英夫利昔单抗治疗难治性抑郁症

点击:次 更新日期:2013年02月06日
内容: 增加的炎症标志物的浓度预测抗抑郁药无反应,可以破坏和炎性细胞因子和规避传统的抗抑郁药的作用机制。

目的: 为确定是否抑制炎性细胞因子肿瘤坏死因子(TNF)减少抑郁症状的难治性抑郁症患者,以及是否增加基线血浆炎性标志物,包括高敏C-反应蛋白(HS-CRP),肿瘤坏死因子,它的可溶性受体,预测治疗反应。

设计的双盲,安慰剂对照,随机临床试验。在佐治亚州亚特兰大埃默里大学设置门诊输液中心。

参加者共60病情稳定的门诊抑郁症是一致的抗抑郁药方案组(n = 37)或无药物组(n = 23),4星期或以上,由美国麻省总医院精神科治疗中的分期方法决定。

干预注射TNF拮抗剂英夫利昔单抗(5毫克/千克)组(n = 30)或安慰剂组(n = 30)在基线和2和6周的12周的试验。

主要观察指标: 17项汉密尔顿抑郁量表(HAM-D)总分。

结果:治疗组之间跨越时间的HAM-D分数的变化没有整体差异被发现。然而,有一个显着之间的相互作用治疗,时间,记录基线hs-CRP浓度(P = .01),有利于英利昔单抗治疗的患者在基线hs-CRP的变化,HAM-D分数(基线到第12周)浓度大于500 mg / L和有利于安慰剂治疗的患者在基线hs-CRP浓度为5 mg / L或更低。对患者的基线hs-CRP浓度大于5 mg / L的探索性分析,重点揭示了治疗的反应(HAM-D得分≥50%,减少治疗过程中的任何一点),62%(13例),英夫利昔单抗治疗的患者和33%(9例),在安慰剂治疗的患者(P = 0.19)。基线肿瘤坏死因子及其可溶性受体的浓度均显着较高的英夫利昔单抗治疗的反应者和无反应者(P <0.05),英夫利昔单抗治疗的反应显着更大的hs-CRP的下降,从基线到12周,与安慰剂治疗的反应比较( P <0.01)。辍学率和不良事件是有限的,各组之间没有显着差异。

结论:这证明了概念研究表明,肿瘤坏死因子拮抗作用没有广义难治性抑郁症的疗效,但在与高基线炎症标志物的患者可以改善抑郁症状
 
Context Increased concentrations of inflammatory biomarkers predict antidepressant nonresponse, and inflammatory cytokines can sabotage and circumvent the mechanisms of action of conventional antidepressants.
Objectives To determine whether inhibition of the inflammatory cytokine tumor necrosis factor (TNF) reduces depressive symptoms in patients with treatment‑resistant depression and whether an increase in baseline plasma inflammatory biomarkers, including high‑sensitivity C‑reactive protein (hs‑CRP), TNF, and its soluble receptors, predicts treatment response.
Design Double‑blind, placebo‑controlled, randomized clinical trial.
Setting Outpatient infusion center at Emory University in Atlanta, Georgia.
Participants A total of 60 medically stable outpatients with major depression who were either on a consistent antidepressant regimen (n = 37) or medication‑free (n = 23) for 4 weeks or more and who were moderately resistant to treatment as determined by the Massachusetts General Hospital Staging method.
Interventions Three infusions of the TNF antagonist infliximab (5 mg/kg) (n = 30) or placebo (n = 30) at baseline and weeks 2 and 6 of a 12‑week trial.
Main Outcome Measures The 17‑item Hamilton Scale for Depression (HAM‑D) scores.
Results No overall difference in change of HAM‑D scores between treatment groups across time was found. However, there was a significant interaction between treatment, time, and log baseline hs‑CRP concentration (P = .01), with change in HAM‑D scores (baseline to week 12) favoring infliximab‑treated patients at a baseline hs‑CRP concentration greater than 5 mg/L and favoring placebo‑treated patients at a baseline hs‑CRP concentration of 5 mg/L or less. Exploratory analyses focusing on patients with a baseline hs‑CRP concentration greater than 5 mg/L revealed a treatment response (≥50% reduction in HAM‑D score at any point during treatment) of 62% (8 of 13 patients) in infliximab‑treated patients vs 33% (3 of 9 patients) in placebo‑treated patients (P = .19). Baseline concentrations of TNF and its soluble receptors were significantly higher in infliximab‑treated responders vs nonresponders (P < .05), and infliximab‑treated responders exhibited significantly greater decreases in hs‑CRP from baseline to week 12 compared with placebo‑treated responders (P < .01). Dropouts and adverse events were limited and did not differ between groups.
Conclusions This proof‑of‑concept study suggests that TNF antagonism does not have generalized efficacy in treatment‑resistant depression but may improve depressive symptoms in patients with high baseline inflammatory biomarkers

常见疾病