A standard definition of treatment-resistant Depression (TRD) is the failure to respond or achieve remission after two or more trials of medication treatment of MDD of adequate doses and duration. Treatment-resistant Depression may respond to interventions other than antidepressants, including brain stimulation such as electroconvulsive therapy (ECT) or Ketamine, approved in an intranasal form. Patients diagnosed with severe Depression sometimes report suicidal ideations with or without plans—this systematic review aimed at comparing the efficacy of Ketamine and ECT in treating TRD in adult patients. The purpose of this scholarly project is to determine what is currently understood about how ECT compares to Ketamine in the treatment of TRD. As the two most common modalities in psychiatric mental health for treating TRD, it will be beneficial to know the better option for evidence-based practice.