Adding ketamine to ECT for treatment-resistant depression

The Additive Effect of Ketamine in Combination With ElectroConvulsive Stimulation (ECS) in Major Depressive Disorder (MDD): a Translational Study

This trial will test whether giving IV ketamine during ECT helps adults with treatment-resistant major depression get better faster and have fewer thinking problems.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Università Vita-Salute San Raffaele (Academic / other)
• Locations: 1 site (Milan)
• Trial ID: NCT07088380 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled Phase 3 trial comparing IV ketamine versus saline given during electroconvulsive therapy (ECT) in hospitalized adults with treatment-resistant major depressive disorder. Thirty patients aged 18–70 who have failed at least two antidepressant medications will be randomized to receive ketamine or placebo during ECT sessions 2, 4, and 6. The primary outcome is change in depressive symptoms measured by the MADRS at 4 weeks, and cognitive side effects will also be tracked. The trial is conducted at IRCCS Ospedale San Raffaele Turro in Milan under standard anesthesia and ECT protocols.

Who should consider this trial

Good fit: Adults 18–70 with major depressive disorder that has not responded to at least two antidepressant trials and who are medically cleared for ECT and anesthesia would be typical candidates.

Not a fit: People who are pregnant or breastfeeding, have recent substance use disorders, chronic neurological disease, major cardiac or other contraindications to ECT or ketamine, or who cannot be hospitalized at the trial site are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, adding ketamine could speed improvement in depressive symptoms and reduce cognitive side effects associated with ECT for people with treatment-resistant depression.

How similar studies have performed: Previous small randomized and open-label studies have suggested ketamine can speed antidepressant response and may influence cognitive outcomes when used with ECT, but results have been mixed and larger confirmatory trials are limited.

Eligibility criteria

Inclusion Criteria:

* Male and female subjects ages 18-70,
* diagnosed with MDD (according to SCID5-CV interview)
* treatment resistant (defined as at least 2 different antidepressant agents used without success),
* ability to give informed consent,
* adequacy of the score for anesthesia.

Exclusion Criteria:

* Chronic neurological diseases,
* Intellectual disability
* Contraindications to the electroconvulsive therapy (severe aortic valve stenosis, implantable cardiac defibrillators, uncontrolled hypertension, clinically significant respiratory, renal or hepatic disease, abdominal aortic aneurysm, endocrine disorders, neuromuscular diseases, space occupying brain lesions, stroke in the last 6 months),
* Patients with Alcohol Use Disorder or Substance Use Disorder or Substance Abuse history in the past year,
* Pregnancy and lactation
* Cardiovascular conditions,
* Psychiatric Disorders,
* Hepatic impairment,
* Participants with a known hypersensitivity to ketamine or any of its excipients will be excluded from the study,
* Participants with any contraindications to the use of ketamine, such as a history of severe cardiovascular conditions (e.g., uncontrolled hypertension, significant arrhythmias), intracranial hypertension, or severe liver impairment, will also be excluded to prevent potential adverse events.

Where this trial is running

Milan

• IRCCS Ospedale San Raffaele Turro — Milan, Italy (Recruiting)

Study contacts

• Principal investigator: Alberto AZ Zangrillo, MD — Università Vita-Salute San Raffaele
• Study coordinator: Alberto AZ Zangrillo, MD

Conditions Major Depressive Disorder; Treatment Resistant Depression; ketamine; TRD; depression; electroconvulsive therapy