Comparing Ketamine and Propofol Anesthesia for Electroconvulsive Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University of Saskatchewan
Sponsor:
Collaborators:
Saskatoon Health Region
Royal University Hospital Foundation
Schulman Research Award
Information provided by (Responsible Party):
University of Saskatchewan
ClinicalTrials.gov Identifier:
NCT01935115
First received: August 26, 2013
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Treatment Resistant Depression
Drug: Propofol
Drug: Ketamine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Prospective Randomized Double Blinded Control Trial Using Ketamine or Propofol Anesthesia for Electroconvulsive Therapy: Improving Treatment-Resistant Depression

Resource links provided by NLM:


Further study details as provided by University of Saskatchewan:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • Change in ALS-18 (Affective Lability Scale) [ Time Frame: 30 days after final ECT session for an expected average duration of 2 months ] [ Designated as safety issue: No ]
    A baseline ALS-18 score will be obtained. 30 days after completion of therapy, another score will be collected.

  • Change in ECT energy settings and seizure quality [ Time Frame: Within 30 minutes of each treatment for an expected average of 4 weeks ] [ Designated as safety issue: No ]
    We will document energy settings used by the psychiatrist as well as duration and quality of seizures achieved.

  • Hemodynamic instability and respiratory complications [ Time Frame: 1 hour after each ECT for an expected average of 4 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Time to discharge [ Time Frame: 1 hour after each treatment for an expected average of 4 weeks ] [ Designated as safety issue: No ]
    Total time spend in the post-anesthetic recovery unit will be recorded.

  • Change in MADRS score [ Time Frame: 24 hours after each treatment and 30 days after final treatment for an expected average of 2 months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 72
Study Start Date: September 2013
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Propofol
The control group will receive propofol 1 mg/kg
Drug: Propofol
Propofol anesthesia for ECT
Other Name: Diprivan
Experimental: Ketamine
Study group will receive ketamine 0.75 mg/kg intravenously
Drug: Ketamine
Ketamine anesthesia for ECT
Other Name: Ketalar

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01935115

Contacts
Contact: Jonathan Gamble, MD 1-306-655-1183 J_Gamble@yahoo.com
Contact: Rudy Bowen, MD 1-306-966-8223 R.Bowen@usask.ca

Locations
Canada, Saskatchewan
Royal University Hospital Recruiting
Saskatoon, Saskatchewan, Canada, S7N 0W8
Principal Investigator: Jonathan Gamble, MD         
Sponsors and Collaborators
University of Saskatchewan
Saskatoon Health Region
Royal University Hospital Foundation
Schulman Research Award
Investigators
Principal Investigator: Jonathan Gamble, MD University of Saskatchewan
  More Information

Publications:

Responsible Party: University of Saskatchewan
ClinicalTrials.gov Identifier: NCT01935115     History of Changes
Other Study ID Numbers: UofSKetamine-01
Study First Received: August 26, 2013
Last Updated: April 22, 2014
Health Authority: Canada: Health Canada

Keywords provided by University of Saskatchewan:
Depression
MDD
Treatment Resistant Depression
Electroconvulsive Therapy
ECT
Ketamine
Propofol
NMDA

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders
Anesthetics
Ketamine
Propofol
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Hypnotics and Sedatives

ClinicalTrials.gov processed this record on September 14, 2014