The Canadian Journal of Psychiatry
November 11, 2020
Jennifer Swainson, Alexander McGirr, Pierre Blier et al.
109 citations
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.
Frontiers in Psychiatry
September 19, 2023
Nicolas Garel, Jessica Drury, Julien Thibault Lévesque et al.
32 citations
A biopsychosocial approach to ketamine for treatment-resistant depression, called the Montreal model, pairs ketamine infusions with structured psychiatric care and psychotherapy. Developed over six years in public healthcare settings, the model conceptualizes ketamine as a brief intervention that creates windows of opportunity for enhanced care and psychological growth. It combines six ketamine infusions with psychedelic-inspired nonpharmacological adjuncts, including preparative and integrative psychological support. The model aims to bridge biomedical and psychedelic perspectives, offering a standardized yet flexible approach for severe, real-world patients. Further research is needed to assess its effectiveness and hypothesized psychological mechanisms.
Frontiers in Human Neuroscience
July 18, 2023
Nicolas Garel, Julien Thibault Lévesque, Dasha A. Sandra et al.
29 citations
Past environmental exposures can significantly shape psychedelic drug experiences and their therapeutic outcomes, a concept the authors call 'imprinting.' In a clinical trial of ketamine for treatment-resistant depression, two patients' subjective experiences were altered by the type and amount of digital media they consumed in the days before treatment: higher media exposure reduced mystical and emotional qualities of the ketamine experience, overriding standard intention-setting practices and changing therapeutic results. Eight additional patients spontaneously reported past environmental exposures manifesting as visual hallucinations during ketamine sessions. Similar imprinting effects appear in historical reports of other psychedelic drugs and in dreaming. The authors propose expanding the contextual model of psychedelic action to include imprinting, which may help clinicians and researchers better understand these drug effects.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
November 1, 2023
Nicolas Garel, Kyle T. Greenway, Lê-Anh Dinh-Williams et al.
10 citations
A course of six sub-anesthetic ketamine infusions over four weeks helped patients with treatment-resistant depression discontinue long-term benzodiazepine or z-drug use. Of 22 patients, 91% (20/22) successfully stopped all such medications by the end of the infusions, confirmed by urine tests. Fewer than 25% experienced significant worsening of anxiety, depression, sleep problems, or suicidality during withdrawal. Over a mean follow-up of one year, 64% (14/22) remained abstinent. These preliminary results suggest ketamine infusions may facilitate benzodiazepine deprescription even in patients with active depression and significant comorbidity.
Psychological Medicine
May 8, 2026
Lou-Anne Chavigny, Véronique Desbeaumes Jodoin, Nicolas Garel et al.
A systematic review of 21 studies involving approximately 900–1,180 participants with treatment-resistant depression found that low-dose intravenous ketamine preserves and enhances certain cognitive functions. Improvements were frequently observed in processing speed and working memory, while attention remained stable or modestly improved. Results for verbal and visual memory varied across studies. Executive control, especially inhibitory performance on Stroop tasks, improved in several trials. No cognitive worsening was reported. Two studies directly examined cognition in relation to suicidal behaviors, suggesting that procognitive effects, particularly in executive control, may mediate ketamine's antisuicidal action. Standardized longitudinal studies are needed to clarify durability and clinical significance.
BMJ Open
March 1, 2026
Christina Mcanulty, Philippe Lavoie, Samuel Cyr et al.
A new treatment combining ketamine infusions with acceptance and commitment therapy (ACT) may be feasible for people who have both alcohol use disorder and treatment-resistant depression. In an open-label trial at a Montreal hospital, 30 participants will receive six ketamine infusions plus eight weekly therapy sessions, either in person or online. The study primarily tests whether the combined approach is practical and acceptable by measuring completion rates, safety, and data quality. Exploratory measures will track changes in depressive symptoms, alcohol use, and quality of life. Some participants will also be interviewed about their experiences.
Frontiers in Aging Neuroscience
January 1, 2022
Magnus Bein, Myriam Lesage, Elena Dikaios et al.
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.