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Addiction (Abingdon, England) Dec 2020We assessed how opioid agonist treatment (OAT) for opioid use disorder (OUD), specifically methadone and buprenorphine, including buprenorphine-naloxone, is delivered in... (Review)
Review
AIMS
We assessed how opioid agonist treatment (OAT) for opioid use disorder (OUD), specifically methadone and buprenorphine, including buprenorphine-naloxone, is delivered in routine clinical practice, with a focus on factors that affect access to and delivery of these services. The aims of this review were to summarize eligibility criteria for entry to OAT, doses in routine clinical practice, access to and eligibility for unsupervised dosing and urine drug screening practices in OAT programs globally.
METHODS
We completed searches of PubMed, Embase, and grey literature databases for cross-sectional or observational cohort studies of OAT using either methadone or buprenorphine. Dose data extracted from eligible studies were compared with guidelines provided by WHO.
RESULTS
We found 140 reports from 41 countries that contained data for at least one of the relevant indicators. A diagnosis of opioid dependence or opioid use disorder was the most common eligibility requirement for OAT (13 or 17 countries). Reported mean or median doses for methadone ranged from 16-131 mg whereas range for buprenorphine was 2.5-19 mg. Access to unsupervised dosing under some conditions was reported in 18 of 27 countries. Frequency of regular urine drug screenings (UDS) ranged from several times a week to eight times per year (methadone) or as clinically indicated.
CONCLUSIONS
Opioid agonist treatment practices, including doses prescribed, vary greatly both within and across countries. Of particular concern is the persistence of lower dose prescribing practices, in which patients may be prescribed doses below those proven to yield significant clinical benefits.
Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 32289189
DOI: 10.1111/add.15087 -
Bosnian Journal of Basic Medical... Apr 2021Methadone has a wide pharmacokinetic interindividual variability, resulting in unpredicted treatment response. Pharmacogenomic biomarkers seem promising for personalized... (Review)
Review
Methadone has a wide pharmacokinetic interindividual variability, resulting in unpredicted treatment response. Pharmacogenomic biomarkers seem promising for personalized methadone maintenance treatment. The evidence supports the use of ABCB1 single-nucleotide polymorphism (SNP) 1236C>T with genotypes C/T or C/C (Jewish) and haplotypes AGCTT carrier, AGCGC heterozygote, or non-carrier (Caucasian), which have a predicted lower methadone dose requirement. In contrast, ABCB1 SNP 1236C>T with genotype T/T (Jewish); haplotypes AGCGC homozygote, AGCTT non-carrier (Caucasian), and ABCB1 3435C>T variant carrier; and haplotypes CGT, TTC, and TGT (Han Chinese) have a predicted higher methadone dose. For methadone plasma levels, ABCB1 diplotype non-CGC/TTT (Malay) predicted lower, and diplotype CGC/TTT (Malay), 3435C>T allelic carrier, haplotypes (CGT, TTC, TGT) (Han Chinese) predicted higher methadone levels. In terms of metabolism biomarkers, a lower methadone requirement was related to carriers of CYP2B6 genotypes *4(G/G) and *9(T/T) among Jewish patients, CYP2B6*9 genotype (T/T) and haplotypes (TA/TG); and CYP2C19 (*2/*2,*2/*3, and *3/*3; Han Chinese). Higher methadone dose was observed in CYP2C19*1 allelic carriers (Han Chinese) and CYP2D6 ultrarapid metabolizer (Caucasian). Lower methadone levels were reported in CYP2B6 SNPs, haplotypes TTT, and AGATAA (Han Chinese), CYP2C19 genotype *1/*1 (Han Chinese), allelic carrier *1xN (Caucasian), and CYP3A4 genotype *1/*1 (Caucasian). Carriers of CYP2B6 genotype *6/*6 (Caucasian), CYP2B6 haplotypes ATGCAG and ATGCTG (Han Chinese), and CYP3A4 genotype *1/*1B (Caucasian) had predicted higher methadone plasma levels. Specific pharmacokinetics biomarkers have potential uses for personalized methadone treatment in specific populations.
