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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 -
Anesthesiology Clinics Sep 2018As part of a national effort to combat the current US opioid epidemic, use of currently Food and Drug Administration-approved drugs for the treatment of opioid use... (Review)
Review
As part of a national effort to combat the current US opioid epidemic, use of currently Food and Drug Administration-approved drugs for the treatment of opioid use disorder/opioid addiction (buprenorphine, methadone, and naltrexone) is on the rise. To provide optimal pain control and minimize the risk of relapse and overdose, providers need to have an in-depth understanding of how to manage these medications in the perioperative setting. This article reviews key principles and discusses perioperative considerations for patients with opioid use disorder on buprenorphine, methadone, or naltrexone.
Topics: Buprenorphine; Humans; Methadone; Naltrexone; Opioid-Related Disorders; Pain Management; Perioperative Care
PubMed: 30092933
DOI: 10.1016/j.anclin.2018.04.002 -
Molecular Diagnosis & Therapy Feb 2018The efficacy of methadone maintenance treatment (MMT) in opioid use disorder is well established but responses vary. The influence of methadone pharmacodynamics and... (Review)
Review
The efficacy of methadone maintenance treatment (MMT) in opioid use disorder is well established but responses vary. The influence of methadone pharmacodynamics and pharmacokinetics on dose requirements and program outcomes remains controversial despite the increasing number of studies evaluating genetic influences on response to methadone treatment. Furthermore, patients require different doses (usually between 60 and 100 mg/day), and there are no clear data on a plasma concentration associated with treatment success. We review the evidence regarding the influence of genetics on pharmacokinetic and pharmacodynamic factors in terms of MMT outcome. We also analyse the influence of genetics on the occurrence of severe adverse events such as respiratory depression and ventricular arrhythmia in methadone treatment. The outcomes of MMT may be influenced by a combination of environmental, drug-induced, and genetic factors. The influence of pharmacokinetic genetic variability can be clinically managed by modifying the posology. A better understanding of pharmacodynamic factors could help in selecting the best opioid for substitution treatment, but patient phenotype must still be considered when establishing a maintenance treatment. Pharmacogenetic studies represent a promising field that aims to individualize treatments according to genetic backgrounds, adapting medication and doses according to possible outcomes and the risk of adverse events.
Topics: Gene Regulatory Networks; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pharmacogenomic Variants; Precision Medicine; Treatment Outcome
PubMed: 29168075
DOI: 10.1007/s40291-017-0311-y -
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 -
Journal of Substance Abuse Treatment Oct 2022Opioid misuse is a nationwide public health crisis. Methadone treatment is proven to be highly successful in preventing opioid use disorder, reducing the use of illicit...
INTRODUCTION
Opioid misuse is a nationwide public health crisis. Methadone treatment is proven to be highly successful in preventing opioid use disorder, reducing the use of illicit drugs, and preventing overdoses. Clients acquire methadone daily from clinics, making geographic access crucial for the initiation of and adherence to treatment.
METHODS
This work estimates unsatisfied methadone demand due to lack of geographic access at a census tract level and models the problem of identifying optimal locations to open new methadone clinics. The objective function of the model is a weighted combination of providing access to individuals with unmet methadone demand and improving the travel time of individuals currently attending a clinic. Data on existing methadone clinics and statewide methadone demand is acquired from Substance Abuse and Mental Health Services Administration (SAMHSA) surveys from 2019. Unsatisfied demand is estimated through a linear regression model after aggregating the population, heroin use, and satisfied methadone demand at the state level.
RESULTS
Nationwide, we find 18.2 % of the United States population does not have geographic access to a methadone clinic and estimate 77,973 individuals in these areas would attend a clinic if geographic access barriers were removed (95 % CI: 67,413-88,532). In a case study of six Midwestern states, we find that geography significantly contributes to the value of opening additional clinics and we see large differences in expected gains between states sharing similar characteristics such as population and satisfied methadone demand. The number of additional clients served by opening one new clinic ranges from 180 to 804 across these six states, representing between 8.4 % and 16.2 % of state unmet demand. Between 1.2 % and 14.1 % of existing clients were reassigned with a single newly opened clinic, with a one-way average travel distance improvement between 6.3 and 11.9 miles / person / day for these clients.
CONCLUSIONS
The results demonstrate the large unserved methadone demand in the United States, the significant improvement in methadone access for new and existing clients that can be achieved by opening new clinics, and the important role state-specific geography plays in these decisions.
Topics: Ambulatory Care Facilities; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Surveys and Questionnaires; Travel; United States
PubMed: 35870438
DOI: 10.1016/j.jsat.2022.108836 -
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 -
Canadian Family Physician Medecin de... Feb 2021
Topics: British Columbia; Humans; Methadone
PubMed: 33608353
DOI: 10.46747/cfp.670281_3 -
Journal of Pharmaceutical Sciences Dec 2018Methadone is utilized for the treatment of individuals with opiate dependence. Methadone undergoes N-demethylation by multiple cytochrome P450 (CYP) enzymes including... (Review)
Review
Methadone is utilized for the treatment of individuals with opiate dependence. Methadone undergoes N-demethylation by multiple cytochrome P450 (CYP) enzymes including CYP3A4, CYP2B6, CYP2C19, CYP2D6, CYP2C9, and CYP2C8. In vivo, polymorphism effects on methadone systemic exposure have been noted for CYP2B6, CYP3A4, and CYP2D6. Clinical drug interaction studies with antiviral drugs in methadone maintenance treatment patients yield varying results on methadone pharmacokinetics and pharmacodynamics. In general, CYP inhibitors altered methadone exposure with no adverse effects. CYP inducers generally decreased methadone exposure with some reports of withdrawal symptoms in the subjects. Interaction studies with antiviral drug combinations yielding differing results depend on the enzyme(s) affected. For certain antiviral medicines which are dual inhibitor(s) and inducer(s) for CYP enzymes, their effect on methadone pharmacokinetics can change with time since the effect of induction is usually delayed compared to the effect of inhibition.
Topics: Analgesics, Opioid; Animals; Antiviral Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Methadone
PubMed: 30205091
DOI: 10.1016/j.xphs.2018.08.025 -
American Journal of Public Health Apr 2022
Topics: Humans; Methadone; Opioid-Related Disorders; Policy
PubMed: 35349312
DOI: 10.2105/AJPH.2021.306665