Consistent superiority of selective serotonin reuptake inhibitors over placebo in reducing depressed mood in patients with major depression
Consistent superiority of selective serotonin reuptake inhibitors over placebo in reducing depressed mood in patients with major depression
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DOI：
10.1038/mp.2015.53
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发表时间：
2016-04-01
影响因子：
11
通讯作者：
Eriksson, E.
中科院分区：
文献类型：
--
作者：
Hieronymus, F.;Emilsson, J. F.;Eriksson, E.
最近对选择性5-羟色胺再摄取抑制剂（SSRIs）抗抑郁作用的质疑部分是基于这样的观察，即大约一半的公司赞助的试验未能揭示活性药物和安慰剂之间的显著差异。大多数研究采用汉密尔顿抑郁量表评定症状严重程度，其17个条目的总分（HDRS-17-sum）作为效应参数。在这项研究中，我们检查了许多SSRI试验的负面结果是否部分是由于使用这种经常受到质疑的反应措施造成的。我们对18项行业赞助的安慰剂对照试验进行了患者水平的事后分析，这些试验涉及帕罗西汀、西酞普兰、舍曲林或氟西汀，共纳入6669例成人重度抑郁症患者，目的是评估如果单项抑郁情绪（0-4级）被用作疗效指标，结果会如何。总共重新评估了32个药物-安慰剂比较。虽然32个比较中有18个（56%）在第6周时未能就HDRS-17-总和的降低将活性药物与安慰剂分开，但当抑郁情绪用作效应参数时，32个比较中只有3个（9%）是阴性的（P < 0.001）。在32项比较中，有29项从测试的SSRI中检测到抗抑郁信号，这一观察结果表明，这些药物的效果在试验中比以前假设的更一致。此外，频繁使用HDRS-17总和作为效应参数可能扭曲了目前对SSRIs有用性的看法，并阻碍了新型抗抑郁药的开发。
The recent questioning of the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs) is partly based on the observation that approximately half of company-sponsored trials have failed to reveal a significant difference between active drug and placebo. Most of these have applied the Hamilton depression rating scale to assess symptom severity, the sum score for its 17 items (HDRS-17-sum) serving as effect parameter. In this study, we examined whether the negative outcomes of many SSRI trials may be partly caused by the use of this frequently questioned measure of response. We undertook patient-level post-hoc analyses of 18 industry-sponsored placebo-controlled trials regarding paroxetine, citalopram, sertraline or fluoxetine, and including in total 6669 adults with major depression, the aim being to assess what the outcome would have been if the single item depressed mood (rated 0-4) had been used as a measure of efficacy. In total, 32 drug-placebo comparisons were reassessed. While 18 out of 32 comparisons (56%) failed to separate active drug from placebo at week 6 with respect to reduction in HDRS-17-sum, only 3 out of 32 comparisons (9%) were negative when depressed mood was used as an effect parameter (P < 0.001). The observation that 29 out of 32 comparisons detected an antidepressant signal from the tested SSRI suggests the effect of these drugs to be more consistent across trials than previously assumed. Further, the frequent use of the HDRS-17-sum as an effect parameter may have distorted the current view on the usefulness of SSRIs and hampered the development of novel antidepressants.