泛性焦虑障碍量表的第 6 项评估激惹性。采用协方差分析（ANCOVA）模型评估抑郁严重程度（蒙哥马利-阿斯伯格抑郁评定量表[MADRS]总分）的变化。采用多变量逻辑回归模型检查 MADRS 反应（与基线总分相比下降≥50%）和缓解（总分≤12）的发生率。
在 560 名 TRD 参与者中，分别有 52.9%、23.2%和 23.9%的患者激惹性较高、较低和变化不定。基线激惹性和治疗组之间在 MADRS 总分的变化、治疗反应或缓解方面未观察到显著交互作用；在第 28 天，无论基线激惹性水平如何，ESK+AD 与 AD+PBO 相比，所有结局的改善均更明显。在三个基线激惹性组中，报告不良反应的患者比例相似。
TRANSFORM-1 和 TRANSFORM-2 并非旨在前瞻性评估预定的激惹性结局。
这些事后结果支持 ESK+AD 对 TRD 患者的疗效，无论基线激惹性如何。
ClinicalTrials.gov 标识符：NCT02417064（TRANSFORM-1），NCT02418585（TRANSFORM-2）。
