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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 -
Pharmacologic Treatment of Opioid Use Disorder: a Review of Pharmacotherapy, Adjuncts, and Toxicity.Journal of Medical Toxicology :... Dec 2018Opioid use disorder continues to be a significant source of morbidity and mortality in the USA and the world. Pharmacologic treatment with methadone and buprenorphine... (Review)
Review
Opioid use disorder continues to be a significant source of morbidity and mortality in the USA and the world. Pharmacologic treatment with methadone and buprenorphine has been shown to be effective at retaining people in treatment programs, decreasing illicit opioid use, decreasing rates of hepatitis B, and reducing all cause and overdose mortality. Unfortunately, barriers exist in accessing these lifesaving medications: users wishing to start buprenorphine therapy require a waivered provider to prescribe the medication, while some states have no methadone clinics. As such, users looking to wean themselves from opioids or treat their opioid dependence will turn to alternative agents. These agents include using prescription medications, like clonidine or gabapentin, off-label, or over the counter drugs, like loperamide, in supratherapeutic doses. This review provides information on the pharmacology and the toxic effects of pharmacologic agents that are used to treat opioid use disorder. The xenobiotics reviewed in depth include buprenorphine, clonidine, kratom, loperamide, and methadone, with additional information provided on lofexidine, akuamma seeds, kava, and gabapentin.
Topics: Buprenorphine; Humans; Methadone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 30377951
DOI: 10.1007/s13181-018-0685-1 -
BMJ (Clinical Research Ed.) Apr 2017To compare the risk for all cause and overdose mortality in people with opioid dependence during and after substitution treatment with methadone or buprenorphine and... (Meta-Analysis)
Meta-Analysis Review
To compare the risk for all cause and overdose mortality in people with opioid dependence during and after substitution treatment with methadone or buprenorphine and to characterise trends in risk of mortality after initiation and cessation of treatment. Systematic review and meta-analysis. Medline, Embase, PsycINFO, and LILACS to September 2016. Prospective or retrospective cohort studies in people with opioid dependence that reported deaths from all causes or overdose during follow-up periods in and out of opioid substitution treatment with methadone or buprenorphine. Two independent reviewers performed data extraction and assessed study quality. Mortality rates in and out of treatment were jointly combined across methadone or buprenorphine cohorts by using multivariate random effects meta-analysis. There were 19 eligible cohorts, following 122 885 people treated with methadone over 1.3-13.9 years and 15 831 people treated with buprenorphine over 1.1-4.5 years. Pooled all cause mortality rates were 11.3 and 36.1 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 3.20, 95% confidence interval 2.65 to 3.86) and reduced to 4.3 and 9.5 in and out of buprenorphine treatment (2.20, 1.34 to 3.61). In pooled trend analysis, all cause mortality dropped sharply over the first four weeks of methadone treatment and decreased gradually two weeks after leaving treatment. All cause mortality remained stable during induction and remaining time on buprenorphine treatment. Overdose mortality evolved similarly, with pooled overdose mortality rates of 2.6 and 12.7 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 4.80, 2.90 to 7.96) and 1.4 and 4.6 in and out of buprenorphine treatment. Retention in methadone and buprenorphine treatment is associated with substantial reductions in the risk for all cause and overdose mortality in people dependent on opioids. The induction phase onto methadone treatment and the time immediately after leaving treatment with both drugs are periods of particularly increased mortality risk, which should be dealt with by both public health and clinical strategies to mitigate such risk. These findings are potentially important, but further research must be conducted to properly account for potential confounding and selection bias in comparisons of mortality risk between opioid substitution treatments, as well as throughout periods in and out of each treatment.
Topics: Buprenorphine; Drug Overdose; Humans; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Risk
PubMed: 28446428
DOI: 10.1136/bmj.j1550 -
JAMA Pediatrics Aug 2018Although opioids are used to treat neonatal abstinence syndrome (NAS), the best pharmacologic treatment has not been established. (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Although opioids are used to treat neonatal abstinence syndrome (NAS), the best pharmacologic treatment has not been established.
OBJECTIVE
To compare the safety and efficacy of methadone and morphine in NAS.
DESIGN, SETTING, AND PARTICIPANTS
In this randomized, double-blind, intention-to-treat trial, term infants from 8 US newborn units whose mothers received buprenorphine, methadone, or opioids for pain control during pregnancy were eligible. A total of 117 infants were randomized to receive methadone or morphine from February 9, 2014, to March 6, 2017. Mothers who declined randomization could consent to data collection and standard institutional treatment.
INTERVENTIONS
Infants were assessed with the Finnegan Neonatal Abstinence Scoring System every 4 hours and treated with methadone or placebo every 4 hours or morphine every 4 hours. Infants with persistently elevated Finnegan scores received dose increases. Infants who exceeded a predetermined opioid dose received phenobarbital. Dose reductions occurred every 12 to 48 hours when signs of NAS were controlled with therapy, stopping at 20% of the original dose.
MAIN OUTCOMES AND MEASURES
The primary end point was length of hospital stay (LOS). The secondary end points were LOS attributable to NAS and length of drug treatment (LOT).
