Ongoing Clinical Trials with Monoclonal Antibodies in Schizophrenia

Abstract

BACKGROUND: In recent years, there have been advances in the comprehension of the aetiology of schizophrenia, relating immune dysregulation as causal factor. Lifelong cytokine concentrations alterations are detected, which depend on the timing or severity of the disease. Several anti-inflammatory drugs have been tested as an adjunctive treatment to antipsychotics, showing beneficial effects. Monoclonal antibody therapies have also been suggested and tested, and this article aims to assess their efficacy. METHODS: A systematic review following PRISMA guidelines was conducted, searching in different databases with the intention of gathering all existing trials, concluded and ongoing, and case reports using monoclonal antibodies. RESULTS: Overall, ten studies, three concluded and seven ongoing, and one case report were found. Only two drugs have been tested so far: Tocilizumab (targeting IL-6) in two trials, with cognition improvement seen in one study, and Canakinumab (targeting IL-1β) with positive symptomatology amelioration. Seven additional trials are currently testing Canakinumab, Siltuximab (targeting IL-6), Toclizumab, Natalizumab (targeting α4-integrin), Rituximab (targeting CD-20) and Infliximab (targeting TNF-α). CONCLUSION: The results are promising, although more studies are needed. Stable schizophrenic patients with evidence of baseline inflammation were selected, but the drugs used target cytokines elevated solely in acute episodes. Thus, in the future judicious selection criteria, choice of drug and timing of action are required.