TY - JOUR
T1 - The IL-6 antagonist tocilizumab is associated with worse depression and related symptoms in the medically ill
AU - Knight, Jennifer M.
AU - Costanzo, Erin S.
AU - Singh, Suraj
AU - Yin, Ziyan
AU - Szabo, Aniko
AU - Pawar, Deepa S.
AU - Hillard, Cecilia J.
AU - Rizzo, J. Douglas
AU - D’Souza, Anita
AU - Pasquini, Marcelo
AU - Coe, Christopher L.
AU - Irwin, Michael R.
AU - Raison, Charles L.
AU - Drobyski, William R.
N1 - Funding Information:
This project was supported in part by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Numbers UL1TR001436, KL2TR001438, K07CA136966, R21CA133343, KL2RR0205012, UL1RR025011, and P30CA014520; the Research and Education Component of the Advancing a Healthier Wisconsin Research Endowment at the Medical College of Wisconsin; the Laura Gralton Philanthropic Fund; and the Forward Lymphoma Foundation. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. These data have been presented in part at the Blood and Marrow Transplantation, Psychoneuroimmunology Research Society, and the Academy of Consultation Liaison Psychiatry Annual Meetings, 2018.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
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U2 - 10.1038/s41398-020-01164-y
DO - 10.1038/s41398-020-01164-y
M3 - Article
C2 - 33462203
AN - SCOPUS:85100097244
VL - 11
JO - Translational Psychiatry
JF - Translational Psychiatry
SN - 2158-3188
IS - 1
M1 - 58
ER -