A McGill-led study could change the way this new treatment is administered in hospitals and clinics.
A first-of-its-kind clinical trial has shown that ketamine’s effectiveness in treating severe depression can be enhanced when combined with psychotherapy and supportive care settings.
Conducted by researchers at McGill University, the study indicates that this combined approach can provide meaningful therapeutic benefits that last longer than standard ketamine treatments.
The trial involved patients with chronic, treatment-resistant depression, many of whom were experiencing suicidal thoughts and additional mental health challenges.
On average, patients’ depression scores dropped by about 30 percent, with notable reductions in suicidal thoughts and anxiety by the end of the four-week program. Unlike typical ketamine treatments, which often lose their effect within days, participants continued to experience improvements for at least eight weeks.
“Ketamine has been called the most exciting antidepressant innovation in decades but major questions remain about how it works,” said lead author Dr. Kyle Greenway, Assistant Professor in McGill’s Division of Social and Transcultural Psychiatry and a researcher at the Lady Davis Institute for Medical Research.
The study was co-led by Dr. Nicolas Garel, Assistant Professor at the University of Montreal and psychiatrist at the Centre hospitalier de l’Université de Montréal, who added: “As ketamine clinics emerge in hospitals and private retreats across Canada, there’s also an urgent need for more standardized treatment models.”
Unwanted side effect or source of healing?
Ketamine, an anesthetic now widely used for its rapid antidepressant effects, can lead to altered perceptions, a distorted sense of time, out-of-body experiences, and other intense psychological effects. In this study, participants who described their sessions as especially emotional or mystical experienced the most significant improvements.
While often dismissed as side effects, these experiences may actually be central to the healing process, the researchers say.
“There’s been a lot of debate about whether the unusual experiences that ketamine induces are part of what makes it effective, similar to ‘classical’ psychedelic drugs like psilocybin,” Greenway said. “The study is the first to strongly link certain aspects of ketamine experiences to its benefits in severe depression.”
Prioritizing patients’ experiences
In the randomized trial, 32 adults received ketamine infusions in rooms with soft lighting and plants, and either curated music or guided mindfulness, depending on group assignment. They also received weekly psychotherapy sessions.
“We know that how people feel in the room can shape how they respond to treatment,” said Greenway. “Most of our patients have spent years in clinical settings. Creating a space that feels safe enough to allow for psychological exploration during ketamine treatments may be part of what made this approach so effective.”
The Montreal Ketamine Clinic at the Jewish General Hospital is decorated with soft lighting and greenery for patient comfort.
The ‘Montreal Model’
The treatment approach used in the study – known as the Montreal Model – was developed by Dr. Greenway and Dr. Garel during their psychiatry residencies at McGill, under the supervision of Dr. Stephane Richard-Devantoy and a wide network of collaborators. Dr. Greenway and Dr. Garel both now direct ketamine-therapy programs in academic hospitals in Montreal.
The Montreal Model blends traditional psychiatry with strategies developed for psychedelic therapies. It is increasingly being applied in and private healthcare services in Canada and internationally.
“Our study shows that our approach not only yields more durable relief, but that it can be implemented safely and effectively in real-world, resource-lean public healthcare settings that care for patients who are much more complex than those typically enrolled in clinical studies,” said Greenway. “It could bring some order and structure to a field that’s currently a bit of a Wild West.”
The research team recently hosted the first training session on the Montreal Model of ketamine therapy for 80 healthcare professionals from around the world at McGill’s Jewish General Hospital.
Reference: “The Music for Subanesthetic Infusions of Ketamine randomised clinical trial: ketamine as a psychedelic treatment for highly refractory depression” by Kyle T. Greenway, Nicolas Garel, Lê-Anh L. Dinh-Williams, Julien Thibault Lévesque, Mendel Kaelen, Vincent Dagenais-Beaulé, Sara de la Salle, David Erritzoe, Karl Looper, Gustavo Turecki, Soham Rej and Séphane Richard-Devantoy, 18 June 2025, The British Journal of Psychiatry.
DOI: 10.1192/bjp.2025.102
This study was funded by the Réseau québécois sur le suicide, les troubles de l’humeur et les troubles associés, and supported by the Jewish General Hospital Foundation.
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