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Journal of Pain and Symptom Management Mar 2019Methadone has several unique characteristics that make it an attractive option for pain relief in serious illness, but the safety of methadone has been called into...
Methadone has several unique characteristics that make it an attractive option for pain relief in serious illness, but the safety of methadone has been called into question after reports of a disproportionate increase in opioid-induced deaths in recent years. The American Pain Society, College on Problems of Drug Dependence, and the Heart Rhythm Society collaborated to issue guidelines on best practices to maximize methadone safety and efficacy, but guidelines for the end-of-life scenario have not yet been developed. A panel of 15 interprofessional hospice and palliative care experts from the U.S. and Canada convened in February 2015 to evaluate the American Pain Society methadone recommendations for applicability in the hospice and palliative care setting. The goal was to develop guidelines for safe and effective management of methadone therapy in hospice and palliative care. This article represents the consensus opinion of the hospice and palliative care experts for methadone use at end of life, including guidance on appropriate candidates for methadone, detail in dosing, titration, and monitoring of patients' response to methadone therapy.
Topics: Analgesics, Opioid; Hospice Care; Humans; Methadone; Pain; Palliative Care
PubMed: 30578934
DOI: 10.1016/j.jpainsymman.2018.12.001 -
Canadian Medical Association Journal Oct 1973Methadone and acetylmethadol, although possessing almost all of morphine's pharmacological properties, differ from other morphine-like drugs in their longer action, more... (Comparative Study)
Comparative Study Review
Methadone and acetylmethadol, although possessing almost all of morphine's pharmacological properties, differ from other morphine-like drugs in their longer action, more gradual and less intense withdrawal syndrome, and blockade of euphoric effect of other opiates in addicts. A high percentage of patients maintained on methadone are better able to hold employment or to be otherwise socially productive than when dependent on heroin or morphine.A review of published results and procedures used in methadone maintenance treatment programs for heroin dependence is presented. Former heroin addicts are usually maintained on 80 to 120 mg. (high dose) or 20 to 60 mg. (low dose) oral methadone daily. Some programs are reported to have produced 80% success (patients employed or otherwise socially productive). Selection of patients, availability of allied therapeutic and rehabilitative facilities, strict control of supply, record keeping and periodic evaluation are considered essential.Different criteria ("drug-free" vs. "socially productive") for judging "success" of treatment of heroin-dependent persons by methadone maintenance and administrative problems in large-scale treatment programs constitute the principal aspects of controversy.
Topics: Acetates; Administration, Oral; Adolescent; American Medical Association; Canada; Chemical Phenomena; Chemistry; Drug and Narcotic Control; Female; Heroin Dependence; Humans; Methadone; Pregnancy; Pregnancy Complications; Private Practice; Structure-Activity Relationship; Substance Withdrawal Syndrome; Substance-Related Disorders; United States
PubMed: 4599599
DOI: No ID Found -
American Journal of Public Health Apr 2022
Topics: Humans; Methadone; Opioid-Related Disorders; Policy
PubMed: 35349312
DOI: 10.2105/AJPH.2021.306665 -
Pharmacogenomics Aug 2020Methadone, a synthetic opioid with longer duration of action and lower abuse potential compared with morphine, is used to prevent opioid withdrawal, as well as to... (Review)
Review
Methadone, a synthetic opioid with longer duration of action and lower abuse potential compared with morphine, is used to prevent opioid withdrawal, as well as to manage chronic and acute surgical pain. The variability in response to methadone has been widely recognized. The purpose of this article is to review the literature on the pharmacogenetic factors underlying this variability. This is a narrative overview of the literature on the genetic variants affecting pharmacodynamics and pharmacokinetics of methadone, retrieved from searches of databases such as PubMed and google scholar. Clinical responses to methadone may be affected by genetic variants in the opioidergic, dopaminergic and neurotrophic pathways. Polymorphisms in genes related to disposition and elimination of methadone alter the pharmacokinetics, and possibly pharmacodynamics of methadone. Cytochrome P450 enzymes and P-glycoprotein variants contribute to the interindividual variability in methadone pharmacokinetics. Evidence for single gene variants affecting methadone response remains weak. Multiple genetic variants must be considered in conjunction to improve predictive ability. Evidence remains scarce at this time, to recommend pharmacogenetic testing before methadone administration. Well-powered clinical studies are needed with population pharmacokinetic-pharmacodynamic modeling and multigenetic signature-based predictions to enable tailored use of methadone in clinical practice.
