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British Journal of Clinical Pharmacology Jun 2019A dramatic increase in newborn infants with neonatal abstinence syndrome has been observed and these neonates are frequently treated with complex methadone dosing...
AIMS
A dramatic increase in newborn infants with neonatal abstinence syndrome has been observed and these neonates are frequently treated with complex methadone dosing schemes to control their withdrawal symptoms. Despite its abundant use, hardly any data on the pharmacokinetics (PK) of methadone is available in preterm neonates. Therefore we investigated developmental PK of methadone and evaluated current dosing strategies and possible simplification in this vulnerable population.
METHODS
A single-centre open-label prospective study was performed to collect PK data after a single oral dose of methadone in preterm neonates. A population PK model was built to characterize developmental PK of (R)- and (S)-methadone. Model-based simulations were performed to identify a simplified dosing strategy to reach and maintain target methadone exposure.
RESULTS
A total of 121 methadone concentrations were collected from 31 preterm neonates. A one-compartment model with first order absorption and elimination kinetics best described PK data for (R)- and (S)-methadone. Clearance increases with advancing gestational age and differs between R- and S-enantiomer, being slightly higher for the former (0.244 vs 0.167 L/h). Preterm neonates reached target exposure after 48 hours with currently used dosing schedules. Output from simulations revealed that target exposures can be achieved with a simplified dosing strategy during the first 4 days of treatment.
CONCLUSION
Methadone clearance in preterm neonates increases with advancing gestational age and its disposition is influenced by its chirality. Simulations that account for developmental PK changes indicate a shorter methadone dosing strategy can maintain target exposure to control withdrawal symptoms.
Topics: Administration, Oral; Adolescent; Adult; Age Factors; Analgesics, Opioid; Drug Dosage Calculations; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Male; Methadone; Models, Biological; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Prospective Studies; Treatment Outcome; Young Adult
PubMed: 30805946
DOI: 10.1111/bcp.13906 -
The Western Journal of Medicine May 1990We describe the historical underpinnings of negative attitudes towards methadone and how these affect medical decisions. Current developments have increased the... (Review)
Review
We describe the historical underpinnings of negative attitudes towards methadone and how these affect medical decisions. Current developments have increased the understanding of the origins of opioid addiction, such as how receptor system dysfunction may affect the ability to remain abstinent once out of treatment. Specialized topics include the pregnant addict, the role of methadone maintenance in limiting the spread of the acquired immunodeficiency syndrome, and patients with a dual diagnosis. We also describe issues that arise when methadone is used in conjunction with prescribed or abused drugs, noting pharmacologic alternatives and adjuncts to methadone treatment. Finally, we comment on treatment issues such as methadone patients in 12-step programs and the growing legitimacy of this treatment method.
Topics: Acquired Immunodeficiency Syndrome; Attitude of Health Personnel; Cocaine; Drug Interactions; Ethanol; Female; Heroin Dependence; Humans; Methadone; Opioid-Related Disorders; Pregnancy; Substance Withdrawal Syndrome
PubMed: 2190427
DOI: No ID Found -
British Journal of Pharmacology Apr 2023Opioid use disorder is a worldwide societal problem and public health burden. Strategies for treating opioid use disorder can be divided into those that target the... (Review)
Review
Opioid use disorder is a worldwide societal problem and public health burden. Strategies for treating opioid use disorder can be divided into those that target the opioid receptor system and those that target non-opioid receptor systems, including the dopamine and glutamate receptor systems. Currently, the clinical drugs used to treat opioid use disorder include the opioid receptor agonists methadone and buprenorphine, which are limited by their abuse liability, and the opioid receptor antagonist naltrexone, which is limited by poor compliance. Therefore, the development of effective medications with lower abuse liability and better potential for compliance is urgently needed. Based on recent advances in the understanding of the neurobiological mechanisms underlying opioid use disorder, potential treatment strategies and targets have emerged. This review focuses on the progress made in identifying potential targets and developing medications to treat opioid use disorder, including progress made by our laboratory, and provides insights for future medication development. LINKED ARTICLES: This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.
Topics: Humans; Opioid-Related Disorders; Analgesics, Opioid; Methadone; Buprenorphine; Naltrexone
PubMed: 34128238
DOI: 10.1111/bph.15592 -
Bulletin of the New York Academy of... 1990
Topics: Ambulatory Care Facilities; Humans; Methadone; New York City; Substance-Related Disorders
PubMed: 2364219
DOI: No ID Found -
Evaluation and Program Planning Jun 2022The purpose of this study is to identify the relative strengths of association of medication and health and social services in comprehensive substance use disorder (SUD)...
BACKGROUND
The purpose of this study is to identify the relative strengths of association of medication and health and social services in comprehensive substance use disorder (SUD) treatment.
OBJECTIVES
The study uses a novel variance decomposition method to assess the relative strength of association of six active ingredients of comprehensive SUD treatment: methadone medication, access services, SUD counseling, matched service ratio, client-provider relationship, and treatment duration.
