Biomarkers for response in major depression: comparing paroxetine and venlafaxine from two randomised placebo-controlled clinical studies
Biomarkers for response in major depression: comparing paroxetine and venlafaxine from two randomised placebo-controlled clinical studies
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DOI：
10.1038/s41398-019-0521-7
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发表时间：
2019-08-02
影响因子：
6.8
通讯作者：
Domenici, Enrico
中科院分区：
文献类型：
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作者：
Carboni, Lucia;McCarthy, Dennis J.;Domenici, Enrico
反应生物标志物的鉴定可能会加速药物开发，并为精神病学的临床实践提供帮助。在这项工作中，我们评估了接受帕罗西汀、文拉法辛或安慰剂治疗的抑郁症患者的一组外周生物标志物（包括IL-6、IL-10、TNF-α、TNFRII、BDNF、CRP、MMP 9和PAI 1）。样本来自两项随机安慰剂对照研究，评价一种新型候选药物的疗效和耐受性，使用帕罗西汀或文拉法辛作为活性对照。在这两项研究中，分析了随机化时和安慰剂或活性对照药物治疗10周后采集的血浆中的生物标志物候选物（帕罗西汀和文拉法辛研究中分别共有106名和108名受试者）。通过多重ELISA系统获得数据。对数据进行统计分析，以评估其与基线严重程度和缓解结局的相关性。生物标志物水平的增加与TNF-α、IL-6、IL-10和CRP的抑郁严重程度的降低相关。对帕罗西汀治疗的反应与基线IL-10、IL-6和TNF-α水平相关，在男性中观察到最强的信号。在文拉法辛研究中，仅观察到随机化时CRP水平与应答之间存在相关性，表明两种活性治疗和两项研究之间存在差异。我们的研究表明，促炎细胞因子和抗炎细胞因子的组合可以预测帕罗西汀治疗患者的反应结果。IL-10、IL-6和TNF-α作为更广泛的抗抑郁药的反应生物标志物的潜力值得在其他单胺再摄取抑制剂的临床试验中进一步研究。
The identification of biomarkers of response might speed drug development and set the premises to assist clinical practice in psychiatry. In this work, we evaluated a panel of peripheral biomarkers (including IL-6, IL-10, TNF-alpha, TNFRII, BDNF, CRP, MMP9 and PAI1) in depressed patients receiving paroxetine, venlafaxine, or placebo. Samples were obtained from two randomised placebo-controlled studies evaluating the efficacy and tolerability of a novel drug candidate, using either paroxetine or venlafaxine as active comparators. In both studies, the biomarker candidates were analysed in plasma collected at randomization and after 10 weeks of treatment with either placebo or active comparator (for a total of 106 and 108 subjects in the paroxetine and venlafaxine study, respectively). Data were obtained by multiplexing sandwich-ELISA system. Data were subjected to statistical analysis to assess their correlation with baseline severity and with response outcome. Increases in biomarker levels were correlated with reduction in depression severity for TNF-alpha, IL-6 IL-10 and CRP. Response to paroxetine treatment correlated with baseline IL-10, IL-6 and TNF-alpha levels, with the strongest signal being observed in males. In the venlafaxine study, a correlation was observed only between CRP level at randomisation and response, suggesting differences between the two active treatments and the two studies. Our investigations suggest that a combination of pro- and anti-inflammatory cytokines may predict response outcome in patients treated with paroxetine. The potential for IL-10, IL-6 and TNF-alpha as response biomarkers for a wider range of antidepressants warrants further investigations in clinical trials with other monoamine reuptake inhibitors.