Topics: ATP Binding Cassette Transporter, Subfamily B; Analgesics, Opioid; Cytochrome P-450 Enzyme System; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pharmacogenetics; Polymorphism, Genetic; Precision Medicine
PubMed: 32841585
DOI: 10.17305/bjbms.2020.4897 -
Cost and cost-effectiveness of interim methadone treatment and patient navigation initiated in jail.Drug and Alcohol Dependence Dec 2020Individuals with opioid use disorder (OUD) who are released from pre-trial detention in jail have a high risk of opioid relapse. While several interventions for OUD... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Individuals with opioid use disorder (OUD) who are released from pre-trial detention in jail have a high risk of opioid relapse. While several interventions for OUD initiated during incarceration have been studied, few have had an economic evaluation. As part of a three-group randomized trial, we estimated the cost and cost-effectiveness of a negative urine opioid test. Detainees were assigned to interim methadone (IM) in jail with continued methadone treatment post-release with and without 3 months of post-release patient navigation (PN) compared to an enhanced treatment-as-usual group.
METHODS
We implemented a micro-costing approach from the provider's perspective to estimate the cost per participant in jail and over the 12 months post-release from jail. Economic data included jail-based and community-based service utilization, self-reported healthcare utilization and justice system involvement, and administrative arrest records. Our outcome measure is the number of participants with a negative opioid urine test at their 12-month follow-up. We calculated incremental cost-effectiveness ratios (ICERs) for intervention costs only and costs from a societal perspective.
RESULTS
The average cost of providing patient navigation services per individual beginning in jail and continuing in the community was $283. We find that IM is dominated by ETAU and IM + PN. Per additional participant with a negative opioid urine test, the ICER for IM + PN including intervention costs only is $91 and $305 including societal costs.
CONCLUSIONS
IM + PN is almost certainly the cost-effective choice from both an intervention provider and societal perspective.
Topics: Adult; Analgesics, Opioid; Cost-Benefit Analysis; Female; Humans; Jails; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Acceptance of Health Care; Patient Navigation; Treatment Outcome
PubMed: 32992151
DOI: 10.1016/j.drugalcdep.2020.108292 -
Harm Reduction Journal Apr 2021Methadone and buprenorphine are the most prevalent types of opioid maintenance programs in Andalusia. The main objective is comparing the functional status of patients...
BACKGROUND
Methadone and buprenorphine are the most prevalent types of opioid maintenance programs in Andalusia. The main objective is comparing the functional status of patients with pharmacological opioid maintenance treatments according to different socio-demographic characteristic, health and disabilities domains and sexual difficulties.
METHODS
A total of 593 patients from the Andalusia community, 329 were undergoing methadone treatment and 264 were undergoing buprenorphine treatment. The patients were interviewed by socio-demographic and opioid-related variables, assessed by functioning, disability and health domains (WHODAS 2.0.) and for sexual problems (PRSexDQ-SALSEX).
RESULTS
We found significant differences in the socio-demographic and the opioid-related variables as the onset of opioid use, being on previous maintenance programs, opioid intravenous use, the length of previous maintenance programs, polydrug use and elevated seroprevalence rates (HCV and HIV) between the methadone group and the buprenorphine group. Regarding health and disability domains there were differences in the Understanding and communication domain, Getting around domain, Participation in society domain and in the WHODAS 2.0. simple and complex score, favoring buprenorphine-treated patients. The methadone group referred elevated sexual impairments compared with the buprenorphine group. Opioid-related variables as seroprevalence rates, other previous lifetime maintenance program, the daily opioid dosage and the daily alcohol use are the most discriminative variables between both groups. Participation in society variables and sexual problems were the most important clinical variables in distinguishing the methadone group from the buprenorphine group regarding their functional status.
CONCLUSIONS
The methadone group showed higher prevalence in opioid dependence-related variables, elevated disabilities in participation in society activities and sexual problems compared with the buprenorphine group. This study shows the importance of carry out a functional evaluation in the healthcare follow-up, especially in those areas related with social activity and with sexual problems.
Topics: Buprenorphine; Functional Status; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Seroepidemiologic Studies
PubMed: 33849574
DOI: 10.1186/s12954-021-00488-2 -
The Canadian Veterinary Journal = La... Nov 2023Opioid analgesics are routinely used during the perioperative period, to provide analgesia and reduce anesthetics doses required to maintain a surgical plane of... (Review)
Review
Opioid analgesics are routinely used during the perioperative period, to provide analgesia and reduce anesthetics doses required to maintain a surgical plane of anesthesia in companion animals. Acting on receptors in the brain, spinal cord, and peripheral nervous system, opioids provide reliable and consistent analgesia; however, they are not without adverse effects. Methadone, a mu agonist opioid analgesic, was recently licensed for veterinary use in Canada. In addition to its action on opioid receptors, methadone contributes to analgesia through other pathways, including inhibition of N-methyl-D-aspartate (NMDA) receptors. It has physiologic effects similar to other mu opioid agents, but fewer adverse gastrointestinal effects. This review discusses methadone's mechanism of action, pharmacologic characteristics, and clinical effects in dogs and cats. Current recommendations for using methadone in companion animals are also provided.
