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Major Depressive DisorderPhase 3KetaminaNCT07088380

Ketamine Augmentation of ECT in Treatment-Resistant Depression

A Phase 3 study testing Ketamine Hydrochloride in people with Major Depressive Disorder and Treatment Resistant Depression, run by Università Vita-Salute San Raffaele at 1 site in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Ketamine Hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
30 participants
Where
1 siteItaly
Study dates
10 Jul 2025to Sep 2026
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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,
Show all 10Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Alberto AZ Zangrillo, MD contact

0226436154 ext. +39

zangrillo.alberto@hsr.it

Cristina CC Colombo, MD contact

0226435278 ext. +39

colombo.cristina@hsr.it

Italy1 site, 1 recruiting

  • IRCCS Ospedale San Raffaele Turro

    Milan, 20127

    Alberto AZ Zangrillo, MD, 0226436154 ext. +39, zangrillo.alberto@hsr.it

    Cristina CC Colombo, MD, 0226435278 ext. +39, colombo.cristina@hsr.it

    Recruiting

Other trials in Italy

About this study

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

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.

Being tested
Ketamine Hydrochloride, Placebo
Keywords
ketamine, TRD, depression, electroconvulsive therapy (ECT)
Medical subject headings
Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant, Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ketamine HydrochlorideDrug

    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.

  • PlaceboDrug

    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.

Study groups in NCT07088380
Study groupRoleWhat they receive
KetamineExperimentalPatients 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.
Receives: Drug: Ketamine Hydrochloride
PlaceboPlacebo comparatorPatients 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: 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

Secondary outcomes (5)

  1. 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)

    Measured: 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)

  2. 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)

    Measured: 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)

  3. 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)

    Measured: 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)

  4. 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)

    Measured: 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

  5. 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.

    Measured: Assessment will be performed at: Baseline (Day 0, before first ECT session); Weekly during ECT treatment period (Weeks 1, 2, 3)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jul 2025
  2. Study start10 Jul 2025
  3. Primary completionAug 2026 (estimated)
  4. Study completionSep 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07088380
Sponsor's protocol ID
PRIN - 20227EA9AN
Acronym
Ketamina
Status last verified
May 2026
First submitted
8 Jul 2025
Last updated
11 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Schwartz J, Murrough JW, Iosifescu DV. Ketamine for treatment-resistant depression: recent developments and clinical applications. Evid Based Ment Health. 2016 May;19(2):35-8. doi: 10.1136/eb-2016-102355. Epub 2016 Apr 6.

    PubMed 27053196

  • Anderson IM, Blamire A, Branton T, Clark R, Downey D, Dunn G, Easton A, Elliott R, Elwell C, Hayden K, Holland F, Karim S, Loo C, Lowe J, Nair R, Oakley T, Prakash A, Sharma PK, Williams SR, McAllister-Williams RH; Ketamine-ECT Study team. Ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT): a multicentre, double-blind, randomised, parallel-group, superiority trial. Lancet Psychiatry. 2017 May;4(5):365-377. doi: 10.1016/S2215-0366(17)30077-9. Epub 2017 Mar 27.

    PubMed 28359862

  • Fava M, Freeman MP, Flynn M, Judge H, Hoeppner BB, Cusin C, Ionescu DF, Mathew SJ, Chang LC, Iosifescu DV, Murrough J, Debattista C, Schatzberg AF, Trivedi MH, Jha MK, Sanacora G, Wilkinson ST, Papakostas GI. Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD). Mol Psychiatry. 2020 Jul;25(7):1592-1603. doi: 10.1038/s41380-018-0256-5. Epub 2018 Oct 3.

    PubMed 30283029

  • Nuzzi M, Delmonte D, Barbini B, Pasin L, Sottocorna O, Casiraghi GM, Colombo C, Landoni G, Zangrillo A. Thiopental is better than propofol for electroconvulsive therapy. Acta Biomed. 2018 Jan 16;88(4):450-456. doi: 10.23750/abm.v88i4.6094.

    PubMed 29350659

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ketamine Hydrochloride in people with Major Depressive Disorder and Treatment Resistant Depression, run by Università Vita-Salute San Raffaele at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Alberto AZ Zangrillo, MD (0226436154 ext. +39, zangrillo.alberto@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean change in depressive symptoms, as measured by MADRS 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07088380, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2026.

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