ELEKT-D: Electroconvulsive Therapy (ECT) vs. Ketamine in Patients With Treatment Resistant Depression (TRD)

NCT03113968 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ELEKT-D
• Study Type: interventional
• Target: 403
• Locations: 1 country
• Sites: 5

Brief Summary

The goal of the study is to conduct a comparative randomized trial of electroconvulsive therapy (ECT) vs. ketamine for patients with treatment resistant depression (TRD) in a real world setting with patient reported outcomes as primary and secondary outcome measures.

Conditions

Treatment Resistant Depression; Electroconvulsive Therapy; ECT; Ketamine; Psychiatric Disorder; Depression; Major Depressive Disorder; Major Depressive Episode; Unipolar Depression

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment Responses Based on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report Scale (QIDS-SR-16)

  Response is defined as at least a 50% improvement in the QIDS-SR-16 scale from baseline to the End of Treatment visit. The End of Treatment visit will occur 3-5 weeks after the Baseline visit.

  Acute Study Phase (Baseline Visit to End of Treatment Visit) - approximately 3-5 weeks

Secondary Outcomes (1)

• Number of Participants With Treatment Responses Based on the Montgomery-Åsberg Rating Scale (MADRS)

  Acute Study Phase (Baseline Visit to End of Treatment Visit) - approximately 3-5 weeks

Study Arms (2)

electroconvulsive therapy (ECT)

ACTIVE COMPARATOR

Treatments will be given 3 times a week up to a total of 9 treatments over 3 - 5 weeks. Initial ECT treatment is Right Unilateral (RUL) ultra-brief pulse at 6X seizure threshold. Seizure threshold and dose can be increased per investigator and patient discretion.

Procedure: electroconvulsive therapy (ECT)

ketamine infusion

ACTIVE COMPARATOR

Treatments will be given 2 times a week up to a total of 6 treatment over 3 - 5 weeks. Initial standard dose will be 0.5 mg/kg infusion over 40 min. The dose can be modified if clinically warranted per investigator and patient discretion.

Drug: Ketamine

Interventions

electroconvulsive therapy (ECT) PROCEDURE

ECT is a procedure done under general anesthesia where small electric currents are passed through the brain, intentionally triggering a brief seizure. Patients who have not responded to antidepressant medications may be candidates for ECT. ECT is FDA approved for treatment resistant depression.

electroconvulsive therapy (ECT)

Ketamine DRUG

Ketamine is a medication that is used as a short acting anesthetic in pediatric and adult medicine. Subanesthetic (low) doses will be given to patients via infusion in order to assess whether it helps with depression symptoms in patients who have not responded to antidepressant therapy. Ketamine is not FDA approved for this indication and its effectiveness in treatment resistant depression has not been proven. Prior studies have indicated that subanesthetic doses of ketamine may be helpful for treatment resistant depression.

ketamine infusion

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent before any study related procedures are performed
• Inpatients or outpatients referred by their providers for ECT treatment and eligible for ECT treatment
• Males/females at least 21 years of age but no older than 75 years of age
• Meet DSM-5 criteria for Major Depressive Episode as determined by both:
• A. a clinician's diagnostic evaluation and B. confirmed with the MINI International Neuropsychiatric Interview (MINI 7.0.2)
• A current depressive episode that has lasted a minimum of 4 weeks
• Meet all of the following criteria on symptom rating scales at screening:
• A. Montgomery Asberg Depression Rating Scale (MADRS) score \>20 B. Young Mania Rating Scale (YMRS) of ≤ 5 C. Montreal Cognitive Assessment (MoCA) of ≥18
• Have had ≥2 adequate trials of antidepressants or augmentation strategies during their lifetime. An adequate trial is defined as 4 weeks of medication at the minimum FDA approved dose. This will be equal to a trial rating of 3 or more.
• In the opinion of the investigator, the patient is willing and able to comply with scheduled visits, treatment plan, and other trial procedures for the duration of the study

You may not qualify if:

• Meet DSM-5 criteria for bipolar disorder, schizophrenia, schizophreniform disorder, schizoaffective disorder, mental retardation, or pervasive developmental disorder
• The patient is pregnant or breast feeding
• The patient has a severe medical illness or severe neurological disorder
• The patient has a known ketamine allergy or is taking a medication that may interact with ketamine
• Diagnosis of major depressive disorder with psychotic features during the current depressive episode
• Unable to give informed consent
• Was previously enrolled/randomized into the trial

Sponsors & Collaborators

• Bo Hu: lead
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (5)

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (8)

• Nemeroff CB. Prevalence and management of treatment-resistant depression. J Clin Psychiatry. 2007;68 Suppl 8:17-25.

