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Medical Care May 2023Long-term treatment with medications for opioid use disorder (OUD), including methadone, is lifesaving. There has been little examination of how to measure methadone... (Observational Study)
Observational Study
BACKGROUND
Long-term treatment with medications for opioid use disorder (OUD), including methadone, is lifesaving. There has been little examination of how to measure methadone continuity in claims data.
OBJECTIVES
To develop an approach for measuring methadone continuity in claims data, and compare estimates of methadone versus buprenorphine continuity.
RESEARCH DESIGN
Observational cohort study using de-identified commercial claims from OptumLabs Data Warehouse (January 1, 2017-June 30, 2021).
SUBJECTS
Individuals diagnosed with OUD, ≥1 methadone or buprenorphine claim and ≥180 days continuous enrollment (N=29,633).
MEASURES
OUD medication continuity: months with any use, days of continuous use, and proportion of days covered.
RESULTS
5.4% (N=1607) of the study cohort had any methadone use. Ninety-seven percent of methadone claims (N=160,537) were from procedure codes specifically used in opioid treatment programs. Place of service and primary diagnosis codes indicated that several methadone procedure codes were not used in outpatient OUD care. Methadone billing patterns indicated that estimating days-supply based solely on dates of service and/or procedure codes would yield inaccurate continuity results and that an approach incorporating the time between service dates was more appropriate. Among those using methadone, mean [s.d.] months with any use, days of continuous use, and proportion of days covered were 4.8 [1.8] months, 79.7 [73.4] days, and 0.64 [0.36]. For buprenorphine, the corresponding continuity estimates were 4.6 [1.9], 80.7 [70.0], and 0.73 [0.35].
CONCLUSIONS
Estimating methadone continuity in claims data requires a different approach than that for medications largely delivered by prescription fills, highlighting the importance of consistency and transparency in measuring methadone continuity across studies.
Topics: Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Analgesics, Opioid; Buprenorphine
PubMed: 36917776
DOI: 10.1097/MLR.0000000000001838 -
Anesthesiology Oct 2023
Topics: Methadone; Analgesics
PubMed: 37698432
DOI: 10.1097/ALN.0000000000004681 -
Addiction (Abingdon, England) Feb 2022Opioid agonist treatment is effective but resource intensive to administer safely in custodial settings, leading to significant under-treatment of opioid dependence in...
BACKGROUND AND AIMS
Opioid agonist treatment is effective but resource intensive to administer safely in custodial settings, leading to significant under-treatment of opioid dependence in these settings world-wide. This study assessed the safety of subcutaneous slow-release depot buprenorphine in custody.
DESIGN
Open-label, non-randomized trial.
SETTING
Correctional centres in New South Wales, Australia.
PARTICIPANTS
Sixty-seven men and women, aged ≥ 18 years of various security classifications with a diagnosis of moderate to severe DSM-5 opioid use disorder currently serving a custodial sentence of ≥ 6 months were recruited between November 2018 and July 2019. Patients not in opioid agonist treatment at recruitment commenced depot buprenorphine; patients already stable on oral methadone treatment were recruited to the comparison arm.
INTERVENTION AND COMPARATOR
Depot buprenorphine (CAM2038 weekly for 4 weeks then monthly) and daily oral methadone.
MEASUREMENTS
Safety was assessed by adverse event (AE) monitoring and physical examinations at every visit. Participants were administered a survey assessing self-reported diversion and substance use at baseline and weeks 4 and 16.
FINDINGS
Retention in depot buprenorphine treatment was 92.3%. Ninety-four per cent of patients reported at least one adverse event, typically mild and transient. No diversion was identified. The prevalence of self-reported non-prescribed opioid use among depot buprenorphine patients decreased significantly between baseline (97%) and week 16 (12%, odds ratio = 0.0035, 95% confidence interval = 0.0007-0.018, P < 0.0001).
CONCLUSIONS
This first study of depot buprenorphine in custodial settings showed treatment retention and outcomes comparable to those observed in community settings and for other opioid agonist treatment used in custodial settings, without increased risk of diversion.
Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Male; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 34184798
DOI: 10.1111/add.15627 -
American Journal of Perinatology Jul 2021This pilot study evaluated the relationship between maternal and neonatal R- and S-methadone and R- and S-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)...
