Canadian Researchers Propose Head-to-Head Trial Protocol of Ketamine vs Electroconvulsive Therapy

A randomized study protocol is presented which is designed to compare antidepressant ketamine with electroconvulsive therapy for the treatment of major depressive episodes.

Researchers from Canada presented a randomized study protocol designed to compare antidepressant ketamine with electroconvulsive therapy for the treatment of major depressive episodes (MDEs), according to a paper published in BMC Psychiatry.

Phillips and colleagues presented the protocol in an effort to highlight the limited number of large randomized trials that have provided a head-to-head comparison of intravenous ketamine infusions with other antidepressant regimens.

The investigators describe a study conducted across 4 Canadian institutions with a planned enrollment of 240 patients with major depressive disorder or bipolar disorder. Only patients with MDEs are eligible for inclusion in the study. Patients in the trial would be randomized (1:1) to either electroconvulsive therapy or racemic intravenous ketamine at 0.5 mg/kg, which would be administered 3 times per week for 3 or 4 weeks. This trial compares the efficacy, speed of therapeutic effects, side effect profiles, and health care resource use associated with ketamine and ECT.

Nonresponders, defined as a <50% improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS) score, could crossover to the alternate treatment. Those who do respond during either the randomization or crossover phase would have the option to enter a 6-month maintenance phase. During the maintenance phase, patients would undergo clinical assessments. Maintenance with electroconvulsive therapy would involve standard of care, whereas ketamine maintenance would include weekly treatment infusions for 1 month followed by bi-weekly infusions for 2 months and then monthly infusions for 3 months. Treatment will return to bi-weekly administration if the patient relapses.

The primary outcome measure would include the change in MADRS score. Additionally, investigators of this trial would assess clinical, cognitive, neuroimaging, and molecular biomarkers to identify predictive elements and moderators of therapy response.

The researchers who proposed this treatment protocol suggest that the identification of “biomarkers of response to electroconvulsive therapy or ketamine could shorten delay to clinical improvement and increase remission rates.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Phillips JL, Jaworska N, Kamler E, et al. A randomized, crossover comparison of ketamine and electroconvulsive therapy for treatment of major depressive episodes: a Canadian biomarker integration network in depression (CAN-BIND) study protocol. BMC Psychiatry. 2020;20(1):268.