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

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

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder; Treatment Resistant Depression; Severe Depression
• Intervention / Treatment: Drug: Ketamine; Drug: Midazolam

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation Center for Behavioral Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males/females at least 18 years of age but no older than 65 years of age
2. 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)
3. A current depressive episode that has lasted a minimum of 4 weeks.
4. Have > 3 trials of antidepressants/augmentation strategies.
5. Have a support system capable of transporting the patient post-treatment.

Exclusion Criteria:

1. Meeting Diagnostic and Statistical Manual of Mental Disorders criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, mental retardation, pervasive developmental disorder.
2. 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.
3. Patients who meet exclusion criteria for ketamine and/or midazolam infusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ketamine Infusions; Subjects who are randomized to be on this group will receive a standard dose of ketamine interleaved with Electroconvulsive Treatments.	Drug: Ketamine; inter venous injections; Other Names: Ketalar; Calypsol; Ketanest; Tekam
ACTIVE_COMPARATOR: Midazolam; Subjects who are randomized to be on this group will receive midazolam infusions interleaved with Electroconvulsive Treatments.	Drug: Midazolam; inter venous injections; Other Names: Versed; Dormicum; Hypnovel

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Murat Altinay, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (ACTUAL): March 1, 2018
• Study Completion (ACTUAL): March 1, 2018

Study Registration Dates

• First Submitted: August 7, 2015
• First Submitted That Met QC Criteria: August 12, 2015
• First Posted (ESTIMATE): August 13, 2015

Study Record Updates

• Last Update Posted (ACTUAL): August 29, 2019
• Last Update Submitted That Met QC Criteria: August 28, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Ketamine; Electroconvulsive Therapy; Major Depressive Disorder; Treatment Resistant Depression; Severe depression; electroconvulsive treatment
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Ketamine; Midazolam
• Other Study ID Numbers: Ketamine ECT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED