Therrien François, Chokka Pratap, Habert Jeffrey, Ismail Zahinoor, McIntyre Roger S, Dine Jennifer, Brown T Michelle, Zhang Zhen, MacKenzie Erin M, Ward Caroline
Otsuka Canada Pharmaceutical Inc., Saint-Laurent, Quebec, Canada.
Chokka Center for Integrative Health, Edmonton, AB, Canada.
Curr Med Res Opin. 2025 Sep 6:1-15. doi: 10.1080/03007995.2025.2558140.
In ENGAGE, patients with major depressive disorder (MDD) demonstrated improvements in patient-reported depression and life engagement while taking adjunctive brexpiprazole. This analysis aimed to further characterize patient perspectives on the effects of adjunctive brexpiprazole, using patient diary data from ENGAGE, and describe development of a 'word of the day' activity.
Prior to ENGAGE, word lists describing a 'good,' 'average,' and 'bad' day with depression were generated from semi-structured interviews with patients with MDD. ENGAGE (ClinicalTrials.gov identifier: NCT04830215) was an 8-week, phase 4, single-arm, open-label study of adjunctive brexpiprazole 0.5-2 mg/day in patients with MDD and inadequate response to antidepressant treatment. Patient diaries were completed periodically at home, comprising the Patient Global Impression - Severity of illness (PGI-S), Patient Global Impression - Improvement (PGI-I), and a 'word of the day' activity in which patients selected one word to describe how they felt that day. This analysis evaluated mean change in PGI-S scores (mixed model for repeated measures), mean PGI-I scores (descriptive statistics), PGI-S response and PGI-S sustained response (Kaplan-Meier), PGI-I response (normal approximation), and 'word of the day' (descriptive statistics).
In the interviews, 20 patients used 132 words to describe living with depression. Five words of each valence (positive, neutral, negative) were selected for ENGAGE. 122 patients were enrolled in ENGAGE; 120 had evaluable diary data. PGI-S score improved from baseline to week 8 (least squares mean change [standard error]: -1.5 [0.2]; nominal < 0.001; effect size: 1.04). PGI-I scores at week 8 indicated "minimal improvement" to "much improvement" (mean [standard deviation]: 2.6 [1.1]). At week 8, rates of PGI-S response, sustained PGI-S response, and PGI-I response were 86.0% (95% confidence interval: 77.1, 92.8), 67.9% (54.5, 80.6), and 47.1% (38.1, 56.0), respectively. On 'word of the day,' the proportion of positive and neutral words increased from baseline to week 8, and the proportion of negative words decreased.
Patient-reported diary data revealed early and sustained improvements in depressive symptom severity during 8 weeks of adjunctive brexpiprazole treatment. 'Word of the day' may be an effective qualitative tool for future trials.
在ENGAGE研究中，重度抑郁症（MDD）患者在服用辅助性布雷哌唑时，患者报告的抑郁症状和生活参与度有改善。本分析旨在利用ENGAGE研究中的患者日记数据，进一步描述患者对辅助性布雷哌唑效果的看法，并描述“每日一词”活动的开展情况。
在ENGAGE研究之前，通过对MDD患者的半结构化访谈，生成了描述抑郁状态下“好”“一般”和“差”的日子的词汇列表。ENGAGE（ClinicalTrials.gov标识符：NCT04830215）是一项为期8周的4期单臂开放标签研究，研究对象为MDD患者，这些患者对抗抑郁治疗反应不足，给予每日0.5 - 2毫克的辅助性布雷哌唑治疗。患者在家中定期完成日记，包括患者总体印象 - 疾病严重程度（PGI - S）、患者总体印象 - 改善情况（PGI - I），以及一项“每日一词”活动，患者选择一个词来描述当天的感受。本分析评估了PGI - S评分的平均变化（重复测量混合模型）、PGI - I评分的平均值（描述性统计）、PGI - S反应和PGI - S持续反应（Kaplan - Meier法）、PGI - I反应（正态近似法）以及“每日一词”（描述性统计）。
在访谈中，20名患者用132个词描述了与抑郁症共处的情况。为ENGAGE研究从每个效价（积极、中性、消极）中挑选了5个词。122名患者参与了ENGAGE研究；120名患者有可评估的日记数据。PGI - S评分从基线到第8周有所改善（最小二乘均值变化[标准误]：-1.5[0.2]；名义值<0.001；效应大小：1.04）。第8周时PGI - I评分表明“最小改善”至“显著改善”（均值[标准差]：2.6[1.1]）。在第8周时，PGI - S反应率、PGI - S持续反应率和PGI - I反应率分别为86.0%（95%置信区间：77.1，92.8）、67.9%（54.5，80.6）和47.1%（38.1，56.0）。关于“每日一词”，从基线到第8周，积极和中性词的比例增加，消极词的比例下降。
患者报告的日记数据显示，在8周的辅助性布雷哌唑治疗期间，抑郁症状严重程度有早期且持续的改善。“每日一词”可能是未来试验中一种有效的定性工具。