METHODS
The study uses data from the National Treatment Improvement Evaluation Study (1992-1997), a dataset with an unusual number of services and service strategies measured. The data include 3012 clients from 45 SUD treatment programs. Linear mixed models are used to assess the relation of service variables to the outcome of posttreatment substance use. Variance decomposition methods are used to assess the relative importance of the ingredients in the treatment model.
RESULTS
Along with a random intercept and background variables, receipt of methadone accounted for the greatest relative strength of association at 35.4%, compared with 23.8% for treatment duration, 15.4% for client-provider relationship, and 11.2% for matched service ratio. Access and SUD counseling accounted for modest strengths of association at 1% and 3% each.
CONCLUSION
Findings indicate somewhat greater strength of association of methadone compared with other services and service strategies and overall, reinforce the importance of both medication and services and service strategies in the design and development of effective models of service delivery.
SIGNIFICANCE
This study, among the first to evaluate the relative importance of specific services and service strategies of comprehensive SUD treatment, provides insights relevant to the development of effective models of service delivery.
Topics: Humans; Methadone; Program Evaluation; Social Work; Substance-Related Disorders
PubMed: 35247677
DOI: 10.1016/j.evalprogplan.2022.102060 -
Anesthesiology Oct 2023
Topics: Methadone; Analgesics
PubMed: 37698432
DOI: 10.1097/ALN.0000000000004681 -
Frontiers in Public Health 2021From the health care and societal perspectives, this study aimed to evaluate the clinical and economic effects of acupuncture as an adjunctive therapy for patients... (Randomized Controlled Trial)
Randomized Controlled Trial
Clinical and Economic Evaluation of Acupuncture for Opioid-Dependent Patients Receiving Methadone Maintenance Treatment: The Integrative Clinical Trial and Evidence-Based Data.
From the health care and societal perspectives, this study aimed to evaluate the clinical and economic effects of acupuncture as an adjunctive therapy for patients receiving methadone maintenance treatment (MMT). We conducted a parallel-arm RCT in China in 2019. Patients were included who met the diagnostic criteria and receive MMT for more than 30 days. Patients were randomly assigned to the exposed group (acupuncture plus MMT) or control group (MMT) at a 1:1 ratio. Daily methadone dosage, drug cravings using the VAS score, and insomnia using the Pittsburgh Sleep Quality Index (PSQI) were chosen as the effectiveness indexes, and the quality-adjusted life years (QALYs) was chosen as the utility index. Overall, 123 patients were included. The exposed group was significantly ( < 0.05) better than the control group in the improvement of daily methadone dosage (17.68 vs. 1.07), VAS (38.27 vs. 2.64), and PSQI (2.18 vs. 0.30). The QALY was 0.0784 (95%CI: 0.0761-0.0808) for the exposed group and 0.0762 (95%CI: 0.0738-0.0787) for the control group. The total cost of the exposed group (2869.50 CNY) was higher than the control group (2186.04 CNY). The ICER of daily methadone dosage (41.15), VAS (17.86), and PSQI (313.51) were shown to be economically efficient. While ICUR (310,663.64 CNY/QYLY) was higher than the cost suggested by WHO. Acupuncture as an adjuvant therapy for MMT patients realizes its cost-effectiveness by reducing the dosage of methadone, improving drug cravings, and alleviating insomnia. It helps to improve quality of life, but since its cost exceeds what society is willing to pay, further study is needed.
Topics: Acupuncture Therapy; Analgesics, Opioid; Cost-Benefit Analysis; Humans; Methadone; Quality of Life
PubMed: 34485219
DOI: 10.3389/fpubh.2021.689753 -
Harm Reduction Journal Sep 2023Opioid relapse, one of the common and severe problems during methadone maintenance treatment, can give rise to poor treatment outcomes. This study measured the opioid...
BACKGROUND
Opioid relapse, one of the common and severe problems during methadone maintenance treatment, can give rise to poor treatment outcomes. This study measured the opioid relapse rate and its associated factors among methadone maintenance patients in Vietnam.
METHODS
Information about the demographic characteristics and social support of 655 patients was collected through direct interviews. Medical records were used to gather data on treatment characteristics. Relapse was determined via urine opioid test results.
RESULTS
The overall relapse rate of patients during treatment was 13.1%. According to the multivariate logistic regression model, living in mountainous areas (adjusted odds ratio (aOR) = 3.63, 95% CI 1.90-7.46) and long duration of drug use in the past (aOR = 1.06, 95% CI 1.03-1.09) were associated with an increase in the odds of opioid relapse. By contrast, living with many family members (aOR = 0.69, 95% CI 0.55-0.85), having longer treatment time (aOR = 0.80, 95% CI 0.73-0.87), and completely adhering to treatment (aOR = 0.38, 95% CI 0.23-0.64) were protective for opioid relapse. As per the univariate analyses, the odds of opioid relapse declined by 25% for each increase of one close friend or relative (OR = 0.75, 95% CI 0.66-0.86). Regarding social support (range score: 0-100), each additional increase of one score was associated with a 1% decrease in the odds of opioid relapse (OR = 0.99, 95% CI 0.98-0.99). Patient sex, education level, occupation type, patient's monthly income, family's monthly income, the number of previous treatments, daily methadone dose, comorbidity, and received antiretroviral therapy were not associated with opioid relapse among patients (p > 0.05).
