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Abstract: Acupuncture possesses the antidepressant potential. In this 6-week randomized controlled trial with 4-week follow-up, 160 patients with major depressive disorder (MDD) were randomly assigned to paroxetine (PRX) alone (n = 48) or combined with 18 sessions of manual acupuncture (MA, n = 54) or electrical acupuncture (EA, n = 58). Treatment outcomes were measured mainly using the 17-item Hamilton Depression Rating Scale (HAMD-17), Self-rating Depression Scale (SDS), clinical response and remission rates. Average PRX dose taken and proportion of patients who required an increased PRX dose due to symptom aggravation were also obtained. Both additional MA and EA produced a significantly greater reduction from baseline in score on HAMD-17 and SDS at most measure points from week 1 through week 6 compared to PRX alone. The clinical response was markedly greater in MA (69.8%) and EA (69.6%) groups than the group treated with PRX alone (41.7%, P = 0.004). The proportion of patients who required an increase dose of PRX due to symptom aggravation was significantly lower with MA (5.7%) and EA (8.9%) than PRX alone (22.9%, P = 0.019). At 4 weeks follow-up after completion of acupuncture treatment, patients with EA, but not MA, continued to show significantly greater clinical improvement. Incidence of adverse events was not different in the three groups. Our study indicates that acupuncture can accelerate the clinical response to selective serotonin reuptake inhibitors (SSRIs) and prevent the aggravation of depression. Electrical acupuncture may have a long-lasting enhancement of the antidepressant effects (Trial Registration: ChiCTR-TRC-08000278). [Copyright &y& Elsevier]