Administration of Subanesthetic Dose of Ketamine and Electroconvulsive Treatment for Treatment Resistant Depression

Study Overview
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Brief Summary
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In this proof of concept study, the investigators plan to administer iv ketamine interleaved with ECT days. Patients with treatment resistant depression who are deemed to be eligible for ECT treatment will randomly be assigned to either ketamine or active placebo.

Detailed Description
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The study will compare the effects of standard ketamine dosing with an active placebo arm. Hypothesis 1: The investigators hypothesize that interleaved Electroconvulsive Treatment and active ketamine treatment will lead to a meaningful clinical improvement compared to Electroconvulsive Treatment and placebo treatment arm. Hypothesis 2: The investigators hypothesize that interleaved Electroconvulsive Treatment and active ketamine treatment will attenuate cognitive side effects. Methods and Design: Patients with treatment resistant depression who are deemed to be eligible for Electroconvulsive Treatment will randomly be assigned to either ketamine or active placebo Electroconvulsive Treatments: All patients (independent of their depression scores) will receive the same Electroconvulsive Treatment parameters: Bi-frontal brief pulse (0.5 miliseconds) Electroconvulsive Treatment administered by using Thymatron Electroconvulsive Treatment machine. Study blinding: Neither the patients, nor the treating psychiatrist or the nurse will be aware of the patient's assigned arm. The success of blinding will be tested after each ketamine treatment with a questionnaire given to the subject, raters, and treating physician.

Official Title
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Administration of Subanesthetic Dose of Ketamine and Electroconvulsive Treatment on Alternate Week Days in Patients With Treatment Resistant Depression: A Double Blind Placebo Controlled Trial

Conditions
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Treatment Resistant Depression, Major Depressive Disorder, Severe Depression

Intervention / Treatment
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* Drug: Ketamine
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males/females at least 18 years of age but no older than 65 years of age Meet Diagnostic and Statistical Manual of Mental Disorders-4th Edition (DSM-IV) criteria for Major Depression or Bipolar Disorder, depressed phase, as determined by a clinician's diagnostic evaluation and confirmed by interview using the Mini International Neuropsychiatric Interview (MINI PLUS 5.0.0) A current depressive episode that has lasted a minimum of 4 weeks. Have > 3 trials of antidepressants/augmentation strategies. Have a support system capable of transporting the patient post-treatment. Exclusion Criteria: Meeting Diagnostic and Statistical Manual of Mental Disorders criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, mental retardation, pervasive developmental disorder. Meeting Diagnostic and Statistical Manual of Mental Disorders criteria for other substance/alcohol dependence within the past 6 months or abuse in the past 3 months. Patients who meet exclusion criteria for ketamine and/or midazolam infusion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine Infusions<br>Subjects who are randomized to be on this group will receive a standard dose of ketamine interleaved with Electroconvulsive Treatments. | Drug: Ketamine<br>* inter venous injections<br>* Other names: Tekam;|
| Active Comparator: Midazolam<br>Subjects who are randomized to be on this group will receive midazolam infusions interleaved with Electroconvulsive Treatments. | Drug: Midazolam<br>* inter venous injections<br>* Other names: Versed;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Rating Scale (HAMD-17) at Last Infusion | Change in HAMD-17 at Infusion 6. Scores range from 0 to 50, with higher scores representing more depression. | visit 17 | 
| Montgomery Asberg Depression Rating Scale (MADRS) at Last Infusion | Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60 | visit 17 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montreal Cognitive Assessment (MOCA) at Last Infusion | MoCA scores range between 0 and 30. Higher scores reflect higher cognition. | visit 17 | 
| Hopkins Verbal Learning Test - Revised (HVLT-R) at Last Infusion | The number of words remembered are recorded. Scores range from 0 to 12 with higher scores reflecting better acquisition. | visit 17 | 
| Controlled Oral Word Association Test (COWAT) at Last Infusion | This is a verbal fluency measure. Outcome is the count of words that meet criteria within 1 minute, so the minimum is 0 and no fixed maximum exists. Higher scores reflect a better outcome. | visit 17 | 
| Responder Rate on HAMD-17 by Last Infusion | Count of the patients who showed response (>50% decrease). | visit 17 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketamine, Electroconvulsive Therapy, Major Depressive Disorder, Treatment Resistant Depression, electroconvulsive treatment, Severe depression