The LIFT-MOOD study was conducted at St. Michael's Hospital, Unity Health Toronto. Recruitment began in June 2021, with randomization completed by February 2022. All participants were outpatients screened for study eligibility at the Centre for Depression and Suicide Studies at St. Michael's Hospital. Participants were included if they were between 18 and 65 years of age, had a diagnosis of MDD without psychotic features according to the Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition criteria, were in a major depressive episode as confirmed by the Mini International Neuropsychiatric Interview,26 (link) and had a score of 18 or greater on the Hamilton Depression Rating Scale (HAMD).27 (link) According to the definition of TRD, all participants had to have failed at least 2 trials of antidepressant therapy of an adequate dose and duration during the current depressive episode.28 (link) Data regarding antidepressant history and current medication use were collected using the Antidepressant Treatment History Form.29 Participants were required to maintain their current antidepressant regimen 28 days before the screening visit and during the study. Highly effective or double-barrier contraceptive methods were used for women of childbearing potential.
Participants presenting with comorbidity of neuropsychological disorders (eg, PTSD, dementia) or with a diagnosis of depression secondary to medical illnesses were excluded. Participants were also excluded if they presented with acute suicidality or underwent electroconvulsive therapy within the current depressive episode. The full list of inclusion and exclusion criteria is presented inSupplemental Materials (Table S1) . A research coordinator carried out all screening assessments. The Research Ethics Board of St. Michael's Hospital, Unity Health Toronto, approved the study (20-301). The trial is registered at http://clinicaltrials.gov (NCT04727229). All participants provided written informed consent after fully reviewing the study protocol and prior to participating.
Participants presenting with comorbidity of neuropsychological disorders (eg, PTSD, dementia) or with a diagnosis of depression secondary to medical illnesses were excluded. Participants were also excluded if they presented with acute suicidality or underwent electroconvulsive therapy within the current depressive episode. The full list of inclusion and exclusion criteria is presented in
