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.

中文翻译：

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在 GUIDED 随机对照试验中比较使用 6 项汉密尔顿抑郁评定量表和 17 项汉密尔顿抑郁评定量表对变化的敏感性。

背景 先前的研究表明，17 项汉密尔顿抑郁评定量表 (HAM-D17) 在检测重度抑郁症 (MDD) 的积极治疗和安慰剂之间的差异方面，不如 HAM-D6 量表敏感，后者侧重于六项核心抑郁症症状。在比较两个活跃的 MDD 治疗组时，HAM-D6 是否表现出更高的敏感性尚不清楚。方法 这项事后分析使用了用于改善抑郁决策的基因组学 (GUIDED) 试验意向治疗 (ITT) 队列 (N = 1541) 的数据，这是一项评估者和患者盲法随机对照试验。GUIDED 比较了 MDD 患者的组合药物基因组学指导护理与常规治疗 (TAU)。使用两种量表评估从基线到第 8 周的症状改善百分比、缓解率和缓解率。对整个队列和基线时正在服用经测试预测具有中度或显着基因药物相互作用的药物的患者子集进行了分析。进行 Mokken 标度分析以比较 HAM-D17 与 HAM-D6 的均匀性。结果 在第 8 周，当使用 HAM-D6（Δ = 4.4%，p = 0.023）作为症状改善的连续衡量指标时，指导护理组表现出比 TAU 具有统计学显着性的益处，但使用 HAM-D17 时则没有这种效果（ Δ = 3.2%，p = 0.069）。当使用 HAM-D6 (Δ = 7.0%，p = 0.004) 和 HAM-D17 (Δ = 6.3%，p = 0.007) 进行评估时，指导护理的反应率显着高于 TAU。使用这两种措施时，指导护理的缓解率也显着高于 TAU（HAM-D6 Δ = 4.6%，p = 0.031；HAM-D17 Δ = 5.5%，p = 0.005）。指导护理组中的患者在基线时正在服用预计会产生基因药物相互作用的药物，在第 8 周时，与 TAU 相比，在症状改善方面显示出进一步增加的益处（Δ = 7.3%，p = 0.004）反应（Δ = 10.0%，p = 0.001）和使用 HAM-D6 缓解（Δ = 7.9%，p = 0.005）。所有结果均在第 24 周持续改善。Mokken 量表分析表明，在各治疗组中，HAM-D6 具有同质性和一维性，但 HAM-D17 则不然。结论 HAM-D6 量表发现组合药物基因组学指导的护理和 TAU 在症状改善方面存在统计学显着差异，而 HAM-D17 则没有。HAM-D6 检测到的药物基因组学指导治疗相对于 TAU 的实用性凸显了其对于未来比较积极治疗组的生物标志物指导试验的价值。试验注册 ClinicalTrials.gov：NCT02109939。2014 年 4 月 10 日注册。