OBJECTIVE
This pilot study evaluated the relationship between maternal and neonatal R- and S-methadone and R- and S-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) exposure and the severity of neonatal abstinence syndrome (NAS). The use of dried blood spots (DBS) as an alternative for plasma in assessing methadone and EDDP was also assessed.
STUDY DESIGN
Women receiving methadone for medication assisted treatment of opioid use disorder during pregnancy were eligible for recruitment. Plasma and DBS samples were collected from mothers during labor, from cord blood, and from newborns during genetic screen. R-/S-methadone and EDDP were measured by high-performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS). Associations between methadone exposure, neonatal morphine requirements, and severity of NAS were examined.
RESULTS
Twenty women and infants completed the study. Maternal methadone dose at delivery was 112 mg/day (range = 60-180 mg/day). Sixteen neonates experienced NAS requiring morphine; three also required phenobarbital. Higher cord blood concentrations of R-methadone, R- and S-EDDP were associated with higher maximum doses of morphine ( < 0.05).
CONCLUSION
Maternal methadone and cord blood concentration at delivery are variable and may be potential markers of neonatal abstinence syndrome.
Topics: Analgesics, Opioid; Anticonvulsants; Dried Blood Spot Testing; Female; Humans; Infant, Newborn; Labor, Obstetric; Methadone; Morphine; Neonatal Abstinence Syndrome; Phenobarbital; Pregnancy; Pyrrolidines
PubMed: 32052397
DOI: 10.1055/s-0040-1701505 -
Early Human Development Aug 2022The potential long-term developmental effects of prenatal methadone and buprenorphine exposure during pregnancy are still largely unknown.
BACKGROUND
The potential long-term developmental effects of prenatal methadone and buprenorphine exposure during pregnancy are still largely unknown.
AIMS
We investigated memory function in school-aged children of women enrolled in opioid maintenance therapy (OMT) during pregnancy.
STUDY DESIGN
Prospective longitudinal cohort study.
SUBJECTS
Participants included 41 children (aged 9-11 years), 20 of which had histories of prenatal methadone or buprenorphine exposure.
OUTCOME MEASURES
Verbal and non-verbal memory function was assessed using four subtests from the Test of Memory and Learning - Second edition (TOMAL-2).
RESULTS
The OMT group scored lower on both the two non-verbal as well as the two verbal memory tasks, all p-values <.05. Group differences remained for three out of the four subtests after controlling for general IQ. Including maternal tobacco use during pregnancy increased the explanatory power of the model, R change of 0.07, p = .04.
CONCLUSIONS
Children prenatally exposed to methadone or buprenorphine had significantly lower memory performance, however, this association may in part be explained by maternal tobacco use during pregnancy. Consequently, smoking cessation programs should be systematically integrated into opioid maintenance therapy programs for pregnant women.
Topics: Analgesics, Opioid; Buprenorphine; Child; Female; Humans; Longitudinal Studies; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies
PubMed: 35772183
DOI: 10.1016/j.earlhumdev.2022.105614 -
Electrophoresis Sep 2021The enantioselectivity of the pharmacokinetics of methadone was investigated in anesthetized Shetland ponies after a single intravenous (0.5 mg/kg methadone...
The enantioselectivity of the pharmacokinetics of methadone was investigated in anesthetized Shetland ponies after a single intravenous (0.5 mg/kg methadone hydrochloride; n = 6) or constant rate infusion (0.25 mg/kg bolus followed by 0.25 mg/kg/h methadone hydrochloride; n = 3) administration of racemic methadone. Plasma concentrations of l-methadone and d-methadone and their major metabolites, l- and d-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), respectively, were analyzed by CE with highly sulfated γ-cyclodextrin as chiral selector and electrokinetic analyte injection from liquid/liquid extracts prepared at alkaline pH. In both trials, the d-methadone concentrations were lower than those of l-methadone and the d-EDDP levels were lower than those of L-EDDP. For the case of a single intravenous bolus injection, the plasma concentration versus time profile of methadone enantiomers was analyzed with a two-compartment pharmacokinetic model. l-methadone showed a slower elimination rate constant, a lower body clearance, and a smaller steady-state volume of distribution than d-methadone. d-methadone and d-EDDP were eliminated faster than their respective l-enantiomers. This is the first study that outlines that the disposition of racemic methadone administered to anesthetized equines is enantioselective.
