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The International Journal on Drug Policy Apr 2022Opioid use disorder (OUD) is a global public health concern. The standard of care for OUD involves treatment using medications such as buprenorphine, methadone, or... (Review)
Review
BACKGROUND
Opioid use disorder (OUD) is a global public health concern. The standard of care for OUD involves treatment using medications such as buprenorphine, methadone, or naltrexone. No known review exists to assess the contextual factors associated with medication for opioid use disorder (MOUD) in the Arab World. This systematic review serves as an implementation science study to address this research gap and improve the uptake of MOUD in the Arab World.
METHODS
Systematic searches of Medline, PsycINFO, and EMBASE, and a citation analysis, were used to identify peer-reviewed articles with original data on MOUD in the Arab World. Quality assessment was conducted using the CASP appraisal tools, and main findings were extracted and coded according to the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework.
RESULTS
652 research articles were identified, and 10 met inclusion criteria for final review. Four studies considered health-systems aspects of MOUD administration, such as cost-effectiveness, the motivations for and impact of national MOUD policies, the types of social, political, and scientific advocacy that led to the adoption of MOUD in Arab countries, and the challenges limiting its wide-scale adoption in the Arab World. Six papers considered MOUD at individual and group patient levels by evaluating patient quality of life, addiction severity, patient satisfaction, and patient perspectives on opioid agonist therapy.
CONCLUSION
Despite financial and geographic barriers that limit access to MOUD in the Arab World, this review found MOUD to be cost-effective and associated with positive health outcomes for OUD patients in the Arab World. MOUD can be successfully established and scaled to the national level in the Arab context, and strong coalitions of health practitioners can lobby to establish MOUD programs in Arab countries. Still, the relative novelty of MOUD in this context precludes an abundance of research to address its long-term delivery in the Arab World.
Topics: Analgesics, Opioid; Arab World; Buprenorphine; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pharmaceutical Preparations; Quality of Life
PubMed: 35182841
DOI: 10.1016/j.drugpo.2022.103617 -
International Journal of Legal Medicine Sep 2021In cases where there is a question as to whether children have come into contact with drugs, examinations of their scalp hair are frequently carried out. Positive test...
In cases where there is a question as to whether children have come into contact with drugs, examinations of their scalp hair are frequently carried out. Positive test results are often discussed in the forensic community due to the various possible modes via which drugs and their metabolites can be incorporated into the hair. These include drug uptake by the child (e.g. oral ingestion or inhalation), but also contamination of hair via contact with the sweat from drug users. In this study, the possibility of methadone and its metabolite EDDP being incorporated into children's hair by contact with sweat from persons undergoing opiate maintenance therapy (methadone) was examined. The transfer of methadone and EDDP via sweat from methadone patients (n = 15) to children's hair was simulated by close skin contact of drug-free children's hair, encased in mesh-pouches, for 5 days. Sweat-collecting patches (hereafter referred to as 'sweat patches') were applied to the test persons' skin. One strand of hair and one sweat patch were collected daily from each patient. Analyses were performed using GC-MS/MS (hair) and LC-MS/MS (serum, sweat patches). After 4 days of skin contact, methadone was detectable in the formerly drug-free hair strands in all 15 study participants. EDDP was detectable in 34 of 75 hair strands, with the maximum number of positive results (11 EDDP-positive hair strands) being detected after 5 days. These results show that transfer of methadone and EDDP to drug-free hair is possible through close skin contact with individuals taking part in methadone substitution programmes. A correlation between serum concentration, sweat concentration and substance concentration in hair strands could not be demonstrated, but a tendency towards higher concentrations due to longer contact time is clearly evident.
Topics: Adult; Child; Chromatography, Liquid; Female; Gas Chromatography-Mass Spectrometry; Germany; Hair Analysis; Humans; Male; Methadone; Middle Aged; Pyrrolidines; Sweat; Tandem Mass Spectrometry
PubMed: 33821333
DOI: 10.1007/s00414-021-02576-1 -
JAMA Network Open Apr 2023Methadone treatment is the most effective evidence-based treatment for opioid use disorder (OUD), but challenges related to dosing and premature treatment dropout argue... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Methadone treatment is the most effective evidence-based treatment for opioid use disorder (OUD), but challenges related to dosing and premature treatment dropout argue for adjunct interventions to improve outcomes. One potential behavioral intervention with low risk involves harnessing placebo effects.
OBJECTIVE
To determine the effect of a pharmacologically conditioned open-label placebo (C-OLP) on 90-day methadone dose, retention, drug use, withdrawal, craving, quality of life, and sleep.
