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

NCT ID: NCT03113968

Last Updated: 2023-09-28

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

403 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-04-07

Study Completion Date

2022-11-17

Brief Summary

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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.

Detailed Description

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Patients with treatment resistant depression who meet all inclusion criteria and do not meet any exclusion criteria will be randomized to either electroconvulsive therapy (ECT) three times per week or ketamine infusion two times per week. Patients will answer questionnaires about their symptoms prior to treatments. The acute treatment phase of the study will last three to five weeks. Depending on response to treatment, some patients will be followed for an additional six months.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

unblinded prospective randomized open-label
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Due to the nature of the study treatments it is not possible to blind patients or investigators.

Study Groups

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electroconvulsive therapy (ECT)

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.

Group Type ACTIVE_COMPARATOR

electroconvulsive therapy (ECT)

Intervention Type 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.

ketamine infusion

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.

Group Type ACTIVE_COMPARATOR

Ketamine

Intervention Type 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.

Interventions

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electroconvulsive therapy (ECT)

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.

Intervention Type PROCEDURE

Ketamine

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Written informed consent before any study related procedures are performed
2. Inpatients or outpatients referred by their providers for ECT treatment and eligible for ECT treatment
3. Males/females at least 21 years of age but no older than 75 years of age
4. 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)
5. A current depressive episode that has lasted a minimum of 4 weeks
6. 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
7. 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.
8. 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

Exclusion Criteria

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

21 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role collaborator

Bo Hu

OTHER

Sponsor Role lead

Responsible Party

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Bo Hu

Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Amit Anand, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

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Yale School of Medicine

New Haven, Connecticut, United States

Site Status

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Site Status

Mount Sinai

New York, New York, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Countries

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United States

References

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

Reference Type BACKGROUND
PMID: 17640154 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23212054 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 17989386 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26423481 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27640324 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40900112 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37224232 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30572160 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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ELEKT-D

Identifier Type: -

Identifier Source: org_study_id

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