Abstract: Objective:To explore the efficacy and safety of small-dose aripiprazole combined with mirtazapine in the treatment of treatment-resistant depression.Methods:Forty-six patients with treatment-resistant depression were randomly divided into combined group(treated with aripiprazole plus mirtazapine)and single group(treated with mirtazapine alone),23 cases in each group,period of treatment was 6 weeks.Hamilton depression scale and treatment emergent symptom scale were used to evaluate the clinical efficacy and adverse effects before treatment and at the end of 1st,2nd,4th and 6th week treatment.Results:The therapeutic efficacy of aripiprazole combined with mirtazapine was significantly better than that of mirtazapine group after 4 weeks treatment(P0.05).There was no significant difference in adverse events between the two groups.Conclusions:Small-dose aripiprazole combined with mirtazapine can augment the efficacy in the treatment of treatment-resistant depression and has a better safety.