{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:22:42Z","timestamp":1791804162892,"version":"4.3.4"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T00:00:00Z","timestamp":1653609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Pediatric palliative care (PPC) is defined as the prevention and relief from suffering of families and children with life-limiting (LLDs) or life-threatening diseases (LTDs). These patients often experience pain, with morphine being the most widely used drug to treat it. Few studies investigated the role of methadone in PPC patients, although it is considered among the most effective and underutilized drugs in PPC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Our aim was to evaluate the efficacy, safety, and dosage of methadone in PPC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Between August and October 2021 PubMed, Scopus and the Cochrane Library were searched for studies on the use of methadone in children with LLDs and LTDs. Articles were included if they met the following criteria: published in the last 10 years, English language, patients aged 0\u201323 years; children enrolled in a PPC center or receiving declared support from a PPC service; reporting of specific data on methadone in interventional trials, observational studies, or case series on &amp;gt;10 patients. The reporting of the article was guided by the PRISMA guidelines, and a critical appraisal of the included studies was performed using the JBI-tool.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After duplicates removal and full-text assessment, four studies were included and another one was added after checking the references of the retrieved papers. All were retrospective, and the literature is concordant in documenting the lack of evidence. A total of 116 children received methadone in PPC. From our review emerges the poor quality of data collection: in only one study pain was assessed with standardized scales. All studies documented the effectiveness of methadone in treating complex pain, either nociceptive or neuropathic. No serious adverse events were reported, with no cases of cardiac arrhythmias.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that methadone could represent a suitable strategy for treating pain in PPC. However, the evidence base is insufficient, and further research is warranted.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2022.874529","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T06:02:37Z","timestamp":1654063357000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Old Drug, New Pain. Roles and Challenges of Methadone Therapy in Pediatric Palliative Care: A Systematic Review"],"prefix":"10.3389","volume":"10","author":[{"given":"Francesca","family":"Benedetti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Zoletto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Salerno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Avagnina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franca","family":"Benini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,27]]},"reference":[{"key":"B1","volume-title":"Integrating Palliative Care and Symptom Relief Into Paediatrics: A WHO Guide for Health Care Planners, Implementers and Managers.","year":""},{"key":"B2","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.2147\/JPR.S138153","article-title":"Pain reporting and analgesia management in 270 children with a progressive neurologic, metabolic or chromosomally based condition with impairment of the central nervous system: cross-sectional, baseline results from an observational, longitudinal study","volume":"10","author":"Friedrichsdorf","year":"2017","journal-title":"J Pain Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"Cd010750","DOI":"10.1002\/14651858.CD010750.pub2","article-title":"Pharmacological interventions for pain in children and adolescents with life-limiting conditions","volume":"2015","author":"Beecham","year":"2015","journal-title":"Cochrane Database Syst Rev."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1002\/pbc.25493","article-title":"Patient-controlled analgesia at the end of life at a pediatric oncology institution","volume":"62","author":"Anghelescu","year":"2015","journal-title":"Pediatr Blood Cancer."},{"key":"B5","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.jpainsymman.2014.10.007","article-title":"Patient-controlled analgesia for children at home","volume":"49","author":"Mherekumombe","year":"2015","journal-title":"J Pain Symptom Manage."},{"key":"B6","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1007\/s40267-020-00772-4","article-title":"Methadone is an option to treat cancer pain in carefully selected patients","volume":"36","author":"Fenton","year":"2020","journal-title":"Drugs Ther Perspect."