• Roxanne Sholevar, William Kromka, and Yvan Beaussant.
• Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
• J Palliat Med. 2025 Jan 22.

AbstractContext: Psychiatric and existential distress are common and difficult-to-treat symptoms that are frequently encountered in the palliative care setting; current treatment options are limited in efficacy and tolerability. Psychedelic-assisted therapies (PAT) have gained public and scientific interest in their potential to induce rapid and effective reductions in psychiatric and existential distress in patients with serious medical illness, but remain available only in the research setting. Ketamine as a pharmacologic agent has a large body of evidence in the treatment of refractory depression. Objectives: To review the evidence that exists for use of ketamine or ketamine-assisted psychotherapy (KAP) for psychiatric and existential distress in patients with serious medical illness, aiming to identify therapeutic signals and gaps in research. Methods: A literature search identified publications of (1) ketamine or KAP, (2) psychiatric or existential distress, and (3) palliative care or patients with serious medical illness. Identified reports were carefully reviewed with attention to population and treatment-related factors, which were described in a narrative and aggregate format. Results: Nine studies and 12 case reports were identified that reported positive results and a good safety profile. There was significant variation in patient population, setting, route of administration, dosing schedule, and concurrent treatments. Most reports were of ketamine as a pharmacologic agent for symptoms of psychiatric distress. Conclusion: Evidence suggests that ketamine may induce rapid and transient improvements in psychiatric symptoms in patients with serious medical illness. A large gap in research exists for KAP and symptoms of existential distress. There is a signal that suggests ketamine could be used in a psychedelic therapy model with potential benefits over classical psychedelics.

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