Comparing Ketamine and Propofol Anesthesia for Electroconvulsive Therapy

September 12, 2017 updated by: Jonathan Gamble, University of Saskatchewan

A Prospective Randomized Double Blinded Control Trial Using Ketamine or Propofol Anesthesia for Electroconvulsive Therapy: Improving Treatment-Resistant Depression

To determine the effect of ketamine, compared to propofol, when used an an anesthetic agent for electroconvulsive therapy (ECT) in the treatment of major depressive disorder (MDD). We hypothesize that ketamine, compared to propofol, will improve the the symptoms of MDD when used as the anesthetic agent to facilitate ECT. Additionally, we hypothesize the dissociative and cardiovascular effects of ketamine will be minimal.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Treatment resistant depression is a common and disabling condition. The delayed onset of action and side effects exhibited by oral antidepressants are significant limitations. An alternative and well-established therapy is electroconvulsive therapy (ECT). ECT has rapid antidepressant effect beginning with the completion of the first session. Nevertheless, like oral medications, patients treated with ECT can develop treatment resistance or failure to respond. There is great need for a novel approach to treatment-resistant depression; one that that is safe, has rapid onset, and is sustained.

Pharmaceutical agents with rapid antidepressant effects are a new and promising paradigm in the research for treatment of MDD. A potential therapeutic target is glutamate based signal transmission because glutamate transmission is abnormally regulated in the limbic/cortical areas of many depressed people. Glutamatergic modulating agents, in particular ketamine, have been shown to induce rapid antidepressant effects both in both preclinical models and humans. Additionally, ketamine has been shown to have persistent antidepressive effect.

Presently worldwide, propofol is one of the most commonly used anesthetic agents for ECT. There are 2 main disadvantages to this practice. First, propofol has no antidepressive effect. Second, propofol is a potent anticonvulsant that may worsen the quality of the ECT induced seizures. A recent open-label trial compared ketamine to propofol for anesthesia during ECT and demonstrated a significant improvement of depression in the ketamine arm. Ketamine is routinely used to provide safe general anesthesia as well as procedural sedation, analgesia, and amnesia. The combination of the intrinsic antidepressant effects of ketamine with electroconvulsive therapy is a promising concept in clinical research.

This study will include planned interim analysis to ensure patients safety. This analysis will be performed by a statistician who is blinded to group allocation after 20 and after 40 patients. An independent safety committee will informed of the results of the interim analysis including side effects and complications and will have the option to adjust the drug dosage or to discontinue the trial.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 0W8
        • Royal University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Fulfill the diagnostic criteria for major depression according to the Diagnostic and Statistical Manual of Mental Disorders (most recent edition)
  • Failure to respond to at least 2 adequate drug therapies for the current depression episode
  • MADRS score of 20 or above (moderate - severe
  • ASA physical status classification I to III

Exclusion Criteria:

  • Inability to obtain informed consent
  • ASA physical status classification IV
  • Complication by any serious physical diseases such as cardiovascular disease (including untreated HTN), respiratory disease, cerebrovascular disease, intracranial HTN (including glaucoma), or seizures
  • Presence of foreign body (including pacemaker)
  • Pregnancy
  • Allergies to anesthetics used in study Includes: a) Ketamine b) Propofol c) Eggs d) Egg products e) Soybeans f) Soy products

