Tocilizumab Augmentation in Treatment-Refractory Major Depressive Disorder

As the understanding of the complex relationship between pro-inflammatory cytokines
(specifically interleukin-6 [IL-6]) and depression symptoms becomes clearer, clinical trials
to evaluate effective and novel treatments are needed. As there have been no published
tocilizumab trials among patients with major depression, this pilot study will adopt a
single-arm, open-label design. Due to the notion that inflammatory cytokines may play a role
in a sub-type of depression, this study will recruit patients with treatment refractory major
depressive disorder, for whom established depression treatments have not been effective. In
conducting this trial, the investigators seek to examine the potential role of tocilizumab as
an augmentation agent, with the hypothesis that it could reduce depression symptomatology in
patients with major depression who have not experienced symptom reduction through more
traditional antidepressant therapies.

Inclusion Criteria:

- Current diagnosis of major depressive episode

- Hamilton Depression Rating Scale (HDRS) score of >20

- In treatment for depression for a minimum of 8 weeks

Exclusion criteria:

- Active drug or alcohol disorder in the last three months

- History of psychosis, mania or hypomania

- Acute suicide or homicide risk

- History of liver disease including HCV and HBV

- HIV

- History of heart disease or a heart attack

- Active or latent tuberculosis, a history of a positive tuberculosis test, or having
received the Bacillus Calmette-Guérin (BCG) vaccine

- Epilepsy or a history of seizures

- Abnormal thyroid-stimulating hormone (TSH <0.4 or >5.0mlU/L)

- Abnormal liver function tests on screening (ALT>50 U/L or AST>50 U/L)

- Low absolute neutrophil count (ANC) on screening (<4000/mm3

- Abnormal white blood cell count (<4,500 or > 10,000mcL)

- Low platelet count on screening (<150,000/mm3

- Patients with an active or recent infection, for example cellulitis, bacteremia,
pneumonia, and pyelonephritis.

- Recent exposure to uncommon infections (e.g. histoplasmosis, blastomycosis,
coccidiomycosis) through recent travel to the Ohio and Mississippi River Valleys and
the Southwest

- Pregnant women, breastfeeding women or women of child-bearing age not using
contraception

- History of or current autoimmune disease, including multiple sclerosis and
inflammatory bowel disease

- Diagnosis of chronic fatigue syndrome

- Temperature greater than 100.3F at the screening visit or any subsequent visits

- Dyslipidemia

- Currently taking oral steroids

- Currently taking statins

- Chronic aspirin or NSAID takers

- Currently taking any immunomodulating medications

- Inability to consent due to cognitive impairment