Ketamine for Cancer-Related Pain in Palliative Care: A Systematic Review of Clinical Use and Safety

Ketamine has emerged as an adjuvant for opioid-refractory cancer-related pain in palliative care, but evidence remains limited. This systematic review examined ketamine use for cancer-related pain in palliative and end-of-life care. MEDLINE, Cochrane Library, Web of Science, and Scopus were searched for English-language studies (publication 2017-2025). Participants were adults with advanced/metastatic cancer and cancer-related pain receiving ketamine in palliative or end-of-life care. Outcomes included pain relief, opioid consumption, dosing regimens and routes, incidental/breakthrough pain, feasibility, acceptability, and adverse effects. Twelve studies were included: nine case reports, one cohort study, one pilot feasibility study, and one prospective phase II study. Ketamine was used mainly as an adjuvant. Many reports described reduced pain and/or lower opioid use, although certainty was very low and attribution was limited by polypharmacy and regimen changes. Intravenous infusions were most common, but subcutaneous, oral, and intranasal routes were also used. Intranasal ketamine showed pragmatic utility for breakthrough pain, while oral ketamine was described in ambulatory palliative care settings. Adverse-effect reporting was heterogeneous; when reported, events were usually mild to moderate and often psychotomimetic. Subanesthetic ketamine may be a useful adjuvant in selected palliative care patients, but higher-quality studies are needed to clarify dosing, durability, and safety.