DESIGN, SETTING, AND PARTICIPANTS
This 2-arm, open-label, single-blind randomized clinical trial was conducted between December 5, 2017, and August 2, 2019, in an academically affiliated community opioid treatment program. Analyses were conducted between October 1, 2019, and April 30, 2020. A total of 320 newly enrolled adults seeking treatment for moderate to severe OUD were assessed for study eligibility; 131 met eligibility criteria, provided informed consent, and were randomized to either C-OLP or treatment as usual (TAU) in an unequal-block (3:2) manner. Exclusion criteria were pregnancy, hospital/program transfers, and court-ordered treatment.
INTERVENTIONS
Participants randomized to C-OLP received pharmacologic conditioning and a placebo pill and methadone, and participants randomized to TAU were given methadone only. Participants met with the study team 5 times: at baseline (treatment intake) and 2, 4, 8, and 12 weeks postbaseline. Interactions were balanced between the 2 groups.
MAIN OUTCOMES AND MEASURES
Outcomes included 90-day methadone dose (primary) and treatment retention, drug use, withdrawal, craving, quality of life, and sleep quality (secondary). Analyses were conducted as intention-to-treat.
RESULTS
Of the 131 people enrolled in the study, 54 were randomized to TAU and 77 to C-OLP. Mean (SD) age was 45.9 (11.2) years; most of the participants were Black or African American (83 [63.4%]) and male (84 [64.1%]). No significant group differences were observed in the mean (SD) 90-day methadone dose (83.1 [25.1] mg for group TAU, 79.4 [19.6] mg for group C-OLP; t = 0.621991; P = .43), but the groups differed significantly in their retention rates: 33 (61.1%) for TAU and 60 (77.9%) for C-OLP (χ21 = 4.356; P = .04; number needed to treat for the beneficial outcome of 3-month treatment retention, 6; 95% CI, 4-119). C-OLP participants also reported significantly better sleep quality.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, C-OLP had no effect on the primary outcome of 90-day methadone dose. However, C-OLP participants were significantly more likely to remain in treatment. These findings support the use of C-OLP as a methadone treatment adjunct, but larger trials are needed to further examine the use of C-OLP.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02941809.
Topics: Adult; Male; Humans; Middle Aged; Methadone; Quality of Life; Single-Blind Method; Opioid-Related Disorders; Analgesics, Opioid
PubMed: 37043203
DOI: 10.1001/jamanetworkopen.2023.7099 -
Annual Review of Medicine Jan 2024Opioid use disorder continues to drive overdose deaths in many countries, including the United States. Illicit fentanyl and its analogues have emerged as key... (Review)
Review
Opioid use disorder continues to drive overdose deaths in many countries, including the United States. Illicit fentanyl and its analogues have emerged as key contributors to the complications and mortality associated with opioid use disorder. Medications for opioid use disorder treatment, such as methadone and buprenorphine, are safe and substantially reduce opioid use, infectious complications, and mortality risk, but remain underutilized. Polysubstance use and emerging substances such as xylazine and designer benzodiazepines create additional treatment challenges. Recent clinical and policy innovations in treatment delivery, including telemedicine, bridge clinics, and expanded models for accessing methadone have the potential to increase access to life-saving care for people living with opioid use disorder.
Topics: Humans; United States; Opioid-Related Disorders; Methadone; Buprenorphine; Drug Overdose; Analgesics, Opioid
PubMed: 37827194
DOI: 10.1146/annurev-med-050522-033924 -
British Journal of Clinical Pharmacology Jul 2019Our study aimed to evaluate the impacts of the cytochrome P450 (CYP) 2B6-G516T and CYP2D6 genetic polymorphisms on pharmacokinetic and clinical parameters in patients... (Observational Study)
Observational Study
AIMS
Our study aimed to evaluate the impacts of the cytochrome P450 (CYP) 2B6-G516T and CYP2D6 genetic polymorphisms on pharmacokinetic and clinical parameters in patients receiving methadone maintenance treatment.
METHODS
Opioid PhArmacoLogy (OPAL) was a clinical survey of the sociodemographic characteristics, history and consequences of pathology associated with methadone maintenance treatment response and current addictive comorbidities. A subgroup of 72 methadone patients was genotyped.
RESULTS
When comparing the three CYP2B6 genotype groups, the methadone (R)- and (S)-methadone enantiomer concentrations/doses (concentrations relative to doses) were different (P = .029, P = .0019). The CYP2D6 phenotypes did not seem to be relevant with regard to methadone levels. On multivariate analysis, neither the CYP2B6 genotype nor the CYP2D6 phenotype explained the (R)-methadone concentration/dose values (P = .92; P = .86); the (S)-methadone concentration/dose values (P = .052; P = .95 [although there was a difference between the TT group and GT and GG groups {P = .019}]); or opiate cessation (P = .12; P = .90).
