{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T21:01:35Z","timestamp":1792875695128,"version":"4.5.0"},"reference-count":42,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Background and Objective: Cancer-related neuropathic pain (CRNP) is often a significant burden on patients\u2019 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: \u201cmethadone AND cancer pain AND neuropathic pain\u201d and \u201ccancer-related opioid treatment\u201d. Results: Studies were included if they evaluated methadone\u2019s 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\u2019s 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\u2013neuropathic 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\u2019s preferential use in specific sub-groups of patients.<\/jats:p>","DOI":"10.3390\/curroncol31120561","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T09:30:18Z","timestamp":1733391018000},"page":"7613-7624","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Methadone in Cancer-Related Neuropathic Pain: A Narrative Review"],"prefix":"10.3390","volume":"31","author":[{"given":"Faten","family":"Ragaban","sequence":"first","affiliation":[{"name":"Division of Palliative Medicine, Department of Internal Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Om","family":"Purohit","sequence":"additional","affiliation":[{"name":"Division of Palliative Medicine, Department of Internal Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egidio","family":"Del Fabbro","sequence":"additional","affiliation":[{"name":"Division of Palliative Medicine, Department of Internal Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.pain.2011.10.028","article-title":"Prevalence and Aetiology of Neuropathic Pain in Cancer Patients: A Systematic Review","volume":"153","author":"Bennett","year":"2012","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.5055\/jom.2006.0040","article-title":"Methadone for Cancer-Related Neuropathic Pain: A Review of the Literature","volume":"2","author":"Mannino","year":"2006","journal-title":"J. Opioid Manag."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3325","DOI":"10.1200\/JCO.20.01399","article-title":"Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update","volume":"38","author":"Loprinzi","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"iv166","DOI":"10.1093\/annonc\/mdy152","article-title":"Management of Cancer Pain in Adult Patients: ESMO Clinical Practice Guidelines","volume":"29","author":"Fallon","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1016\/j.annonc.2020.07.003","article-title":"Systemic Anticancer Therapy-Induced Peripheral and Central Neurotoxicity: ESMO\u2013EONS\u2013EANO Clinical Practice Guidelines for Diagnosis, Prevention, Treatment and Follow-Up","volume":"31","author":"Jordan","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.1007\/s11136-022-03154-7","article-title":"Assessing Chemotherapy-Induced Peripheral Neuropathy with Patient Reported Outcome Measures: A Systematic Review of Measurement Properties and Considerations for Future Use","volume":"31","author":"Li","year":"2022","journal-title":"Qual. Life Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1097\/j.pain.0000000000002076","article-title":"Neuropathic Pain: Clinical Classification and Assessment in Patients with Pain due to Cancer","volume":"162","author":"Shkodra","year":"2020","journal-title":"Pain"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Edwards, H., Mulvey, M., and Bennett, M. (2019). Cancer-Related Neuropathic Pain. Cancers, 11.","DOI":"10.3390\/cancers11030373"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1093\/bja\/aex175","article-title":"Neuropathic Pain in Cancer: Systematic Review, Performance of Screening Tools and Analysis of Symptom Profiles","volume":"119","author":"Mulvey","year":"2017","journal-title":"Br. J. Anaesth."},{"key":"ref_10","unstructured":"(2024, October 10). PubChem. Methadone. Nih.gov, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Methadone."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1089\/pmr.2023.0018","article-title":"Differences in the Analgesic Effect of Opioids on Pain in Cancer Patients with Spinal Metastases","volume":"4","author":"Takemura","year":"2023","journal-title":"Palliat. Med. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1007\/s40263-020-00743-3","article-title":"Methadone for Pain Management: A Pharmacotherapeutic Review","volume":"34","author":"Kreutzwiser","year":"2020","journal-title":"CNS Drugs"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1213\/ANE.0000000000004472","article-title":"Methadone: New indications for an old drug?","volume":"129","author":"Murphy","year":"2019","journal-title":"Anesth. Analg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"174480692091153","DOI":"10.1177\/1744806920911536","article-title":"Bone Cancer-Induced Pain Is Associated with Glutamate Signaling in Peripheral Sensory Neurons","volume":"16","author":"Zhu","year":"2020","journal-title":"Mol. Pain"},{"key":"ref_15","unstructured":"(2024, October 11). College of Physicians and Surgeons of British Columbia Methadone for Analgesia Guidelines. Available online: https:\/\/www.cpsbc.ca\/files\/pdf\/DP-Methadone-for-Analgesia-Guidelines.pdf."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"200","DOI":"10.25259\/IJPC_58_2022","article-title":"Oral Methadone versus Morphine IR for Patients with Cervical Cancer and Neuropathic Pain: A Prospective Randomised Controlled Trial","volume":"29","author":"Adumala","year":"2023","journal-title":"Indian J. Palliat. Care"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ejca.2016.06.025","article-title":"Methadone Is Superior to Fentanyl in Treating Neuropathic Pain in Patients with Head-And-Neck Cancer","volume":"65","author":"Haumann","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1089\/jpm.2015.0303","article-title":"A Retrospective Study on the Effectiveness of Switching to Oral Methadone for Relieving Severe Cancer-Related Neuropathic Pain and Limiting Adjuvant Analgesic Use in Japan","volume":"19","author":"Sugiyama","year":"2016","journal-title":"J. Palliat. