A rapid systematic review of palliative uses of ketamine for depression and pain in people living with advanced cancer.

BACKGROUND: Given the growing population of patients living with metastatic cancer, palliative care providers need every available tool for symptom management. We conducted a rapid review of the literature on palliative uses of ketamine for pain and depression in people with cancer. METHODS: We systematically searched for studies published since 2015 that examined palliative uses of ketamine in adults with cancer using clinical trial, experiment, quasi-experiment, or meta-analytic designs. We excluded studies focused on perioperative or post-operative sedation and/or pain, and studies lacking patient-reported outcomes. RESULTS: There were 13 articles included in the final review. One open-label phase II study reported positive antidepressant effects of intranasal ketamine. Four open-label pilot studies found promising benefits for acute and chronic cancer-related pain in outpatient settings. Seven studies-pilot trials, retrospective chart reviews, and one mechanistic trial-reported improvements in refractory cancer pain near end of life. However, a cost-effectiveness analysis of the only adequately powered randomized controlled trial found no analgesic benefit and greater toxicity for ketamine among inpatients near end of life. CONCLUSIONS: Ketamine may alleviate refractory pain, depression, and acute cancer‑related pain, but findings remain inconsistent, particularly considering the negative randomized trial. More rigorous, practice‑aligned research is needed to define ketamine's benefits, potential synergistic effects, and the role of supportive psychotherapy in palliative care. Palliative care clinicians should cautiously consider time-limited, individualized trials of ketamine for cancer patients with high symptom burden.