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Journal of Addiction MedicineThis paper offers a review and recommendations for clinicians working with patients interested in discontinuing opioid agonist treatment. As buprenorphine/naloxone has... (Review)
Review
This paper offers a review and recommendations for clinicians working with patients interested in discontinuing opioid agonist treatment. As buprenorphine/naloxone has gained widespread acceptance for opioid addiction, many treatment providers and patients have a range of hopes and expectations about its optimal use. A surprising number assume buprenorphine/naloxone is primarily useful as a medication to transition off illicit opioid use, and success is partially defined by discontinuing the medication. Despite accumulating evidence that a majority of patients will need to remain on medication to preserve their gains, clinicians often have to address a patient's fervent desire to taper. Using the concept of "recovery capital," our review addresses (1) the appropriate duration of opioid agonist treatment, (2) risks associated with discontinuing, (3) a checklist that guides the patient through self-assessment of the wisdom of discontinuing opioid agonist treatment, and (4) shared decision making about how to proceed.
Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 33323695
DOI: 10.1097/ADM.0000000000000789 -
BMC Medical Imaging Jan 2020Accidental ingestion or consumption of supra-therapeutic doses of methadone can result in neurological sequelae in humans. We aimed to determine the neurological... (Review)
Review
BACKGROUND
Accidental ingestion or consumption of supra-therapeutic doses of methadone can result in neurological sequelae in humans. We aimed to determine the neurological deficits of methadone-poisoned patients admitted to a referral poisoning hospital using brain magnetic resonance (MR) and diffusion weighted (DW) imaging.
METHODS
In this retrospective study, brain MRIs of the patients admitted to our referral center due to methadone intoxication were reviewed. Methadone intoxication was confirmed based on history, congruent clinical presentation, and confirmatory urine analysis. Each patient had an MRI with Echo planar T1, T2, FLAIR, and DWI and apparent deficient coefficient (ADC) sequences without contrast media. Abnormalities were recorded and categorized based on their anatomic location and sequence.
RESULTS
Ten patients with abnormal MRI findings were identified. Eight had acute- and two had delayed-onset encephalopathy. Imaging findings included bilateral confluent or patchy T2 and FLAIR high signal intensity in cerebral white matter, cerebellar involvement, and bilateral occipito-parietal cortex diffusion restriction in DWI. Internal capsule involvement was identified in two patients while abnormality in globus pallidus and head of caudate nuclei were reported in another. Bilateral cerebral symmetrical confluent white matter signal abnormality with sparing of subcortical U-fibers on T2 and FLAIR sequences were observed in both patients with delayed-onset encephalopathy.
CONCLUSIONS
Acute- and delayed-onset encephalopathies are two rare adverse events detected in methadone-intoxicated patients. Brain MRI findings can be helpful in detection of methadone-induced encephalopathy.
Topics: Adolescent; Adult; Brain Diseases; Child; Child, Preschool; Diffusion Magnetic Resonance Imaging; Disease Progression; Female; Humans; Male; Methadone; Radiographic Image Interpretation, Computer-Assisted; Retrospective Studies; White Matter; Young Adult
PubMed: 31952488
DOI: 10.1186/s12880-020-0410-9 -
Clinical Pharmacology and Therapeutics Oct 2021Methadone, a widely prescribed medication for chronic pain and opioid addiction, is associated with respiratory depression and increased predisposition for torsades de...
