Objective: To analyze the effect of amisulpride combined with duloxetine in clinical treatment of depression in forced detoxification patients. Methods: 60 cases of patients with compulsory detoxification depression were admitted to our hospital from January 2019 to June 2023 were divided into groups according to the computer random number table method. 30 cases of patients in the control group were treated with duloxetine, and 30 cases of patients in the observation group were treated with amsulpride combined with duloxetine. The clinical efficacy, disease symptoms, neurotransmitter levels and safety of the two groups were compared. Results: After treatment, in the observation group, the total effective rate was 96.67%, which was higher than 76.67% that in the control group (P < 0.05). In the observation group, the PWS score and HAMD-17 score were (14.02±2.03) points and (10.02±2.63) points, which were lower than (12.12±2.91) points and (16.17±2.11) points those of control group, respectively (P < 0.05). In the observation group, the levels of 5-HT, GABA and DA were higher than the control group (P < 0.05). The incidence of adverse reactions was 20.00% in the observation group and 16.67% in the control group, and there was no statistical significance between groups (P > 0.05). Conclusion: The combination of amsulpride and duloxetine in the treatment of forced detoxification patients with depression can increase the therapeutic effect of patients, promote the further remission of their disease symptoms, improve the neurotransmitter indicators, and have high safety.