Methadone in Cancer-Related Neuropathic Pain: A Narrative Review

Background and Objective: Cancer-related neuropathic pain (CRNP) is often a significant burden on patients' quality of life. There are limited treatment guidelines for cancer-related neuropathic pain outside of CIPN. Although opioids are considered a third-line treatment option, no consensus exists on which opioid is most effective, either as a single agent or in combination with other medications. Our aim is to review and update the literature for methadone use in CRNP, since the last review was conducted in 2006. Methods: A comprehensive literature search was performed to evaluate the use of methadone in cancer-related neuropathic pain. Articles were identified from PubMed, Google Scholar, and Cochrane Library using the following keywords: "methadone AND cancer pain AND neuropathic pain" and "cancer-related opioid treatment". Results: Studies were included if they evaluated methadone's efficacy or safety in neuropathic pain management for patients with cancer. This review focused on randomized controlled trials (RCTs), systematic reviews, meta-analyses, and observational studies published between 2000 and 2024. Studies were excluded if they lacked specific data on cancer-related neuropathic pain or were case reports. Conclusions: The unique mechanisms of action and preliminary clinical trials support methadone's status as the first opioid to consider for CRNP when non-opioid first-line treatments have failed to alleviate patient symptoms. Methadone can also be considered as a first-line opioid in patients with mixed nociceptive-neuropathic pain and any of the following features: renal dysfunction; administration of opioids through a feeding tube; a lack of financial resources/insurance; and a switch from another high-dose opioid. More research is needed regarding methadone for CRNP and methadone's preferential use in specific sub-groups of patients.