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Addiction (Abingdon, England) Jul 2023Phenobarbital interacts with the mortality-reducing opioid agonist therapies buprenorphine and methadone, risking delayed opioid withdrawal and relapse when administered...
Phenobarbital interacts with the mortality-reducing opioid agonist therapies buprenorphine and methadone, risking delayed opioid withdrawal and relapse when administered concurrently. With increased adoption of phenobarbital into alcohol withdrawal protocols there should be safeguards in place to—in most cases—avoid phenobarbital for patients with a concurrent opioid use disorder.
Topics: Humans; Analgesics, Opioid; Substance Withdrawal Syndrome; Alcoholism; Opioid Epidemic; Buprenorphine; Methadone; Phenobarbital; Opioid-Related Disorders; Opiate Substitution Treatment
PubMed: 36967706
DOI: 10.1111/add.16194 -
EBioMedicine Nov 2022Opioid use disorder (OUD) is a chronic relapsing psychiatric disorder. An unconditioned stimulus (US)-triggers a memory reconsolidation updating procedure (MRUP) that... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Opioid use disorder (OUD) is a chronic relapsing psychiatric disorder. An unconditioned stimulus (US)-triggers a memory reconsolidation updating procedure (MRUP) that has been developed and demonstrated its effectiveness in decreasing relapse to cocaine and heroin in preclinical models. However, utilizations of abused drugs as the US to initiate MRUP can be problematic. We therefore designed a translational rat study and human study to evaluate the efficacy of a novel methadone-initiated MRUP.
METHODS
In the rodent study, male rats underwent heroin self-administration training for 10 consecutive days, and were randomly assigned to receive saline or methadone at 10 min, 1 h or 6 h before extinction training after 28-day withdrawal. The primary outcome was operant heroin seeking after reinstatement. In the human experimental study, male OUD patients were randomly assigned to get MRUP at 10 min or 6 h after methadone or methadone alone. The primary outcomes included experimental cue-induced heroin craving change, sustained abstinence and retention in the study at post intervention and the 5 monthly follow-up assessments. The secondary outcomes were changes in physiological responses including experimental cue-induced blood pressure and heart rate.
FINDINGS
Methadone exposure but not saline exposure at 10 min or 1 h before extinction decreased heroin-induced reinstatement of heroin seeking after 28-day of withdrawal in rats (F = 8.26, p < 0.001). In the human study, when the MRUP was performed 10 min, but not 6 h after methadone dosing, the MRUP promoted sustained abstinence from heroin throughout 5 monthly follow-up assessments compared to giving methadone alone without MRUP (Hazard Ratio [95%CI] of 0.43 [0.22, 0.83], p = 0.01). The MRUP at 10 min, but not at 6 h after dosing also decreased experimental cue-induced heroin craving and blood pressure increases during the 6-month study duration (group × months × cue types, F = 2.41, p = 0.01).
INTERPRETATION
The approach of MRUP within about 1 to 6 h after a methadone dose potently improved several key outcomes of OUD patients during methadone maintenance treatment, and could be a potentially novel treatment to prevent opioid relapse.
FUNDING
National Natural Science Foundation of China (NO. U1802283, 81761128036, 82001400, 82001404 and 31671143) and Chinese National Programs for Brain Science and Brain-like Intelligence Technology (NO. 2021ZD0200800).
Topics: Humans; Male; Animals; Rats; Methadone; Heroin; Narcotics; Substance Withdrawal Syndrome; Neoplasm Recurrence, Local; Opioid-Related Disorders
PubMed: 36182773
DOI: 10.1016/j.ebiom.2022.104283 -
JAMA Network Open Jul 2022The opioid crisis has been exacerbated by the COVID-19 pandemic in the US, with concerns over major disruptions to medication treatment of opioid use disorder.
IMPORTANCE
The opioid crisis has been exacerbated by the COVID-19 pandemic in the US, with concerns over major disruptions to medication treatment of opioid use disorder.
OBJECTIVE
To investigate whether the COVID-19 pandemic was associated with disruption of buprenorphine and methadone supplies in the US.
DESIGN, SETTING, AND PARTICIPANTS
This repeated cross-sectional study used ARCOS (Automated Reports and Consolidated Ordering System) data, which monitor the flow of controlled substances in the US, from January 1, 2012, through June 30, 2021. Manufacturers and point of sale or distribution at the dispensing or retail level, including hospitals, retail pharmacies, clinicians, midlevel clinicians, and teaching institutions, were included in the analysis.
