St Michael's Hospital, 193 Yonge St, Ste 6-001A, Toronto, ON M5B1M4, Canada.
Department of Psychiatry, Krembil Research Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
J Clin Psychiatry. 2019 Feb 5;80(2):18m12202. doi: 10.4088/JCP.18m12202.
To report the symptomatic and functional outcomes in patients with major depressive disorder (MDD) during a 2-phase treatment trial and to estimate the value of early improvement after 2 weeks in predicting clinical response to escitalopram and subsequently to adjunctive treatment with aripiprazole.
Participants with MDD (N = 211) identified with the Montgomery-Asberg Depression Rating Scale (MADRS) and confirmed with the Mini-International Neuropsychiatric Interview were recruited from 6 outpatient centers across Canada (August 2013 through December 2016) and treated with open-label escitalopram (10-20 mg) for 8 weeks (Phase 1). Clinical and functional outcomes were evaluated using the MADRS, Quick Inventory of Depressive Symptomatology-Self-Rated (QIDS-SR), Sheehan Disability Scale (SDS), and Lam Employment Absence and Productivity Scale (LEAPS). Participants were evaluated at 8 and 16 weeks for clinical and functional response and remission. Phase 1 responders continued escitalopram while nonresponders received adjunctive aripiprazole (2-10 mg) for a further 8 weeks (Phase 2).
After Phase 1, MADRS response (≥ 50% decrease from baseline) and remission (score ≤ 10) were, respectively, 47% and 31%, and SDS response (score ≤ 12) and remission (score ≤ 6) were, respectively, 53% and 24%. Response to escitalopram was maintained in 91% of participants at week 16, while 61% of the adjunctive aripiprazole group achieved MADRS response during Phase 2. Response and remission rates with the QIDS-SR were lower than with the MADRS. The LEAPS demonstrated significant occupational improvement (P < .05). Early symptomatic improvement predicted outcomes with modest accuracy.
This study demonstrates comparable symptomatic and functional outcomes to those of other large practical-design studies. There was a high response rate with the adjunctive use of aripiprazole in escitalopram nonresponders. Given the limited value of early clinical improvement to predict outcome, integration of clinical and biological markers deserves further exploration.
ClinicalTrials.gov identifier: NCT01655706.
报告在 2 期治疗试验中患有重度抑郁症（MDD）患者的症状和功能结局，并评估治疗 2 周后早期改善对依地普仑临床反应的预测价值，进而预测对阿立哌唑辅助治疗的反应。
从加拿大 6 个门诊中心（2013 年 8 月至 2016 年 12 月）招募符合蒙哥马利-阿斯伯格抑郁评定量表（MADRS）和迷你国际神经精神访谈诊断的 MDD 患者（N=211），并给予依地普仑（10-20mg）进行为期 8 周的开放性治疗（第 1 阶段）。使用 MADRS、抑郁症状自评快速清单（QIDS-SR）、Sheehan 残疾量表（SDS）和 Lam 就业缺勤和生产力量表（LEAPS）评估临床和功能结局。在第 8 周和第 16 周评估临床和功能反应和缓解情况。第 1 阶段的反应者继续接受依地普仑治疗，而无反应者在第 2 阶段再接受阿立哌唑辅助治疗（2-10mg）8 周。
第 1 阶段后，MADRS 反应（与基线相比下降≥50%）和缓解（评分≤10）分别为 47%和 31%，SDS 反应（评分≤12）和缓解（评分≤6）分别为 53%和 24%。第 16 周时，91%的参与者对依地普仑有反应，而在第 2 阶段，阿立哌唑辅助治疗组中有 61%的患者达到 MADRS 反应。QIDS-SR 的反应和缓解率低于 MADRS。LEAPS 显示出显著的职业改善（P<.05）。早期症状改善对结果的预测准确性中等。
本研究显示出与其他大型实用设计研究相当的症状和功能结局。在依地普仑无反应者中，阿立哌唑辅助治疗的反应率较高。鉴于早期临床改善对预测结局的价值有限，整合临床和生物学标志物值得进一步探索。
ClinicalTrials.gov 标识符：NCT01655706。