CONCLUSIONS
Residence, the role of family and social support, and treatment adherence should be paid more attention to guarantee and enhance the success of methadone maintenance treatment.
Topics: Humans; Analgesics, Opioid; Cross-Sectional Studies; Vietnam; Opiate Substitution Treatment; Methadone
PubMed: 37717002
DOI: 10.1186/s12954-023-00872-0 -
Harm Reduction Journal Jan 2019Opioid dependence, characterised by socio economic disadvantage and significant morbidity and mortality, remains a major public health problem in Ireland. Through the... (Review)
Review
BACKGROUND
Opioid dependence, characterised by socio economic disadvantage and significant morbidity and mortality, remains a major public health problem in Ireland. Through the methadone treatment protocol (MTP), Irish general practice has been a leader in the introduction and expansion of Irish harm reduction services, including opioid substitution treatment (OST), needle and syringe programs (NSP) and naloxone provision. These services have been effective in engaging opiate users in treatment, reducing human deficiency virus (HIV) and hepatitis C virus (HCV) transmission and reducing-drug related morbidities. Challenges remain in relation to choice of substitution treatments, timely access to OST services, adequate coverage of NSP, naloxone provision and increasing drug-related deaths.
METHODS
A narrative review was conducted and designed to present a broad perspective on the Irish MTP and to describe its history and development in terms of clinical care, stakeholder views and changing trends.
RESULTS
Three themes emerged from the analysis; The History of the Methadone Treatment Protocol, Service User and Provider Views and Challenges and Developments. Despite the initial concern about methadone maintenance treatment (MMT) in Ireland, increased participation by Irish GPs in the treatment of opioid dependence is observed over the last two decades. There are now over 10,000 people on methadone treatment in Ireland, with 40% treated in general practice. The MTP provides structure, remuneration and guidance to GPs and is underpinned by training, ongoing education and a system of quality assurance provided by the Irish College of General Practice (ICGP). Challenges include the negative views of patients around how methadone services are delivered, the stigma associated with methadone treatment, the lack of choice around substitution medication, waiting lists for treatment in certain areas and rates of fatal overdose.
CONCLUSION
Twenty years of the MTP has been the mainstay of harm reduction services in Ireland. It has provided a network of specially trained GPs who provide methadone to over 10,000 patients across Ireland within a structured framework of training, quality assurance and remuneration. With the ongoing commitment of Irish specialists in the field of addiction medicine, further improvements to support and treat patients can be made.
Topics: General Practice; Harm Reduction; History, 20th Century; History, 21st Century; Humans; Ireland; Methadone; Naloxone; Narcotic Antagonists; Narcotic-Related Disorders; Narcotics; Needle-Exchange Programs; Opiate Substitution Treatment
PubMed: 30654803
DOI: 10.1186/s12954-018-0272-4 -
BMC Veterinary Research Jan 2021The present study aimed to collect pharmacokinetic data of a methadone continuous rate infusion (CRI) and to investigate its effect on mechanical and thermal nociceptive...
BACKGROUND
The present study aimed to collect pharmacokinetic data of a methadone continuous rate infusion (CRI) and to investigate its effect on mechanical and thermal nociceptive thresholds. Seven, 47 to 54 months old beagle dogs, weighing 9.8 to 21.2 kg, were used in this experimental, randomized, blinded, placebo-controlled crossover study. Each dog was treated twice with either a methadone bolus of 0.2 mg kg followed by a 0.1 mg kg h methadone CRI (group M) or an equivalent volume of isotonic saline solution (group P) for 72 h. Mechanical and thermal thresholds, as well as vital parameters and sedation were measured during CRI and for further 24 h. Blood samples for methadone plasma concentrations were collected during this 96 h period.
RESULTS
Percentage thermal excursion (%TE) increased significantly from baseline (BL) until 3 h after discontinuation of CRI in M. Within P and between treatment groups differences were not significant. Mechanical threshold (MT) increased in M until 2 h after CRI discontinuation. Bradycardia and hypothermia occurred in M during drug administration and dogs were mildly sedated for the first 47 h. Decreased food intake and regurgitation were observed in M in five and four dogs, respectively. For methadone a volume of distribution of 10.26 l kg and a terminal half-life of 2.4 h were detected and a clearance of 51.44 ml kg min was calculated. Effective methadone plasma concentrations for thermal and mechanical antinociception were above 17 ng ml.
CONCLUSION
A methadone CRI of 0.1 mg kg h for 3 days after a loading dose results in steady anti-nociceptive effects in an acute pain model in healthy dogs. Main side effects were related to gastrointestinal tract, hypothermia, bradycardia and sedation.
Topics: Administration, Intravenous; Analgesics, Opioid; Animals; Bradycardia; Cross-Over Studies; Dogs; Female; Hot Temperature; Hypothermia; Male; Methadone; Nociception; Pain; Random Allocation
PubMed: 33461553
DOI: 10.1186/s12917-020-02735-3