Ketamine, Psychedelics, and Psychotherapy: Reframing, Redefining, Renaming Treatment Models

There has been a renewed interest in the use of various psychedelic agents as potential therapies for multiple psychiatric conditions, including post-traumatic stress disorder (PTSD), major depressive disorder (MDD), generalized anxiety disorder (GAD), to name a few. This follows the recent accumulation of evidence for ketamine pharmacotherapy and a rapid proliferation of clinics/programs offering a variety of ketamine based treatments. A quick glance at the existing evidence, however, reveals a confusing scenario for patients, healthcare providers, and regulators. Overall, there are no standard definitions of what constitutes a psychotherapeutic intervention within a psychedelic-based or a ketamine-based treatment. More specifically, studies have not always distinguished between using a well-known, manualized psychotherapy, providing psychoeducation and psychological support, or providing a therapy specifically to integrate the drug experience in psychedelic trials. Also, it is difficult to determine the role of the psychedelic agent as a stand-alone treatment, and the relative importance (if any) of the psychedelic experience for the desired therapeutic effect. In this perspective, we discuss the evolving landscape of psychedelic-based and ketamine-based treatments, highlighting different therapeutic models, their methodologies, and the need for clearer definitions and rigorous clinical trials. The document proposes three new definitions to improve clarity in evaluating the effects of these agents and the role of psychotherapies. We suggest language that will distinguish: (1) when the drug is used for its pharmacologic effects as a stand-alone treatment, without requiring the psychedelic experience or combined psychotherapy; (2) when the treatment requires the acute psychological effects of the drug to assist psychotherapy and (3) When ketamine or a psychedelic agent is used in combination with a structured, manualized psychotherapy that could be implemented even in the absence of these agents. We hope that this new terminology and definitions will help distinguish the various therapeutic roles of these agents (as stand-alone treatments or in combination with psychotherapies), and facilitate study designs, regulatory pathways, and more informed patient care.Plain Language Summary TitleKetamine, Psychedelics, and Psychotherapy: Understanding treatment models to better inform practice.