Objective: To evaluate the clinical efficacy and safety of combining acanthopanax senticosus and lithium carbonate for the treatment of adolescent depression. Methods: 65 outpatients or inpatients were enrolled in a double-blind randomized clinical study which was conducted comparing combining acanthopanax senticosus and lithium versus combining fluoxetine and lithium for 6 weeks. Efficacy and side effects were assessed with Hamilton depression rating scale (HAMD) and treatment emergent symptom scale (TESS) respectively before and after the treatment. Results: 63 patients finished the trial, the rate of dropout was 3.08%. Altogether, 65 patients were enrolled in the study, only 32 were enrolled in ITT analysis and PP analysis in acanthopanax senticosus group, while 33 were enrolled in ITT analysis and 31 were eligible for PP analysis in fluoxetine group. The HAMD scores were significantly decreased after treatment at each weekly point in both groups. The difference of decreased HAMD scores between the two groups was not significant in weeks after treatment. At the end of treatment, the rate of utility and significant utility had no significant difference between the two groups. There were two patients who developed mania, while the rate of mania-conversion had no significant difference. Conclusion: Combined acanthopanax senticosus and lithium carbonate is an effect therapeutic scheme to adolescent bipolar depression.