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Transferring Patients From Methadone to Buprenorphine: The Feasibility and Evaluation of Practice Guidelines.

ABSTRACT: INTRODUCTION AND AIMS:Transfer from methadone to buprenorphine is problematic for many opioid-dependent patients, with limited documented evidence or practical clinical guidance, particularly for the range of methadone doses routinely prescribed for most patients (>50?mg). This study aimed to implement and evaluate recent national Australian guidelines for transferring patients from methadone to buprenorphine. DESIGN AND METHODS:A multisite prospective cohort study. Participants were patients who transferred from methadone to buprenorphine-naloxone at 1 of 4 specialist addiction centers in Australia and New Zealand. Clinicians were trained in the guidelines, and medical records were reviewed to examine process (eg, transfer setting, doses, and guideline adherence) and safety (precipitated withdrawal) measures. Participants completed research interviews before and after transfer-assessing changes in substance use, health outcomes, and side effects. RESULTS:In all, 33 participants underwent transfer, 9 from low methadone doses (<30?mg), 9 from medium doses (30-50?mg), and 15 from high doses (>50?mg). The majority of high-dose transfers occurred in inpatient settings. There was reasonable guideline adherence, and no complications identified in the low and medium-dose transfers. Three high-dose transfers (20%) experienced precipitated withdrawal, and 7/33 participants (21%) returned to methadone within 1 week of attempted transfer. DISCUSSIONS AND CONCLUSIONS:Transfer is feasible in outpatient settings for those transferring from methadone doses below 50?mg; however, inpatient settings and specialist supervision is recommended for higher-dose transfers. The Australian clinical guidelines appear safe and feasible, although further research is required to optimize high-dose transfer procedures.

SUBMITTER: Lintzeris N

PROVIDER: S-EPMC5976217 | biostudies-literature | 2018 May/Jun

REPOSITORIES: biostudies-literature

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Transferring Patients From Methadone to Buprenorphine: The Feasibility and Evaluation of Practice Guidelines.

Lintzeris Nicholas N Monds Lauren A LA Rivas Consuelo C Leung Stefanie S Dunlop Adrian A Newcombe David D Walters Carina C Galea Susanna S White Nancy N Montebello Mark M Demirkol Apo A Swanson Nicola N Ali Robert R

Journal of addiction medicine 20180501 3

<h4>Introduction and aims</h4>Transfer from methadone to buprenorphine is problematic for many opioid-dependent patients, with limited documented evidence or practical clinical guidance, particularly for the range of methadone doses routinely prescribed for most patients (>50 mg). This study aimed to implement and evaluate recent national Australian guidelines for transferring patients from methadone to buprenorphine.<h4>Design and methods</h4>A multisite prospective cohort study. Participants w ...[more]

PMID: 29509558

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Project description:BackgroundMethadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy.MethodsWe conducted a double-blind, double-dummy, flexible-dosing, randomized, controlled study in which buprenorphine and methadone were compared for use in the comprehensive care of 175 pregnant women with opioid dependency at eight international sites. Primary outcomes were the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, the length of the hospital stay for neonates, and neonatal head circumference.ResultsTreatment was discontinued by 16 of the 89 women in the methadone group (18%) and 28 of the 86 women in the buprenorphine group (33%). A comparison of the 131 neonates whose mothers were followed to the end of pregnancy according to treatment group (with 58 exposed to buprenorphine and 73 exposed to methadone) showed that the former group required significantly less morphine (mean dose, 1.1 mg vs. 10.4 mg; P<0.0091), had a significantly shorter hospital stay (10.0 days vs. 17.5 days, P<0.0091), and had a significantly shorter duration of treatment for the neonatal abstinence syndrome (4.1 days vs. 9.9 days, P<0.003125) (P values calculated in accordance with prespecified thresholds for significance). There were no significant differences between groups in other primary or secondary outcomes or in the rates of maternal or neonatal adverse events.ConclusionsThese results are consistent with the use of buprenorphine as an acceptable treatment for opioid dependence in pregnant women. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00271219.).