CONCLUSION
The genotyping of CYP2B6 G516T could be an interesting tool to explore methadone intervariability.
Topics: Adult; Cross-Sectional Studies; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2D6; Dose-Response Relationship, Drug; Female; Genotype; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Stereoisomerism
PubMed: 30907440
DOI: 10.1111/bcp.13936 -
Addiction Science & Clinical Practice Nov 2021Patients with opioid use disorder (OUD) display an interindividual variability in their response to medications for opioid use disorder (MOUD). A genetic basis may... (Review)
Review
BACKGROUND
Patients with opioid use disorder (OUD) display an interindividual variability in their response to medications for opioid use disorder (MOUD). A genetic basis may explain the variability in this response. However, no consensus has been reached regarding which genetic variants significantly contribute to MOUD outcomes.
OBJECTIVES
This systematic review aims to summarize genome-wide significant findings on MOUD outcomes and critically appraise the quality of the studies involved.
METHODS
Databases searched from inception until August 21st, 2020 include: MEDLINE, Web of Science, EMBASE, CINAHL and Pre-CINAHL, GWAS Catalog and GWAS Central. The included studies had to be GWASs that assessed MOUD in an OUD population. All studies were screened in duplicate. The quality of the included studies was scored and assessed using the Q-Genie tool. Quantitative analysis, as planned in the protocol, was not feasible, so the studies were analyzed qualitatively.
RESULTS
Our search identified 7292 studies. Five studies meeting the eligibility criteria were included. However, only three studies reported results that met our significance threshold of p ≤ 1.0 × 10. In total, 43 genetic variants were identified. Variants corresponding to CNIH3 were reported to be associated with daily heroin injection in Europeans, OPRM1, TRIB2, and ZNF146 with methadone dose in African Americans, EYS with methadone dose in Europeans, and SPON1 and intergenic regions in chromosomes 9 and 3 with plasma concentrations of S-methadone, R-methadone, and R-EDDP, respectively, in Han Chinese.
LIMITATIONS
The limitations of this study include not being able to synthesize the data in a quantitative way and a conservative eligibility and data collection model.
CONCLUSION
The results from this systematic review will aid in highlighting significant genetic variants that can be replicated in future OUD pharmacogenetics research to ascertain their role in patient-specific MOUD outcomes. Systematic review registration number CRD42020169121.
Topics: Buprenorphine; Calcium-Calmodulin-Dependent Protein Kinases; Eye Proteins; Genome-Wide Association Study; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Polymorphism, Single Nucleotide
PubMed: 34838141
DOI: 10.1186/s13722-021-00278-y -
Journal of Addiction Medicine Apr 2021Methadone regulations have changed minimally since 1974, despite advances in the understanding of the nature of opioid use disorder (OUD) and the role of medications in... (Review)
Review
Methadone regulations have changed minimally since 1974, despite advances in the understanding of the nature of opioid use disorder (OUD) and the role of medications in its treatment. At that time, most patients with OUD were considered to have anti-social personality disorders and the regulations aimed to exert maximal control over medication access. Six- or seven-day clinic attendance is required for months, regardless of distance, or childcare and other social responsibilities. Take home medications are not allowed unless rigid and formulaic conditions are met. Although addiction medicine has rejected the "criminal" paradigm in favor of OUD as a treatable medical disorder, methadone regulations have not kept pace with the science. Pregnancy is characterized by an ultra-rapid metabolic state, but regulations prevent the use of daily divided doses of methadone to maintain stability. This results in repeated episodes of maternal/fetal opioid withdrawal, as well as other fetal physiologic abnormalities. Interference with dose regimen adjustments prevents optimal outcomes. Further, methadone clinics are mostly urban, leaving patients in rural areas without access. This led to excessive morbidity and mortality when the opioid crisis hit. The response of merely expanding capacity in overcrowded urban clinics created a contagion menace when Covid-19 arrived. Pregnant women (and parents with children) were forced to negotiate dosing in dangerous conditions. A revised methadone system must provide treatment that is local, flexible, and limited in size to manage viral contagion risks. This regulatory change can most easily be started by changing regulations that adversely affect pregnant women.
Topics: Analgesics, Opioid; Dose-Response Relationship, Drug; Female; Health Policy; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; United States
PubMed: 32826620
DOI: 10.1097/ADM.0000000000000720 -
Journal of Substance Abuse Treatment Feb 2022In response to the COVID-19 pandemic, a federal exemption allowed stable and less stable patients greater take-home doses of methadone. We assessed the adoption of...
