Influence of baseline severity on the effects of SSRIs in depression: an item-based, patient-level post-hoc analysis
Influence of baseline severity on the effects of SSRIs in depression: an item-based, patient-level post-hoc analysis
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DOI：
10.1016/s2215-0366(19)30216-0
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发表时间：
2019-09-01
影响因子：
64.3
通讯作者：
Eriksson, Elias
中科院分区：
文献类型：
--
作者：
Hieronymus, Fredrik;Lisinski, Alexander;Eriksson, Elias
背景报告声称抗抑郁药物只对重度抑郁症患者有效，这影响了治疗指南，但这些报告通常使用一种有争议的改善措施，即17项汉密尔顿抑郁量表(HDRS-17)总分的下降，并且基于组水平而不是患者水平的数据。方法在这项基于项目、患者水平的特别后分析中，我们汇集了所有完成的、急性期的、安慰剂对照的、行业赞助的、基于H DRS的SSRIs西酞普兰、帕罗西汀或舍曲林在成人重度抑郁症中的试验数据。患者水平的数据被汇集并接受基于项目的事后分析，以评估基线抑郁严重程度对治疗反应的影响，使用HDRS-17总分、HDRS中的抑郁情绪项目、6个项目的HDRS子量表(HDRS-6)以及未包括在该子量表中的其余11个HDRS项目(非HDRS-6)进行评估。如果基线HDRS-17总分小于或等于18分，患者被定义为非重度抑郁症，如果他们的总分为27分或更高，则被定义为重度抑郁症。参与者接受西酞普兰(n=744)、帕罗西汀(n=2981)、舍曲林(n=1202)、氟西汀(主动对照组；n=754)或安慰剂(n=2581)治疗。654例患者被定义为非重度抑郁症，1377例患者被定义为重度抑郁症。非重度和重度抑郁症患者在SSRI诱导的抑郁情绪下降和属于HDRS-6子量表的其他HDRS症状方面没有区别。然而，在排除了罕见的极端基线值的患者后，当使用HDRS-17总分作为疗效参数时，病情严重程度和疗效之间存在正相关。这一结果在很大程度上是由于重度抑郁症患者对非HDRS-6项目的治疗反应比非重度抑郁症患者更明显。这一结果可以用非HDRS-6条目来解释，比HDRS-6条目更严重，在基线时，重度抑郁症比非重度抑郁症患者更严重和普遍；因此，在非重度抑郁症患者中，这些方面的改善空间较小。解释使用包括非严重抑郁症患者基线时较低的症状的结果衡量标准，可能会导致SSRI在这些患者中无效。关于HDRS-6条目的缓解，SSRI似乎对非重度抑郁症患者和重度抑郁症患者同样有效。版权所有(C)2019爱思唯尔有限公司。保留所有权利。
Background Reports claiming that antidepressants are effective only in patients with severe depression have affected treatment guidelines but these reports usually use a disputed measure of improvement, a decrease in the sum-score of the 17-item Hamilton Depression Rating Scale (HDRS-17), and are based on group-level rather than patient-level data.Method In this item-based, patient-level, post-hoc analysis, we pooled data from all completed, acute-phase, placebo-controlled, industry-sponsored, H DRS-based trials of the SSRIs citalopram, paroxetine, or sertraline in adult major depression. Patient-level data were pooled and subjected to item-based post-hoc analyses to assess the effect of baseline severity of depression on the response to treatment as assessed with HDRS-17 sum score, the depressed mood item of the HDRS, a six-item HDRS subscale (HDRS-6), and the remaining 11 HDRS items not included in this subscale (non-HDRS-6). Patients were defined as having non-severe depression if they had a baseline HDRS-17 sum score of 18 points or less and as having severe depression if they had a score of 27 points or more.Findings Our study population consisted of 8262 patients from 28 placebo-controlled SSRI trials. Participants were treated with either citalopram (n=744), paroxetine (n=2981), sertraline (n=1202), fluoxetine (active-control group; n=754), or placebo (n=2581). 654 patients were defined as having non-severe depression and 1377 as having severe depression. Patients with non-severe and severe depression did not differ with respect to SSRI-induced decrease in depressed mood and other HDRS symptoms belonging to the HDRS-6 subscale. However, after exclusion of patients with rare extreme baseline values, a positive association was seen between severity and efficacy when using HDRS-17 sum score as the effect parameter. This result was largely due to a more pronounced response to treatment with respect to non-HDRS-6 items in patients with severe depression than in those with non-severe depression. This outcome could be explained by non-HDRS-6 items, more so than HDRS-6 items, being more severe and prevalent at baseline in severe than in non-severe cases; hence, less room was left for improvement in these areas in patients with non-severe depression.Interpretation The use of an outcome measure that includes symptoms that rate low at baseline in patients with non-severe depression might result in the interpretation that SSRIs are ineffective in these patients. With respect to alleviation of HDRS-6 items, SSRIs appear to be as effective in patients with non-severe depression as in those with severe depression. Copyright (C) 2019 Elsevier Ltd. All rights reserved.