EXPOSURES
COVID-19 pandemic.
MAIN OUTCOMES AND MEASURES
Quarterly supplies of buprenorphine and methadone per capita in milligrams.
RESULTS
The per capita supply of methadone dropped from 13.2 mg in the first quarter of 2020 to 10.5 mg in the second quarter of 2020, whereas the per capita supply of buprenorphine increased from 3.6 mg to 3.7 mg in the same period. The per capita supply of methadone declined 20% (-2.7 mg) in the second quarter of 2020 compared with the first quarter of 2020, and the supply had not returned to 2019 levels as of June 2021, whereas the supply of buprenorphine per person increased consistently during the same period. There were considerable state disparities in the reduction of the methadone supply during the pandemic, with many states experiencing pronounced per capita supply decreases, including reductions as great as 50% in New Hampshire and Florida. These decreases in per capita methadone supply were not compensated by proportional increases in the per capita buprenorphine supply (linear fit, 0.17 [95% CI, -0.43 to 0.76]; P = .47).
CONCLUSIONS AND RELEVANCE
This cross-sectional study of buprenorphine and methadone supplies during the COVID-19 pandemic found a pronounced decline in the methadone supply but no disruption to the buprenorphine supply. Future research is needed to explain the pronounced state disparities in the methadone supply.
Topics: Buprenorphine; Cross-Sectional Studies; Humans; Methadone; Opiate Substitution Treatment; Pandemics; COVID-19 Drug Treatment
PubMed: 35881394
DOI: 10.1001/jamanetworkopen.2022.23708 -
Journal of Feline Medicine and Surgery Dec 2022The aims of this study were to evaluate and compare the effects that dexmedetomidine and methadone, either alone or in combination, have on the ocular variables of...
OBJECTIVES
The aims of this study were to evaluate and compare the effects that dexmedetomidine and methadone, either alone or in combination, have on the ocular variables of healthy adult cats when administered intramuscularly, as well as their reversal with atipamezole.
METHODS
A randomized crossover blinded study of 10 healthy cats was used to assess the effect of 0.2 mg/kg methadone (MET), 7.5 μg/kg dexmedetomidine (D7), 10 μg/kg dexmedetomidine (D10), 7.5 μg/kg dexmedetomidine and 0.2 mg/kg methadone (DM7) and 10 μg/kg dexmedetomidine and 0.2 mg/kg methadone (DM10) on intraocular pressure (IOP), tear production and pupil diameter (PD). The animals were evaluated for 30 mins. Afterwards, atipamezole was administered and ocular variables were evaluated for 30 mins.
RESULTS
D10, DM7 and DM10 significantly decreased mean IOP but MET or D7 did not. Tear production decreased significantly in all treatments, corresponding to 18%, 59%, 63%, 86% and 98% in MET, D7, D10, DM7 and DM10, respectively. PD increased in all treatments, but MET showed the highest PD. Thirty minutes after atipamezole (RT30), IOP returned to baseline with no difference between groups, and there was a significant increase in tear production, but the means were still different from baseline.
CONCLUSIONS AND RELEVANCE
Dexmedetomidine decreases IOP and tear production but increases PD in healthy cats. Atipamezole can partly reverse those alterations. Low-dose dexmedetomidine (7.5 µg/kg) promotes sedation without changing the IOP. All protocols significantly decrease tear production, and Schirmer tear test after sedation is not representative of non-sedated values. Methadone induces quick onset mydriasis without changing the IOP.
Topics: Cats; Animals; Methadone
PubMed: 35616047
DOI: 10.1177/1098612X221077023 -
Journal of Pain and Symptom Management Jan 2020Methadone is a complex but useful medication for pain management in palliative care. Recent expert opinions have been published on the safe and effective use of... (Comparative Study)
Comparative Study
CONTEXT
Methadone is a complex but useful medication for pain management in palliative care. Recent expert opinions have been published on the safe and effective use of methadone.
OBJECTIVES
To determine the success of methadone rotations and evaluate concordance with consensus recommendations by a palliative care consult service.
METHODS
A retrospective study of methadone rotation practice by a palliative care consult service and outcomes for patients hospitalized between January 1, 2012 and December 31, 2018 at a single academic medical center. A successful rotation was defined as a 30% reduction in pain or as-needed medication use sustained for at least three consecutive days. Patient outcomes were compared with expert consensus recommendations.
