Acute Suicidal Depression (ASD)Phase 4REaKT-SDNCT06034821
Comparative Effectiveness of ECT vs. KETAMINE Over the Lifespan
A Phase 4 study testing Subanesthetic dose intravenous ketamine (KET) and Electroconvulsive therapy (ECT) in people with Acute Suicidal Depression (ASD), run by Brigham and Women's Hospital at 10 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Acute Suicidal Depression (ASD)
- What is being tested?
- Subanesthetic dose intravenous ketamine (KET) and Electroconvulsive therapy (ECT)
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,500 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 1 Oct 2023to 1 Dec 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Considered by a clinician as appropriate for referral to treatment services for rapid reversal of acute suicidal depression.
- Adults 18 - 90 years of age.
- Meet DSM-5 criteria for Major Depressive Episode (MDE) as determined by Mini International Neuropsychiatric Interview (MINI PLUS 5.0.0).
- 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). *
- Continue to express suicidal ideation since referral as evidenced by Scale for Suicidal Ideation (SSI) ≥6)**
- Meet the following criteria on symptom rating scales at screening:
- Hamilton Depression Scale (HAM-D 17) >15
- Montreal Cognitive Assessment (MoCA) of ≥23(to rule out baseline significant cognitive impairment)
Who cannot join
- Meeting DSM-5 criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder.
- Not able to give informed consent to receive ECT or KET treatment.
- Not able to give informed consent to participate in the study.
- Meet exclusion criteria for ECT treatment as described in guidelines.
- Meet exclusion criteria for KET treatment such as:
- Pregnant or breast feeding
Show all 10Show fewer
- Satisfying DSM-V criteria of current Mood Depressive Disorder Episode with Psychotic Features (i.e. delusions of hallucinations)
- Severe uncontrolled medical illness
- Ketamine allergy
- Intellectual disability and unable to provide consent or follow study procedures.
Trial locations and contacts
10 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
10 sites in 2 countries
United States9 sites
Johns Hopkins University
Baltimore, Maryland, 21287
McLean Hospital
Belmont, Massachusetts, 02478
Massachusetts General Hospital
Boston, Massachusetts, 02114
Cleveland Clinic
Cleveland, Ohio, 44195
UTHealth Houston
Houston, Texas, 77030
Mount Sinai School of Medicine
New York, New York, 10029
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
University of Utah
Salt Lake City, Utah, 84132
UC San Francisco
San Francisco, California, 94143
Canada1 site
Center for Addiction and Mental Health (University of Toronto)
Toronto, Ontario, M6J 1H4
About this study
Official title: Rapid Reversal of Suicidal Depression: Comparative Effectiveness of ECT vs. KETAMINE Over the Lifespan (REaKT-SD)
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).
Read the 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)
- Being tested
- Subanesthetic dose intravenous ketamine (KET), Electroconvulsive therapy (ECT)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Subanesthetic dose intravenous ketamine (KET)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)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.
| Study group | Role | What they receive |
|---|---|---|
| Subanesthetic dose intravenous ketamine (KET) | Active comparator | 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. Receives: Drug: Subanesthetic dose intravenous ketamine (KET) |
| Electroconvulsive therapy (ECT) | Active comparator | ECT will be given in a standard manner 3 times a week for 4 weeks. Receives: Device: Electroconvulsive therapy (ECT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Scale for Suicidal Ideation (SSI)
The Scale for Suicidal Ideation (SSI is excellent in terms of test construction and psychometrics (validity and reliability). It has been shown that a SSI score >6 has been found to be predictive of suicide within 6 months of discharge from hospital. At the end of treatment, patients will be assessed for remission of suicidality which is defined as a SSI score <4 i.e. no clinically significant suicidal ideation70. A stringent criterion for remission was chosen as ASD is a life-threatening illness and full remission should be the treatment goal.
