ECT with Ketamine vs High-Intensity Ketamine for Depression

Recruiting in Palo Alto (17 mi)

Overseen by Jonathan Gamble, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Saskatchewan

Disqualifiers: Schizoaffective disorder, Cardiovascular disease, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests if using high doses of ketamine for a short period can help people with severe depression who haven't responded to other treatments. If ketamine doesn't work, they can switch to another treatment. The goal is to see if this approach reduces depression faster and with fewer side effects compared to traditional methods. Ketamine has recently emerged as a fast-acting treatment alternative for patients with treatment-resistant depression, and it has been used in conjunction with other treatments to potentially enhance its effects.

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 trial coordinators or your doctor.

Is ECT with ketamine safe for treating depression?

Ketamine used in ECT can cause side effects like nausea, dizziness, and dissociative experiences (feeling disconnected from reality). Some patients prefer not to use ketamine again due to these effects, but it has been well tolerated in other cases when used with antidepressants. ^{1 2 3 4 5}

How does the treatment of ECT with Ketamine differ from other treatments for depression?

ECT with Ketamine is unique because it combines electroconvulsive therapy (ECT), a highly effective treatment for severe depression, with ketamine, a fast-acting antidepressant. This combination may offer rapid relief from depressive symptoms, potentially faster than traditional antidepressants, and could be an alternative for those who refuse ECT due to stigma or perceived risks. ^{3 6 7 8 9}

Research Team

Jonathan Gamble, MD

Principal Investigator

University of Saskatchewan

Eligibility Criteria

This trial is for adults with treatment-resistant depression, defined as not responding to at least two standard drug therapies. Participants must have a significant level of depression (MADRS score >20) and be planned for ECT therapy. It's not for those with severe physical health risks, electronic medical implants, schizoaffective disorder, pregnant women or those who could become pregnant and refuse testing.

Inclusion Criteria

My depression is severe, scoring over 20 on MADRS, and I am planning for ECT therapy.

I have depression that didn't improve after trying at least 2 different treatments.

Exclusion Criteria

Implanted medical device with electronic parts (e.g. pacemaker, defibrillator, intrathecal pump, spinal cord stimulator, deep brain stimulator)

I have been diagnosed with schizoaffective disorder.

I am not pregnant or willing to take a pregnancy test if I can bear children.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either high intensity ketamine treatment for eight consecutive days or ECT with ketamine anesthesia for 8 sessions over 2-3 weeks

2-3 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of suicidal ideation and cognitive impairment

4 weeks

1 visit (in-person), 1 visit (virtual)

Long-term follow-up

Participants are assessed for long-term outcomes such as patient satisfaction and cognitive function

8 weeks

Treatment Details

Interventions

• ECT (Procedure)
• Ketamine (NMDA Receptor Antagonist)

Trial Overview The study compares two approaches: HIKER involves high intensity ketamine treatments over eight days; EAST combines ECT with ketamine anesthesia across 2-3 sessions per week. The goal is to see if HIKER can quickly alleviate symptoms with fewer side effects and reduce the need for ECT.

Participant Groups

Group I: Ketamine (HIKER) Experimental Treatment 1 Intervention

Patients in the HIKER arm will receive a single dose of ketamine 0.50 mg/kg, which is enough to achieve a full anaesthetic effect (i.e., unconsciousness mimicking the GA regimen above), on 8 successive weekdays.

Group II: Ketamine-ECT (EAST) Active Control 2 Interventions

Patients in the EAST arm will initially receive intravenous ketamine 0.75 mg/kg, remifentanil 1 mcg/kg (to reduce discomfort), and succinylcholine 0.75 mg/kg (for safety). Based on patients' anaesthetic response, the attending anaesthesiologist is given the freedom to vary the dose of remifentanil and succinylcholine as well as administer propofol to achieve safe and acceptable anaesthetic conditions. As per the Saskatoon Health Region's care standard, patients in the EAST arm will receive eight ECT sessions (on a bi/triweekly schedule) delivered by the attending psychiatrist with either unilateral or bilateral electrode placement and monitoring of seizure threshold by the half-age method.

ECT is already approved in Canada for the following indications:

Approved in Canada as Electroconvulsive therapy for:

• Major depressive disorder
• Mania
• Autism
• Catatonia

Who Is Running the Clinical Trial?

University of Saskatchewan

Lead Sponsor

Trials

261

Recruited

156,000+

Scott Livingstone

University of Saskatchewan

Chief Executive Officer since 2024

Bachelor of Science in Pharmacy and Master of Science in Clinical Pharmacy from the University of Saskatchewan

Dr. Angela Bedard-Haughn

University of Saskatchewan

Chief Medical Officer

MD from McGill University

Royal University Hospital Foundation

Collaborator

Trials

23

Recruited

7,900+

Findings from Research

In a case series of 14 patients undergoing electroconvulsive therapy (ECT), switching to ketamine as an anesthetic led to significant adverse effects, including nausea, dizziness, and dissociative symptoms, prompting all patients to express a strong preference against its use in the future.

Despite ketamine's potential antidepressant benefits and theoretical advantages in reducing cognitive side effects of ECT, clinicians should be cautious and consider using benzodiazepines to mitigate the adverse effects associated with ketamine anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Some considerations of the tolerability of ketamine for ECT anesthesia: a case series and review of the literature. Rasmussen, KG., Ritter, MJ.[2014]

Current evidence does not clearly support the idea that adding ketamine to electroconvulsive therapy (ECT) provides greater antidepressant effects than ECT alone, based on systematic reviews and meta-analyses of randomized controlled trials.