RESULTS
About 59 patients met the inclusion criteria. The study population was mostly Caucasian men and women of equal proportions who were started on methadone for inadequate pain control. Sixty-eight percent of patients were successfully rotated. Subjects who were rotated using a standardized protocol were six times more likely to have a successful rotation (odds ratio 6.28 [1.25-30.92]; P = 0.0238).
CONCLUSION
The utilization of a standardized protocol was associated with better patient outcomes.
Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Drug Substitution; Female; Humans; Male; Methadone; Middle Aged; Pain; Pain Management; Palliative Care; Retrospective Studies; Young Adult
PubMed: 31560968
DOI: 10.1016/j.jpainsymman.2019.09.014 -
Molecules (Basel, Switzerland) Apr 2022In this article, we studied physicochemical and microbiological stability and determined the beyond-use date of two oral solutions of methadone in three storage...
In this article, we studied physicochemical and microbiological stability and determined the beyond-use date of two oral solutions of methadone in three storage conditions. For this, two oral solutions of methadone (10 mg/mL) were prepared, with and without parabens, as preservatives. They were packed in amber glass vials kept unopened until the day of the test, and in a multi-dose umber glass bottle opened daily. They were stored at 5 ± 3 °C, 25 ± 2 °C and 40 ± 2 °C. pH, clarity, and organoleptic characteristics were obtained. A stability-indicating high-performance liquid chromatography method was used to determine methadone. Microbiological quality was studied and antimicrobial effectiveness testing was also determined following European Pharmacopoeia guidelines. Samples were analyzed at days 0, 7, 14, 21, 28, 42, 56, 70, and 91 in triplicate. After 91 days of storage, pH remained stable at about 6.5-7 in the two solutions, ensuring no risk of methadone precipitation. The organoleptic characteristics remained stable (colorless, odorless, and bitter taste). The absence of particles was confirmed. No differences were found with the use of preservatives. Methadone concentration remained within 95-105% in all samples. No microbial growth was observed. Hence, the two oral methadone solutions were physically and microbiologically stable at 5 ± 3 °C, 25 ± 2 °C, and 40 ± 2 °C for 91 days in closed and opened amber glass bottles.
Topics: Amber; Chromatography, High Pressure Liquid; Drug Compounding; Drug Stability; Drug Storage; Methadone; Solutions
PubMed: 35566167
DOI: 10.3390/molecules27092812 -
Value in Health : the Journal of the... Feb 2021The rapid increase in opioid overdose and opioid use disorder (OUD) over the past 20 years is a complex problem associated with significant economic costs for healthcare...
OBJECTIVES
The rapid increase in opioid overdose and opioid use disorder (OUD) over the past 20 years is a complex problem associated with significant economic costs for healthcare systems and society. Simulation models have been developed to capture and identify ways to manage this complexity and to evaluate the potential costs of different strategies to reduce overdoses and OUD. A review of simulation-based economic evaluations is warranted to fully characterize this set of literature.
METHODS
A systematic review of simulation-based economic evaluation (SBEE) studies in opioid research was initiated by searches in PubMed, EMBASE, and EbscoHOST. Extraction of a predefined set of items and a quality assessment were performed for each study.
RESULTS
The screening process resulted in 23 SBEE studies ranging by year of publication from 1999 to 2019. Methodological quality of the cost analyses was moderately high. The most frequently evaluated strategies were methadone and buprenorphine maintenance treatments; the only harm reduction strategy explored was naloxone distribution. These strategies were consistently found to be cost-effective, especially naloxone distribution and methadone maintenance. Prevention strategies were limited to abuse-deterrent opioid formulations. Less than half (39%) of analyses adopted a societal perspective in their estimation of costs and effects from an opioid-related intervention. Prevention strategies and studies' accounting for patient and physician preference, changing costs, or result stratification were largely ignored in these SBEEs.
CONCLUSION
The review shows consistently favorable cost analysis findings for naloxone distribution strategies and opioid agonist treatments and identifies major gaps for future research.
Topics: Analgesics, Opioid; Costs and Cost Analysis; Humans; Methadone; Models, Economic; Naloxone; Narcotic Antagonists; Opiate Overdose; Opiate Substitution Treatment; Opioid Epidemic; Opioid-Related Disorders
PubMed: 33518022
DOI: 10.1016/j.jval.2020.07.013 -
Anesthesiology May 2021
Topics: Double-Blind Method; Humans; Ketamine; Methadone; Pain, Postoperative; Spine
PubMed: 33740051
DOI: 10.1097/ALN.0000000000003752 -
BMC Public Health Mar 2022Epidemiological data from Mexico have documented an increase in heroin use in the last decade. However, there is no comprehensive care strategy for heroin users,...
