A comparison of the safety, feasibility, and tolerability of ECT and ketamine for treatment-resistant depression

Treatment-resistant depression (TRD) is a problematic and prevalent public health and societal concern. Although electroconvulsive therapy (ECT) is the gold standard TRD intervention, the treatment evokes apprehension due to public perceptions, feasibility, and tolerability. Despite significant medical advancements, few medications have been approved by the U.S. Food and Drug Administration for TRD. In 2019, intranasal esketamine, the S-isomer of racemic ketamine, was approved for TRD, garnering significant excitement about the potential for the drug to act as an alternative treatment to ECT. The goal of this narrative review is to compare the safety, efficacy, and tolerability of ketamine and ECT; clarify whether ketamine is a reasonable alternative to ECT; and to facilitate improved treatment assignment for TRD. Empirical quantitative and qualitative studies and national and international guidelines for these treatments are reviewed. The field awaits the results of two ongoing large comparative effectiveness trials of ECT and IV ketamine for TRD, which should help guide clinicians and patients as to the relative risk and benefit of these interventions. Over the next five years we anticipate further innovations in neuromodulation and in drug development which broadly aim to develop more tolerable versions of ECT and ketamine, respectively.