A first-of-its-kind clinical trial found that ketamine's benefits for treating severe depression can be improved when combined with psychotherapy and supportive treatment environments.
Led by researchers at McGill University, the study suggests this approach can yield valuable therapeutic experiences that lead to longer-lasting relief than standard treatment.
The study enrolled patients with chronic, treatment-resistant depression, most of which were experiencing suicidal thoughts and struggling with other mental health conditions.
Patients' depression scores dropped by an average of about 30 per cent, and both suicidal thoughts and anxiety improved significantly by the end of the four-week intervention. Unlike typical ketamine treatments, where benefits tend to fade within days, participants' improvement lasted 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 medication increasingly used for its fast-acting antidepressant properties, can cause altered perceptions, a distorted sense of time, out-of-body sensations and many other mind-bending effects. In this study, participants who rated their sessions as particularly emotional or mystical saw the greatest 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.
About the study
"The MUSIK Randomized Clinical Trial: ketamine as a psychedelic treatment for highly refractory depression" Kyle Greenway, Nicolas Garel and Stéphane Richard-Devantoy et al. was published in the British Journal of Psychiatry.
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.
