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

Ketamine

Brief Summary

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.

Intervention / Treatment

  • Ketamine (DRUG)
    inter venous injections
  • Midazolam (DRUG)
    inter venous injections

Condition or Disease

  • Treatment Resistant Depression
  • Major Depressive Disorder
  • Severe Depression

Phase

  • Not Applicable

    • Study Design

    Study type: INTERVENTIONAL
    Status: Completed
    Study results: No Results Available
    Age: 18 Years to 65 Years
    Enrollment: 15 (ACTUAL)
    Funded by: Other
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    QUADRUPLE:
    • Participant
    • Care Provider
    • Investigator
    • Outcomes Assessor

    Clinical Trial Dates

    Start date: Aug 01, 2015
    Primary Completion: Mar 01, 2018 ACTUAL
    Completion Date: Mar 01, 2018 ACTUAL
    Study First Posted: Aug 13, 2015 ESTIMATED
    Results First Posted: Aug 29, 2019 ACTUAL
    Last Updated: Aug 28, 2019

    Sponsors / Collaborators

    Lead Sponsor: The Cleveland Clinic
    Responsible Party: N/A

    Location

    Cleveland, Ohio, USA

    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.

    Participant Groups

    • Subjects who are randomized to be on this group will receive a standard dose of ketamine interleaved with Electroconvulsive Treatments.

    • Subjects who are randomized to be on this group will receive midazolam infusions interleaved with Electroconvulsive Treatments.

    Eligibility Criteria

    Sex: All
    Minimum Age: 18
    Maximum Age: 65
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    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.

    Primary Outcomes

    • Change in HAMD-17 at Infusion 6. Scores range from 0 to 50, with higher scores representing more depression.

    • 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

    Secondary Outcomes

    • MoCA scores range between 0 and 30. Higher scores reflect higher cognition.

    • The number of words remembered are recorded. Scores range from 0 to 12 with higher scores reflecting better acquisition.

    • 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.

    • Count of the patients who showed response (\>50% decrease).

    More Details

    NCT Number: NCT02522377
    Other IDs: Ketamine ECT
    Study URL: https://clinicaltrials.gov/study/NCT02522377
    Last updated: Sep 29, 2023