INTRODUCTION
In response to the COVID-19 pandemic, a federal exemption allowed stable and less stable patients greater take-home doses of methadone. We assessed the adoption of increased take-home medication during COVID-19 and whether increased take-home doses is associated with clients' characteristics.
METHODOLOGY
We completed a pre-post study of adults receiving methadone for OUD from an OTP in Spokane, Washington. Our outcome was the change in the number of take-home methadone doses three months before and three months after the March 2020 take-home medication exemption. Clients' characteristics included age, gender, ethnicity, education level, homelessness, spatial access to the clinic, and methamphetamine use.
RESULTS
The study included 194 clients in treatment for a median of three years. All study participants experienced an average increase in take-home medication of 41.4 in the three-month period after the COVID-19 exemption. In the final adjusted models, clients who reported using methamphetamine in the last 30 days experienced a significantly larger increase in take-home dosage (55.6 days) compare to clients who did not use methamphetamine (p ≤0.001). Most of the clients who reported using methamphetamine were also likely to be homeless. All other variables were not associated with a change in take-home doses.
CONCLUSION
These results suggest that the Spokane OTP quickly expanded take-home medication dosing in response to the COVID-19 exemption and broadly expanded take-home dosing among established clients. Clients with concurrent methamphetamine use were allowed fewer take-home doses prior to COVID-19, but after the exemption the clinic provided them the same number of take-home doses as clients who had not used methamphetamine.
Topics: Adult; COVID-19; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pandemics; SARS-CoV-2
PubMed: 34304950
DOI: 10.1016/j.jsat.2021.108552 -
BMC Pediatrics Jun 2022Neonatal Opioid Withdrawal Syndrome (NOWS) is a significant public health issue and while millions of neonates are affected each year, an optimal pharmacologic weaning... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Neonatal Opioid Withdrawal Syndrome (NOWS) is a significant public health issue and while millions of neonates are affected each year, an optimal pharmacologic weaning protocol has yet to be demonstrated. In this study, we compare hospital length of stay (LOS) and length of treatment (LOT) for treatment of neonatal opioid withdrawal (NOWS) with morphine versus methadone.
METHODS
This was a single-site, open-label, randomized controlled pilot study conducted from October 2016-September 2018. Infants were eligible if their primary in-utero drug exposure was heroin, oral opioids, or methadone and they were born at greater than or equal to 34 weeks gestation. Infants were excluded for serious medical comorbidities and primary in-utero exposure to buprenorphine.
RESULTS
Sixty-one infants were enrolled; 30 were randomized to methadone treatment, and 31 to morphine treatment. Overall 46% of infants required treatment for NOWS. LOS and LOT for infants treated with morphine was 17.9 days and 14.7 days respectively, compared to 16.1 days and 12.8 days for babies treated with methadone (p = 0.5, p = 0.54). Infants treated with morphine received lower total morphine equivalents than those treated with methadone (9.7 vs. 33, p < 0.01). Three treated infants in the methadone group required transfer to the Neonatal Intensive Care Unit, versus no infants in the morphine group.
CONCLUSIONS
Infants treated with morphine versus methadone had no significant differences in LOS or LOT in this pilot study. Infants treated with methadone received up to 3 times the opioid based on morphine equivalents as infants treated with morphine and had more transfers to the NICU for over sedation.
CLINICAL TRIAL REGISTRATION
Morphine Versus Methadone for Opiate Exposed Infants With Neonatal Abstinence Syndrome NCT02851303 , initiated 01/08/2016.
Topics: Analgesics, Opioid; Humans; Infant, Newborn; Length of Stay; Methadone; Morphine; Neonatal Abstinence Syndrome; Pilot Projects
PubMed: 35705944
DOI: 10.1186/s12887-022-03401-3 -
Journal of Diabetes Investigation Jan 2023Hypoglycemia is rare in patients without diabetes mellitus. Methadone is a synthetic μ-opioid receptor agonist used for cancer or non-cancer pain and the treatment of...
Hypoglycemia is rare in patients without diabetes mellitus. Methadone is a synthetic μ-opioid receptor agonist used for cancer or non-cancer pain and the treatment of opioid dependence. Here, we report a case of a 31-year-old man who presented with recurrent hypoglycemic events that resolved on discontinuation of methadone. Thus, if hypoglycemia occurs while a patient takes methadone, the amount should be reduced or replaced with another opioid before a full investigation for inappropriate hyperinsulinism is initiated.
Topics: Male; Humans; Adult; Methadone; Analgesics, Opioid; Hypoglycemia; Hypoglycemic Agents
PubMed: 36201002
DOI: 10.1111/jdi.13919