A systematic review by the Canadian Network for Mood and Anxiety Treatments evaluated evidence for racemic ketamine in treatment-resistant depression. Single intravenous infusions have Level 1 evidence for efficacy in adults, while multiple or maintenance infusions have only Level 3 evidence. Adverse events include dissociative symptoms and hypertension. Non-IV formulations have Level 3 or 4 evidence. Single-dose IV racemic ketamine is a third-line recommendation; repeated use requires careful case-by-case risk-benefit assessment. Oral and other formulations should be limited to specialists with ketamine expertise at tertiary centers due to limited evidence and risk of misuse.
Serotonergic psychedelics are being reconsidered as potential treatments for major depressive disorder. A Canadian task force systematically reviewed clinical trials from 1990 to 2021 and found that only psilocybin and ayahuasca have been tested in contemporary studies. Two pilot studies of single-dose ayahuasca for treatment-resistant depression showed preliminary positive effects (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy for major depressive disorder showed superiority to waitlist controls and comparable efficacy and safety to escitalopram with supportive psychotherapy, with additional trials showing efficacy in cancer-related depression (Level 3 evidence).
Late-life depression affects up to 18% of older adults and is linked to elevated dementia risk. Mindfulness-based cognitive therapy (MBCT) may help treat depressive symptoms and cognitive deficits in this population, but a definitive randomized controlled trial has not yet been conducted. This protocol describes a multi-site blinded trial comparing MBCT to an active control, a Health Enhancement Program, in 213 patients with late-life depression. Changes in depression severity, processing speed, executive functioning, and brain biomarkers will be assessed at baseline, post-intervention (8 weeks), and 26 weeks after baseline. The study will evaluate MBCT's potential to improve depression, cognitive impairments, and neurobiological markers.