Grant: Canada Postdoctoral Research Award (CPRA) program

Depression affects over 280 million people worldwide, including more than 6 million Canadians. For 30-40% standard treatments like medication or therapy are not effective, resulting in treatment-resistant depression (TRD) and ongoing emotional, physical, and social difficulties. Two promising alternatives are intravenous ketamine (IVK), a fast-acting medication, and personalized accelerated theta-burst stimulation (PaiTBS), a non-invasive magnetic stimulation technique that safely alters brain activity in brief sessions. While IVK helps about 30% of patients, PaiTBS appears more effective in early studies and is completed in 5 days.. This three-year study will explore which of these two treatments is more acceptable, manageable, safe, and effective for people with TRD. Eighty adults will be recruited from hospitals in Toronto and Edmonton and randomly assigned to receive IVK or PaiTBS. We will assess how many people participate, complete treatment, and attend follow-ups. Side effects like headache, fatigue, and more serious issues, such as seizures or dropouts due to discomfort, will be monitored. Changes in depression symptoms will be measured using standardized tools. We will also conduct interviews to understand how gender, background, or other life experiences influence access to and experience with these treatments. These insights will guide the design of a future, larger study and promote more inclusive, patient-centered care. This research could improve personal health by offering faster, more tolerable relief for people who have not benefited from standard options. At a population level, better treatments for TRD could reduce disability, improve day-to-day functioning, and help prevent hospitalization, suicide, and related conditions such as anxiety or substance use. Identifying safe, fast-acting, easier delivery treatments at the health system level could ease clinic burdens, reduce wait times, and lower long-term mental health care costs.