Methadone, a widely prescribed medication for chronic pain and opioid addiction, is associated with respiratory depression and increased predisposition for torsades de pointes, a potentially fatal arrhythmia. Most methadone-related deaths occur during sleep. The objective of this study was to determine whether methadone's arrhythmogenic effects increase during sleep, with a focus on cardiac repolarization instability using QT variability index (QTVI), a measure shown to predict arrhythmias and mortality. Sleep study data of 24 patients on chronic methadone therapy referred to a tertiary clinic for overnight polysomnography were compared with two matched groups not on methadone: 24 patients referred for overnight polysomnography to the same clinic (clinic group), and 24 volunteers who had overnight polysomnography at home (community group). Despite similar values for heart rate, heart rate variability, corrected QT interval, QTVI, and oxygen saturation (SpO ) when awake, patients on methadone had larger QTVI (P = 0.015 vs. clinic, P < 0.001 vs. community) and lower SpO (P = 0.008 vs. clinic, P = 0.013 vs. community) during sleep, and the increase in their QTVI during sleep vs. wakefulness correlated with the decrease in SpO (r = -0.54, P = 0.013). QTVI positively correlated with methadone dose during sleep (r = 0.51, P = 0.012) and wakefulness (r = 0.73, P < 0.001). High-density ectopy (> 1,000 premature beats per median sleep period), a precursor for torsades de pointes, was uncommon but more frequent in patients on methadone (P = 0.039). This study demonstrates that chronic methadone use is associated with increased cardiac repolarization instability. Methadone's pro-arrhythmic impact may be mediated by sleep-related hypoxemia, which could explain the increased nocturnal mortality associated with this opioid.
Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Arrhythmias, Cardiac; Electrocardiography; Female; Heart Conduction System; Humans; Male; Methadone; Middle Aged; Polysomnography; Sleep
PubMed: 34287835
DOI: 10.1002/cpt.2368 -
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 -
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 -
Pharmacogenomics Aug 2020Methadone, a synthetic opioid with longer duration of action and lower abuse potential compared with morphine, is used to prevent opioid withdrawal, as well as to... (Review)
Review
Methadone, a synthetic opioid with longer duration of action and lower abuse potential compared with morphine, is used to prevent opioid withdrawal, as well as to manage chronic and acute surgical pain. The variability in response to methadone has been widely recognized. The purpose of this article is to review the literature on the pharmacogenetic factors underlying this variability. This is a narrative overview of the literature on the genetic variants affecting pharmacodynamics and pharmacokinetics of methadone, retrieved from searches of databases such as PubMed and google scholar. Clinical responses to methadone may be affected by genetic variants in the opioidergic, dopaminergic and neurotrophic pathways. Polymorphisms in genes related to disposition and elimination of methadone alter the pharmacokinetics, and possibly pharmacodynamics of methadone. Cytochrome P450 enzymes and P-glycoprotein variants contribute to the interindividual variability in methadone pharmacokinetics. Evidence for single gene variants affecting methadone response remains weak. Multiple genetic variants must be considered in conjunction to improve predictive ability. Evidence remains scarce at this time, to recommend pharmacogenetic testing before methadone administration. Well-powered clinical studies are needed with population pharmacokinetic-pharmacodynamic modeling and multigenetic signature-based predictions to enable tailored use of methadone in clinical practice.
Topics: Analgesics, Opioid; Animals; Genetic Variation; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pharmacogenetics
PubMed: 32705966
DOI: 10.2217/pgs-2020-0040 -
JAMA Network Open Mar 2023Opioid-stimulant co-use is a common problem with few evidence-based treatments. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Opioid-stimulant co-use is a common problem with few evidence-based treatments.
OBJECTIVE
To examine bupropion slow release (SR) enhancement of a tailored abstinence incentive program for stimulant use in persons with opioid use disorder.
DESIGN, SETTING, AND PARTICIPANTS
This 26-week, double-blind, placebo-controlled randomized clinical trial with a 4-week follow-up period was conducted at 4 methadone treatment programs in Baltimore, Maryland. Included participants were persons receiving methadone for the treatment of opioid use disorder with past 3-month cocaine use and current cocaine use disorder between March 2015 and September 2019. Data were analyzed from November 2020 through August 2022.
INTERVENTIONS
A 6-week incentive induction period with monetary incentives for evidence of cocaine abstinence during thrice-weekly urine testing was conducted. Persons achieving 2 weeks of consecutive abstinence during induction were assigned to the relapse prevention group (20 individuals); otherwise, individuals were assigned to the abstinence initiation group (60 individuals). Participants were randomized within incentive groups to bupropion SR (150 mg oral twice daily; 40 participants) or placebo (40 participants). Incentives were available until week 26, and study medication ended week 30.
