在 GUIDED 随机对照试验中，使用 6 项和 17 项汉密尔顿抑郁量表评估变化敏感性的比较。
Comparing sensitivity to change using the 6-item versus the 17-item Hamilton depression rating scale in the GUIDED randomized controlled trial.
机构信息
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 12 Executive Park Dr. NE, 3rd Floor, Atlanta, GA, 30329, USA.
Department of Psychiatry, and National Network of Depression Centers, University of Michigan Comprehensive Depression Center, Ann Arbor, MI, USA.
出版信息
BMC Psychiatry. 2019 Dec 27;19(1):420. doi: 10.1186/s12888-019-2410-2.
BACKGROUND
Previous research suggests that the 17-item Hamilton Depression Rating Scale (HAM-D17) is less sensitive in detecting differences between active treatment and placebo for major depressive disorder (MDD) than is the HAM-D6 scale, which focuses on six core depression symptoms. Whether HAM-D6 shows greater sensitivity when comparing two active MDD treatment arms is unknown.
METHODS
This post hoc analysis used data from the intent-to-treat (ITT) cohort (N = 1541) of the Genomics Used to Improve DEpression Decisions (GUIDED) trial, a rater- and patient-blinded randomized controlled trial. GUIDED compared combinatorial pharmacogenomics-guided care with treatment as usual (TAU) in patients with MDD. Percent of symptom improvement, response rate and remission rate from baseline to week 8 were evaluated using both scales. Analyses were performed for the full cohort and for the subset of patients who at baseline were taking medications predicted by the test to have moderate or significant gene-drug interactions. A Mokken scale analysis was conducted to compare the homogeneity of HAM-D17 with that of HAM-D6.
RESULTS
At week 8, the guided-care arm demonstrated statistically significant benefit over TAU when the HAM-D6 (∆ = 4.4%, p = 0.023) was used as the continuous measure of symptom improvement, but not when using the HAM-D17 (∆ = 3.2%, p = 0.069). Response rates increased significantly for guided-care compared with TAU when evaluated using both HAM-D6 (∆ = 7.0%, p = 0.004) and HAM-D17 (∆ = 6.3%, p = 0.007). Remission rates also were significantly greater for guided-care versus TAU using both measures (HAM-D6 ∆ = 4.6%, p = 0.031; HAM-D17 ∆ = 5.5%, p = 0.005). Patients in the guided-care arm who at baseline were taking medications predicted to have gene-drug interactions showed further increased benefit over TAU at week 8 for symptom improvement (∆ = 7.3%, p = 0.004) response (∆ = 10.0%, p = 0.001) and remission (∆ = 7.9%, p = 0.005) using HAM-D6. All outcomes showed continued improvement through week 24. Mokken scale analysis demonstrated the homogeneity and unidimensionality of HAM-D6, but not of HAM-D17, across treatment arms.
CONCLUSIONS
The HAM-D6 scale identified a statistically significant difference in symptom improvement between combinatorial pharmacogenomics-guided care and TAU, whereas the HAM-D17 did not. The demonstrated utility of pharmacogenomics-guided treatment over TAU as detected by the HAM-D6 highlights its value for future biomarker-guided trials comparing active treatment arms.
TRIAL REGISTRATION
Clinicaltrials.gov: NCT02109939. Registered 10 April 2014.
背景
先前的研究表明，17 项汉密尔顿抑郁量表（HAM-D17）在检测重度抑郁症（MDD）的活性治疗与安慰剂之间的差异方面不如专注于六个核心抑郁症状的 HAM-D6 量表敏感。当比较两种活性 MDD 治疗臂时，HAM-D6 是否显示出更大的敏感性尚不清楚。
方法
这是 GUIDED 试验的意向治疗（ITT）队列（N=1541）的事后分析，这是一项盲法随机对照试验，使用基因组学来改善抑郁决策。GUIDED 比较了组合药物基因组学指导护理与常规治疗（TAU）在 MDD 患者中的效果。使用这两种量表评估从基线到第 8 周的症状改善百分比、反应率和缓解率。为全队列和基线时正在服用测试预测具有中度或显著基因-药物相互作用的药物的患者亚组进行了分析。进行莫肯量表分析以比较 HAM-D17 与 HAM-D6 的同质性。
结果
第 8 周时，当使用 HAM-D6（∆=4.4%，p=0.023）作为症状改善的连续测量值时，指导护理组与 TAU 相比显示出统计学上的显著益处，但使用 HAM-D17 时则不然（∆=3.2%，p=0.069）。当使用 HAM-D6（∆=7.0%，p=0.004）和 HAM-D17（∆=6.3%，p=0.007）评估时，与 TAU 相比，指导护理组的反应率显著增加。使用两种测量方法，与 TAU 相比，指导护理组的缓解率也显著更高（HAM-D6 ∆=4.6%，p=0.031；HAM-D17 ∆=5.5%，p=0.005）。基线时正在服用预测具有基因-药物相互作用的药物的指导护理组患者在第 8 周时与 TAU 相比，在症状改善（∆=7.3%，p=0.004）、反应（∆=10.0%，p=0.001）和缓解（∆=7.9%，p=0.005）方面表现出进一步的获益。所有结果在第 24 周时均继续改善。莫肯量表分析表明，HAM-D6 在治疗臂之间具有同质性和单维性，但 HAM-D17 则不然。HAM-D6 检测到的药物基因组学指导治疗优于 TAU 的效用表明其在未来比较活性治疗臂的生物标志物指导试验中的价值。
试验注册
Clinicaltrials.gov：NCT02109939。2014 年 4 月 10 日注册。
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