ArticleJAMA internal medicine2015
Out-of-hospital mortality among patients receiving methadone for noncancer pain.
Article in JAMA internal medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 4 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 4 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- Evidence-based framework for identifying opioid use disorder in administrative data: A systematic review and methodological development study.Pain medicine (Malden, Mass.) · 2026Pooled it
- Predictors of fatal and nonfatal overdose after prescription of opioids for chronic pain: a systematic review and meta-analysis of observational studies.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2023Pooled it
- Methadone for neuropathic pain in adults.The Cochrane database of systematic reviews · 2017Pooled it
- Guideline
- [Clinical pharmacology of opioid analgesics].Schmerz (Berlin, Germany) · 2025Review
- Sensitization to common foods and early vascular aging: associations and the mitigating effects of health behaviors.BMC public health · 2025Article
- The impact of medication-assisted treatment for opioid use disorder on congestive heart failure outcomes.American heart journal plus : cardiology research and practice · 2024Article
- Effects of opioid receptor agonist and antagonist medications on electrocardiogram changes and presentation of cardiac arrhythmia: review article.Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing · 2022Review
- Obesity Potentiates the Risk of Drug-Induced Long QT Syndrome - Preliminary Evidence from WNIN/Ob Spontaneously Obese Rat.Cardiovascular toxicology · 2021Article
- Mortality and concurrent use of opioids and hypnotics in older patients: A retrospective cohort study.PLoS medicine · 2021Article
- Methadone for Pain Management: A Pharmacotherapeutic Review.CNS drugs · 2020Review
- Clinical characteristics and time trends of hospitalized methadone exposures in the United States based on the Toxicology Investigators Consortium (ToxIC) case registry: 2010-2017.BMC pharmacology & toxicology · 2020Article
- All-cause mortality in patients with long-term opioid therapy compared with non-opioid analgesics for chronic non-cancer pain: a database study.BMC medicine · 2020Article
- Mortality in a cohort of 3.1 million children, adolescents and young adults.Journal of epidemiology and community health · 2020Article
- Long-acting Opioid Use and the Risk of Serious Infections: A Retrospective Cohort Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Article
- Outcomes associated with hospital admissions for accidental opioid overdose in British Columbia: a retrospective cohort study.BMJ open · 2019Article
- Deaths among opioid users: impact of potential inappropriate prescribing practices.The American journal of managed care · 2019Article
- Evaluation and optimization of take-home naloxone in an academic medical center.The mental health clinician · 2019Article
- Differences in Characteristics and Downstream Drug Use Among Opioid-Naïve and Prior Opioid Users with Low Back Pain.Pain practice : the official journal of World Institute of Pain · 2019Observational
- Time to initiate randomized controlled clinical trials with methadone in cancer patients.F1000Research · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
importanceGrowing methadone use in pain management has raised concerns regarding its safety relative to other long-acting opioids. Methadone hydrochloride may increase the risk for lethal respiratory depression related to accidental overdose and life-threatening ventricular arrhythmias.
objectiveTo compare the risk of out-of-hospital death in patients receiving methadone for noncancer pain with that in comparable patients receiving sustained-release (SR) morphine sulfate. DESIGN, SETTING, AND
participantsA retrospective cohort study was conducted using Tennessee Medicaid records from 1997 through 2009. The cohort included patients receiving morphine SR or methadone who were aged 30 to 74 years, did not have cancer or another life-threatening illness, and were not in a hospital or nursing home. At cohort entry, 32 742 and 6014 patients had filled a prescription for morphine SR or methadone, respectively. The patients' median age was 48 years, 57.9% were female, and comparable proportions had received cardiovascular, psychotropic, and other musculoskeletal medications. Nearly 90% of the patients received the opioid for back pain or other musculoskeletal pain. The median doses prescribed for morphine SR and methadone were 90 mg/d and 40 mg/d, respectively. MAIN OUTCOMES AND MEASURES: The primary study end point was out-of-hospital mortality, given that opioid-related deaths typically occur outside the hospital.
resultsThere were 477 deaths during 28 699 person-years of follow-up (ie, 166 deaths per 10 000 person-years). After control for study covariates, patients receiving methadone had a 46% increased risk of death during the follow-up period, with an adjusted hazard ratio (HR) of 1.46 (95% CI, 1.17-1.83; P < .001), resulting in 72 (95% CI, 27-130) excess deaths per 10 000 person-years of follow-up. Methadone doses of 20 mg/d or less, the lowest dose quartile, were associated with an increased risk of death (HR, 1.59; 95% CI, 1.01-2.51, P = .046) relative to a comparable dose of morphine SR (<60 mg/d). CONCLUSIONS AND RELEVANCE: The increased risk of death observed for patients receiving methadone in this retrospective cohort study, even for low doses, supports recommendations that it should not be a drug of first choice for noncancer pain.
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