ECT vs. Ketamine for Depression

(REaKT-SD Trial)

Enrolling by invitation at 12 trial locations

Overseen By Sanjay Mathew, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Brigham and Women's Hospital

Disqualifiers: Schizophrenia, Schizoaffective, Psychotic features, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two treatments, electroconvulsive therapy (ECT) and low-dose intravenous ketamine, to determine which is more effective for severe depression with suicidal thoughts. The goal is to assess whether ketamine can match ECT in quickly reversing these symptoms. This study suits adults diagnosed with major depression who are currently experiencing suicidal thoughts or behaviors. As a Phase 4 trial, the research focuses on understanding how these FDA-approved treatments can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What is the safety track record for these treatments?

Research has shown that both electroconvulsive therapy (ECT) and low-dose intravenous ketamine (KET) are generally well-tolerated treatments for depression.

In studies of ECT, some patients experienced temporary memory and thinking issues, which often improved or stabilized within six months. ECT effectively reduces severe depression symptoms and suicidal thoughts, and it is likely more effective than traditional medications.

Research on ketamine indicates it can quickly improve depression symptoms. Most side effects are mild and short-lived, though a few patients discontinued treatment due to them.

Both treatments have proven effective and are considered safe options for managing severe depression, though individual experiences may vary. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for depression because they offer unique approaches compared to traditional options like SSRIs and psychotherapy. Electroconvulsive therapy (ECT) is distinctive for its rapid action, often providing relief in a matter of weeks, which can be crucial for severe depression cases. On the other hand, ketamine, administered intravenously at subanesthetic doses, acts on the brain's NMDA receptors, offering a novel mechanism of action that can result in fast-acting antidepressant effects. Both treatments bring promising alternatives for patients who haven't responded well to more conventional therapies.

What evidence suggests that this trial's treatments could be effective for Acute Suicidal Depression?

This trial will compare electroconvulsive therapy (ECT) with subanesthetic dose intravenous ketamine (KET) for treating major depression. Research has shown that ECT is highly effective, often providing quick relief from symptoms. Studies indicate that about 74% of patients respond well, and 52% achieve remission after one course of treatment. ECT also tends to enhance quality of life and mental function. Meanwhile, ketamine produces fast antidepressant effects, often within hours to days, with around 55% of patients experiencing significant improvement in their symptoms. Some studies suggest that ketamine is as effective as ECT for depression. Both treatments have strong evidence supporting their effectiveness in treating depression. ^{1 2 6 7 8}

Who Is on the Research Team?

Amit Anand, MD

Principal Investigator

Brigham and Woman's Hospital, Harvard Medical School

Are You a Good Fit for This Trial?

This trial is for adults aged 18-90 with acute suicidal depression who are candidates for ECT treatment. Participants must show ongoing suicidal thoughts and meet criteria for a major depressive episode, but not have schizophrenia or severe cognitive impairment. Pregnant individuals, those unable to consent, or with certain medical conditions like uncontrolled illness or ketamine allergy cannot join.

Inclusion Criteria

My doctor thinks I should get ECT treatment.

I have been diagnosed with a major depressive episode.

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

Exclusion Criteria

I am not eligible for ECT based on standard guidelines.

I cannot consent to ECT or KET treatment.

I am unable to understand or agree to the study's procedures and risks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ECT 3 times a week for 4 weeks or subanesthetic dose intravenous ketamine

4 weeks

12 visits (in-person for ECT), multiple visits for ketamine

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Electroconvulsive therapy (ECT)
• Subanesthetic dose intravenous ketamine (KET)

Trial Overview The study compares the effectiveness of Electroconvulsive therapy (ECT) versus intravenous Ketamine (KET) in treating acute suicidal depression. It's randomized and single-blind, meaning participants won't know which treatment they receive but researchers will.

How Is the Trial Designed?