},{"key":"B7","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s40265-019-01234-6","article-title":"Emerging challenges to the safe and effective use of methadone for cancer-related pain in paediatric and adult patient populations","volume":"80","author":"Edmonds","year":"2020","journal-title":"Drugs."},{"key":"B8","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1097\/AJP.0000000000000704","article-title":"From tramadol to methadone: opioids in the treatment of pain and dyspnea in pediatric palliative care","volume":"35","author":"Friedrichsdorf","year":"2019","journal-title":"Clin J Pain."},{"key":"B9","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1007\/s13318-019-00552-0","article-title":"Opioids: a review of pharmacokinetics and pharmacodynamics in neonates, infants, and children","volume":"44","author":"Thigpen","year":"2019","journal-title":"Eur J Drug Metab Pharmacokinet."},{"key":"B10","doi-asserted-by":"publisher","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":"B11","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1016\/j.jpainsymman.2013.12.241","article-title":"Variation of opioid use in pediatric inpatients across hospitals in the U","volume":"48","author":"Womer","year":"2014","journal-title":"J Pain Symptom Manage."},{"key":"B12","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.pop.2019.05.010","article-title":"Pediatric palliative care","volume":"46","author":"Norris","year":"2019","journal-title":"Prim Care."},{"key":"B13","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1007\/s10880-021-09764-6","article-title":"Ethical issues in providing end-of-life cancer care for transitional-aged youth","volume":"28","author":"Emerson","year":"2021","journal-title":"J Clin Psychol Med Settings."},{"key":"B14","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/s00482-008-0690-4","article-title":"[IMPaCCT: standards of paediatric palliative care]","volume":"22","author":"Craig","year":"2008","journal-title":"Schmerz."},{"key":"B15","doi-asserted-by":"publisher","first-page":"b2700","DOI":"10.1136\/bmj.b2700","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration","volume":"339","author":"Liberati","year":"2009","journal-title":"BMJ."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2127","DOI":"10.11124\/JBISRIR-D-19-00099","article-title":"Methodological quality of case series studies: an introduction to the JBI critical appraisal tool","volume":"18","author":"Munn","year":"2020","journal-title":"JBI Evid Synth."},{"key":"B17","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1177\/1049909120963641","article-title":"Methadone for cancer pain in pediatric end-of-life care","volume":"38","author":"Hall","year":"2021","journal-title":"Am J Hosp Palliat Care."},{"key":"B18","doi-asserted-by":"publisher","first-page":"86","DOI":"10.3390\/children5070086","article-title":"Methadone for analgesia in children with life-limiting illness: experience from a tertiary children's health service","volume":"5","author":"Mott","year":"2018","journal-title":"Children"},{"key":"B19","doi-asserted-by":"publisher","first-page":"133","DOI":"10.4103\/IJPC.IJPC_109_20","article-title":"The use of methadone in pediatric cancer pain\u2014a retrospective study from a Governmental Cancer Center in India","volume":"27","author":"Palat","year":"2021","journal-title":"Indian J Palliat Care."},{"key":"B20","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1002\/pbc.21584","article-title":"Methadone analgesia for children with advanced cancer","volume":"51","author":"Davies","year":"2008","journal-title":"Pediatr Blood Cancer."},{"key":"B21","doi-asserted-by":"publisher","first-page":"60","DOI":"10.5935\/1806-0013.20150012","article-title":"Revisiting methadone: pharmacokinetics, pharmacodynamics and clinical indication","volume":"16","author":"Barbosa Neto","year":"2015","journal-title":"Revista Dor."},{"key":"B22","first-page":"1353","article-title":"Methadone treatment for pain states","volume":"71","author":"Toombs","year":"2005","journal-title":"Am Fam Physician."},{"key":"B23","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1177\/1049909107312597","article-title":"Methadone","volume":"25","author":"Chhabra","year":"2008","journal-title":"Am J Hosp Palliat Care."},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.1093\/med\/9780190626761.001.0001","volume-title":"Perioperative Pain Management for Orthopedic and Spine Surgery","author":"Reach","year":"2018"},{"key":"B25","doi-asserted-by":"crossref","DOI":"10.1093\/med\/9780199595105.001.0001","volume-title":"Oxford Textbook of Palliative Care for Children","author":"Goldman","year":"2012"},{"key":"B26","doi-asserted-by":"publisher","first-page":"Cd012538","DOI":"10.1002\/14651858.CD012538","article-title":"Opioids for chronic non-cancer pain in children and adolescents","volume":"7","author":"Cooper","year":"2017","journal-title":"Cochrane Database Syst Rev."