Behavioural Activation Therapy and Ketamine for Treatment-Resistant Depression

Sponsor
The Royal's Institute of Mental Health Research
Study ID
NCT07801703
Phase
PHASE2/PHASE3
Status
Not Yet Recruiting

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Conditions

  • Major Depressive Disorder (MDD)
  • Treatment Resistant Depression

Eligibility Criteria

Sex
ALL
Age
18 Years - 65 Years
Healthy Volunteers
Not accepted

Interventions

  • Ketamine (0.5 mg/kg) — DRUG
    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.
  • Behavioural Activation Therapy — BEHAVIORAL
    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.

Study Details

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).

Key Dates

First listed
Sep 3, 2026
Start date
Sep 30, 2026
Status verified
Aug 2026
Primary completion
Sep 30, 2029
Completion
Sep 30, 2029

Study Design

Enrollment
60 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm 1: Ketamine + Behavioural Activation Therapy
    Participants receive IV ketamine infusions and concurrent BA therapy, both administered twice weekly for three weeks (Induction Phase). Responders to Induction Phase treatment will proceed to undergo an additional 12 weeks of ketamine infusions and BA therapy in the Maintenance and Discharge Preparation Phases (weekly for 8 weeks, then every other week for 4 weeks, respectively). Nonresponders to the Induction Phase will cease receiving ketamine infusions and will undergo an additional 12 weeks of BA therapy in the Maintenance and Discharge Preparation Phases (weekly for 8 weeks, then every other week for 4 weeks).
  • Active Comparator: Arm 2: Ketamine Only
    Participants will undergo IV ketamine infusions administered twice weekly for three weeks (Induction Phase). Responders to Induction Phase treatment will proceed to undergo an additional 12 weeks of ketamine infusions in the Maintenance and Discharge Preparation Phases (weekly for 8 weeks, then every other week for 4 weeks, respectively). Nonresponders to the Induction Phase will complete their study participation at this point.

Primary Outcome Measure

Change in MADRS from Baseline [ Time Frame: Week 0 to end of Week 3 and end of Week 15 ]

Central Contacts

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