Ketamine Augmentation of ECT in Treatment-Resistant Depression

NCT ID: NCT07088380

Last Updated: 2025-07-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-10
• Study Completion Date: 2026-02-28

Brief 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). 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.

Conditions

Major Depressive Disorder; Treatment Resistant Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Ketamine

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.

Group Type: EXPERIMENTAL

Ketamine Hydrochloride

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

Ketamine Hydrochloride

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Università Vita-Salute San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

Giovanni Landoni

MD, Full Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alberto AZ Zangrillo, MD

Role: PRINCIPAL_INVESTIGATOR

Università Vita-Salute San Raffaele

Cristina CC Colombo, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Ospedale San Raffaele Turro

Locations

IRCCS Ospedale San Raffaele Turro

Milan, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Alberto AZ Zangrillo, MD

Role: CONTACT

zangrillo.alberto@hsr.it

0226436154 ext. +39

Cristina CC Colombo, MD

Role: CONTACT

colombo.cristina@hsr.it

0226435278 ext. +39

Facility Contacts

Alberto AZ Zangrillo, MD

Role: primary

zangrillo.alberto@hsr.it

0226436154 ext. +39

Cristina CC Colombo, MD

Role: backup

colombo.cristina@hsr.it

0226435278 ext. +39

References

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.

Reference Type: BACKGROUND

PMID: 27053196 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28359862 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30283029 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29350659 (View on PubMed)

Other Identifiers

PRIN - 20227EA9AN

Identifier Type: -

Identifier Source: org_study_id