Topics: Animals; Electrophoresis, Capillary; Horses; Methadone; Pyrrolidines; Stereoisomerism
PubMed: 33978252
DOI: 10.1002/elps.202100115 -
The American Journal of Psychiatry Sep 2021The authors conducted a scoping review to survey the evidence landscape for studies that assessed outcomes of treating patients with opioid use disorder with methadone...
OBJECTIVE
The authors conducted a scoping review to survey the evidence landscape for studies that assessed outcomes of treating patients with opioid use disorder with methadone in office-based settings.
METHODS
Ovid MEDLINE and the Cochrane Database of Systematic Reviews were searched, and reference lists were reviewed to identify additional studies. Studies were eligible if they focused on methadone treatment in office-based settings conducted in the United States or other highly developed countries and reported outcomes (e.g., retention in care). Randomized trials and controlled observational studies were prioritized; uncontrolled and descriptive studies were included when stronger evidence was unavailable. One investigator abstracted key information, and a second verified data. A scoping review approach broadly surveyed the evidence, and therefore study quality was not rated formally.
RESULTS
Eighteen studies of patients treated with office-based methadone were identified, including six trials, eight observational studies, and four additional articles discussing use of pharmacies to dispense methadone. Studies on office-based methadone treatment, including primary care-based dispensing, were limited but consistently found that stable methadone patients valued office-based care and remained in care with low rates of drug use; outcomes were similar compared with stable patients in regular care. Office-based methadone treatment was associated with higher treatment satisfaction and quality of life. Limitations included underpowered comparisons and small samples.
CONCLUSIONS
Limited research suggests that office-based methadone treatment and pharmacy dispensing could enhance access to methadone treatment for patients with opioid use disorder without adversely affecting patient outcomes and, potentially, inform modifications to federal regulations. Research should assess the feasibility of office-based care for less stable patients.
Topics: Drug Prescriptions; Humans; Methadone; Narcotics; Opioid-Related Disorders; Pharmacies
PubMed: 34315284
DOI: 10.1176/appi.ajp.2021.20101548 -
The Western Journal of Emergency... Apr 2022Like buprenorphine, methadone is a life-saving medication that can be initiated in the emergency department (ED) to treat patients with an opioid use disorder (OUD). The...
INTRODUCTION
Like buprenorphine, methadone is a life-saving medication that can be initiated in the emergency department (ED) to treat patients with an opioid use disorder (OUD). The purpose of this study was to better understand the attitudes of emergency physicians (EP) on offering methadone compared to buprenorphine to patients with OUD in the ED.
METHODS
We distributed a perception survey to emergency physicians through a national professional network.
RESULTS
In this study, the response rate was 18.4% (N = 141), with nearly 70% of the EPs having ordered either buprenorphine or methadone. 75% of EPs strongly or somewhat agreed that buprenorphine was an appropriate treatment for opioid withdrawal and craving, while only 28% agreed that methadone was an appropriate treatment. The perceived barriers to using buprenorphine and methadone in the ED were similar.
CONCLUSION
It is essential to create interventions for EPs to overcome stigma and barriers to methadone initiation in the ED for patients with opioid use disorder. Doing so will offer additional opportunities and pathways for initiation of multiple effective medications for OUD in the ED. Subsequent outpatient treatment linkage may lead to improved treatment retention and decreased morbidity and mortality from ongoing use.
Topics: Analgesics, Opioid; Attitude; Buprenorphine; Cross-Sectional Studies; Emergency Service, Hospital; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Physicians
PubMed: 35679506
DOI: 10.5811/westjem.2022.2.54681 -
Addiction (Abingdon, England) Jun 2022To investigate the real-world effectiveness of pharmacological treatments (buprenorphine, methadone) of opioid use disorder (OUD).
AIM
To investigate the real-world effectiveness of pharmacological treatments (buprenorphine, methadone) of opioid use disorder (OUD).
DESIGN
A nation-wide, register-based cohort study.
SETTING
Sweden.
PARTICIPANTS
All residents aged 16-64 years living in Sweden using OUD medication from July 2005 to December 2016 (n = 5757, 71.8% men) were identified from registers of prescriptions, inpatient and specialized outpatient care, causes of death, sickness absence and disability pensions.
