Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Brain Behav Immun. 2020 Aug;88:631-639. doi: 10.1016/j.bbi.2020.04.063. Epub 2020 May 4.
We investigated the efficacy of tumour necrosis factor (TNF)-α antagonist infliximab on a measure of anhedonia amongst individuals with bipolar I/II depression (ClinicalTrials.gov identifier NCT02363738). Adults (ages 18-65) with bipolar I/II disorder currently experiencing a major depressive episode with a higher probability of inflammatory activity (i.e., meeting one or more of the following inflammatory/metabolic criteria: obesity and dyslipidemia/hypertension, daily cigarette smoking, diabetes mellitus, migraine, inflammatory bowel disease, and/or C-reactive protein level of ⩾5 mg/L) were enrolled in a double-blind, 12-week clinical trial of adjunctive infliximab (5 mg/kg) and saline control, which were administered at weeks 0, 2, and 6. The primary outcome measure for the present secondary analysis was change in the Snaith-Hamilton Pleasure Scale (SHAPS) total score between placebo- and infliximab-treated subjects from baseline to weeks 6 and 12. Plasma concentrations of TNF-α and soluble TNF receptors (sTNFR) 1 and 2 were assessed at weeks 0, 2, 6, and 12. Sixty eligible adults received treatment with infliximab (n=29) or placebo (n=31); 47 subjects completed the study (infliximab: n=21, placebo: n=26). Overall, infliximab-randomized subjects exhibited significantly larger increases in SHAPS total score, denoting greater reductions in anhedonic symptoms, when compared to placebo-randomized subjects (treatment × time interaction effect: χ=7.15,df=2,p=0.03). Anti-anhedonic efficacy was moderated by baseline plasma levels of TNF-α and sTNFR1, but not by changes in TNF-α or sTNFR1 concentrations. Baseline and changes in sTNFR2 concentrations did not moderate anti-anhedonic efficacy. Infliximab significantly improved a measure of anhedonia relative to placebo in adults with bipolar I/II depression at week 6; intervention efficacy was not sustained 6 weeks after the final infusion.
我们研究了肿瘤坏死因子 (TNF)-α拮抗剂英夫利昔单抗在双相 I/II 型抑郁症患者快感缺失评估中的疗效（ClinicalTrials.gov 标识符 NCT02363738）。目前患有双相 I/II 障碍且正在经历伴有更高炎症活动可能性的重度抑郁发作的成年人（年龄 18-65 岁，符合以下一项或多项炎症/代谢标准：肥胖和血脂异常/高血压、每日吸烟、糖尿病、偏头痛、炎症性肠病和/或 C-反应蛋白水平 ⩾5mg/L），被纳入一项为期 12 周的英夫利昔单抗（5mg/kg）联合生理盐水对照的双盲临床试验，分别在第 0、2 和 6 周给药。本二次分析的主要结局指标是从基线到第 6 周和第 12 周安慰剂和英夫利昔单抗治疗组患者的 Snaith-Hamilton 快感量表 (SHAPS) 总分变化。在第 0、2、6 和 12 周评估 TNF-α 和可溶性 TNF 受体 (sTNFR) 1 和 2 的血浆浓度。60 名符合条件的成年人接受英夫利昔单抗（n=29）或安慰剂（n=31）治疗；47 名受试者完成了研究（英夫利昔单抗：n=21，安慰剂：n=26）。总体而言，与安慰剂随机组相比，英夫利昔单抗随机组的 SHAPS 总分增加更大，表明快感缺失症状减轻更多（治疗×时间交互效应：χ=7.15，df=2，p=0.03）。抗快感缺失疗效受基线 TNF-α 和 sTNFR1 血浆水平的调节，但不受 TNF-α 或 sTNFR1 浓度变化的调节。sTNFR2 浓度的基线和变化不能调节抗快感缺失疗效。与安慰剂相比，英夫利昔单抗在双相 I/II 型抑郁症成年患者中在第 6 周显著改善了快感缺失的评估；在最后一次输注后 6 周，干预效果并未持续。
