Neutralizing Interleukin (IL)-6 Signaling to Reverse Immune Related Anhedonia in Patients With Major Depressive Disorder
The proposed study aims to establish the feasibility and safety of subcutaneous tocilizumab, a monoclonal antibody (mAb) against interleukin (IL)-6 receptor, in adults with Major Depressive Disorder (MDD) and evidence of peripheral immune activation. IL-6 is a pro-inflammatory cytokine implicated in the pathophysiology of depression. The investigators hypothesize that neutralizing peripheral immune signaling via IL-6 receptor blockade with tocilizumab will improve neural and behavioral measures of reward processing. This is an open-label, proof-of concept, trial in which up to N=20 adults with MDD meeting a specific immune enrichment criterion will receive open-label tocilizumab over 8 weeks. A healthy control (HC) group (N=20) will undergo baseline neuroimaging and blood-based biomarker assessment without receiving the study drug to aid interpretation of findings. Blood-based immune markers and brain MRI scans (including task-based reward activation and resting-state functional connectivity) will be assessed at baseline for all participants and again post treatment for the MDD group.
⁃ For MDD participants:
• Written informed consent;
• Ability to comply with the requirements of the study as determined by the PI;
• Ages 18-70 years;
• Any gender;
• DSM-5 diagnosis of MDD in a current Major Depressive Episode;
• Immune enrichment criterion: elevated monocyte count ≥ 500 cells/μL at screening;
• If patient is on antidepressant medication, they must be on a stable dose for ≥4 weeks prior to treatment;
• SHAPS score ≥20
• If female of childbearing potential, must agree to use of a medically accepted form of contraception, or else agree to abstinence until 6 months after the last dose of study drug;
• Male patients, if heterosexually active with a partner who is female of childbearing potential, pregnant, or breastfeeding, must agree to barrier contraception for the treatment period and for at least 6 months after the last dose of the study drug. Female partners of male participants must use at least one form of highly effective contraception starting at least one cycle prior to male patient study drug initiation until 6 months after the last dose of study drug.
• Meet all MRI safety criteria.
⁃ For Healthy Volunteers:
• Written informed consent;
• Ability to comply with the requirements of the study as determined by the PI;
• Ages 18-70
• Any gender;
• No current or past DSM-5 psychiatric disorder;
• Meet all MRI safety criteria.