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

Study Overview
=================
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.

Detailed Description
-----------------
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.

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

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

Intervention / Treatment
-----------------
* Procedure: electroconvulsive therapy (ECT)
* Drug: Ketamine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Exclusion Criteria: Meet DSM-5 criteria for bipolar disorder, schizophrenia, schizophreniform disorder, schizoaffective disorder, mental retardation, or pervasive developmental disorder Meets any exclusion criteria for ECT or ketamine treatment as described in the clinical guidelines or according to investigator judgment 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

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: unblinded prospective randomized open-label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: electroconvulsive therapy (ECT)<br>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)<br>* 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.<br>|
| Active Comparator: ketamine infusion<br>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<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Responses Based on the Montgomery-Åsberg Rating Scale (MADRS) | The outcome measure was the percentage of responders at the end-of-treatment visit, defined as a ≥50% decrease in MADRS score from the baseline visit (i.e., first treatment visit) to the end-of-treatment visit (within 3 days of last treatment). | Acute Study Phase (Baseline Visit to End of Treatment Visit) - approximately 3-5 weeks |