What side effects are associated with this type of intervention?

Ketamine, used for its rapid antidepressant effects in treating Major Depressive Disorder, can cause side effects such as disorientation, restlessness, dissociation, dizziness, delirium, psychosis, nausea, vomiting, and increased blood pressure. Electroconvulsive therapy (ECT), another common treatment, can lead to cognitive side effects like memory loss, confusion, and disorientation, as well as physical side effects such as headaches, muscle aches, and nausea. Combining ketamine with ECT may enhance seizure duration but also carries the risk of the aforementioned side effects from both treatments.

What prior FDA approvals exist?

The FDA has approved several treatments for Major Depressive Disorder (MDD) that involve NMDA receptor antagonism. Notably, ketamine and its enantiomer esketamine have been approved for treatment-resistant depression. Esketamine, marketed as Spravato, is administered as a nasal spray and is used in conjunction with an oral antidepressant. These treatments are particularly relevant to the high-intensity ketamine approach being studied in clinical trials for their rapid-acting antidepressant effects.

What other types of research exist?

Promising novel alternatives to High Intensity Ketamine for Major Depressive Disorder in 2024 include: 1) Psilocybin-assisted therapy, which has shown substantial and sustained decreases in depression and anxiety in clinical trials. 2) Electroconvulsive Therapy (ECT) with alternative anesthetics like propofol and dexmedetomidine, which have been studied for their efficacy and cognitive outcomes. 3) Augmentation therapies such as combining SSRIs with cognitive-behavioral therapy (CBT) or other pharmacological agents like aripiprazole or mirtazapine, which have shown benefits in treatment-resistant cases.

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ECT with Ketamine vs High-Intensity Ketamine for Depression

Phase 4

Recruiting

Led By Jonathan Gamble, MD

Research Sponsored by University of Saskatchewan

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Montgomery Asberg Depression Rating Scale (MADRS) score of greater than 20) planned for ECT therapy

Subjects must meet clinical criteria for TRD defined as failure to respond to at least 2 standard-of-care drug therapies of adequate treatment duration.

Must not have

Schizoaffective disorder

Women of child-bearing potential will be asked to undergo a commercial urine pregnancy screening test. Those who refuse or screen positive will be excluded

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks

Awards & highlights

Approved for 5 Other Conditions

All Individual Drugs Already Approved

Drug Has Already Been Approved

Pivotal Trial

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Ketamine may cause disorientation, nausea, increased blood pressure, mood swings or dissociation. ECT might lead to memory loss, muscle soreness or headaches. Side effects vary by individual.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been diagnosed with schizoaffective disorder.

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

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My health is severely impacted by my illness.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and from date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of treatments required to reach disease remission

Secondary study objectives

Cognitive Impairment

Patient satisfaction with treatment

Rate of rescue ECT in the HIKER arm

+2 more

Awards & Highlights

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Ketamine (HIKER)Experimental Treatment1 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 Control2 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ketamine

FDA approved

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Ketamine, used in the High Intensity Ketamine (HIKER) approach, acts as an NMDA receptor antagonist, leading to rapid increases in glutamate and activation of AMPA receptors, which enhance synaptic plasticity and connectivity. This results in quick antidepressant effects. Electroconvulsive therapy (ECT) induces controlled seizures that cause widespread neurochemical changes, including increased release of serotonin, norepinephrine, and dopamine, and enhanced neuroplasticity. These mechanisms are important for Major Depressive Disorder patients, especially those with treatment-resistant depression, as they offer faster relief compared to traditional antidepressants, which often take weeks to become effective.