Effects of Low-dose Ketamine as an Adjunct to Propofol-based Anesthesia for Electroconvulsive Therapy

NCT02579642 | Completed Phase 4 DMC

• 1 other identifier: PRO00044771
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

Ketamine has been used successfully as the sole medication for anesthesia in the setting of electroconvulsive therapy (ECT), and has more recently been studied as an adjunct agent in combination with propofol (the most commonly used anesthetic agent) to induce anesthesia for ECT. New literature postulates an anti-depressant effect of ketamine, which in ECT specifically may be helpful with regards to the overall goals of therapy (i.e. ECT indicated for severe or treatment-resistant depression). Current research focusing on ketamine with respect to its anti-depressant effect suggests it may even represent an alternative to ECT. This study will seek to determine whether ketamine when used in low-doses as an adjunct to propofol-based anesthesia for ECT has anti-depressant effects and whether it influences the characteristics of recovery from anesthesia in the ECT setting (i.e. vital sign parameters such as blood pressure and heart rate, quality of recovery, etc.).

Conditions

Depressive Disorder

Keywords

Moderate to severe depression; Monopolar; Bipolar; Ketamine; ECT; Electroconvulsive therapy; NMDA

Outcome Measures

Primary Outcomes (1)

• Number of treatments to achieve 50% change (reduction) in Montgomery Ashberg Depression Rating Scale (MADRS)

  Defined a priori as "response". Assessed at baseline, 24 hours after ECT treatments for the duration of the study and then once at 6 weeks.

  6 weeks

Secondary Outcomes (7)

• Number of treatments to achieve 25% change (reduction) in MADRS

  6 weeks

• Change in Clinical Global Impression - Severity (CGI-S) scores

  6 weeks

• Changes in blood pressure seen during ECT

  4 weeks

• Changes in heart rate seen during ECT

  4 weeks

• Changes in oxygen saturation seen during ECT

  4 weeks

Other Outcomes (1)

• Changes in seizure duration during ECT

  4 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Propofol at usual induction doses for ECT (0.75 - 1 mg/kg IV bolus) with placebo (normal saline)

Drug: Placebo

Ketamine

EXPERIMENTAL

Propofol at usual induction doses for ECT (0.75 - 1 mg/kg IV bolus) with the addition of low-dose ketamine 0.2 mg/kg (or 0.5 mg/kg - see interim analysis)

Drug: Ketamine

Interventions

Ketamine DRUG

Low dose ketamine 0.2 mg/kg (or 0.5 mg/kg depending on results of interim analysis) administered with usual induction drugs for ECT

Also known as: Ketalar

Ketamine

Placebo DRUG

Normal saline administered with usual induction drugs for ECT

Also known as: Normal saline, 0.9% NS

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• referred for ECT with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of major depressive disorder
• considered American Society of Anesthesiologists (ASA) Physical Class I - III
• baseline MADRS score greater than 24 (i.e. at least moderate to severe depression)
• a "first" or "new" episode of depression which has lasted not more than 3 months and requires ECT treatment as judged by a psychiatrist

You may not qualify if:

• ASA Class IV or V as judged by the anesthesiologist
• Any ECT treatment in the previous three months
• Inability or refusal to provide informed consent
• A history of allergic reactions, hypersensitivity, or intolerance to anesthetics or their constituents used in the study (ketamine, propofol, egg phosphatide, soybean oil)
• Anyone taking medications considered contraindicated for ECT or for general anesthesia
• Presence of any of the following DSM-IV diagnoses: Substance or alcohol dependence at enrolment (except dependence in full remission, and except for caffeine or nicotine dependence), abuse of opiates, amphetamines, barbiturates, cocaine, cannabis, or hallucinogen abuse in the 4 weeks prior to enrolment, pervasive developmental disorder, dementia
• Significant medical condition that would contraindicate the use of ketamine, propofol or that is untreated and would need urgent attention (as determined by treating physician)
• Medical conditions that would significantly affect absorption, distribution, metabolism, or excretion of ketamine or propofol
• Unstable or inadequately treated medical illness (e.g. congestive heart failure, angina pectoris, hypertension) as judged by the investigator
• Patients with increased risk of laryngospasm (such as active pulmonary infection, upper respiratory infection, asthma), increased intracranial pressure, glaucoma, thyroid disease/hyperthyroidism
• Any clinically significant deviation from the reference range in clinical laboratory test results as judged by the investigator
• Pregnancy (or female of child-bearing age not using adequate contraception) or lactation
• Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements

Sponsors & Collaborators

• University of Alberta: lead
• Alberta Health services: collaborator

Study Sites (2)

Alberta Hospital Edmonton

Edmonton, Alberta, T5J 2J7, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Related Publications (5)

• 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.

  PMID: 19935085 BACKGROUND

• 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.

  PMID: 22622291 BACKGROUND

• Larkin GL, Beautrais AL. A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department. Int J Neuropsychopharmacol. 2011 Sep;14(8):1127-31. doi: 10.1017/S1461145711000629. Epub 2011 May 5.

  PMID: 21557878 BACKGROUND

• Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, Iqbal S, Pillemer S, Foulkes A, Shah A, Charney DS, Mathew SJ. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013 Oct;170(10):1134-42. doi: 10.1176/appi.ajp.2013.13030392.

  PMID: 23982301 BACKGROUND

• Woolsey AJ, Nanji JA, Moreau C, Sivapalan S, Bourque SL, Ceccherini-Nelli A, Gragasin FS. Low-dose ketamine does not improve the speed of recovery from depression in electroconvulsive therapy: a randomized controlled trial. Braz J Psychiatry. 2022 Jan-Feb;44(1):6-14. doi: 10.1590/1516-4446-2020-1705.

  PMID: 34076068 DERIVED

MeSH Terms

Conditions

Depressive Disorder

Interventions

Ketamine; Saline Solution

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Ferrante S Gragasin, MD, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Clinical Professor and Postgraduate Research Director

Study Record Dates

• First Submitted: October 13, 2015
• First Posted: October 19, 2015
• Study Start: October 1, 2015
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2019
• Last Updated: April 28, 2021

Record last verified: 2021-04

Locations

CA (2)