BACKGROUND
Epidemiological data from Mexico have documented an increase in heroin use in the last decade. However, there is no comprehensive care strategy for heroin users, especially those who have been accused of a crime. The objective of this study was to describe the heroin and methadone use of intravenous heroin users of both sexes who have been in jail, to offer evidence for the formulation of health policy.
METHODS
This study used an ethnographic approach, with open-ended interviews carried out from 2014 to the present. Heroin users of both sexes attending a private methadone clinic in Mexico City were invited to participate. The sample was non-probabilistic. All interviews were audiotaped and transcribed, and narratives were analyzed using thematic analysis.
RESULTS
Participants in this study were 33 users of heroin, two of them women, who had been in prison. They ranged in age from 33 to 62 years, had used heroin for a period of 13-30 years, and were from three states: Michoacan, Oaxaca, and Mexico City. Three principal categories of analysis were structured: 1. Pilgrimage for help (dynamics of the drama of suffering, pain, and time through health care spaces); 2) methadone use as self-care; and 3) accessibility to methadone treatment. The impossibility of access to methadone treatment is a condition which motivates users in their journey. The dynamics of methadone use are interpreted as a form of self-care and care to avoid substance use. Reducing the psychological, physical, and harmful effects of the substance allows them to perform daily activities. The inability to access treatment leads to a significant effect on users who experience structural violence.
CONCLUSION
Compassionate methadone treatment and holistic attention should be considered as a way to meet patients' needs and mitigate their suffering, based on public health policy that allows for human rights-based care.
Topics: Adult; Compassionate Use Trials; Female; Heroin Dependence; Humans; Male; Methadone; Mexico; Middle Aged; Violence
PubMed: 35351061
DOI: 10.1186/s12889-022-12955-x -
Addiction Science & Clinical Practice May 2024Delivering methadone treatment in community health facilities by primary care providers is a task-shifting strategy to expand access to drug use treatment, especially in...
BACKGROUND
Delivering methadone treatment in community health facilities by primary care providers is a task-shifting strategy to expand access to drug use treatment, especially in rural mountainous areas. This study aims to investigate factors related to confidence in providing methadone treatment among primary care providers in Vietnam to inform good practice development.
METHODS
We conducted a cross-sectional survey with 276 primary care providers who were physicians, physician assistants, nurses, pharmacists or dispensing staff from 67 communes in a mountainous province in Northern Vietnam. Using self-report scales, we measured providers' confidence in providing methadone treatment, beliefs in harm reduction, perceived work-related support, perceived stigma and risk in working with drug-using patients, and empathy towards this population. We used multiple linear regression analyses to explore factors associated with providers' confidence in providing methadone treatment in the whole sample and to compare two groups of providers who did and did not have experience providing methadone. Potential associated factors were measured at facility and provider levels.
RESULT
114 (41.3%) participants had previously experience in providing methadone treatment. Providers with methadone treatment experiences had higher confidence in and more accurate knowledge of methadone treatment, perceived less stigma of working with drug-using patients, and reported more work-related support than those without experiences. Higher medical education is associated with lower confidence in providing methadone treatment among providers without methadone experiences, but higher confidence among providers with methadone experiences. Better methadone knowledge was associated with greater confidence in providing methadone treatment among inexperienced providers but not among those with experiences. Receiving work-related support was associated with greater confidence in providing treatment in both groups, regardless of their past methadone experiences.
CONCLUSION
In rural provinces where methadone treatment has been expanded to primary care clinics, interventions to improve primary care providers' confidence should benefit professionals with diverse experiences in providing methadone treatment. Continued training and support at work for providers is essential to ensuring quality in decentralized methadone treatment.
Topics: Humans; Methadone; Vietnam; Cross-Sectional Studies; Female; Male; Primary Health Care; Opiate Substitution Treatment; Adult; Attitude of Health Personnel; Middle Aged; Health Personnel; Opioid-Related Disorders; Social Stigma; Harm Reduction; Health Knowledge, Attitudes, Practice
PubMed: 38778428
DOI: 10.1186/s13722-023-00419-5