Subanesthetic Ketamine for Opioid-Refractory Cancer Pain: Efficacy, Safety, and Opioid-Sparing Effects

N Mohabbath Zikrullah Satyaharaman Maruapey, Satrio Adi, Nasim Amar, Isngadi Isngadi

Abstract

Background: Opioid-refractory cancer pain is a major clinical challenge, affecting an estimated 20–40% of patients despite optimized opioid therapy. Subanesthetic-dose ketamine, an NMDA receptor antagonist, has emerged as a potential adjunct for managing such pain.Methods: A scoping review was conducted through April 2025 in PubMed, ScienceDirect, SpringerLink, and the Cochrane Library. Included studies involved cancer patients with opioid-refractory pain treated with subanesthetic ketamine. One RCT, one cohort study, and eight case reports were analyzed. Outcomes included pain relief, opioid dose reduction, and adverse effects.Results: Ten studies met inclusion criteria. Subanesthetic ketamine provided rapid pain relief in most cases, with pain scores decreasing by 37–100% within 1–2 days. All eight case reports demonstrated clinically meaningful reductions in pain intensity, with opioid-sparing effects reported across all cases. Daily opioid dose reductions ranged from 46% to 99%, with several cases reporting over 90% reduction in oral morphine equivalents. The RCT showed a non-significant trend toward improved pain outcomes, likely due to small sample size and limited power. Adverse effects were generally mild (e.g., hallucinations, sedation), with rare serious events. Ketamine was overall well tolerated across case reports, the RCT, and the cohort study.

Conclusions: Subanesthetic ketamine is a promising adjunct for opioid-refractory cancer pain, offering effective analgesia and substantial opioid reduction potential. Its safety profile is acceptable under careful monitoring. However, heterogeneity among studies and the limited high-quality evidence emphasize the need for larger, well-designed trials to establish optimized dosing, long-term safety, and standardized clinical guidelines

Keywords

Adjunct Therapy; Cancer Pain; Ketamine Infusion; Opioid-Refractory Pain; Subanesthetic Ketamine

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DOI: https://doi.org/10.20961/soja.v6i2.105719

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