Behavioural Activation Therapy and Ketamine for Treatment-Resistant Depression

Inclusion Criteria: 1. English speaking 2. Age 18-65 at Screening 3. Meeting criteria for major depressive disorder (MDD), in a major depressive episode without psychotic symptoms according to the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) 4. Have not responded adequately to at least two separate courses of treatment with different antidepressants, each of adequate dose and duration, in the current depressive episode 5. Currently in a moderate to severe depressive episode, with a minimum MADRS score of ≥22 at Screening 6. Be under the care of a designated health care provider (e.g., family physician or psychiatrist) to follow their care after the completion of the study 7. Willing to maintain stable doses of concomitant psychotropic medications throughout the study 8. Willing to abstain from taking prohibited medications on the days of treatment (i.e., for 12 hours prior to treatment) as per study physician instruction (e.g., benzodiazepines, cannabis) 9. Able to secure a ride/chaperone home from all ketamine infusions. Exclusion Criteria: 1. Body mass index (BMI) ≥35 2. Depression secondary to a stroke, cancer, or other clinically significant medical illness, per study physician judgement 3. Not medically cleared to receive ketamine treatment due to presence of clinically relevant disease, per study physician judgement (e.g., uncontrolled hypertension, renal or hepatic impairment, significant coronary artery disease, vascular disease, diabetes mellitus, seizure disorder, intracerebral hemorrhage, history of cerebrovascular accident \[CVA\]) 4. Pregnant, breastfeeding or of childbearing potential and unwilling to use an approved method of contraception during the study, as assessed during the Screening Visit medical clearance 5. History of a primary psychotic disorder (e.g., schizophrenia), or current or recent (\<2 years) acute episode of psychosis 6. Current and/or recent history (\<12 months) of substance use disorder/dependence (except for alcohol, cannabis, caffeine or nicotine) as defined by DSM-5 criteria 7. Current and/or recent history (\<6 months) of cannabis use disorder as defined by DSM-5 criteria, or unable to abstain from using cannabis 12 hours before and 12 hours after each ketamine infusion 8. Current and/or recent history (\<6 months) of alcohol use disorder as defined by DSM-5 criteria, or unable to abstain from using alcohol 12 hours before and 12 hours after each ketamine infusion 9. Concurrent use of ketamine or psychedelics in any form 10. A previous history or known diagnosis of major neurocognitive disorder 11. Known or suspected history of intolerance, allergy or hypersensitivity to ketamine 12. Any other condition or circumstance that, in the opinion of the QI/study physicians, would adversely affect the participant's ability to complete the study procedures or its measures 13. Concurrent psychotherapy treatment outside the clinical trial. A participant may opt to pause or terminate their current ongoing psychotherapy to participate in the study, at their own discretion. 14. Concurrent active electroconvulsive therapy (ECT) or repetitive transcranial magnetic stimulation (rTMS) therapy.