MAIN OUTCOMES AND MEASURES
The mean percentage of participants with cocaine abstinence (by negative urinalysis or self-report) during weeks 7 to 26 (ie, the incentive intervention period) and 27 to 30 (ie, the follow-up period) and the percentage of participants testing negative for cocaine at weeks 26 and 30 were assessed. Main effects of medication collapsed across incentive conditions and sensitivity analyses of medications within incentive conditions were assessed. Analyses were conducted in the modified intention-to-treat sample (ie, 80 individuals who received ≥1 dose of study medication) and completers (ie, 52 individuals who completed ≥1 visit during week 30).
RESULTS
Among 80 participants (42 Black [52.5% ] and 35 White [43.8%]; mean [SD] age, 45.7 (9.4) years; 52 males [65.0%]) receiving methadone for opioid use disorder, 40 participants were randomized to receive bupropion SR and 40 participants to receive placebo. No significant difference on urinalysis or self-reported cocaine use was observed between medication groups. Sensitivity analyses revealed differential patterns for incentive subgroups. Participants in the relapse prevention group had high abstinence (>80%; eg, during weeks 7-26 in the modified intention-to-treat analysis, 410 of 456 samples [89.9%] from participants in the bupropion SR group tested negative for cocaine) throughout the trial regardless of whether they were randomized to bupropion SR or placebo. Participants in the abstinence initiation group had better outcomes with bupropion SR than placebo throughout the trial (mean [SD] total number of samples testing negative for cocaine, 30.3 [21.6] samples for bupropion SR vs 17.1 [14.9] samples for placebo; P = .05) and more participants receiving bupropion SR than placebo were abstinent at the end of the study (20 of 30 participants [66.7%] vs 9 of 30 participants [30.0%]; P = .04).
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, an overall benefit for bupropion SR vs placebo when combined with a financial abstinence incentive program was not observed. Results among incentive subgroups suggest that continued evaluation of medications, including bupropion SR, for stimulant treatment using a tailored approach that factors early abstinence into study design and interpretation may be needed.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02111798.
Topics: Male; Humans; Middle Aged; Bupropion; Motivation; Methadone; Smoking Cessation; Dopamine Uptake Inhibitors; Opioid-Related Disorders; Cocaine; Cocaine-Related Disorders
PubMed: 36920397
DOI: 10.1001/jamanetworkopen.2023.2278 -
BMC Palliative Care Nov 2022Methadone is commonly considered an alternative opioid treatment for refractory cancer pain. This study aims to investigate the efficacy, safety, and cost of methadone...
BACKGROUND
Methadone is commonly considered an alternative opioid treatment for refractory cancer pain. This study aims to investigate the efficacy, safety, and cost of methadone in the treatment of refractory cancer pain.
METHODS
A retrospective study was conducted in patients who used methadone for refractory cancer pain from April 2016 to December 2020 at a cancer specialized hospital. Pain control, evaluated via pain score and breakthrough pain frequency, and adverse events of methadone were compared with analgesic regimens prior to methadone administration. The factors potentially affecting the switching outcome were analyzed via multivariate analysis. Moreover, the cost of pain control was estimated.
RESULTS
Ninety patients received methadone for poor pain control (74.4%), intolerable adverse events (10.0%), or both (15.6%) after prior opioid treatments. Sixty-four patients (71.1%) were successfully switched to methadone with median pain score significantly decreased from 4.0 to 2.0 (p < 0.001) and median daily frequency of breakthrough pain from 3.0 to 0.0 (p < 0.001) at a maintained median conversion ratio of 6.3 [interquartile range (IQR): 4.0-10.0] to prior opioid treatment. Similar adverse event profiles of constipation, nausea, vomiting, and dizziness were observed between methadone and prior opioid regimens. The median daily cost of analgesic regimens was significantly reduced from $19.5 (IQR: 12.3-46.2) to $10.8 (IQR: 7.1-18.7) (p < 0.01) after switching to methadone. The 3-day switch method significantly improved the rate of successful switching compared with the stop and go method (odds ratio = 3.37, 95% CI: 1.30-8.76, p = 0.013).
