Because medical illness is associated with increased inflammation and an increased risk for treatment-resistant major depressive disorder, anti-cytokine therapy may represent a novel, and especially efficacious, treatment for depression. We hypothesized that blockade of the interleukin (IL)-6 signaling pathway with tocilizumab would decrease depression and related symptomatology in a longitudinal cohort of allogeneic hematopoietic stem cell transplantation (HCT) patients, a medically ill population with a significant inflammation and psychopathology. Patients undergoing allogeneic HCT received either a single dose of tocilizumab one day prior to HCT (n = 25), or HCT alone (n = 62). The primary outcome included depressive symptoms at 28 days post HCT; anxiety, fatigue, sleep, and pain were assessed at pretreatment baseline and days +28, +100, and +180 post HCT as secondary outcomes. Multivariate regression demonstrated that preemptive treatment with tocilizumab was associated with significantly higher depression scores at D28 vs. the comparison group (β = 5.74; 95% CI 0.75, 10.73; P = 0.03). Even after adjustment for baseline depressive symptoms, propensity score, and presence of acute graft-versus-host disease (grades II–IV) and other baseline covariates, the tocilizumab-exposed group continued to have significantly higher depression scores compared to the nonexposed group at D28 (β = 4.73; 95% CI 0.64, 8.81; P = 0.02). Despite evidence that IL-6 antagonism would be beneficial, blockade of the IL-6 receptor with tocilizumab among medically ill patients resulted in significantly more—not less—depressive symptoms.

由于内科疾病与炎症增加和难治性重度抑郁症的风险增加有关，抗细胞因子疗法可能代表一种新的、特别有效的抑郁症治疗方法。我们假设用托珠单抗阻断白细胞介素 (IL)-6 信号通路将减少同种异体造血干细胞移植 (HCT) 患者的纵向队列中的抑郁症和相关症状，这是一个具有显着炎症和精神病理学的内科疾病人群。接受异基因 HCT 的患者在 HCT 前一天接受单剂托珠单抗（n  = 25），或单独接受 HCT（n = 62)。主要结果包括 HCT 后 28 天的抑郁症状；在治疗前基线和 HCT 后 +28、+100 和 +180 天评估焦虑、疲劳、睡眠和疼痛作为次要结果。多变量回归表明，与对照组相比，托珠单抗抢先治疗与 D28 时显着更高的抑郁评分相关（β  = 5.74；95% CI 0.75, 10.73；P  = 0.03）。即使在对基线抑郁症状、倾向评分和急性移植物抗宿主病（II-IV 级）和其他基线协变量进行调整后，与未暴露组相比，托珠单抗暴露组的抑郁评分仍然显着高于未暴露组。 D28 ( β  = 4.73；95% CI 0.64, 8.81；P = 0.02)。尽管有证据表明 IL-6 拮抗作用是有益的，但在疾病患者中用托珠单抗阻断 IL-6 受体会导致明显更多（而不是更少）的抑郁症状。