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CNS Drugs Aug 2020Methadone is increasingly being used for its analgesic properties. Despite the increasing popularity, many healthcare providers are not familiar with methadone's complex... (Review)
Review
Methadone is increasingly being used for its analgesic properties. Despite the increasing popularity, many healthcare providers are not familiar with methadone's complex pharmacology and best practices surrounding its use. The purpose of this narrative review article is to discuss the pharmacology of methadone, the evidence surrounding methadone's use in acute pain management and both chronic cancer and non-cancer pain settings, as well as highlight pertinent safety, monitoring, and opioid rotation considerations. Methadone has a unique mechanism of action when compared with all other opioids and for this reason methadone has come to hold a niche role in the management of opioid-induced hyperalgesia and central sensitization. Understanding of the mechanisms of variability in methadone disposition and drug interactions has evolved over the years, with the latest evidence revealing that CYP 2B6 is the major determinant of methadone elimination and plays a key role in methadone-related drug interactions. From an acute pain perspective, most studies evaluating the use of intraoperative intravenous methadone have reported lower pain scores and post-operative opioid requirements. Oral methadone is predominantly used as a second-line opioid treatment for select chronic pain conditions. As a result, several oral morphine to oral methadone conversion ratios have been proposed, as have methods in which to rotate to methadone. From an efficacy standpoint, limited literature exists regarding the effectiveness of methadone in the chronic pain setting with most of the available efficacy data pertaining to methadone's use in the treatment of cancer pain. Many of the prospective studies that exist feature low participant numbers. Few clinical trials investigating the role of methadone as an analgesic treatment are currently underway. The complicated pharmacokinetic properties of methadone and risks of harm associated with this drug highlight how critically important it is that healthcare providers understand these features before prescribing/dispensing methadone. Particular caution is required when converting patients from other opioids to methadone and for this reason only experienced healthcare providers should undertake such a task. Further randomized trials with larger sample sizes are needed to better define the effective and safe use of methadone for pain management.
Topics: Analgesics, Opioid; Cancer Pain; Chronic Pain; Humans; Methadone; Pain Management; Prospective Studies
PubMed: 32564328
DOI: 10.1007/s40263-020-00743-3 -
Biological Psychiatry Jan 2020Opioid use disorder (OUD) is a chronic, relapsing condition, often associated with legal, interpersonal, and employment problems. Medications demonstrated to be... (Review)
Review
Opioid use disorder (OUD) is a chronic, relapsing condition, often associated with legal, interpersonal, and employment problems. Medications demonstrated to be effective for OUD are methadone (a full opioid agonist), buprenorphine (a partial agonist), and naltrexone (an opioid antagonist). Methadone and buprenorphine act by suppressing opioid withdrawal symptoms and attenuating the effects of other opioids. Naltrexone blocks the effects of opioid agonists. Oral methadone has the strongest evidence for effectiveness. Longer duration of treatment allows restoration of social connections and is associated with better outcomes. Treatments for OUD may be limited by poor adherence to treatment recommendations and by high rates of relapse and increased risk of overdose after leaving treatment. Treatment with methadone and buprenorphine has the additional risk of diversion and misuse of medication. New depot and implant formulations of buprenorphine and naltrexone have been developed to address issues of safety and problems of poor treatment adherence. For people with OUD who do not respond to these treatments, there is accumulating evidence for supervised injectable opioid treatment (prescribing pharmaceutical heroin). Another medication mode of minimizing risk of overdose is take-home naloxone. Naloxone is an opioid antagonist used to reverse opioid overdose, and take-home naloxone programs aim to prevent fatal overdose. All medication-assisted treatment is limited by lack of access and by stigma. In seeking to stem the rising toll from OUD, expanding access to approved treatment such as methadone, for which there remains the best evidence of efficacy, may be the most useful approach.
Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 31420089
DOI: 10.1016/j.biopsych.2019.06.020 -
Anaesthesia and Intensive Care Mar 2022
Topics: Humans; Methadone; Morphine
PubMed: 35112583
DOI: 10.1177/0310057X211070686 -
American Journal of Obstetrics &... Jan 2021
Topics: Buprenorphine; Methadone
PubMed: 33451602
DOI: 10.1016/j.ajogmf.2020.100236 -
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 -
Mayo Clinic Proceedings Oct 2019The United States is in the midst of a national opioid epidemic. Physicians are encouraged both to prevent and treat opioid-use disorders (OUDs). Although there are 3... (Review)
Review
The United States is in the midst of a national opioid epidemic. Physicians are encouraged both to prevent and treat opioid-use disorders (OUDs). Although there are 3 Food and Drug Administration-approved medications to treat OUD (methadone, buprenorphine, and naltrexone) and there is ample evidence of their efficacy, they are not used as often as they should. We provide a brief review of the 3 primary medications used in the treatment of OUD. Using data from available medical literature, we synthesize existing knowledge and provide a framework for how to determine the optimal approach for outpatient management of OUD with medication-assisted treatments.
Topics: Algorithms; Buprenorphine; Decision Trees; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 31543255
DOI: 10.1016/j.mayocp.2019.03.029 -
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 -
Therapeutic Drug Monitoring Apr 2020Buprenorphine and methadone are international gold standards for managing opioid use disorders. Although they are efficacious in treating opioid dependence,... (Review)
Review
PURPOSE
Buprenorphine and methadone are international gold standards for managing opioid use disorders. Although they are efficacious in treating opioid dependence, buprenorphine and methadone present risks, especially during pregnancy, causing neonatal abstinence syndrome and adverse obstetrical outcomes. Buprenorphine and methadone are also abused during pregnancy, and identifying their use is important to limit unprescribed prenatal exposure. Previous studies have suggested that concentrations of buprenorphine, but not methadone markers in unconventional matrices may predict child outcomes, although currently only limited data exist. We reviewed the literature on concentrations of buprenorphine, methadone, and their metabolites in unconventional matrices to improve data interpretation.
METHODS
A literature search was conducted using scientific databases (PubMed, Scopus, Web of Science, and reports from international institutions) to review published articles on buprenorphine and methadone monitoring during pregnancy.
RESULTS
Buprenorphine and methadone and their metabolites were quantified in the meconium, umbilical cord, placenta, and maternal and neonatal hair. Methadone concentrations in the meconium and hair were typically higher than those in other matrices, although the concentrations in the placenta and umbilical cord were more suitable for predicting neonatal outcomes. Buprenorphine concentrations were lower and required sensitive instrumentation, as measuring buprenorphine glucuronidated metabolites is critical to predict neonatal outcomes.
CONCLUSIONS
Unconventional matrices are good alternatives to conventional ones for monitoring drug exposure during pregnancy. However, data are currently scarce on buprenorphine and methadone during pregnancy to accurately interpret their concentrations. Clinical studies should be conducted with larger cohorts, considering confounding factors such as illicit drug co-exposure.
Topics: Analgesics, Opioid; Buprenorphine; Drug Monitoring; Female; Hair; Humans; Meconium; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Prenatal Exposure Delayed Effects; Umbilical Cord
PubMed: 31425444
DOI: 10.1097/FTD.0000000000000693 -
Pediatric Annals Jan 2020Opioid use and abuse have skyrocketed in the United States over the last decade. As a result, we have seen a substantial increase in neonates who are exposed to opioids...
Opioid use and abuse have skyrocketed in the United States over the last decade. As a result, we have seen a substantial increase in neonates who are exposed to opioids in-utero. Anywhere from 55% to 94% of infants exposed to opioids will experience withdrawal, known as neonatal abstinence syndrome (NAS), and will require management of their symptoms in the hospital. It is important to know what to look for in an infant who is experiencing NAS, how to determine if treatment is needed and what type of treatment is indicated, and how to prepare the infant for discharge once they are stable. Unfortunately, there are no standardized care plans in place for the management of this population. Although assessment tools such as the Finnegan scoring systems are available, they are not validated and can be cumbersome and difficult to administer. Other methods of assessment are being studied and may prove to be more useful in the clinical setting of neonatal withdrawal. Neither nonpharmacologic nor pharmacologic interventions are standardized, with individual institutions determining their plan of care. Development of more standardized care could significantly improve the management of these patients. [Pediatr Ann. 2020;49(1):e3-e7.].
Topics: History, 19th Century; History, 20th Century; Humans; Infant, Newborn; Methadone; Morphine; Neonatal Abstinence Syndrome; United States
PubMed: 31930416
DOI: 10.3928/19382359-20191211-01