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Boen, C., Ridley, J., and Hawley, P. (2024). Methadone for Pain Management in Chemotherapy-Induced Peripheral Neuropathy: A Retrospective Review. J. Pain Palliat. Care Pharmacother., 1\u201310.","DOI":"10.1080\/15360288.2024.2383423"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.21037\/apm-20-1455","article-title":"Combination Therapy with Methadone and Duloxetine for Cancer-Related Pain: A Retrospective Study","volume":"10","author":"Curry","year":"2021","journal-title":"Ann. Palliat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1080\/24740527.2019.1660575","article-title":"Methadone vs. Morphine SR for Treatment of Neuropathic Pain: A Randomized Controlled Trial and the Challenges in Recruitment","volume":"3","author":"Lynch","year":"2019","journal-title":"Can. J. Pain"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.3904\/kjim.2018.162","article-title":"Neuropathic Cancer Pain: Prevalence, Pathophysiology, and Management","volume":"33","author":"Yoon","year":"2018","journal-title":"Korean J. Intern. Med."},{"key":"ref_23","first-page":"e45485","article-title":"Opioid Prescription in Patients with Chronic Kidney Disease: A Systematic Review of Comparing Safety and Efficacy of Opioid Use in Chronic Kidney Disease Patients","volume":"15","author":"Odoma","year":"2023","journal-title":"Cureus"},{"key":"ref_24","unstructured":"(2024, September 30). UpToDate. Uptodate.com. Available online: https:\/\/www.uptodate.com\/contents\/methadone-drug-information."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1089\/jpm.2017.0712","article-title":"Methadone as the Initial Long-Acting Opioid in Children with Advanced Cancer","volume":"21","author":"Madden","year":"2018","journal-title":"J. Palliat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1089\/jpm.2017.0098","article-title":"Very-Low-Dose Methadone to Treat Refractory Neuropathic Pain in Children with Cancer","volume":"20","author":"Madden","year":"2017","journal-title":"J. Palliat. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.jpainsymman.2018.12.001","article-title":"Safe and Appropriate Use of Methadone in Hospice and Palliative Care: Expert Consensus White Paper","volume":"57","author":"McPherson","year":"2019","journal-title":"J. Pain Symptom Manag."},{"key":"ref_28","first-page":"e2416954","article-title":"Buprenorphine\/Naloxone vs. Methadone for the Treatment of Opioid Use Disorder","volume":"17","author":"Nosyk","year":"2024","journal-title":"JAMA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1089\/jpm.2017.0475","article-title":"Levorphanol for Treatment of Intractable Neuropathic Pain in Cancer Patients","volume":"21","author":"Reddy","year":"2018","journal-title":"J. Palliat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e638","DOI":"10.1016\/j.jpainsymman.2023.06.022","article-title":"Should Buprenorphine Be Considered a First-Line Opioid for the Treatment of Moderate to Severe Cancer Pain?","volume":"66","author":"Chwistek","year":"2023","journal-title":"J. Pain Symptom Manag."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41581-021-00484-6","article-title":"Opioids for Chronic Pain Management in Patients with Dialysis-Dependent Kidney Failure","volume":"18","author":"Tobin","year":"2021","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jpainsymman.2024.05.022","article-title":"Shifting Views on Cancer Pain Management: A Systematic Review and Network Meta-Analysis","volume":"68","author":"Imkamp","year":"2024","journal-title":"J. Pain Symptom Manag."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1159\/000446429","article-title":"Methadone-Related Overdose Deaths in a Liberal Opioid Maintenance Treatment Programme","volume":"22","author":"Tjagvad","year":"2016","journal-title":"Eur. Addict. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e1002396","DOI":"10.1371\/journal.pmed.1002396","article-title":"Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case-control study","volume":"14","author":"Gomes","year":"2017","journal-title":"PLoS Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1002\/(SICI)1097-0142(19980315)82:6<1167::AID-CNCR23>3.0.CO;2-3","article-title":"Dose Ratio between Morphine and Methadone in Patients with Cancer Pain","volume":"82","author":"Lawlor","year":"1998","journal-title":"Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1007\/s00520-011-1320-8","article-title":"Practicability, Safety, and Efficacy of a \u201cGerman Model\u201d for Opioid Conversion to Oral Levo-Methadone","volume":"20","author":"Ostgathe","year":"2011","journal-title":"Support. Care Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1016\/j.jpainsymman.2023.10.018","article-title":"Routine Monitoring of QTc Interval as a Barrier for Efficient Use of Methadone in Palliative Care","volume":"67","author":"Pawate","year":"2024","journal-title":"J. Pain Symptom Manag."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"154","DOI":"10.7326\/0003-4819-139-2-200307150-00021","article-title":"The Impact of Methadone Induction on Cardiac Conduction in Opiate Users","volume":"139","author":"Martell","year":"2003","journal-title":"Ann. Intern. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.jpainsymman.2004.07.001","article-title":"Oral Methadone for Cancer Pain: No Indication of Q-T Interval Prolongation or Torsades de Pointes","volume":"28","author":"Reddy","year":"2004","journal-title":"J. Pain Symptom Manag."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6335","DOI":"10.1007\/s00520-021-06211-y","article-title":"First-Line Methadone for Cancer Pain: Titration Time Analysis","volume":"29","author":"Mammana","year":"2021","journal-title":"Support. Care Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1093\/oncolo\/oyab081","article-title":"Methadone as First-Line Opioid for the Management of Cancer Pain","volume":"27","author":"Mercadante","year":"2022","journal-title":"Oncologist"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1200\/JCO.2004.03.172","article-title":"Methadone versus Morphine as a First-Line Strong Opioid for Cancer Pain: A Randomized, Double-Blind Study","volume":"22","author":"Bruera","year":"2004","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/31\/12\/561\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:44:03Z","timestamp":1760114643000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/31\/12\/561"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,1]]},"references-count":42,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["curroncol31120561"],"URL":"https:\/\/doi.org\/10.3390\/curroncol31120561","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,1]]}}}