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Propofol
The control group will receive propofol 1 mg/kg and remifentanil 1 mcg/kg intravenously
Drug: Propofol
Propofol anesthesia for ECT
Other Names:
  • Diprivan
Experimental: Ketamine
Study group will receive ketamine 0.75 mg/kg and remifentanil 1 mcg/kg intravenously
Drug: Ketamine
Ketamine anesthesia for ECT
Other Names:
  • Ketalar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The primary outcome is defined as the number of ECT treatments required to reach a 50% reduction in baseline MADRS (Montgomery-Asberg Depression Scale) score.
Time Frame: After 8 treatments or completion of therapy for an expected average of 4 weeks
Standard of care for ECT in the Saskatoon Health Region are biweekly sessions for a total of 8 treatments. Occasionally, a patient meets early remission and may not require the full 8 treatments and may be eligible for early withdrawal.
After 8 treatments or completion of therapy for an expected average of 4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in CADSS (Clinician Administered Dissociative States Scale)
Time Frame: 30 minutes after each ECT session and one day after each ECT session for an expected average of 4 weeks
The CADSS is used to assess states of clinical dissociation; a potential side effect of ketamine. A baseline CADSS will be obtained one day prior to start of ECT. Additional scores will be assessed 30 minutes after each therapy as well as one day post-therapy on the ward.
30 minutes after each ECT session and one day after each ECT session for an expected average of 4 weeks
Change in ALS-18 (Affective Lability Scale)
Time Frame: 30 days after final ECT session for an expected average duration of 2 months
A baseline ALS-18 score will be obtained. 30 days after completion of therapy, another score will be collected.
30 days after final ECT session for an expected average duration of 2 months
Change in ECT energy settings and seizure quality
Time Frame: Within 30 minutes of each treatment for an expected average of 4 weeks
We will document energy settings used by the psychiatrist as well as duration and quality of seizures achieved.
Within 30 minutes of each treatment for an expected average of 4 weeks
Hemodynamic instability and respiratory complications
Time Frame: 1 hour after each ECT for an expected average of 4 weeks
Any hemodynamic or respiratory instability requiring unanticipated intervention will be recorded as well as the treatment for the event recorded. Type of intervention will also be documented.
1 hour after each ECT for an expected average of 4 weeks
Time to discharge
Time Frame: 1 hour after each treatment for an expected average of 4 weeks
Total time spend in the post-anesthetic recovery unit will be recorded.
1 hour after each treatment for an expected average of 4 weeks
Change in MADRS score
Time Frame: 24 hours after each treatment and 30 days after final treatment for an expected average of 2 months
A baseline MADRS score will be conducted one day prior to ECT. Additional scores will be obtained one day after each ECT session. A final MADRS score will be assessed 30 days after completion of ECT.
24 hours after each treatment and 30 days after final treatment for an expected average of 2 months
The number of ECT sessions required to achieve depression remission (MADRS ≤10)
Time Frame: Number of ECT treatments to achieve depression remission (MADRS) or completion of therapy up to 4 weeks
Standard of care for ECT in the Saskatoon Health Region are biweekly sessions for a total of 8 treatments. Occasionally, a patient meets early remission and may not require the full 8 treatments and may be eligible for early withdrawal.
Number of ECT treatments to achieve depression remission (MADRS) or completion of therapy up to 4 weeks
The proportion of depressed patients (MADRS > 20) at 30 days after the last ECT session
Time Frame: 30 days after the last ECT session, up to 60 days after ECT initiation.
The proportion of patients in each group who have severe depression 30 days after their last ECT session. This is a measure of longer term efficacy of treatment effect.
30 days after the last ECT session, up to 60 days after ECT initiation.
Change in systolic blood pressure
Time Frame: During ECT, up to 8 treatments or 4 weeks
Increases or decreases in baseline systolic blood pressure at any point during the anesthetic care will be categorically recorded as minimal change (20 - 50 mm Hg from baseline) and significant change (more than 50 mm Hg from baseline)
During ECT, up to 8 treatments or 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Saskatchewan

Collaborators

Royal University Hospital Foundation
Saskatoon Health Region
Schulman Research Award

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Actual)

March 1, 2016

Study Completion (Actual)

March 1, 2016

Study Registration Dates

First Submitted

August 26, 2013

First Submitted That Met QC Criteria

August 29, 2013

First Posted (Estimate)

September 4, 2013

Study Record Updates

Last Update Posted (Actual)

September 13, 2017

Last Update Submitted That Met QC Criteria

September 12, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UofSKetamine-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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