Objective: To investigate the effects of sleep electroencephalogram-modulated repetitive transcranial magnetic stimulation （SEM-rTMS） and conventional rTMS （C-rTMS） on the activity of hypothalamic-pituitary-adrenal （HPA） axis in patients with depression. Methods: In a double-blind

randomized controlled trial

164 patients diagnosed with depression were randomized to treatment with SEM-rTMS （n=57）

C-rTMS （n=55） or sham rTMS （n=52） for 30 min every day for 10 d. Before and after treatment plasma concentrations of adrenocorticotropic hormone （ACTH） and cortisol （CORT） were measured

and the 24-item Hamilton Depression Rating Scale （HAMD-24） was used for assessment. Results: The HAMD-24 scores and plasma ACTH and CORT concentrations of these depressive patients before treatment were significantly different from those of the normal control group （P<0.05）. The HAMD-24 scores and plasma ACTH and CORT concentrations in the SEM-r TMS group and conventional rTMS group were decreased significantly （P<0.05）. There was a significant positive correlation between the HAMD-24 scores and plasma ACTH （n=240

r=0.105

P=0.048） and CORT concentrations （n=240

r=0.126

P=0.023） in the patients with depression before and after treatment. Conclusion: The antidepressant effect of rTMS

including SEM-rTMS

may be related to its decreasing HPA axis activity. （This trail was registered. No: ChiCTR-TRC-00000465）