A Prospective Randomized Double Blinded Control Trial Using Ketamine or Propofol Anesthesia for Electroconvulsive Therapy: Improving Treatment-Resistant Depression
Overview
- Phase
- Phase 4
- Intervention
- Propofol
- Conditions
- Treatment Resistant Depression
- Sponsor
- University of Saskatchewan
- Enrollment
- 27
- Locations
- 1
- Primary Endpoint
- 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.
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
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.
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.
Investigators
Jonathan Gamble
M.D.
University of Saskatchewan
Eligibility 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
Arms & Interventions
Propofol
The control group will receive propofol 1 mg/kg and remifentanil 1 mcg/kg intravenously
Intervention: Propofol
Ketamine
Study group will receive ketamine 0.75 mg/kg and remifentanil 1 mcg/kg intravenously
Intervention: Ketamine
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Change in CADSS (Clinician Administered Dissociative States Scale)(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)(30 days after final ECT session for an expected average duration of 2 months)
- Change in ECT energy settings and seizure quality(Within 30 minutes of each treatment for an expected average of 4 weeks)
- Hemodynamic instability and respiratory complications(1 hour after each ECT for an expected average of 4 weeks)
- Time to discharge(1 hour after each treatment for an expected average of 4 weeks)
- Change in MADRS score(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)(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(30 days after the last ECT session, up to 60 days after ECT initiation.)
- Change in systolic blood pressure(During ECT, up to 8 treatments or 4 weeks)