Objective To investigate the overall effectiveness and tolerance of low-dose amisulpride combined with escitalopram oxalate in the treatment of depression patients with fatigue symptoms. Methods From September 2017 to June 2018， a total of 100 patients with depression in our hospital were selected as subjects. According to random number table method， the patients were divided into study group and control group， with 50 cases in each group.Tthe control group was given escitalopram oxalate orally， while the study group was given escitalopram oxalate combined with small doses of amisulfapride. Hamilton Depression Scale（ HAMD-17） and Fatigue Severity Scale（ FSS） were used before and after treatment to evaluate the overall treatment effectiveness in the two groups. Results （1）There was no significant difference in general data between the two groups（ P ＞ 0.05）.（ 2）There was no significant difference in HAMD score between the two groups before treatment. After 1， 2 and 4 weeks of treatment， the HAMD score of the two groups decreased significantly， with the study group's score change significantly more dramatically than the control group（ P＜0.01）. （3）There was no significant difference in the FSS scores between the two groups before treatment. The FSS scores decreased in both groups after 2 weeks of treatment， while the change in the score was only significant for the study group（ P＜0.05） not for the control group（ P＞0.05）. At the end of 4 weeks of treatment， the FSS scores in both groups continued to decrease， with the study group's score change more dramatically than the control group. There were significant differences between the two groups in intra-group comparison and inter group comparison（ P＜0.05）.（ 4）The incidence of adverse reactions was 16%（ 8/50） in the study group and 14% （7/50） in the control group. There was no significant difference between the two groups. Conclusions Lowdose amisulfapride combined with escitalopram oxalate is more effective for depression and fatigue symptoms in patients with depression， with similar adverse reactions.