Group I: Electroconvulsive therapy (ECT) Active Control 1 Intervention

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

Group II: Subanesthetic dose intravenous ketamine (KET) Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

The University of Texas Health Science Center, Houston

Collaborator

Trials

974

Recruited

361,000+

University of Arizona

Collaborator

Trials

545

Recruited

161,000+

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

Collaborator

Trials

1

Recruited

1,500+

Icahn School of Medicine at Mount Sinai

Collaborator

Trials

933

Recruited

579,000+

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Published Research Related to This Trial

Ketamine, at sub-anesthetic doses, shows promise as a rapid-acting treatment for patients with treatment-resistant depression (TRD), potentially improving response rates to electroconvulsive therapy (ECT) when used alone or as an adjunct.

While ketamine can enhance the effectiveness of ECT, it may also increase seizure duration and has been associated with cardiovascular and psychotomimetic side effects, necessitating careful monitoring and consideration of concurrent medications to mitigate risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of ketamine's role in ECT and non-ECT settings. Jankauskas, V., Necyk, C., Chue, J., et al.[2020]

A 49-year-old woman with severe treatment-resistant major depression experienced significant improvement after receiving 36 sessions of ketamine intravenous therapy over 10 months, resulting in nearly a 50% reduction in her depressive symptoms.

The case suggests that long-term repeated ketamine therapy could be a viable option for patients with treatment-resistant depression, but further research is needed to determine the best treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ketamine infusion for a patient with treatment-resistant major depression: a 10-month follow-up. Kwon, JH., Sim, WS., Hong, JP., et al.[2018]

A review of 11 studies, including 7 on humans with major depressive disorder (MDD), found that intravenous ketamine can reduce brain activation related to depression and improve cognitive flexibility without causing significant cognitive impairments in most patients.

Some studies indicated that ketamine may enhance cognitive functions such as processing speed, verbal learning, and attention, suggesting it has a normalizing effect on brain functions involved in emotional processing for MDD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurocognitive impact of ketamine treatment in major depressive disorder: A review on human and animal studies. Crisanti, C., Enrico, P., Fiorentini, A., et al.[2021]

Subanaesthetic doses of ketamine have shown substantial efficacy in treating depression, with response rates averaging 77% and remission rates around 43% within 4 to 72 hours after a single dose.

Despite the rapid improvement in mood for many patients, the effects are often short-lived, highlighting the need for further research on dosing regimens and strategies to maintain the antidepressant response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine as a new treatment for depression: a review of its efficacy and adverse effects. Katalinic, N., Lai, R., Somogyi, A., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8461517/

Efficacy of electroconvulsive therapy as a potential first- ... ECT as compared to other treatments is found to be the most efficacious for symptom remission of major depressive disorder (MDD) (3).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10701215/

Treatment outcomes and cognitive function following ... Here, ECT led to more pronounced improvements in depressive symptoms, quality of life, and cognitive function than non-ECT treatments.

3. sciencedirect.com sciencedirect.com/science/article/pii/S3050529125000881

Early comparative outcomes of electroconvulsive therapy ... Among adult patients with depression of at least moderate severity, the ECT group had more rapid improvement in depressive symptom severity compared to TMS as ...

4. nature.com nature.com/articles/s41386-023-01677-2

How electroconvulsive therapy works in the treatment of ... ECT is a highly efficacious treatment for major depression and several other psychiatric disorders. Several meta-analyses support ECT's superior ...

5. academic.oup.com academic.oup.com/ijnp/article/26/1/53/6747463

Predictors of Electroconvulsive Therapy Outcome in Major ... A recent meta-analysis found that for MDD patients, the response rate reaches 74.2%, and the remission rate reaches 52.3% after 1 acute course of ECT (Bahji et ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2772408525001127

Electroconvulsive therapy reduces suicidality and all-cause ... We observed a moderate reduction in suicidal ideation with ECT, as assessed by standardized tools in studies focusing on this outcome. However, such an effect ...

7. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(03)12705-5/fulltext

Efficacy and safety of electroconvulsive therapy in ... ECT is an effective short-term treatment for depression, and is probably more effective than drug therapy. Bilateral ECT is moderately more effective than ...

8. mayoclinic.org mayoclinic.org/tests-procedures/electroconvulsive-therapy/about/pac-20393894

Electroconvulsive therapy (ECT) This procedure can greatly and rapidly improve severe symptoms of depression, mania, catatonia or other mental health conditions.