Topics: Animals; Cats; Dogs; Methadone; Pets; Cat Diseases; Dog Diseases; Analgesics, Opioid; Anesthesia; Pain
PubMed: 37915778
DOI: No ID Found -
American Journal of Veterinary Research Jun 2022To assess the pharmacokinetics, clinical efficacy, and adverse effects of injectable methadone with the pharmacokinetic enhancer fluconazole (methadone-fluconazole),...
Long-acting injectable methadone (methadone-fluconazole) provides safe and effective postoperative analgesia in a randomized clinical trial for dogs undergoing soft tissue surgery.
OBJECTIVE
To assess the pharmacokinetics, clinical efficacy, and adverse effects of injectable methadone with the pharmacokinetic enhancer fluconazole (methadone-fluconazole), compared with the standard formulation of injectable methadone, in dogs after ovariohysterectomy. We hypothesized that 2 doses of methadone-fluconazole would provide 24 hours of postoperative analgesia.
ANIMALS
3 purpose-bred dogs (pharmacokinetic preliminary study) and 42 female dogs from local shelters (clinical trial) were included.
PROCEDURES
Pharmacokinetics were preliminarily determined. Clinical trial client-owned dogs were blocked by body weight into treatment groups: standard methadone group (methadone standard formulation, 0.5 mg/kg, SC, q 4 h; n = 20) or methadone-fluconazole group (0.5 mg/kg methadone with 2.5 mg/kg fluconazole, SC, repeated once at 6 h; n = 22). All dogs also received acepromazine, propofol, and isoflurane. Surgeries were performed by experienced surgeons, and dogs were monitored perioperatively using the Glasgow Composite Measure Pain Scale-Short Form (CMPS-SF) and sedation scales. Evaluators were masked to treatment.
RESULTS
Findings from pharmacokinetic preliminary studies supported that 2 doses of methadone-fluconazole provide 24 hours of drug exposure. The clinical trial had no significant differences in treatment failures or postoperative CMPS-SF scores between treatments. One dog (methadone-fluconazole group) had CMPS-SF > 6 and received rescue analgesia. All dogs had moderate sedation or less by 1 hour (methadone-fluconazole group) or 4 hours (standard methadone group) postoperatively. Sedation was completely resolved in all dogs the day after surgery.
CLINICAL RELEVANCE
Methadone-fluconazole with twice-daily administration was well tolerated and provided effective postoperative analgesia for dogs undergoing ovariohysterectomy. Clinical compliance and postoperative pain control may improve with an effective twice-daily formulation.
Topics: Analgesia; Analgesics, Opioid; Animals; Dog Diseases; Dogs; Female; Fluconazole; Hysterectomy; Methadone; Ovariectomy; Pain, Postoperative
PubMed: 35895789
DOI: 10.2460/ajvr.22.01.0014 -
Molecules (Basel, Switzerland) Nov 2022(1) Background: Methadone, along with buprenorphine, is the most commonly used drug for the treatment of opioid dependence. This study aimed to analyze methadone and its...
(1) Background: Methadone, along with buprenorphine, is the most commonly used drug for the treatment of opioid dependence. This study aimed to analyze methadone and its major metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenyl pyrrolidine (EDDP), in the urine and plasma of opiate addicts. The study group consisted of drug users voluntarily admitted to the detoxification center C.E.T.T.T. "St. Stelian" of Bucharest. Secondly, the study aimed to identify whether urine or plasma provides better results for the proposed method. (2) Methods: A GC-MS method, using an internal standard (diphenylamine) in the FULL-SCAN and SIM modes of operation and using the m/z = 72 ion for methadone and the m/z = 277 ion for EDDP, combined with a liquid-liquid extraction procedure was performed. (3) Results: The applied procedure allows the detection and quantification of methadone in both urine and plasma samples. EDDP was identified in patients with higher levels of methadone. Higher levels of methadone were detected in urine than in plasma samples. (4) Conclusions: This procedure can be used in clinical laboratories for the rapid determination of methadone levels in urine rather than in plasma. The procedure can be applied for the monitoring of methadone substitution treatment.
