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Converging evidence suggests that low doses of ketamine have antidepressant effects. The feasibility and safety of administering low doses of ketamine as adjunctive medication during electroconvulsive therapy (ECT) to enhance ECT efficacy and mitigate cognitive impairment has attracted much attention. This study investigated the effects of low doses of ketamine on learning and memory in patients undergoing ECT under propofol anesthesia.This randomized, placebo-controlled, double-blind study recruited patients with moderate to severe depressive disorders who failed to respond to antidepressants and were scheduled to receive ECT. Participants were randomly assigned to a study group, which received an intravenous administration of 0.3 mg/kg ketamine and then underwent ECT under propofol anesthesia, and a control group, which received isovolumetric placebo (normal saline) and then underwent ECT under propofol anesthesia. The Hamilton Depression Rating Scale was used to assess the severity of depression after ECT. Before and after the ECT course, the Mini-mental State Examination and the Wechsler Memory Scale-Chinese-Revision were used to assess global cognitive and learning and memory functions, respectively. Psychotropic effects were assessed using the Brief Psychiatric Rating Scale. Vital signs and other adverse events were recorded for each ECT procedure.Of 132 patients recruited, 66 were assigned to each group; 63 patients in study groups and 64 patients in the control group completed the ECT course during the study. Afterward, the incidence of global cognitive impairment in the control group was higher than it was in the study group. In addition, the decline in the Wechsler Memory Scale-Chinese-Revision scale was greater in the control group than in the study group. The necessary ECT treatment times were shorter in the study group than in the control group (8 [7, 9] vs 9 [8, 10]). No significant escalations of the positive Brief Psychiatric Rating Scale scores or adverse events were observed in the study group when compared with the control group.As adjunctive medication, ketamine can attenuate learning and memory impairment, especially for short-term memory, caused by ECT performed under propofol anesthesia. Ketamine can also reduce ECT treatment times during the therapy course without inducing significant adverse effects.