BMJ Open. 2026 Jun 12;16(6):e111421. doi: 10.1136/bmjopen-2025-111421.
ABSTRACT
INTRODUCTION: Emerging evidence supports a role for interleukin 6 (IL-6), a pro-inflammatory cytokine, in the pathogenesis of treatment-resistant major depressive disorder (TRD). However, interventional studies targeting IL-6 in this population remain scarce. Tocilizumab is a humanised monoclonal antibody that inhibits IL-6 signalling and is approved for the treatment of autoimmune conditions such as rheumatoid arthritis. The primary objective of this study is to examine whether IL-6 inhibition via tocilizumab can impact depressive symptoms, inflammation-related biomarkers and cognition in patients with TRD. A secondary objective is to compare the biological profiles of patients with TRD with elevated inflammation to those of healthy controls.
METHODS AND ANALYSIS: This is a proof-of-concept, randomised, parallel-group, triple-blind, placebo-controlled clinical trial. 22 adult outpatients diagnosed with TRD and evidence of low-grade inflammation (serum C reactive protein≥3 mg/L) will be randomised (1:1) to receive either one intravenous infusion of tocilizumab (8 mg/kg; maximum 800 mg) or normal saline, administered as an add-on to their ongoing treatment. Psychiatric, cognitive and biomarker assessments will be performed at baseline and at follow-up visits on days 7, 14 and 28 post-infusion. Additionally, 10 healthy controls with no psychiatric history will undergo the same baseline assessments for biomarker comparison.
ETHICS AND DISSEMINATION: The study has been approved by the Research Ethics Committee of the Hospital de Clínicas de Porto Alegre (Project number: 2025-0245, CAAE: 88904825.7.0000.5327). Findings will be disseminated through peer-reviewed publications, scientific meetings and, on request, lay summaries for participants.
TRIAL REGISTRATION NUMBER: NCT07052058.
PMID:42285573 | DOI:10.1136/bmjopen-2025-111421
