Turkoz Ibrahim, Alphs Larry, Singh Jaskaran, Jamieson Carol, Daly Ella, Shawi May, Sheehan John J, Trivedi Madhukar H, Rush A John
Janssen Research and Development, LLC, Titusville, NJ, USA.
Janssen Scientific Affairs, LLC, Titusville, NJ, USA.
Acta Psychiatr Scand. 2021 Mar;143(3):253-263. doi: 10.1111/acps.13260. Epub 2021 Jan 22.
To use the Clinical Global Impression-Severity (CGI-S) scale to estimate clinically meaningful and clinically substantial changes as measured using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Sheehan Disability Scale (SDS), and the Patient Health Questionnaire-9 (PHQ-9) in patients with treatment-resistant depression (TRD).
Pooled data were derived from two 4-week, randomized, active-controlled studies evaluating esketamine nasal spray (ESK) plus oral antidepressant (OAD) or OAD plus placebo nasal spray (PBO) in adults with TRD (N = 565). CGI-S, MADRS, SDS, and PHQ-9 scores were obtained at baseline and over 4 weeks of treatment. In this post hoc analysis, change scores on the MADRS, SDS, and PHQ-9 that corresponded to a clinically meaningful (1-point) or clinically substantial (2-point) change on the CGI-S scale were identified.
Clinically meaningful changes in CGI-S scores after 28 days corresponded to 6-, 4-, and 3-point changes from baseline on the MADRS, SDS, and PHQ-9, respectively. Similarly, a 2-point CGI-S score change (clinically substantial change) corresponded to a 12-, 8-, and 6-point change on the MADRS, SDS, and PHQ-9, respectively. The proportion of patients showing substantial clinical improvement in the ESK plus OAD group versus the OAD plus PBO group after 28 days of treatment favored ESK plus OAD: 69.0% vs 55.3% (MADRS), 64.5% vs 48.9% (SDS), and 77.1% vs 64.7% (PHQ-9).
We provide a basis for identifying clinically meaningful and clinically substantial changes as assessed with commonly used outcome measures for depression to facilitate the translation of clinical trial results into clinical practice.
使用临床总体印象-严重程度（CGI-S）量表，评估难治性抑郁症（TRD）患者中，通过蒙哥马利-Åsberg抑郁评定量表（MADRS）、希恩残疾量表（SDS）和患者健康问卷-9（PHQ-9）所测量的具有临床意义和临床实质意义的变化。
汇总数据来自两项为期4周的随机、活性对照研究，这些研究评估了艾氯胺酮鼻喷雾剂（ESK）加口服抗抑郁药（OAD）或OAD加安慰剂鼻喷雾剂（PBO）在成年TRD患者（N = 565）中的疗效。在基线和4周治疗期间获取CGI-S、MADRS、SDS和PHQ-9评分。在这项事后分析中，确定了MADRS、SDS和PHQ-9上与CGI-S量表上具有临床意义（1分）或临床实质意义（2分）变化相对应的变化分数。
28天后CGI-S评分的临床意义变化分别对应于MADRS、SDS和PHQ-9相对于基线的6分、4分和3分变化。同样，CGI-S评分2分的变化（临床实质意义变化）分别对应于MADRS、SDS和PHQ-9上的12分、8分和6分变化。治疗28天后，ESK加OAD组与OAD加PBO组相比，显示出显著临床改善的患者比例有利于ESK加OAD组：69.0%对55.3%（MADRS），64.5%对48.9%（SDS），以及77.1%对64.7%（PHQ-9）。
我们为识别抑郁症常用结局指标所评估的具有临床意义和临床实质意义的变化提供了依据，以促进将临床试验结果转化为临床实践。
