Behavioural Activation Therapy and Ketamine for Treatment-Resistant Depression

This phase III study is a single‐site, prospective, parallel‐arm, randomizedproof‐of‐concept clinical trial designed to estimate the preliminary effects ofaugmenting repeated IV ketamine treatment with concurrent BA therapy, in individualsexperiencing moderate to severe treatment resistant depressive episode.The overall goal of this work is to maximize and sustain the beneficial effects ofketamine through combined treatment with BA therapy. The central hypothesis is thatpatients treated concurrently with ketamine and BA will demonstrate preliminary evidenceof benefit, reflected by greater improvement in depressive symptoms andparticipant‐reported functional outcomes compared to those treated with ketamine alone.Participants will be randomized to one of two groups: Arm 1) concurrent ketamine and BAtherapy started from treatment initiation, or Arm 2) ketamine treatment alone. Both armswill undergo IV ketamine infusions administered twice weekly for three weeks (InductionPhase). Participants in Arm 1 will also undergo BA therapy sessions twice weekly forthree weeks during the Induction Phase. Responders to Induction Phase treatment (definedas ≥50% reduction in MADRS total scores from Baseline to end of Induction Phase) willproceed to undergo an additional 12 weeks of ketamine infusions in the Maintenance andDischarge Preparation Phases (weekly for 8 weeks, then every other week for 4 weeks,respectively). Nonresponders to the Induction Phase (<50% reduction in MADRS totalscores) will cease receiving ketamine infusions. Those in Arm 2 (ketamine alone) willcomplete their study participation at this point. Those in Arm 1 (BA+ketamine) willproceed to undergo an additional 12 weeks of BA therapy in the Maintenance and DischargePreparation Phases (weekly for 8 weeks, then every other week for 4 weeks).