Measured: Six weeks
Secondary outcomes (22)
Quick Inventory of Depressive Symptoms Self Report QIDS-SR
Self-reported questionnaire
Measured: Six weeks
Columbia Suicide Severity Rating Scale (CSSR-S)
Clinician rated scales for suicidality and depression
Measured: 6 weeks
Montgomery Asberg Depression Rating Scale (MADRS)
Clinician rated scales
Measured: 6 weeks
Working Alliance Inventory (WAI-SR)
Questionnaire
Measured: 6 weeks
National Alcohol and Drug Institute (NIDA) Questionnaire
Substance use questionnaire
Measured: 6 weeks
Self and clinician rated scales
Measuring length of hospital stay, memory, side effects and quality of life
Measured: 6 weeks
Brief Psychiatric Rating Scale 4 items (BPRS)
4 items for psychosis, higher scores indicate worse outcomes. Range 4-28.
Measured: 6 weeks
Clinician Administered Dissociative Symptoms Scale (CADSS)
Range 0-80, higher scores indicate worse outcomes.
Measured: 6 weeks
CGI-S
Range 1-7, higher scores indicate worse outcomes.
Measured: 6 weeks
CGI-I
Range 1-7, higher scores indicate worse outcomes.
Measured: 6 weeks
Young Mania Rating Scale (YMRS)
Range 0-60, higher scores indicate worse outcomes.
Measured: 6 weeks
MOCA
Range 0-30, higher scores indicate better outcomes.
Measured: 6 weeks
COWAT (Total words T-score)
Range 0-30, higher scores indicate better outcomes.
Measured: 6 weeks
HVLT-R (Total T-score)
Range 0-100, higher scores indicate better outcomes.
Measured: 6 weeks
IAT
Range scores -2-+2
Measured: 6 weeks
Suicidal Behavior Questionnaire-Revised (SBQ-R)
Range 3-18, higher scores indicate worse outcomes.
Measured: 6 weeks
Global Self Evaluation of Memory (GSE-My)
Range 1-7, higher scores indicate worse outcomes.
Measured: 6 weeks
Patient-rated global assessment of severity and improvement (PGI-S/PGI-I)
Range 1-7, higher scores indicate worse outcomes.
Measured: 6 weeks
Patient Rated Inventory of Side Effects (PRISE)
Not scored
Measured: 6 weeks
Quality of Life Scale (QOLS)
Range 16-112, higher scores indicate better outcomes.
Measured: 6 weeks
Likert Scale Treatment Preference Questionnaire
Range 0-7
Measured: 6 weeks
National Alcohol and Drug Institute (NIDA) substance use questionnaire (TAPS-I and II)
Substance specific scores 0-3, higher scores indicate worse outcomes.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2023
- Study start1 Oct 2023
- Primary completion1 Oct 2030 (estimated)
- Study completion1 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Suicidal Depression (ASD)Studies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Johns Hopkins University, University of Pittsburgh, The Cleveland Clinic, Icahn School of Medicine at Mount Sinai, University of Toronto, The University of Texas Health Science Center, Houston, UT Health, Mclean Hospital, Massachusetts General Hospital, University of Utah, UC San Francisco
- Responsible party
- Principal investigator, Amit Anand, Brigham and Women's Hospital
- Investigators
- Amit Anand, MD, Principal investigator, Brigham and Woman's Hospital, Harvard Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06034821
- Sponsor's protocol ID
- 2023P001649
- Acronym
- REaKT-SD
- Status last verified
- Dec 2025
- First submitted
- 30 Aug 2023
- Last updated
- 15 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rapid Reversal of Suicidal Depression: Comparative Effectiveness of ECT vs. KETAMINE Over the Lifespan (REaKT-SD)
- ClinicalTrials.gov ID
- NCT06034821
- Acronym / sponsor ID
- REaKT-SD / 2023P001649
- Conditions
- Acute Suicidal Depression (ASD)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 1,500 participants (estimated)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Johns Hopkins University, University of Pittsburgh, The Cleveland Clinic, Icahn School of Medicine at Mount Sinai, University of Toronto, The University of Texas Health Science Center, Houston, UT Health, Mclean Hospital, Massachusetts General Hospital, University of Utah, UC San Francisco
- Study start
- 1 Oct 2023 (actual)
- Primary completion
- 1 Oct 2030 (estimated)
- Study completion
- 1 Dec 2030 (estimated)
- First posted
- 13 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Subanesthetic dose intravenous ketamine (KET) | Active comparator | Drug: 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. |
| Electroconvulsive therapy (ECT) | Active comparator | Device: Electroconvulsive therapy (ECT)ECT will be given in a standard manner 3 times a week for 4 weeks. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Considered by a clinician as appropriate for referral to treatment services for rapid reversal of acute suicidal depression.
