ECT with Ketamine vs High-Intensity Ketamine for Depression

Overseen By Una Goncin

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Saskatchewan

Disqualifiers: Schizoaffective disorder, Cardiovascular disease, 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: 9

Duration: 2-3 weeks

62 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two treatments to help individuals with treatment-resistant depression feel better faster and with fewer side effects. One group will receive high-intensity ketamine treatment for eight days, while the other will undergo electroconvulsive therapy (ECT, also known as electroshock therapy) with ketamine anesthesia. Researchers aim to determine which method is more effective and preferred by patients. Individuals who have not improved with at least two depression medications and are considering ECT might be suitable for this study. As a Phase 4 trial, the treatments are already FDA-approved and proven effective, and this research seeks to understand how they 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 trial coordinators or your doctor.

What is the safety track record for these treatments?

Research shows that both ECT (electroconvulsive therapy) and ketamine have distinct safety considerations for depression treatment. Studies comparing the two indicate that ketamine usually poses fewer risks of causing headaches and muscle pain, while ECT is less likely to result in blurred vision. Each treatment, therefore, has different side effects, which are generally manageable.

For those considering the high-intensity ketamine option, research suggests that ketamine can quickly improve depression symptoms. Safety data from various studies indicate that ketamine is generally well-tolerated, with common side effects being mild and short-lived, such as dizziness, nausea, and a brief rise in blood pressure.

Overall, previous trials have shown both treatments to be safe, though they have different side effects. These should be considered when deciding which treatment might be most suitable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for depression because they explore innovative uses of ketamine, a fast-acting anesthetic. Unlike traditional antidepressants that often take weeks to show effects, ketamine can potentially alleviate depressive symptoms within hours or days. The Ketamine-ECT (EAST) treatment combines ketamine with electroconvulsive therapy (ECT), aiming to enhance the effectiveness of ECT by reducing discomfort and improving anesthesia conditions. Meanwhile, the Ketamine (HIKER) approach administers ketamine on successive weekdays, providing a high-intensity regimen that could deliver rapid relief. These methods offer a promising alternative to standard antidepressants and ECT alone, potentially leading to quicker and more comfortable treatments for depression.

What evidence suggests that this trial's treatments could be effective for depression?

This trial will compare the effectiveness of two treatment approaches for depression: ECT with ketamine and high-intensity ketamine alone. Research has shown that electroconvulsive therapy (ECT) is very effective for severe depression, especially when other treatments fail. It can lower the risk of suicide and improve overall mental health in people with treatment-resistant depression. In this trial, one group will receive ECT combined with ketamine, which may enhance these benefits and potentially reduce the number of ECT sessions needed.

The other group will receive high-intensity ketamine alone. Studies have found that high doses of ketamine can quickly reduce symptoms of depression, sometimes leading to recovery in just a few days. Using higher doses of ketamine has improved results at different stages of treatment. Both ECT and ketamine have strong evidence supporting their effectiveness in treating depression, offering hope for those who haven't found relief with other therapies. ^{6 7 8 9 10}

Who Is on the Research Team?

Jonathan Gamble, MD

Principal Investigator

University of Saskatchewan

Are You a Good Fit for This Trial?

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)

Allergic to any of the study drugs or their carrier components

Any serious physical condition prior to randomization deemed by the attending psychiatrist or consulting anesthetist to be a contraindication to ECT such as cardiovascular disease (including untreated hypertension), respiratory disease, cerebrovascular disease, intracranial hypertension (including glaucoma), or seizures.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• ECT
• Ketamine

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.

How Is the Trial Designed?

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 European Union, United States, Canada for the following indications:

Approved in European Union as Electroconvulsive therapy for:

• Major depressive disorder
• Mania
• Autism
• Catatonia

Approved in United States as Electroconvulsive therapy for:

• Major depressive disorder
• Mania
• Autism
• Catatonia

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+

Royal University Hospital Foundation

Collaborator

Trials

23

Recruited

7,900+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

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