Tocilizumab as Add-On Treatment For Residual Positive, Negative, and Cognitive Symptoms of Schizophrenia

One of the main mediators of the effects of infection/inflammation in the human body is cytokines. Recent data suggest that cytokines, and in particular IL-6, may mediate the effects of lifetime or prenatal infection on schizophrenia risk. Preclinical models of schizophrenia support a convergence between a role for IL-6 in the pathophysiology of schizophrenia and the major neurochemical hypotheses of schizophrenia-the dopamine and glutamate hypotheses. Namely, IL-6 dysfunction or excess promotes schizophrenia-like behaviors and schizophrenia-like biochemical and electrophysiological profiles, while IL-6 knockout or neutralization mitigates these abnormalities. Furthermore, plasma IL-6 levels are elevated in acutely psychotic but not treated patients, and Positron Emission Tomography (PET) studies have shown active inflammation in the brains of individuals with psychosis. Finally, treatment of individuals with schizophrenia with non-specific anti-inflammatory agents, such as celecoxib and aspirin, has suggested a role for anti-inflammatory agents in schizophrenia. These data also suggest that studies of immunologic agents that more specifically target the underlying pathophysiology of schizophrenia may be more efficacious. Tocilizumab (Actemra®) is an FDA-approved humanized monoclonal antibody against the IL-6 receptor used for treatment of rheumatoid arthritis in individuals who have not responded to at least one TNF-alpha therapy and for juvenile idiopathic arthritis