Topics: Analgesics, Opioid; Animals; Genetic Variation; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pharmacogenetics
PubMed: 32705966
DOI: 10.2217/pgs-2020-0040 -
JAMA Network Open Jul 2022The opioid crisis has been exacerbated by the COVID-19 pandemic in the US, with concerns over major disruptions to medication treatment of opioid use disorder.
IMPORTANCE
The opioid crisis has been exacerbated by the COVID-19 pandemic in the US, with concerns over major disruptions to medication treatment of opioid use disorder.
OBJECTIVE
To investigate whether the COVID-19 pandemic was associated with disruption of buprenorphine and methadone supplies in the US.
DESIGN, SETTING, AND PARTICIPANTS
This repeated cross-sectional study used ARCOS (Automated Reports and Consolidated Ordering System) data, which monitor the flow of controlled substances in the US, from January 1, 2012, through June 30, 2021. Manufacturers and point of sale or distribution at the dispensing or retail level, including hospitals, retail pharmacies, clinicians, midlevel clinicians, and teaching institutions, were included in the analysis.
EXPOSURES
COVID-19 pandemic.
MAIN OUTCOMES AND MEASURES
Quarterly supplies of buprenorphine and methadone per capita in milligrams.
RESULTS
The per capita supply of methadone dropped from 13.2 mg in the first quarter of 2020 to 10.5 mg in the second quarter of 2020, whereas the per capita supply of buprenorphine increased from 3.6 mg to 3.7 mg in the same period. The per capita supply of methadone declined 20% (-2.7 mg) in the second quarter of 2020 compared with the first quarter of 2020, and the supply had not returned to 2019 levels as of June 2021, whereas the supply of buprenorphine per person increased consistently during the same period. There were considerable state disparities in the reduction of the methadone supply during the pandemic, with many states experiencing pronounced per capita supply decreases, including reductions as great as 50% in New Hampshire and Florida. These decreases in per capita methadone supply were not compensated by proportional increases in the per capita buprenorphine supply (linear fit, 0.17 [95% CI, -0.43 to 0.76]; P = .47).
CONCLUSIONS AND RELEVANCE
This cross-sectional study of buprenorphine and methadone supplies during the COVID-19 pandemic found a pronounced decline in the methadone supply but no disruption to the buprenorphine supply. Future research is needed to explain the pronounced state disparities in the methadone supply.
Topics: Buprenorphine; Cross-Sectional Studies; Humans; Methadone; Opiate Substitution Treatment; Pandemics; COVID-19 Drug Treatment
PubMed: 35881394
DOI: 10.1001/jamanetworkopen.2022.23708 -
Toxicology and Applied Pharmacology Nov 2023The use and/or misuse of opioids by pregnant women would expose the fetuses to these drugs during critical stages of development with serious effects for the newborn,...
The use and/or misuse of opioids by pregnant women would expose the fetuses to these drugs during critical stages of development with serious effects for the newborn, like the neonatal abstinence syndrome (NAS). We have revisited an established chicken model for NAS to describe the distribution of morphine and methadone to the brain and explore its validity as a valuable alternative to rodent models. For this purpose, chicken eggs were injected with a single dose of 10 mg/kg or 20 mg/kg morphine or 20 mg/kg methadone onto the chorioallantoic membrane (CAM) on embryonal day 13. Whole brains and lungs were harvested and the concentrations of morphine, methadone and their subsequent metabolites (morphine-3-glucuronide and EDDP, respectively) determined in the brain and lungs at different time points using LC-MS/MS. Morphine and methadone, as well as their metabolites, were detected both in the brain and lungs, with significantly higher concentrations in the lungs. Pharmacokinetic modelling showed that the distribution of morphine to the brain followed a first-order absorption with transit compartments and linear elimination, with concentrations linearly dependent on dose. Moreover, methadone, but not morphine, reduced μ receptor (the main morphine receptor) binding, which can be of relevance for opioid tolerance. The present study is the first to report the brain distribution of morphine, which can be described by standard pharmacokinetic processes, and methadone in the developing chicken embryo. The present findings supplement the already established model and support the use of this chicken model to study NAS.
