Abstract: Objective To explore the effect of escitalopram combined with amisulpride in the treatment of depression patients aged over 65 years and its impact on negative emotions. Methods The clinical data of 190 patients with depression aged over 65 years who were diagnosed and treated in our hospital was analyzed retrospectively, and they were divided into two groups according to different treatment plans: the patients treated with escitalopram alone were selected as control group(n=95), and those treated with escitalopram combined with amisulpride were selected as study group(n=95). The therapeutic efficacy, changes of negative emotions before and after treatment and the incidence of adverse reactions were statistically analyzed. Results The total effective rate of depression in the study group was higher than that in the control group(97.89% vs. 90.53%, P<0.05); after treatment, the Symptom Checklist 90(SCL-90)scores in the study group and the control group were lower than that before treatment, and was lower in the study group than that of the control group(P<0.05); the incidence of side effects in the study group was lower than that in the control group(4.21% vs. 13. 68%, P<0.05). Conclusion Escitalopram combined with amisulpride in the treatment of depression patients aged over 65 years has significant efficacy, which can effectively eliminate the negative emotions of patients, and has higher safety.