A Phase 3 interventional study of Ketamine Hydrochloride and Placebo in Major Depressive Disorder and Treatment Resistant Depression, sponsored by Università Vita-Salute San Raffaele. Recruiting at 1 site in Italy. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-05-11.
Sponsored by Università Vita-Salute San Raffaele · Phase 3, Interventional, and Treatment
This is a randomized, double-blind, placebo-controlled phase 3 clinical trial evaluating the additive effect of intravenous ketamine in combination with electroconvulsive therapy (ECT) in patients with treatment-resistant major depressive disorder (MDD). The study aims to determine whether ketamine enhances the antidepressant efficacy of ECT and reduces associated cognitive side effects. Thirty hospitalized patients diagnosed with treatment-resistant MDD will be randomized to receive either ketamine or placebo (saline) during ECT sessions 2, 4, and 6. Primary outcome is the change in depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at 4 weeks.
3,041 studies on the registry are indexed under Depressive Disorder, Major; 588 are open to participants now.
This study's planned enrollment of 30 is below the median of 79 across 2,530 interventional studies indexed under Depressive Disorder, Major.
Browse Depressive Disorder, Major studies →Università Vita-Salute San Raffaele is the lead sponsor of 85 studies on the registry; 33 are open to participants now.
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Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
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Excipients
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Patients receive standard ECT treatment combined with intravenous ketamine at a subanesthetic dose of 0.5 mg/kg, administered after induction with Propofol. Ketamine is administered during ECT sessions 2, 4, and 6. Intervention: * Drug: Ketamine * Dose: 0.5 mg/kg IV * Timing: ECT sessions 2, 4, and 6 * Background: Investigating the additive antidepressant and potential cognitive-protective effects of ketamine in patients with treatment-resistant depression undergoing ECT.
Drug: Ketamine Hydrochloride
Patients receive standard ECT treatment combined with placebo (0.9% sodium chloride solution), administered intravenously after induction with Propofol, during ECT sessions 2, 4, and 6, mimicking the ketamine group's schedule. Intervention: * Drug: Saline solution (NaCl 0.9%) * Timing: ECT sessions 2, 4, and 6 * Background: Serves as control to assess the specific contribution of ketamine to antidepressant efficacy and cognitive outcomes.
Drug: Placebo
Ketamine will be administered intravenously at a subanesthetic dose of 0.5 mg/kg after a bolus of Propofol, during ECT sessions 2, 4, and 6.
Placebo will be administered intravenously at a subanesthetic dose of 0.5 mg/kg after a bolus of Propofol, during ECT sessions 2, 4, and 6.
Mean change in depressive symptoms, as measured by MADRS scale
The primary efficacy endpoint will be assessed using the MADRS score (Montgomery-Åsberg Depression Rating Scale)
Time frame: From baseline (day 0) to day 28 (7 days after the last ECT session). A follow-up assessment at Week 12 (90 days) will be included
Change in Suicidal Ideation (Beck Scale for Suicide Ideation - BSSI)
To assess the effect of ketamine and ECT on suicidal ideation with Beck Scale for Suicide Ideation (BSSI)
Time frame: Assessment will be performed at: baseline (day 0); Weekly during ECT treatment period (Weeks 1, 2, 3); Week 4 (1 week after last ECT session); Follow-up: Week 12 (3 months after last ECT session)
Change in Anxiety Symptoms (Hamilton Anxiety Rating Scale - HAM-A)
To evaluate the impact of ketamine and ECT on anxiety symptoms with Hamilton Anxiety Rating Scale (HAM-A)
Time frame: Assessment will be performed at: baseline (day 0); Weekly during ECT treatment period (Weeks 1, 2, 3); Week 4 (1 week after last ECT session); Follow-up: Week 12 (3 months after last ECT session)
Change in Cognitive Function (Brief Assessment of Cognition in Affective Disorders - BAC-A)
To determine the cognitive effects of ketamine and ECT with Brief Assessment of Cognition in Affective Disorders (BAC-A)
Time frame: Assessment will be performed at: baseline (day 0); Week 4 (1 week after last ECT session); Follow-up: Week 12 (3 months after last ECT session)
Change in Dissociative and Psychotic Symptoms (Clinician-Administered Dissociative States Scale - CADSS; Brief Psychiatric Rating Scale - BPRS)
To assess the effects of ketamine and ECT on dissociative and psychotic symptoms with Clinician-Administered Dissociative States Scale (CADSS) and Brief Psychiatric Rating Scale (BPRS)
Time frame: Assessment will be performed at: Baseline (Day 0, before first ECT session); Week 1 (After ECT session 2); Week 2 (After ECT session 4); Week 3 (After ECT session 6); Week 4 (1 week after last ECT session); Follow-up: Week 12 (3 months after last ECT
Change in Neurochemical Markers (Plasma Levels of Trp, 5-HT, 5-HIAA, Glutamate, Aspartate)
To evaluate the neurochemical effects of ketamine and ECT with High-Performance Liquid Chromatography (HPLC) analysis of plasma samples. Change in plasma levels of Trp, 5-HT, 5-HIAA, glutamate, and aspartate from baseline to Week 3 will be assessed.
Time frame: Assessment will be performed at: Baseline (Day 0, before first ECT session); Weekly during ECT treatment period (Weeks 1, 2, 3)
Plan to share: No
Started Jul 2025 (actual). Primary completion is estimated for Aug 2026, 13 months after the start.
Of 124 phase 3 interventional studies under Depressive Disorder, Major, half reached primary completion within 27 months of starting (the median), counting those still running; a quarter within 21 and three quarters within 36. This study's planned 13 months is below that.
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Studies of the drug tested here: Ketamine
Università Vita-Salute San Raffaele