Topics: Chick Embryo; Infant, Newborn; Animals; Female; Pregnancy; Humans; Methadone; Morphine; Analgesics, Opioid; Chickens; Chromatography, Liquid; Drug Tolerance; Tandem Mass Spectrometry; Neonatal Abstinence Syndrome; Brain; Receptors, Opioid, mu
PubMed: 37866706
DOI: 10.1016/j.taap.2023.116731 -
International Journal of Cancer Oct 2018Recently, the opioid analgesic d,l-methadone has gained much attention as a potential antineoplastic compound, considerably triggered through lay press and media. In... (Review)
Review
Recently, the opioid analgesic d,l-methadone has gained much attention as a potential antineoplastic compound, considerably triggered through lay press and media. In consequence, physicians and pharmacists are currently confronted with numerous patients willing to use d,l-methadone against their malignancies. Well-performed in vitro and in vivo models have in fact shown pro-apoptotic effects of d,l-methadone or other opioids, but also proliferation-stimulating properties. Moreover, the mechanisms of proposed opioid-stimulated apoptosis are incompletely described or contradicting. Finally, the receptors mostly responsible for induction of apoptosis by d,l-methadone remain unclear as contributions of both µ-opioid receptors, Fas cell death receptors, toll-like receptors, N-Methyl-d-aspartate receptors and opioid growth factor receptors were suggested. Such ambiguity prevents rational application of d,l-methadone or patient stratification to enhance beneficial antineoplastic effects. From a clinical point of view, d,l-methadone and other opioids might in fact prolong survival, but such effects likely originate from their analgesic and neuro-psychotropic properties and, thus, improvements of quality of life. Crucial obstacles to the administration of d,l-methadone are incomplete knowledge about its systemic disposition, highly variable pharmacokinetics, profound drug-drug- or drug-disease interaction and QT-prolongation potential. This article summarizes and rates the pharmacological basis of d,l-methadone as an antineoplastic agent and puts its administration in clinical oncology into perspective. Despite enthralling experimental findings about d,l-methadone-mediated apoptosis in cancerous cells or tissues, clinicians should realize the current lack of evidence for the use of d,l-methadone as an antineoplastic agent. Its administration against cancer pain is, however, tenable, albeit restricted to certain clinical situations.
Topics: Animals; Antineoplastic Agents; Apoptosis; Humans; Methadone; Neoplasms
PubMed: 29516505
DOI: 10.1002/ijc.31356 -
BMC Palliative Care Nov 2022Methadone is commonly considered an alternative opioid treatment for refractory cancer pain. This study aims to investigate the efficacy, safety, and cost of methadone...
BACKGROUND
Methadone is commonly considered an alternative opioid treatment for refractory cancer pain. This study aims to investigate the efficacy, safety, and cost of methadone in the treatment of refractory cancer pain.
METHODS
A retrospective study was conducted in patients who used methadone for refractory cancer pain from April 2016 to December 2020 at a cancer specialized hospital. Pain control, evaluated via pain score and breakthrough pain frequency, and adverse events of methadone were compared with analgesic regimens prior to methadone administration. The factors potentially affecting the switching outcome were analyzed via multivariate analysis. Moreover, the cost of pain control was estimated.
RESULTS
Ninety patients received methadone for poor pain control (74.4%), intolerable adverse events (10.0%), or both (15.6%) after prior opioid treatments. Sixty-four patients (71.1%) were successfully switched to methadone with median pain score significantly decreased from 4.0 to 2.0 (p < 0.001) and median daily frequency of breakthrough pain from 3.0 to 0.0 (p < 0.001) at a maintained median conversion ratio of 6.3 [interquartile range (IQR): 4.0-10.0] to prior opioid treatment. Similar adverse event profiles of constipation, nausea, vomiting, and dizziness were observed between methadone and prior opioid regimens. The median daily cost of analgesic regimens was significantly reduced from $19.5 (IQR: 12.3-46.2) to $10.8 (IQR: 7.1-18.7) (p < 0.01) after switching to methadone. The 3-day switch method significantly improved the rate of successful switching compared with the stop and go method (odds ratio = 3.37, 95% CI: 1.30-8.76, p = 0.013).
CONCLUSION
Methadone is an effective, safe, and cost-saving treatment for patients with refractory cancer pain.
Topics: Humans; Methadone; Cancer Pain; Analgesics, Opioid; Retrospective Studies; Breakthrough Pain; Neoplasms
PubMed: 36324113
DOI: 10.1186/s12904-022-01076-2 -
Canadian Family Physician Medecin de... Feb 2021
Topics: British Columbia; Humans; Methadone
PubMed: 33608353
DOI: 10.46747/cfp.670281_3 -
American Journal of Public Health Apr 2022
Topics: Heroin Dependence; Humans; Methadone; Opioid-Related Disorders
PubMed: 35349318
DOI: 10.2105/AJPH.2022.306806