The IL-6 antagonist tocilizumab is associated with worse depression and related symptoms in the medically ill

Jennifer M. Knight, Erin S. Costanzo, Suraj Singh, Ziyan Yin, Aniko Szabo, Deepa S. Pawar, Cecilia J. Hillard, J. Douglas Rizzo, Anita D’Souza, Marcelo Pasquini, Christopher L. Coe, Michael R. Irwin, Charles L. Raison, William R. Drobyski

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


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.

Original languageEnglish (US)
Article number58
JournalTranslational psychiatry
Issue number1
StatePublished - Jun 2021

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry


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