Objective:To explore the efficacy and safety of amisulpiride at low dosage combined with clozapine in the treatment of refractory schizophrenia. Methods:Totally 160 patients with refractory schizophrenia were chosen from the psychiatric department of 4 hospitals during January to September in 2014 and randomly divided into the observation group and the control group with 80 cases in each. The patients were treated with clozapine plus amisupiride or clozapine plus placebo for 12 weeks. The positive and negative syn-drome scale ( PANSS) and treatment emergent side effect scale ( TESS) was used to respectively evaluate the efficacy and the adverse effects. Results:At the weekend of the 4th, 8th and 12th week after the treatment, the clinical efficacy in the observation group was sig-nificantly better than that in the control group (all P<0. 05). The total and every factors scores of PANSS after the treatment were sig-nificantly lower than those before the treatment in both groups ( P<0. 01), and the decrease in the observation group was more signifi-cant than that in the control group (P<0. 05 or P<0. 01). There was no significant difference in the incidence of adverse effects be-tween the two groups (P>0. 05). Conclusion:Amisulpiride at low dosage combined with clozapine can significantly improve the effi-cacy in the treatment of refractory schizophrenia without added adverse effects.