Clinical trial aimed at evaluating whether a single infusion of tocilizumab, a medication that blocks the action of an inflammatory molecule called interleukin-6 (IL-6), can reduce symptoms of treatment-resistant major depression compared to placebo in non-hospitalized patients.

Inclusion Criteria:

Age ≥ 18 years Provide informed consent Understand written and spoken Portuguese Able and willing to consent to blood sampling Willing to abstain from strenuous exercise for 72 hours prior to assessment Meet DSM-5/MINI criteria for a diagnosis of depression resistant to at least two adequate courses of treatment at the time of eligibility assessment Baseline HDRS score of 19 or higher at Serum/plasma CRP level ≥3 mg/L

Exclusion Criteria:

Diagnosis of bipolar disorder or personality disorder History of substance use disorder in the past six months. Presence of active/recent infection (including TB, Hepatitis B, Hepatitis C, or HIV) or autoimmune disease Pregnancy or breastfeeding History of significant cardiovascular disease, recent cancer, or hematological disorders BMI >40 kg/m² or weight >100 kg Hypersensitivity to tocilizumab or any of its excipients. CRP ≥20 mg/L Active liver disease or transaminase elevation >1.5× the upper limit of normal

Inclusion criteria to the 10 healthy controls recruited for comparison of inflammatory biomarkers:

Age ≥ 18 No current or lifetime psychiatric diagnosis, as measured by the SRQ-20 Provide informed consent Understand written and spoken Portuguese Able and willing to consent to blood sampling