MEASUREMENTS
Main outcome: hospitalization due to OUD.
SECONDARY OUTCOMES
hospitalization due to any cause; death due to all, natural and external causes. Mortality was analyzed with between-individual multivariate-adjusted Cox hazards regression model. Recurrent outcomes, such as hospitalizations, were analyzed with within-individual analyses to eliminate selection bias. OUD medication use versus non-use was modelled with PRE2DUP (from prescription drug purchases to drug use periods) method.
FINDINGS
Buprenorphine [hazard ratio (HR) = 0.73, 95% confidence interval (CI) = 0.54-0.97] and methadone (HR = 0.74, 95% CI = 0.59-0.93) use were associated with significantly lower risk of OUD hospitalization, but not any-cause hospitalizations, compared with the time-periods when the same individual did not use OUD medication. The use of buprenorphine and methadone were both associated with significantly lower risk of all-cause mortality (HR = 0.45, 95% CI = 0.34-0.59; HR = 0.51, 95% CI = 0.41-0.63, respectively), compared with non-use of both medications. Similar results were found for risk of mortality due to external causes (HR = 0.39; 95% CI = 0.27-0.54; HR = 0.40; 95% CI = 0.29-0.53, respectively), but not for mortality due to natural causes. The risk of OUD hospitalization and all-cause mortality was decreased in all duration categories of studied medications (< 30, 31-180, 181-365 and >365 days), except for methadone use less than 30 days.
CONCLUSIONS
The use of buprenorphine and methadone are both associated with a significantly lower risk of hospitalization due to opioid use disorder and death due to all and external causes, when compared with non-use.
Topics: Analgesics, Opioid; Buprenorphine; Cohort Studies; Female; Humans; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 35072314
DOI: 10.1111/add.15814 -
Addiction (Abingdon, England) Feb 2022Pharmacy administration and dispensing of methadone for methadone maintenance treatment (MMT) can expand treatment access for opioid use disorder (OUD). This study... (Clinical Trial)
Clinical Trial
BACKGROUND AND AIMS
Pharmacy administration and dispensing of methadone for methadone maintenance treatment (MMT) can expand treatment access for opioid use disorder (OUD). This study investigated the feasibility and acceptability of a novel model permitting an opioid treatment program (OTP) physician to prescribe methadone for OUD treatment through collaboration with a partnered pharmacy.
DESIGN
Non-randomized, single-arm, open-label feasibility trial.
SETTING
One OTP and one community pharmacy in the United States.
PARTICIPANTS
One OTP physician, two pharmacists and 20 MMT patients receiving between six and 13 take-home methadone doses at 5-160 mg/day.
INTERVENTION
Patients' methadone administration and dispensing of take-home doses was transferred from the OTP to the pharmacy for 3 months.
MEASUREMENTS
Primary outcome was medication adherence. Secondary outcomes were recruitment, treatment retention, substance use, counseling attendance at the OTP, pharmacist prescription drug monitoring program (PDMP) use, safety and satisfaction.
FINDINGS
Of 29 patients eligible at pre-screen, 20 patients (69%) enrolled into the study. Recruitment occurred from 6 August 2020 to 10 October 2020. Treatment retention rate at month 3 was 80% (16 of 20). Two participants returned early to the OTP because of a work/schedule change, one due to pregnancy and one following a non-study-related hospitalization. Medication adherence among 16 patients who were retained was 100%. Intervention fidelity was 100%. All participants attended random call-back visits. None showed evidence of tampering/diversion of methadone. Pharmacists checked the PDMP at all visits. All participants attended psychosocial counseling as planned. There were no positive urine screens for illicit opioid use and no study-related adverse events. All participants endorsed 'pharmacy is the right location for receiving methadone for MMT', 88% endorsed 'convenient or very convenient to receive methadone at the pharmacy' and 88% were satisfied or very satisfied with the quality of treatment offered.
CONCLUSIONS
This feasibility trial has found pharmacy administration and dispensing of physician-prescribed methadone for methadone maintenance treatment to be feasible and acceptable.
Topics: Analgesics, Opioid; Feasibility Studies; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pharmacies; Pharmacy
PubMed: 34286886
DOI: 10.1111/add.15641