This study aimed to investigate the efficacy and safety of intermittent low-dose ketamine on improving the efficacy of ECT. Patients diagnosed with Major Depressive Disorder (MDD) (n = 134) were randomized into 3 groups: routine ECT group (group E, n = 45); repeated ketamine-assisted ECT group (group RK, n = 43), and intermittent ketamine-assisted ECT group (group IK, n = 46). Patients in group RK were given ketamine at the dose of 0.3 mg/kg for each ECT treatment, patients in group IK were given ketamine once a week during ECT course. The depressive symptoms were assessed using the Hamilton Depression Rating Scale (HAM-D) at baseline, the end of ECT course, after 1 and 3 months, followed by an analysis of the psychiatric complications. Results indicated that ketamine-assisted ECT achieved a higher remission rate (P < 0.05), and no difference was observed between repeated and intermittent ketamine administrations. The total incidence rate of psychiatric complications in group RK (20.93%) was higher than that in group E (0%) and group IK (4.35%). In conclusion, intermittent administration of low dose ketamine in ECT significantly improved the effects of ECT and decreased psychiatric complications compared with repeated ketamine addition.