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Objective: To evaluate the therapeutic effect and safety of acupuncture plus TCM medication for treatment of mental depression. Method: 61 cases of mental depression were randomly divided into a treatment group of 30 cases and a control group of 31 cases. The former group was treated by acupuncture plus TCM medication, and the latter with TCM medication alone. The Hamilton Mental Depression (HAMD) scoring system was adopted to evaluate the therapeutic effects, and the Treatment Emergent Symptom Scale (TESS) was used to evaluate the adverse reactions. Results: The treatment group was superior to the control group in the total effective effect (P＜0.05), with a significant difference in the HAMD score before and after treatment between the 2 groups (P＜0.01). There were marked differences in the reducing rate of HAMD score at the end of the second and sixth week of the treatment between the 2 groups (P＜0.05) and the difference was very obvious at the end of the fourth week (P＜0.01). No remarkable difference was found in adverse reactions between the 2 groups (P＞0.05). Conclusion: Acupuncture plus TCM medication may show satisfactory results for mental depression, indicating that a synergic action may exist between acupuncture and TCM medication.