While ketamine may offer some early benefits for patients with acute depressive disorders, its side effects could be undesirable for certain individuals, highlighting the need for careful consideration of risks and benefits in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine and electroconvulsive therapy: so happy together? Cobb, K., Nanda, M.[2018]

In a review of nine patients treated with ketamine during electroconvulsive therapy (ECT), the median induction dose was found to be 1.1 mg/kg, indicating a specific dosing range for its use.

Most patients demonstrated a clinical benefit from using ketamine as an anesthetic agent in ECT, suggesting that it can be an effective alternative for anesthesia in this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosing and effectiveness of ketamine anesthesia for electroconvulsive therapy (ECT): a case series. Bryson, EO., Ahle, GM., Liebman, LS., et al.[2014]

In a study of 28,584 patients with moderate to severe unipolar depression, those who received electroconvulsive therapy (ECT) showed a reduced risk of major adverse cardiovascular events (MACE) both within 90 days and up to 1 year after treatment.

Specifically, only 1.4% of patients in the ECT group experienced MACE compared to 2.3% in the non-ECT group, suggesting that ECT may not only be safe in terms of cardiovascular health but could also contribute to long-term cardiovascular benefits by alleviating depressive symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Major adverse cardiovascular events following electroconvulsive therapy in depression: A register-based nationwide Swedish cohort study with 1-year follow-up. Nordenskjöld, A., Güney, P., Nordenskjöld, AM.[2022]

A patient with resistant depression showed a strong and lasting improvement after receiving six intravenous ketamine infusions, suggesting it may be an effective treatment option for those who do not fully respond to traditional antidepressants.

Ketamine was well tolerated by the patient, indicating its potential as a safe alternative or supplement to standard antidepressant therapies, especially for individuals with limited response to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robust and sustained effect of ketamine infusions coadministered with conventional antidepressants in a patient with refractory major depression. Montes, JM., Luján, E., Pascual, F., et al.[2020]

A systematic review of 6 clinical trials with 340 patients indicates that electroconvulsive therapy (ECT) is more effective than ketamine for reducing depression severity, with a significant pooled effect size of -0.69.

Both treatments have distinct safety profiles, with ketamine associated with fewer headaches and muscle pain, while ECT has lower risks for visual disturbances and dissociative symptoms, suggesting that treatment choice should be tailored to individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ketamine vs Electroconvulsive Therapy Among Patients With Major Depressive Episode: A Systematic Review and Meta-analysis. Rhee, TG., Shim, SR., Forester, BP., et al.[2023]

Intravenous ketamine therapy has been shown to significantly improve symptoms of depression and suicidality in patients who refuse Electro-Convulsive Therapy (ECT), making it a viable alternative for those in need.

The effectiveness of ketamine therapy was assessed through standardized scales, indicating that it provides a rapid response compared to traditional pharmacotherapy for patients with severe depression and suicidal thoughts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective data analysis to determine the effectiveness of intravenous ketamine therapy on patients suffering from depression with suicidal ideation. Chaudhary, P., Shah, P., Mehta, P.[2023]

In a study of 186 hospitalized patients with unipolar depression, electroconvulsive therapy (ECT) resulted in a higher remission rate (63%) compared to ketamine infusions (46%), indicating that while ketamine is effective, it is less effective than ECT for severe depression.

Both treatments required a similar number of sessions (median of 6) to achieve remission, but ECT was associated with more serious and long-lasting adverse effects, such as persistent amnesia, while ketamine led to more treatment-emergent adverse events that caused dropouts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Racemic Ketamine as an Alternative to Electroconvulsive Therapy for Unipolar Depression: A Randomized, Open-Label, Non-Inferiority Trial (KetECT). Ekstrand, J., Fattah, C., Persson, M., et al.[2022]

In a meta-analysis of five trials involving 278 adults with major depressive episodes, electroconvulsive therapy (ECT) demonstrated superior efficacy compared to ketamine, particularly in reducing depression ratings and achieving response and remission rates.

Despite the findings favoring ECT, the study highlights limitations such as a small number of trials and high risk of bias, suggesting that further research is needed to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine vs Electroconvulsive Therapy for Major Depressive Episode: A Systematic Review and Meta-analysis. Menon, V., Varadharajan, N., Faheem, A., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Some considerations of the tolerability of ketamine for ECT anesthesia: a case series and review of the literature. [2014]

2. United States pubmed.ncbi.nlm.nih.gov

Ketamine and electroconvulsive therapy: so happy together? [2018]

3. England pubmed.ncbi.nlm.nih.gov

Dosing and effectiveness of ketamine anesthesia for electroconvulsive therapy (ECT): a case series. [2014]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Major adverse cardiovascular events following electroconvulsive therapy in depression: A register-based nationwide Swedish cohort study with 1-year follow-up. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Robust and sustained effect of ketamine infusions coadministered with conventional antidepressants in a patient with refractory major depression. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ketamine vs Electroconvulsive Therapy Among Patients With Major Depressive Episode: A Systematic Review and Meta-analysis. [2023]

7. India pubmed.ncbi.nlm.nih.gov

Retrospective data analysis to determine the effectiveness of intravenous ketamine therapy on patients suffering from depression with suicidal ideation. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Racemic Ketamine as an Alternative to Electroconvulsive Therapy for Unipolar Depression: A Randomized, Open-Label, Non-Inferiority Trial (KetECT). [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Ketamine vs Electroconvulsive Therapy for Major Depressive Episode: A Systematic Review and Meta-analysis. [2023]