Minocycline adjunctive treatment to risperidone for negative symptoms in schizophrenia: Association with pro-inflammatory cytokine levels

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Background:We attempted to replicate the efficacy of minocycline, a second-generation tetracycline, as adjunctive therapy for the negative symptoms of schizophrenia, and to investigate its association with pro-inflammatory cytokine levels.Methods:Seventy-five schizophrenia patients with negative symptoms entered a 3-month, double blind, randomized, placebo-controlled clinical trial. Subjects were assigned low dose (100mg per day) or high dose minocycline (200mg per day) or placebo combined with risperidone. The outcomes used the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS)-negative subscale. We assessed three pro-inflammatory cytokines in serum: interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor–α (TNF-α).Results:Subjects receiving high dose minocycline not only had greater improvements on the SANS total scores and PANSS negative subscale scores (P<0.01), but also had greater reductions in IL-1β and IL-6 serum levels (P<0.01) when compared with those receiving low dose minocycline or placebo. The improvement in negative symptoms with minocycline was significantly correlated with the reduction of IL-1β and IL-6 serum levels (P<0.05).Conclusions:Schizophrenia patients showed a significant improvement in negative symptoms with the addition of minocycline to risperidone. Reducing pro-inflammatory cytokines may play an important role in the potential mechanism for efficacy.HIGHLIGHTSMinocycline could improve the negative symptoms of patients with schizophrenia.Minocycline could reduce serum levels of cytokines in schizophrenia patients.The improvement in negative symptoms correlates with the reduction in cytokine levels.Inhibiting neuroinflammatory would be a new candidate for treatment of schizophrenia.

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