Sublingual Ketamine as Breakthrough Analgesia in Patients with Advanced Cancer-A Feasibility Randomised Controlled Repeated Cross-over Trial.
Journal of pain & palliative care pharmacotherapy – July 12, 2025
Source: PubMed
Summary
Even a low dose of a new treatment showed promise for severe pain. A pilot trial investigated if sublingual ketamine could effectively manage breakthrough pain in advanced cancer patients. Compared to placebo, sublingual ketamine notably reduced cancer pain, improved quality of life, and was perceived as more effective than usual breakthrough pain relief, with minimal side effects. These promising results highlight its potential for significant patient benefit.
Abstract
This pilot study aimed to determine feasibility of a larger definitive study evaluating sublingual ketamine efficacy as first-line breakthrough analgesia for moderate-to-severe pain in advanced cancer. This prospective, double-blind, randomized, placebo-controlled, repeated cross-over trial included patients (≥18 years) with moderate-to-severe pain from advanced cancer requiring opioid analgesia, randomized to weekly-alternating treatment sequences (APAPAP, APAPPA, APPAAP, APPAPA, PAAPAP, PAAPPA, PAPAAP, PAPAPA; A = sublingual ketamine, P = placebo). The primary outcome was attrition rate, measured by completion of two treatment cycles over 12-months. Of 64 patients referred, 29 were randomized, 11 received intervention. The pre-determined criterion of 24 patients completing 2-cycles over 12-months was not met. Most patients perceived receiving active drugs in placebo (0.71) and active (0.67) periods. Ketamine scored higher than placebo for pain reduction, perceived to be more efficacious than usual breakthrough analgesia, and increased quality-of-life scores. This study design will be infeasible for a larger trial due to a high attrition rate. The patients' inability to discriminate between the placebo versus active medication and the minimal adverse effects suggested that the chosen dose was possibly too low. The potential issue of disease progression over the study period suggests that further target population refinement should be considered.