Comparative Effectiveness of ECT vs. KETAMINE Over the Lifespan

NCT ID: NCT06034821

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE4
• Total Enrollment: 1500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-01
• Study Completion Date: 2030-12-01

Brief Summary

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).

Detailed Description

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.

Conditions

Acute Suicidal Depression (ASD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Subanesthetic dose intravenous ketamine (KET)

This trial will use standard dose of ketamine (0.5mg/kg infusion over 40 min period) in accordance with research studies that have used ketamine as an antidepressant.

Group Type: ACTIVE_COMPARATOR

Subanesthetic dose intravenous ketamine (KET)

Intervention Type: DRUG

This trial will use standard dose of ketamine (0.5mg/kg infusion over 40 min period) in accordance with research studies that have used ketamine as an antidepressant. Treatments will be given two times a week for a maximum of 8 treatments during the acute arm of the study. The investigators will be able to modify dose and number of treatments as indicated clinically per pragmatic clinical trials procedures. Patients will be clinically assessed prior to each treatment to evaluate response and appropriateness of continuation of treatment. Per FDA guidelines a maximum 60mg/dose will be given regardless of body weight.

Electroconvulsive therapy (ECT)

ECT will be given in a standard manner 3 times a week for 4 weeks.

Group Type: ACTIVE_COMPARATOR

Electroconvulsive therapy (ECT)

Intervention Type: DEVICE

ECT will be given in a standard manner 3 times a week for 4 weeks. The Initial ECT treatment will be Right Unilateral (RUL) ultra-brief pulse at 6x seizure threshold determined during titration at first visit. If there is not satisfactory improvement with RUL the investigator may change to Bilateral (BL) utilizing brief pulse using 0.5 modified half-age method to determine stimulus intensity. The seizure threshold may increase during the course of treatment and the dose of the electric stimulus may need to be increased incrementally. It is suggested to change to bilateral after three to five RUL treatments if response to treatment is not satisfactory. Treatments will be given three times a week for up to 4 weeks.

Interventions

Subanesthetic dose intravenous ketamine (KET)

This trial will use standard dose of ketamine (0.5mg/kg infusion over 40 min period) in accordance with research studies that have used ketamine as an antidepressant. Treatments will be given two times a week for a maximum of 8 treatments during the acute arm of the study. The investigators will be able to modify dose and number of treatments as indicated clinically per pragmatic clinical trials procedures. Patients will be clinically assessed prior to each treatment to evaluate response and appropriateness of continuation of treatment. Per FDA guidelines a maximum 60mg/dose will be given regardless of body weight.

Intervention Type: DRUG

Electroconvulsive therapy (ECT)

ECT will be given in a standard manner 3 times a week for 4 weeks. The Initial ECT treatment will be Right Unilateral (RUL) ultra-brief pulse at 6x seizure threshold determined during titration at first visit. If there is not satisfactory improvement with RUL the investigator may change to Bilateral (BL) utilizing brief pulse using 0.5 modified half-age method to determine stimulus intensity. The seizure threshold may increase during the course of treatment and the dose of the electric stimulus may need to be increased incrementally. It is suggested to change to bilateral after three to five RUL treatments if response to treatment is not satisfactory. Treatments will be given three times a week for up to 4 weeks.

Intervention Type: DEVICE

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: collaborator

The Cleveland Clinic

OTHER

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: collaborator

The Center for Addiction and Mental Health (University of Toronto)

UNKNOWN

Sponsor Role: collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: collaborator

UT Health

UNKNOWN

Sponsor Role: collaborator

Mclean Hospital

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

University of Utah

OTHER

Sponsor Role: collaborator

UC San Francisco

UNKNOWN

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Amit Anand

Professor of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Amit Anand, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Woman's Hospital, Harvard Medical School

Locations

UC San Francisco

San Francisco, California, United States

Johns Hopkins University

Baltimore, Maryland, United States

McLean Hospital

Belmont, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Mount Sinai School of Medicine

New York, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

UTHealth Houston

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Center for Addiction and Mental Health (University of Toronto)

Toronto, Ontario, Canada

Countries

United States; Canada

Other Identifiers

2023P001649

Identifier Type: -

Identifier Source: org_study_id