This study is a randomized open-label single-blind non-inferiority comparative effectiveness study of ECT vs. KET for the treatment of Acute Suicidal Depression (ASD).

There is a crisis in the treatment of the imminently suicidal patient. Acute Suicidal Depression (ASD) is a life-threatening illness which requires rapid relief. A number of behavioral programs with varying efficacy are available for prevention of suicide. However, once acute suicidal depression has set in, its treatment is woefully inadequate in the current health system despite availability of efficacious treatments. Patients suffering from ASD are usually admitted as inpatients for safety and started on oral antidepressants (which can take 6 - 12 weeks to have an effect) and given nursing care. They are then discharged from the hospital, usually within 4 -5 days, as soon as immediate safety concerns are ameliorated. Essentially, patients do not receive any specific rapidly acting treatment for their suicidal depression. As The immediate post-discharge period has been shown to be of the highest risk for repeat suicide attempts and completed suicides. One important reason for the inadequate treatment of ASD is the lack of large-scale comparative studies of efficacious treatments such as electroconvulsive therapy (ECT) and subanesthetic dose intravenous ketamine (KET). In the absence of data to guide rational treatment choice, neither treatment is being used adequately. Clinicians are less likely to recommend these treatments in the absence of evidence to base their decision regarding which treatment to give first and under what circumstances. Patients are reluctant to choose between these treatments due to uncertainty regarding efficacy and apprehension regarding side effects and social stigma. Finally, in the absence of effectiveness data, hospital administrators and third-party payers are reticent about committing material and financial resources for these services leading to inaccessibility. Hence, there is a critical need for a large-scale comparative effectiveness trial of ECT vs. intravenous ketamine for rapid reversal of ASD to provide rational guidance for all stakeholders.

This study will address this significant clinical dilemma by conducting a large scale (N = 1500) non-inferiority randomized comparative effectiveness trial of ECT vs. KET for rapid treatment of acute suicidal major depression (ASD) across the lifespan.

Inclusion Criteria:

1. Considered by a clinician as appropriate for referral to treatment services for rapid reversal of acute suicidal depression.

2. Adults 18 - 90 years of age.

3. Meet DSM-5 criteria for Major Depressive Episode (MDE) as determined by Mini International Neuropsychiatric Interview (MINI PLUS 5.0.0).

4. Acute suicidal ideation or behavior (thinking or behavior suggesting harming or hurting oneself with knowledge that death may result) or attempt (any intentional, non-fatal self-injury regardless of medical lethality, if intent to die was indicated). *

5. Continue to express suicidal ideation since referral as evidenced by Scale for Suicidal Ideation (SSI) ≥6)**

6. Meet the following criteria on symptom rating scales at screening:

   1. Hamilton Depression Scale (HAM-D 17) >15
   2. Montreal Cognitive Assessment (MoCA) of ≥23(to rule out baseline significant cognitive impairment)

Exclusion Criteria:

1. Meeting DSM-5 criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder.

2. Not able to give informed consent to receive ECT or KET treatment.

3. Not able to give informed consent to participate in the study.

4. Meet exclusion criteria for ECT treatment as described in guidelines.

5. Meet exclusion criteria for KET treatment such as:

   1. Pregnant or breast feeding
   2. Satisfying DSM-V criteria of current Mood Depressive Disorder Episode with Psychotic Features (i.e. delusions of hallucinations)
   3. Severe uncontrolled medical illness
   4. Ketamine allergy

6. Intellectual disability and unable to provide consent or follow study procedures.