Improvement of adjunctive berberine treatment on negative symptoms in patients with schizophrenia.

The upregulation of immune and inflammatory response may play a role in the negative symptoms of schizophrenia. Berberine is an effective drug with anti-inflammatory property, and may be beneficial for the treatment of negative symptoms. The aim of this study is to test this hypothesis through a randomized, double-blind, placebo-controlled, clinical trial. Eligible patients with schizophrenia were randomized to receive placebo or berberine (900 mg/day) for 8 weeks as adjunctive treatment to single atypical antipsychotic drug. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate clinical symptoms at three time points (baseline, 4th and 8th week). Blood samples were collected at the above three time points to determine the concentrations of inflammatory markers including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). 59 patients with intention-to-treat were analyzed, 32 in the berberine group and 27 in the placebo group. From the baseline to the 8th week, berberine treatment significantly improved the negative symptom subscale of PANSS (F = 18.981; p < 0.001). From the baseline to the 8th week, the plasma CRP concentration decreased in the berberine group, while increased in the placebo group (F = 5.373; p = 0.024). Furthermore, in the berberine group, the change of CRP concentration was significantly positively correlated with the change of PANSS negative symptom subscale within 8 weeks (r = 0.56; p = 0.002). There was no significant difference in adverse events between the two groups (p's > 0.05). Our study suggests that berberine treatment is well tolerated in patients with schizophrenia. Berberine may improve negative symptoms through anti-inflammatory effect.Trial registration: Clinicaltrials.gov identifier: NCT03548155.