RESULTS
A total of 183 mothers consented to have their infants in the study; 117 infants required treatment. Because 1 parent withdrew consent, data were analyzed on 116 infants (mean [SD] gestational age, 39.1 [1.1] weeks; mean [SD] birth weight, 3157 [486] g; 58 [50%] male). Demographic variables and risk factors were similar except for more prenatal cigarette exposure in infants who received methadone. Adjusting for study site and maternal opioid type, methadone was associated with decreased mean number of days for LOS by 14% (relative number of days, 0.86; 95% CI, 0.74-1.00; P = .046), corresponding to a difference of 2.9 days; 14% reduction in LOS attributable to NAS (relative number of days, 0.86; 95% CI, 0.77-0.96; P = .01), corresponding to a difference of 2.7 days; and 16% reduction in LOT (relative number of days, 0.84; 95% CI, 0.73-0.97; P = .02), corresponding to a difference of 2.3 days. Methadone was also associated with reduced median LOS (16 vs 20 days, P = .005), LOS attributable to NAS (16 vs 19 days, P = .005), and LOT (11.5 vs 15 days, P = .009). Study infants had better short-term outcomes than 170 nonrandomized infants treated with morphine per standard institutional protocols.
CONCLUSIONS AND RELEVANCE
With use of weight- and sign-based treatment for NAS, short-term outcomes were better in infants receiving methadone compared with morphine. Assessment of longer-term outcomes is ongoing.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01958476.
Topics: Analgesics, Opioid; Double-Blind Method; Female; Humans; Infant, Newborn; Intention to Treat Analysis; Male; Methadone; Morphine; Neonatal Abstinence Syndrome; Treatment Outcome
PubMed: 29913015
DOI: 10.1001/jamapediatrics.2018.1307 -
Annals of Palliative Medicine Mar 2020Methadone has unique characteristics that make it an attractive agent for the treatment of chronic pain and opioid drug dependence. However, methadone prescription... (Review)
Review
Methadone has unique characteristics that make it an attractive agent for the treatment of chronic pain and opioid drug dependence. However, methadone prescription requires more clinical experience and close monitoring of patients to avoid its undesirable side effects. Recently, levorphanol has emerged as "a forgotten opioid" with a similar profile as methadone. Levorphanol has no impact on QTc prolongation and considerably less drug-drug interactions as compared to methadone. Lack of commercial availability, providers' unfamiliarity, and limited clinical data on its effectiveness remain practical issues. The objective of this article is to review and compare the safety considerations for methadone and levorphanol use.
Topics: Analgesics, Opioid; Central Nervous System; Chronic Pain; Dose-Response Relationship, Drug; Humans; Levorphanol; Methadone; Opioid-Related Disorders; Therapeutic Equivalency
PubMed: 32156130
DOI: 10.21037/apm.2020.02.01 -
Journal of Addiction MedicineThis paper offers a review and recommendations for clinicians working with patients interested in discontinuing opioid agonist treatment. As buprenorphine/naloxone has... (Review)
Review
This paper offers a review and recommendations for clinicians working with patients interested in discontinuing opioid agonist treatment. As buprenorphine/naloxone has gained widespread acceptance for opioid addiction, many treatment providers and patients have a range of hopes and expectations about its optimal use. A surprising number assume buprenorphine/naloxone is primarily useful as a medication to transition off illicit opioid use, and success is partially defined by discontinuing the medication. Despite accumulating evidence that a majority of patients will need to remain on medication to preserve their gains, clinicians often have to address a patient's fervent desire to taper. Using the concept of "recovery capital," our review addresses (1) the appropriate duration of opioid agonist treatment, (2) risks associated with discontinuing, (3) a checklist that guides the patient through self-assessment of the wisdom of discontinuing opioid agonist treatment, and (4) shared decision making about how to proceed.
Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 33323695
DOI: 10.1097/ADM.0000000000000789 -
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 -
Clinical Toxicology (Philadelphia, Pa.) Nov 2021According to the latest medical evidence, Methadone and buprenorphine-naloxone (Suboxone) are effective treatments for opioid use disorder (OUD). While the evidence...
BACKGROUND
According to the latest medical evidence, Methadone and buprenorphine-naloxone (Suboxone) are effective treatments for opioid use disorder (OUD). While the evidence basis for the use of these medications is favorable, less is known about the perceptions of the general public about them.
OBJECTIVE
This study aimed to use Twitter to assess the public perceptions about methadone and buprenorphine-naloxone, and to compare their discussion contents based on themes/topics, subthemes, and sentiment.
METHODS
We conducted a descriptive analysis of a small and automatic analysis of a large volume of microposts ("tweets") that mentioned "" or "". In the manual analysis, we categorized the tweets into themes and subthemes, as well as by sentiment and personal experience, and compared the information posted about these two medications. We performed automatic topic modeling and sentiment analysis over large volumes of posts and compared the outputs to those from the manual analyses.
RESULTS
We manually analyzed 900 tweets, most of which related to (15.3% for methadone; 14.3% for buprenorphine-naloxone), (17.0%; 15.5%), and (12.8%; 15.6%). Only a small proportion of tweets (16.4 for Suboxone and 9.3% for methadone) expressed positive sentiments about the medications, with few tweets describing personal experiences. Tweets mentioning both medications primarily discussed MOUD broadly, rather than comparing the two medications directly. Automatic topic modeling revealed topics from the larger dataset that corresponded closely to the manually identified themes, but sentiment analysis did not reveal any notable differences in chatter regarding the two medications.
CONCLUSIONS
Twitter content about methadone and Suboxone is similar, with the same major themes and similar sub-themes. Despite the proven effectiveness of these medications, there was little dialogue related to their benefits or efficacy in the treatment of OUD. Perceptions of these medications may contribute to their underutilization in combatting OUDs.
Topics: Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Humans; Methadone; Narcotic Antagonists; Natural Language Processing; Opiate Substitution Treatment; Opioid-Related Disorders; Public Opinion; Social Media
PubMed: 33821724
DOI: 10.1080/15563650.2021.1893742 -
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