CONCLUSION
Methadone is an effective, safe, and cost-saving treatment for patients with refractory cancer pain.
Topics: Humans; Methadone; Cancer Pain; Analgesics, Opioid; Retrospective Studies; Breakthrough Pain; Neoplasms
PubMed: 36324113
DOI: 10.1186/s12904-022-01076-2 -
Harm Reduction Journal Jan 2022Opioid use disorder is a public health problem and treatment variability, coverage and accessibility poses some challenges. The study's objective is to review the impact... (Review)
Review
BACKGROUND
Opioid use disorder is a public health problem and treatment variability, coverage and accessibility poses some challenges. The study's objective is to review the impact of interim opioid agonist treatment (OAT), a short-term approach for patients awaiting standard OAT, in terms of treatment retention, access to standard OAT, quality of life and satisfaction with treatment.
METHOD
We conducted a systematic review searching MEDLINE, EMBASE, PsycINFO, and CENTRAL up to May 2020. Due to variability between studies and outcome measurements, we did not pool effect estimates and reported a narrative synthesis of findings rating their certainty according to GRADE.
RESULTS
We identified 266 unique records and included five randomized trials with some limitations in risk of bias and one observational study limited by selection bias. The studies assessed similar approaches to interim OAT but were compared to three different control conditions. Four studies reported on treatment retention at 4 months or less with no significant differences between interim OAT and waiting list or standard OAT. Two studies reported treatment retention at 12 months with no differences between interim OAT and standard OAT. Two trials assessed access to standard OAT and showed significant differences between interim OAT and waiting list for standard OAT. We rated the quality of evidence for these outcomes as moderate due to the impact of risk of bias. Data on quality of life or satisfaction with treatment was suboptimal.
CONCLUSIONS
Interim OAT is likely more effective than a waiting list for standard OAT in access to treatment, and it is probably as effective as standard OAT regarding treatment retention. PROSPERO registration CRD42018116269.
Topics: Analgesics, Opioid; Buprenorphine; Humans; Methadone; Observational Studies as Topic; Opiate Substitution Treatment; Opioid-Related Disorders; Quality of Life
PubMed: 35090475
DOI: 10.1186/s12954-022-00592-x -
Journal of the American College of... Jan 2021Opioids are the most potent of all analgesics. Although traditionally used solely for acute self-limited conditions and palliation of severe cancer-associated pain, a... (Review)
Review
Opioids are the most potent of all analgesics. Although traditionally used solely for acute self-limited conditions and palliation of severe cancer-associated pain, a movement to promote subjective pain (scale, 0 to 10) to the status of a "fifth vital sign" bolstered widespread prescribing for chronic, noncancer pain. This, coupled with rising misuse, initiated a surge in unintentional deaths, increased drug-associated acute coronary syndrome, and endocarditis. In response, the American College of Cardiology issued a call to action for cardiovascular care teams. Opioid toxicity is primarily mediated via potent μ-receptor agonism resulting in ventilatory depression. However, both overdose and opioid withdrawal can trigger major adverse cardiovascular events resulting from hemodynamic, vascular, and proarrhythmic/electrophysiological consequences. Although natural opioid analogues are devoid of repolarization effects, synthetic agents may be proarrhythmic. This perspective explores cardiovascular consequences of opioids, the contributions of off-target electrophysiologic properties to mortality, and provides practical safety recommendations.
Topics: Analgesics, Opioid; Cardiotoxicity; Cardiovascular Diseases; Humans; Methadone; Opioid-Related Disorders
PubMed: 33446314
DOI: 10.1016/j.jacc.2020.11.002