The Montreal model: an integrative biomedical-psychedelic approach to ketamine for severe treatment-resistant depression

Abstract

BackgroundSubanesthetic ketamine has accumulated meta-analytic evidence for rapid antidepressant effects in treatment-resistant depression (TRD), resulting in both excitement and debate. Many unanswered questions surround ketamine’s mechanisms of action and its integration into real-world psychiatric care, resulting in diverse utilizations that variously resemble electroconvulsive therapy, conventional antidepressants, or serotonergic psychedelics. There is thus an unmet need for clinical approaches to ketamine that are tailored to its unique therapeutic properties.MethodsThis article presents the Montreal model, a comprehensive biopsychosocial approach to ketamine for severe TRD refined over 6 years in public healthcare settings. To contextualize its development, we review the evidence for ketamine as a biomedical and as a psychedelic treatment of depression, emphasizing each perspectives’ strengths, weaknesses, and distinct methods of utilization. We then describe the key clinical experiences and research findings that shaped the model’s various components, which are presented in detail.ResultsThe Montreal model, as implemented in a recent randomized clinical trial, aims to synergistically pair ketamine infusions with conventional and psychedelic biopsychosocial care. Ketamine is broadly conceptualized as a brief intervention that can produce windows of opportunity for enhanced psychiatric care, as well as powerful occasions for psychological growth. The model combines structured psychiatric care and concomitant psychotherapy with six ketamine infusions, administered with psychedelic-inspired nonpharmacological adjuncts including rolling preparative and integrative psychological support.DiscussionOur integrative model aims to bridge the biomedical-psychedelic divide to offer a feasible, flexible, and standardized approach to ketamine for TRD. Our learnings from developing and implementing this psychedelic-inspired model for severe, real-world patients in two academic hospitals may offer valuable insights for the ongoing roll-out of a range of psychedelic therapies. Further research is needed to assess the Montreal model’s effectiveness and hypothesized psychological mechanisms.

The Clinical Potential of Dimethyltryptamine: Breakthroughs into the Other Side of Mental Illness, Neurodegeneration, and Consciousness

“…Ketamine is already pursued as a treatment in ketamine clinics, with a market value of USD 3.1 billion in 2022 [192]. DMT could be used similarly to ketamine, using multiple shorter sessions rather than one long session compared to psilocybin treatments [193]. One trial that evaluated the clinical use of DMT with published results highlights that DMT, like ketamine, was administered in a typical hospital setting with minimal psychotherapy, and still resulted in decreased depression scores (NCT04711915) [140].…”

“…Intravenous DMT can be particularly useful as it provides clinicians more control over the psychedelic state (NCT04353024) [92]. Additionally, psilocybin sessions can be resource and manpower intensive [193], lending further credence to the idea that DMT can be a more practical intervention for both the patient and the clinician.…”

Qualitative analysis of a patient’s experience of ketamine-assisted psychotherapy for substance use disorder: Empirical synergies with twelve-step programs.

“…KAP involves dosing sessions intended to elicit so-called mystical experiences (coupled with significant preparation and integration). As opposed to purely pharmacologic approaches, KAP leverages the subjective emotional, cognitive, perceptual, and perhaps spiritual elements of ketamine's acute effects to promote therapeutic outcomes (Garel et al, 2023;.…”