Tocilizumab add-on trial targets IL-6 in treatment-resistant depression with low-grade inflammation

Emerging evidence links interleukin 6 (IL-6), a pro-inflammatory cytokine, to the pathogenesis of treatment-resistant major depressive disorder (TRD). Current antidepressant strategies often fall short for TRD, leaving a significant treatment gap. Tocilizumab, a humanized monoclonal antibody, specifically inhibits IL-6 signaling and is approved for autoimmune conditions like rheumatoid arthritis, making it a promising candidate to target inflammation in TRD.

This proof-of-concept, randomized, parallel-group, triple-blind, placebo-controlled clinical trial will enroll 22 adult outpatients diagnosed with TRD and low-grade inflammation (serum C reactive protein ≥3 mg/L). Participants will be randomized (1:1) to receive a single intravenous infusion of either tocilizumab (8 mg/kg; maximum 800 mg) or normal saline, as an add-on to their ongoing treatment. Psychiatric, cognitive, and biomarker assessments will be performed at baseline and on days 7, 14, and 28 post-infusion. Additionally, 10 healthy controls will undergo baseline assessments for biomarker comparison.

As this is a clinical trial protocol, no results are available yet. The primary objective is to examine whether IL-6 inhibition via tocilizumab can impact depressive symptoms, inflammation-related biomarkers, and cognition in patients with TRD. Researchers will assess changes in psychiatric scales, cognitive performance, and various inflammatory markers. The study aims to provide initial data on the efficacy and safety of targeting IL-6 in this specific patient population. A secondary objective is to compare the biological profiles of TRD patients with elevated inflammation to those of healthy controls, aiming to characterize the inflammatory landscape in TRD more precisely. This proof-of-concept trial is designed to lay the groundwork for larger studies.