- Adults 18 - 90 years of age.
- Meet DSM-5 criteria for Major Depressive Episode (MDE) as determined by Mini International Neuropsychiatric Interview (MINI PLUS 5.0.0).
- 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). *
- Continue to express suicidal ideation since referral as evidenced by Scale for Suicidal Ideation (SSI) ≥6)**
Key exclusion criteria (10 listed)
- Meeting DSM-5 criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder.
- Not able to give informed consent to receive ECT or KET treatment.
- Not able to give informed consent to participate in the study.
- Meet exclusion criteria for ECT treatment as described in guidelines.
- Meet exclusion criteria for KET treatment such as:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Subanesthetic dose intravenous ketamine (KET) |
| 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. | Device | Electroconvulsive therapy (ECT) |
Primary outcome
Scale for Suicidal Ideation (SSI)
Time frame: Six weeks
The Scale for Suicidal Ideation (SSI is excellent in terms of test construction and psychometrics (validity and reliability). It has been shown that a SSI score >6 has been found to be predictive of suicide within 6 months of discharge from hospital. At the end of treatment, patients will be assessed for remission of suicidality which is defined as a SSI score <4 i.e. no clinically significant suicidal ideation70. A stringent criterion for remission was chosen as ASD is a life-threatening illness and full remission should be the treatment goal.
22 secondary outcomes
Quick Inventory of Depressive Symptoms Self Report QIDS-SR
Time frame: Six weeks
Columbia Suicide Severity Rating Scale (CSSR-S)
Time frame: 6 weeks
Montgomery Asberg Depression Rating Scale (MADRS)
Time frame: 6 weeks
Working Alliance Inventory (WAI-SR)
Time frame: 6 weeks
National Alcohol and Drug Institute (NIDA) Questionnaire
Time frame: 6 weeks
Self and clinician rated scales
Time frame: 6 weeks
Brief Psychiatric Rating Scale 4 items (BPRS)
Time frame: 6 weeks
Clinician Administered Dissociative Symptoms Scale (CADSS)
Time frame: 6 weeks
CGI-S
Time frame: 6 weeks
CGI-I
Time frame: 6 weeks
Young Mania Rating Scale (YMRS)
Time frame: 6 weeks
MOCA
Time frame: 6 weeks
COWAT (Total words T-score)
Time frame: 6 weeks
HVLT-R (Total T-score)
Time frame: 6 weeks
IAT
Time frame: 6 weeks
Suicidal Behavior Questionnaire-Revised (SBQ-R)
Time frame: 6 weeks
Global Self Evaluation of Memory (GSE-My)
Time frame: 6 weeks
Patient-rated global assessment of severity and improvement (PGI-S/PGI-I)
Time frame: 6 weeks
Patient Rated Inventory of Side Effects (PRISE)
Time frame: 6 weeks
Quality of Life Scale (QOLS)
Time frame: 6 weeks
Likert Scale Treatment Preference Questionnaire
Time frame: 6 weeks
National Alcohol and Drug Institute (NIDA) substance use questionnaire (TAPS-I and II)
Time frame: 6 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2025.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Amit Anand, MD principal investigator
Brigham and Woman's Hospital, Harvard Medical School
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Subanesthetic dose intravenous ketamine (KET) and Electroconvulsive therapy (ECT) in people with Acute Suicidal Depression (ASD), run by Brigham and Women's Hospital at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 15 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Scale for Suicidal Ideation (SSI) (time frame: Six weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2025.