Topics: Humans; Methadone; Gas Chromatography-Mass Spectrometry; Buprenorphine; Opioid-Related Disorders; Pyrrolidines
PubMed: 36500452
DOI: 10.3390/molecules27238360 -
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 -
Stem Cell Research Dec 2020Prenatal opioids exposure can lead to both neonatal abstinence syndrome in newborns and neurological deficits later in life. Although opioids have been well studied in...
Prenatal opioids exposure can lead to both neonatal abstinence syndrome in newborns and neurological deficits later in life. Although opioids have been well studied in general, the cellular and molecular mechanisms by which opioids affect human fetal brain development has not been well understood. In this work, we have taken advantage of a human 3D-brain cortical organoid (hCO) that facilitated enormously the investigation of early human brain development. Using imaging, immunofluorescence, multi-electrode array (MEA) and patch clamp recording techniques, we have investigated the effect of methadone, a frequently used opioid during pregnancy, on early neural development, including neuronal growth, neural network activity and synaptic transmission in hCOs. Our results demonstrated that methadone dose-dependently halted the growth of hCOs and induced organoid disintegration after a prolonged exposure. In addition, methadone dose-dependently suppressed the firing of spontaneous action potentials in hCOs and this suppression could be reversed upon methadone withdrawal in hCOs treated with lower dosages. Further investigation using patch clamp whole cell configuration revealed that, at clinically relevant concentrations, methadone decreased the frequency and amplitude of excitatory postsynaptic currents in neurons, indicating a critical role of methadone in weakening synaptic transmission in neural networks in hCOs. In addition, methadone significantly attenuated the voltage-dependent Na current in hCOs. We conclude that methadone interrupts neural growth and function in early brain development.
Topics: Action Potentials; Female; Humans; Infant, Newborn; Methadone; Organoids; Patch-Clamp Techniques; Pregnancy; Synaptic Transmission
PubMed: 33137567
DOI: 10.1016/j.scr.2020.102065 -
Addictive Behaviors Dec 2022Opioid use disorder (OUD) has been associated with the emergence of sleep disturbances. Although effective treatments for OUD exist, evidence suggests that these...
Opioid use disorder (OUD) has been associated with the emergence of sleep disturbances. Although effective treatments for OUD exist, evidence suggests that these treatments also may be associated with sleep impairment. The extent to which these effects are an effect of OUD treatment or a result of chronic opioid use remains unknown. We investigated the acute effects of methadone, buprenorphine, and naltrexone on actigraphy-based sleep-like parameters in non-opioid-dependent male rhesus monkeys (Macaca mulatta, n = 5). Subjects were fitted with actigraphy monitors attached to primate collars to measure sleep-like parameters. Actigraphy recordings were conducted under baseline conditions, or following acute injections of vehicle, methadone (0.03-1.0 mg/kg, i.m.), buprenorphine (0.01-1.0 mg/kg, i.m.), or naltrexone (0.03-1.0 mg/kg, i.m.) in the morning (4 h after "lights on") or in the evening (1.5 h before "lights off"). Morning and evening treatments with methadone or buprenorphine significantly increased sleep latency and decreased sleep efficiency. The effects of buprenorphine on sleep-like measures resulted in a biphasic dose-response function, with the highest doses not disrupting actigraphy-based sleep. Buprenorphine induced a much more robust increase in sleep latency and decrease in sleep efficiency compared to methadone, particularly with evening administration, and detrimental effects of buprenorphine on sleep-like measures were observed up to 25.5 h after drug injection. Treatment with naltrexone, on the other hand, significantly improved sleep-like measures, with evening treatments improving both sleep latency and sleep efficiency. The currently available pharmacotherapies for OUD significantly alter sleep-like parameters in non-opioid-dependent monkeys, and opioid-dependent mechanisms may play a significant role in sleep-wake regulation.
Topics: Actigraphy; Analgesics, Opioid; Animals; Buprenorphine; Humans; Macaca mulatta; Male; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; Sleep
PubMed: 35901553
DOI: 10.1016/j.addbeh.2022.107433