Tocilizumab Augmentation in Treatment-Refractory Major Depressive Disorder

Phase 2

Terminated

Brief Summary: This proposed study sets out to examine the antidepressant effects of tocilizumab among patients with treatment-refractory major depression.

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

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

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Tocilizumab	Tocilizumab	Tocilizumab 162 mg sc q2weeks x 4 doses

Primary Outcome Measures

Name	Time	Method
Absolute Change on Hamilton Depression Rating Scale (HDRS)	Baseline to 8 Weeks	Absolute change on Hamilton Depression Rating Scale (HDRS) score

Secondary Outcome Measures

Name	Time	Method
Proportion of Subjects Achieving Remission (HDRS Score < 7)	8 Weeks	Proportion of Subjects with an HDRS score \< 7
Proportion of Subjects Achieving Response (HDRS Score Decreased >50% From Baseline)	8 Weeks	Proportion of Subjects with an HDRS score decreased \>50% from baseline