Objectives: To explore the effects of acupuncture (manual acupuncture or electroacupuncture) combined with SSRIs for moderate to severe depression improving major clinical symptoms and life quality of the patients on secondary outcomes. Design: Pragmatic, parallel, randomized controlled trial. Setting: 6 hospitals in China. Interventions: 6 weeks of manual acupuncture (MA) + selective serotonin reuptake inhibitors (SSRIs), electro-acupuncture (EA) + SSRIs, and SSRIs alone. Main outcome measures: The primary outcome was response rate of 17-item Hamilton Depression Scale (HAMD- 17) total score at 6th week. The secondary outcomes reported in this analysis were HAMD-17 factor scores at 1st, 2nd, 4th, 6th, 10th week and WHO Quality of Life-BREF (WHOQOL-BREF) scores at 6th week. Results: 477 patients were randomly assigned into MA + SSRIs (n = 161), EA + SSRIs (n = 160), or SSRIs alone (n = 156) groups. For HAMD-17 (at 6th week), the MA + SSRIs group was significantly better than the SSRIs alone group in retardation factor (p = 0.008), while the EA + SSRIs group was significantly better than the SSRIs alone group in anxiety/somatization factor (p < 0.001) and sleep disturbance factor (p = 0.002). For WHOQOL-BREF (at 6th week), the EA + SSRIs group, compared with the SSRIs alone group, produced a more significant improvement in the overall quality of life, general health, physical health, and psychological health (p < 0.05). While, the MA + SSRIs group, compared to the SSRIs alone group, showed significant advantage only in psychological health (p = 0.023). Conclusions: Either MA or EA combined SSRIs treatment could improve symptoms and quality of life for patients with moderate to severe depression. The main limitation of this trial was not using a sham control therefore the placebo effect could not be excluded.

Selective serotonin reuptake inhibitors (SSRIs) are first-line antidepressants, however, only around 60% of pa tients could benefit from them. Acupuncture is supported by insufficient evidence to help with symptom re lieving and SSRIs tolerance. This pragmatic randomized controlled trial compared SSRIs alone versus SSRI together with manual acupuncture (MA) or electroacupuncture (EA) in moderate to severe depressed patients Patients were randomly allocated to receive MA + SSRIs (161), EA + SSRIs (160), or SSRIs alone (156) for si: weeks, and then followed up for another four weeks. The primary outcome was response rate of the 17-iten Hamilton Depression Scale (HAMD-17) at 6th week. The secondary outcomes were HAMD-17 (remission rate early onset rate, total score), Self-Rating Depression Scale (SDS: total score), Clinical Global Impression (CGI) Rating Scale for Side Effects (SEAS: total and domain scores), number of patients with adjusted dosage of SSRI and adverse events (AEs). Both MA + SSRIs and EA + SSRIs were significantly better than SSRIs at 6th week of HAMD-17 response rate (RR = 1.21, 95% CI 1.04, 1.42, P = 0.013; RR = 1.27, 95% CI 1.09, 1.48, P = 0.0014) HAMD-17 early onset rate (P < 0.0001), HAMD-17 and SDS total scores (P < 0.05), CGI (P < 0.01), SEAS tota score (P < 0.01), number of patients with increased dosage of SSRIs (P < 0.01). For HAMD-17 remission rate EA + SSRIs was significantly higher than SSRIs (P = 0.0083), while MA + SSRIs showed no significant dif ference at 6th week (P = 0.092). No unintended acupuncture-related severe AE was observed. This stud identified that both MA and EA showed beneficial effects in addition to SSRIs alone in patients with moderate tt severe depression, and were well tolerated.