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The IL-6 antagonist tocilizumab is associated with worse depression and related symptoms in the medically ill. Transl Psychiatry 2021 Jan 18;11(1):58



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Pubmed Central ID




Scopus ID

2-s2.0-85100097244 (requires institutional sign-in at Scopus site)   22 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.

Author List

Knight JM, Costanzo ES, Singh S, Yin Z, Szabo A, Pawar DS, Hillard CJ, Rizzo JD, D'Souza A, Pasquini M, Coe CL, Irwin MR, Raison CL, Drobyski WR


Anita D'Souza MD Associate Professor in the Medicine department at Medical College of Wisconsin
William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Jennifer M. Knight MD Associate Professor in the Psychiatry and Behavioral Medicine department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Professor in the Medicine department at Medical College of Wisconsin
J. Douglas Rizzo MD, MS Director, Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin
Aniko Szabo PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antibodies, Monoclonal, Humanized
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Transplant Recipients