Grant: Project Grant

Late-life depression (LLD) is a serious public health issue, affecting many older adults and significantly reducing their quality of life. Unfortunately, about 50% of individuals with LLD do not respond to standard treatments, leading to Treatment-Resistant Late-Life Depression (TRLLD). People with TRLLD often experience worsening health, social isolation, and a higher risk of mortality. While existing treatments like repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT) can help, a significant number of patients do not benefit from these approaches. Emerging research suggests that loneliness and existential distress-feelings of isolation or a lack of meaning in life-may contribute to poor treatment outcomes. This study will evaluate the potential of psilocybin therapy (PT), a novel treatment that has shown promise for depression in younger adults, but has not yet been studied in older adults with TRLLD. We will conduct a carefully controlled clinical trial at the Centre for Addiction and Mental Health, enrolling 60 older adults with TRLLD. Participants will receive either a full dose of psilocybin (25 mg) with therapy or a low-dose placebo (1 mg) with therapy. We will closely monitor safety, feasibility, and treatment effects over four weeks. This research could pave the way for new, effective treatment options for TRLLD, a condition that is often difficult to manage. If successful, psilocybin therapy could help improve not only depressive symptoms but also feelings of loneliness and existential distress, ultimately enhancing the well-being and quality of life for older adults. By investing in innovative approaches like PT, we can help transform mental health care and offer hope to those who have not found relief with current treatments.