Behavioural Activation Therapy and Ketamine for Treatment-Resistant Depression

Summary

The goal of this clinical trial is to see if combining ketamine with behavioral activation (BA) therapy to treat moderate to severe treatment-resistant depression improves depressive symptoms and general functioning more than ketamine alone.

We aim to find out whether participants who receive both treatments:

1. Have greater reductions in depression symptoms than those who receive ketamine only
2. Have better response and remission rates than those who receive ketamine only
3. Experience better overall functioning, including mood, anxiety, quality of life, and physical activity than those who receive ketamine only

Participants will be randomized to one of two groups: Arm 1) concurrent ketamine and BA therapy started from treatment initiation, or Arm 2) ketamine treatment alone.

* All participants will undergo IV ketamine infusions administered twice weekly for three weeks.
* Half of the participants in will also undergo BA therapy sessions twice weekly for three weeks.
* Individuals with a sufficient treatment response after 3 weeks will proceed to undergo an additional 12 weeks of ketamine infusions (and those receiving BA therapy will continue to receive therapy for an additional 12 weeks).

Conditions

• Treatment Resistant Depression
• Major Depressive Disorder (MDD)

Interventions

DRUG

Ketamine (0.5 mg/kg)

IV ketamine will be administered under medical supervision at a fixed dose of 0.5 mg/kg infused over 40 minutes. Treatments will be administered twice weekly for three weeks during the Induction Phase (6 treatments). Participants' response to ketamine will be assessed after the Induction Phase. Those who do not meet response criteria (\<50% reduction in MADRS score) will be deemed Nonresponders and will conclude receiving ketamine at that time. Those who meet the response criteria (≥50% reduction in MADRS score) will be deemed Responders and will proceed to the Maintenance Phase. During the Maintenance Phase, ketamine treatments will be administered once weekly for 8 weeks (8 treatments), followed by once biweekly for four weeks during the Discharge Preparation Phase (2 treatments). Responders will receive a total of 16 ketamine infusions over 15 weeks.

BEHAVIORAL

Behavioural Activation Therapy

BA therapy is a structured, primarily talk therapy that focuses on helping people with depression increase engagement in positive, meaningful activities and reduce avoidance behaviors that reinforce low mood. The BA therapy protocol will be based on the approach described by Martell et al. (2022). Therapy sessions will be delivered virtually or in person according to participant preference. Participants in Arm 1 will receive a total of 16 BA sessions at a frequency of twice weekly for 3 weeks during the Induction Phase (6 sessions), once weekly for 8 weeks during the Maintenance Phase (8 sessions), and once biweekly for 4 weeks during the Discharge Preparation Phase (2 sessions). BA therapy sessions can occur on the same day as ketamine infusions, but not during or after the infusion.

Sponsors & Collaborators

• The Royal's Institute of Mental Health Research

  lead OTHER

Principal Investigators

• Jeanne Talbot, MD, PhD · The University of Ottawa Institute of Mental Health Research (IMHR) at The Royal

• Jennifer Phillips, PhD · The University of Ottawa Institute of Mental Health Research (IMHR) at The Royal

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-09-30

Primary Completion

2029-09-30

Completion

2029-09-30

Countries

• Canada

Study Locations