Comparing Ketamine and Propofol Anesthesia for Electroconvulsive Therapy

Treatment Resistant Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01935115
• Other study ID #: UofSKetamine-01
• Status: Completed
• Phase: Phase 4
• First received: August 26, 2013
• Last updated: September 12, 2017
• Start date: September 2013
• Est. completion date: March 2016

Study information

• Verified date: September 2017
• Source: University of Saskatchewan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant
• Treatment Resistant Depression

Intervention

Drug:
• Propofol
Propofol anesthesia for ECT
• Ketamine
Ketamine anesthesia for ECT

Locations

Country	Name	City	State
Canada	Royal University Hospital	Saskatoon	Saskatchewan

Sponsors (4)

Lead Sponsor	Collaborator
University of Saskatchewan	Royal University Hospital Foundation, Saskatoon Health Region, Schulman Research Award

Country where clinical trial is conducted

Canada, 

References & Publications (6)

Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. — View Citation

Diazgranados N, Ibrahim L, Brutsche NE, Newberg A, Kronstein P, Khalife S, Kammerer WA, Quezado Z, Luckenbaugh DA, Salvadore G, Machado-Vieira R, Manji HK, Zarate CA Jr. A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch Gen Psychiatry. 2010 Aug;67(8):793-802. doi: 10.1001/archgenpsychiatry.2010.90. — View Citation

Okamoto N, Nakai T, Sakamoto K, Nagafusa Y, Higuchi T, Nishikawa T. Rapid antidepressant effect of ketamine anesthesia during electroconvulsive therapy of treatment-resistant depression: comparing ketamine and propofol anesthesia. J ECT. 2010 Sep;26(3):223-7. doi: 10.1097/YCT.0b013e3181c3b0aa. — View Citation

Wang X, Chen Y, Zhou X, Liu F, Zhang T, Zhang C. Effects of propofol and ketamine as combined anesthesia for electroconvulsive therapy in patients with depressive disorder. J ECT. 2012 Jun;28(2):128-32. doi: 10.1097/YCT.0b013e31824d1d02. — View Citation

Zarate CA Jr, Brutsche NE, Ibrahim L, Franco-Chaves J, Diazgranados N, Cravchik A, Selter J, Marquardt CA, Liberty V, Luckenbaugh DA. Replication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry. 2012 Jun 1;71(11):939-46. doi: 10.1016/j.biopsych.2011.12.010. Epub 2012 Jan 31. — View Citation

Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	Change in CADSS (Clinician Administered Dissociative States Scale)	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
Secondary	Change in ALS-18 (Affective Lability Scale)	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
Secondary	Change in ECT energy settings and seizure quality	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
Secondary	Hemodynamic instability and respiratory complications	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
Secondary	Time to discharge	Total time spend in the post-anesthetic recovery unit will be recorded.	1 hour after each treatment for an expected average of 4 weeks
Secondary	Change in MADRS score	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
Secondary	The number of ECT sessions required to achieve depression remission (MADRS =10)	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
Secondary	The proportion of depressed patients (MADRS > 20) at 30 days after the last ECT session	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.
Secondary	Change in systolic blood pressure	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