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Updated: Jun 19, 2026
Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method
Published on: August 2, 2021
A randomized, crossover comparison of ketamine and electroconvulsive therapy for treatment of major depressive
Jennifer L Phillips1,2, Natalia Jaworska3,4, Elizabeth Kamler3
1The Royal's Institute of Mental Health Research, 1145 Carling Avenue, Ottawa, ON, K1Z 7K4, Canada. Jennifer.Phillips@theroyal.ca.
Background:
Recent evidence underscores the utility of rapid-acting antidepressant interventions, such as ketamine, in alleviating symptoms of major depressive episodes (MDE). However, to date, there have been limited head-to-head comparisons of intravenous (IV) ketamine infusions with other antidepressant treatment strategies in large randomized trials. This study protocol describes an ongoing multi-centre, prospective, randomized, crossover, non-inferiority trial comparing acute treatment of individuals meeting diagnostic criteria for a major depressive episode (MDE) with ketamine and electroconvulsive therapy (ECT) on efficacy, speed of therapeutic effects, side effects, and health care resource utilization. A secondary aim is to compare a 6-month maintenance strategy for ketamine responders to standard of care ECT maintenance. Finally, through the measurement of clinical, cognitive, neuroimaging, and molecular markers we aim to establish predictors and moderators of treatment response as well as treatment-elicited effects on these outcomes.
Methods:
Across four participating Canadian institutions, 240 patients with major depressive disorder or bipolar disorder experiencing a MDE are randomized (1:1) to a course of ECT or racemic IV ketamine (0.5 mg/kg) administered 3 times/week for 3 or 4 weeks. Non-responders (< 50% improvement in Montgomery-Åsberg Depression Rating Scale [MADRS] scores) crossover to receive the alternate treatment. Responders during the randomization or crossover phases then enter the 6-month maintenance phase during which time they receive clinical assessments at identical intervals regardless of treatment arm. ECT maintenance follows standard of care while ketamine maintenance involves: weekly infusions for 1 month, then bi-weekly infusions for 2 months, and finally monthly infusions for 3 months (returning to bi-weekly in case of relapse). The primary outcome measure is change in MADRS scores after randomized treatment as assessed by raters blind to treatment modality.
Discussion:
This multi-centre study will help identify molecular, imaging, and clinical characteristics of patients with treatment-resistant and/or severe MDEs who would benefit most from either type of therapeutic strategy. In addition to informing clinical practice and influencing health care delivery, this trial will add to the robust platform and database of CAN-BIND studies for future research and biomarker discovery.
Trial Registration:
ClinicalTrials.gov identifier NCT03674671. Registered September 17, 2018.
Insights
This trial compares electroconvulsive therapy (ECT) and ketamine for major depressive episodes (MDE). It investigates efficacy, speed, side effects, and biomarkers to personalize rapid-acting antidepressant treatments.
Area of Science:
- Neuroscience
- Psychiatry
- Clinical Trials
Background:
- Major depressive episodes (MDE) often require rapid-acting interventions.
- Ketamine is a rapid-acting antidepressant, but head-to-head trials are limited.
- This study addresses the need for direct comparisons of ketamine and electroconvulsive therapy (ECT).
Purpose of the Study:
- To compare the efficacy, speed of effect, side effects, and healthcare utilization of ketamine versus ECT for MDE.
- To evaluate a 6-month maintenance strategy for ketamine responders compared to standard ECT maintenance.
- To identify predictors and moderators of treatment response using clinical, cognitive, neuroimaging, and molecular markers.
Main Methods:
- A multi-centre, prospective, randomized, crossover, non-inferiority trial involving 240 patients with MDE.
- Patients are randomized to ECT or intravenous ketamine (0.5 mg/kg) thrice weekly.
- Non-responders crossover to the alternate treatment; responders enter a 6-month maintenance phase.
Main Results:
- Primary outcome is change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores.
- Secondary outcomes include speed of therapeutic effects, side effects, and healthcare resource utilization.
- Biomarkers (clinical, cognitive, neuroimaging, molecular) will be analyzed to predict treatment response.
Conclusions:
- This trial will identify patient characteristics that predict response to ketamine or ECT.
- Findings will inform clinical practice for treatment-resistant and severe MDE.
- The study contributes to the CAN-BIND database for future biomarker discovery.
