Efficacy and Safety of Topical Ketamine for Oral Mucositis Pain Due to Chemotherapy: A Scoping Review

This scoping review evaluates the efficacy, safety and dosing regimens of topical ketamine mouthwash for managing oral mucositis pain in cancer patients undergoing chemotherapy and/or radiotherapy. Oral mucositis, characterised by painful inflammation and ulceration of the mucosa, significantly impairs quality of life (QoL) and often requires opioid analgesics. Ketamine, an N-methyl-D-aspartate receptor antagonist with peripheral antinociceptive and anti-inflammatory effects, has been explored as a topical treatment to address refractory mucositis pain. The review included six studies comprising case reports, retrospective audits, a prospective phase II study in adults and a randomised placebo-controlled trial in paediatric patients. Adult studies generally reported pain reduction, improved function and opioid-sparing effects, with good tolerability and minimal adverse events. However, the paediatric trial found no significant benefit at the tested dose. Variability in dosing, formulation and study design limits definitive conclusions. Pharmacokinetic data support localised action with minimal systemic absorption and toxicity. Topical ketamine mouthwash shows promise as an adjunctive therapy for difficult-to-control oral mucositis pain, potentially improving patient comfort and reducing opioid use. Larger, well-designed randomised controlled trials are needed to establish optimal dosing, long-term safety and comparative efficacy against standard treatments. Integration of topical ketamine into supportive care protocols may enhance pain management and QoL for affected patients.