},{"key":"B27","doi-asserted-by":"publisher","first-page":"Cd012564","DOI":"10.1002\/14651858.CD012564","article-title":"Opioids for cancer-related pain in children and adolescents","volume":"7","author":"Wiffen","year":"2017","journal-title":"Cochrane Database Syst Rev."},{"key":"B28","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s40272-018-0304-2","article-title":"Methadone for pain management in children with cancer","volume":"20","author":"Habashy","year":"2018","journal-title":"Paediatr Drugs."},{"key":"B29","doi-asserted-by":"publisher","first-page":"e529","DOI":"10.1016\/j.jpainsymman.2021.12.031","article-title":"International standards for pediatric palliative care: from IMPaCCT to GO-PPaCS","volume":"63","author":"Benini","year":"2022","journal-title":"J Pain Symptom Manage."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e20171002","DOI":"10.1542\/peds.2017-1002","article-title":"Pain assessment and treatment in children with significant impairment of the central nervous system","volume":"139","author":"Hauer","year":"2017","journal-title":"Pediatrics"},{"key":"B31","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1111\/dmcn.12943","article-title":"Parent-reported pain in non-verbal children and adolescents with cerebral palsy","volume":"58","author":"Jayanath","year":"2016","journal-title":"Dev Med Child Neurol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.acap.2017.12.001","article-title":"Agreement between parent proxy report and child self-report of pain intensity and health-related quality of life after surgery","volume":"18","author":"Lifland","year":"2018","journal-title":"Acad Pediatr."},{"key":"B33","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.jpain.2014.01.494","article-title":"Methadone safety: a clinical practice guideline from the American Pain Society and College on problems of drug dependence, in collaboration with the Heart Rhythm Society","volume":"15","author":"Chou","year":"2014","journal-title":"J Pain."},{"key":"B34","doi-asserted-by":"publisher","first-page":"387","DOI":"10.7326\/0003-4819-150-6-200903170-00103","article-title":"QTc interval screening in methadone treatment","volume":"150","author":"Krantz","year":"2009","journal-title":"Ann Intern Med."},{"key":"B35","volume-title":"Linee guida dell'OMS sul trattamento farmacologico del dolore persistente nei bambini con patologie croniche gravi (2014). Traduzione Italiana del Document \u201cWHO Guidelines on the Pharmacological Treatment of Persisting Pain in Children with Medical Illnesses","year":"2012"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1002\/pbc.25392","article-title":"Extreme doses of intravenous methadone for severe pain in two children with cancer","volume":"62","author":"Rasmussen","year":"2015","journal-title":"Pediatr Blood Cancer."},{"key":"B37","doi-asserted-by":"publisher","first-page":"123","DOI":"10.5055\/jom.2016.0324","article-title":"Methadone conversion in infants and children: retrospective cohort study of 199 pediatric inpatients","volume":"12","author":"Fife","year":"2016","journal-title":"J Opioid Manag."},{"key":"B38","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.jpainsymman.2015.02.029","article-title":"Methods of rotation from another strong opioid to methadone for the management of cancer pain: a systematic review of the available evidence","volume":"50","author":"McLean","year":"2015","journal-title":"J Pain Symptom Manage"},{"key":"B39","doi-asserted-by":"publisher","first-page":"129","DOI":"10.2165\/00148581-200911020-00004","article-title":"Pediatric palliative care: use of opioids for the management of pain","volume":"11","author":"Zernikow","year":"2009","journal-title":"Paediatr Drugs."},{"key":"B40","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.pcl.2007.07.007","article-title":"The management of pain in children with life-limiting illnesses","volume":"54","author":"Friedrichsdorf","year":"2007","journal-title":"Pediatr Clin North Am"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2022.874529\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T06:02:44Z","timestamp":1654063364000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2022.874529\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,27]]},"references-count":40,"alternative-id":["10.3389\/fped.2022.874529"],"URL":"https:\/\/doi.org\/10.3389\/fped.2022.874529","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,27]]},"article-number":"874529"}}