  PMID: 17640154 BACKGROUND

• Kellner CH, Greenberg RM, Murrough JW, Bryson EO, Briggs MC, Pasculli RM. ECT in treatment-resistant depression. Am J Psychiatry. 2012 Dec;169(12):1238-44. doi: 10.1176/appi.ajp.2012.12050648.

  PMID: 23212054 BACKGROUND

• Lisanby SH. Electroconvulsive therapy for depression. N Engl J Med. 2007 Nov 8;357(19):1939-45. doi: 10.1056/NEJMct075234. No abstract available.

  PMID: 17989386 BACKGROUND

• Newport DJ, Carpenter LL, McDonald WM, Potash JB, Tohen M, Nemeroff CB; APA Council of Research Task Force on Novel Biomarkers and Treatments. Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression. Am J Psychiatry. 2015 Oct;172(10):950-66. doi: 10.1176/appi.ajp.2015.15040465.

  PMID: 26423481 BACKGROUND

• Sanacora G, Heimer H, Hartman D, Mathew SJ, Frye M, Nemeroff C, Robinson Beale R. Balancing the Promise and Risks of Ketamine Treatment for Mood Disorders. Neuropsychopharmacology. 2017 May;42(6):1179-1181. doi: 10.1038/npp.2016.193. Epub 2016 Sep 19. No abstract available.

  PMID: 27640324 BACKGROUND

• Kumpf KT, Wilkinson ST, Hu B, Chen R, Krishnan K, Chakrabarti S, Rhee TG, Grezmak T, Mathew SJ, Sanacora G, Murrough JW, Goes FS, Collins KA, Barnett BS, Anand A. Comparing the Cognitive Effects of Repeated Intravenous Ketamine and Electroconvulsive Therapy in Patients With Treatment-Resistant Depression: A Secondary Analysis of the ELEKT-D Trial. J Clin Psychiatry. 2025 Sep 3;86(4):25m15781. doi: 10.4088/JCP.25m15781.

  PMID: 40900112 DERIVED

• Anand A, Mathew SJ, Sanacora G, Murrough JW, Goes FS, Altinay M, Aloysi AS, Asghar-Ali AA, Barnett BS, Chang LC, Collins KA, Costi S, Iqbal S, Jha MK, Krishnan K, Malone DA, Nikayin S, Nissen SE, Ostroff RB, Reti IM, Wilkinson ST, Wolski K, Hu B. Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression. N Engl J Med. 2023 Jun 22;388(25):2315-2325. doi: 10.1056/NEJMoa2302399. Epub 2023 May 24.

  PMID: 37224232 DERIVED

• Mathew SJ, Wilkinson ST, Altinay M, Asghar-Ali A, Chang LC, Collins KA, Dale RM, Hu B, Krishnan K, Kellner CH, Malone DA, Murrough JW, Ostroff RB, Sanacora G, Shao M, Anand A. ELEctroconvulsive therapy (ECT) vs. Ketamine in patients with Treatment-resistant Depression: The ELEKT-D study protocol. Contemp Clin Trials. 2019 Feb;77:19-26. doi: 10.1016/j.cct.2018.12.009. Epub 2018 Dec 17.

  PMID: 30572160 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Mental Disorders; Depression; Depressive Disorder, Major; Depressive Disorder

Interventions

Electroconvulsive Therapy; Ketamine

Condition Hierarchy (Ancestors)

Mood Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

Our trial has several limitations. ECT was started with right unilateral placement and was then switched to bilateral placement in the event of inadequate response. The open-label design of our trial could have influenced response. Maintenance treatment was not studied. Other limitations of our trial include a lack of placebo, the flexibility of treatment methods, and a follow-up period during which the patients received treatment as presc

Results Point of Contact

• Title: Dr. Amit Anand
• Organization: Department of Psychiatry, Mass General Brigham, and Harvard Medical School

aanand7@bwh.harvard.edu

6177266421

Study Officials

• Amit Anand, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Due to the nature of the study treatments it is not possible to blind patients or investigators.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Investigator

Model Details: unblinded prospective randomized open-label

Study Record Dates

• First Submitted: February 9, 2017
• First Posted: April 14, 2017
• Study Start: April 7, 2017
• Primary Completion: October 28, 2022
• Study Completion: November 17, 2022
• Last Updated: September 28, 2023
• Results First Posted: August 9, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)