Project description:AimsTo examine patient and medication characteristics associated with retention and continued illicit opioid use in methadone (MET) versus buprenorphine/naloxone (BUP) treatment for opioid dependence.Design, settings and participantsThis secondary analysis included 1267 opioid-dependent individuals participating in nine opioid treatment programs between 2006 and 2009 and randomized to receive open-label BUP or MET for 24 weeks.MeasurementsThe analyses included measures of patient characteristics at baseline (demographics; use of alcohol, cigarettes and illicit drugs; self-rated mental and physical health), medication dose and urine drug screens during treatment, and treatment completion and days in treatment during the 24-week trial.FindingsThe treatment completion rate was 74% for MET versus 46% for BUP (P < 0.01); the rate among MET participants increased to 80% when the maximum MET dose reached or exceeded 60 mg/day. With BUP, the completion rate increased linearly with higher doses, reaching 60% with doses of 30-32 mg/day. Of those remaining in treatment, positive opioid urine results were significantly lower [odds ratio (OR) = 0.63, 95% confidence interval (CI) = 0.52-0.76, P < 0.01] among BUP relative to MET participants during the first 9 weeks of treatment. Higher medication dose was related to lower opiate use, more so among BUP patients. A Cox proportional hazards model revealed factors associated with dropout: (i) BUP [versus MET, hazard ratio (HR) = 1.61, CI = 1.20-2.15], (ii) lower medication dose (<16 mg for BUP, <60 mg for MET; HR = 3.09, CI = 2.19-4.37), (iii) the interaction of dose and treatment condition (those with higher BUP dose were 1.04 times more likely to drop out than those with lower MET dose, and (iv) being younger, Hispanic and using heroin or other substances during treatment.ConclusionsProvision of methadone appears to be associated with better retention in treatment for opioid dependence than buprenorphine, as does use of provision of higher doses of both medications. Provision of buprenorphine is associated with lower continued use of illicit opioids.

Project description:BackgroundNaloxone is the usual drug used in opioid-induced respiratory depression but it has a short half-life, precipitates withdrawal in dependent patients, and thus for persistent reversal of long-acting opioids has to be given by titrated doses and infusions. The partial agonist buprenorphine has a much longer duration of action and causes less severe withdrawal, but still should largely reverse respiratory depression induced by full agonist opioids. We aimed to compare the efficacy/safety of buprenorphine and naloxone in reversing respiratory depression in methadone-poisoned opioid-dependent patients.MethodsPatients with methadone-induced respiratory depression were randomized to receive naloxone (titrated doses), or lower or higher doses of buprenorphine (10 μg/kg or 15 μg/kg). The primary outcome was immediate reversal of respiratory depression. We also recorded acute opioid withdrawal, need for intubation/recurrent apnea, repeated doses of opioid antagonists, length of hospital stay, other morbidity, and mortality. The study was registered with the Iranian Registry of Clinical Trials (Trial ID: 18265; Approval code: IRCT2015011020624N1).ResultsEighty-five patients were randomized; 55/56 patients who received buprenorphine had rapid reversal of respiratory depression, which persisted for at least 12 h. Naloxone was effective in 28/29 patients, but often required very high titrated doses (thus delaying time to respond) and prolonged infusions. Intubation (8/29 vs 5/56) and opioid withdrawal (15/29 vs 7/56) were less common with buprenorphine. There were no serious complications or deaths in those receiving buprenorphine. The 15-μg/kg buprenorphine dose appeared to provide a longer duration of action, but precipitated withdrawal more frequently than the 10-μg/kg dose.ConclusionBuprenorphine appears to be a safe and effective substitute for naloxone in overdosed opioid-dependent patients. Further studies are warranted to explore the optimal dosing strategy for buprenorphine to consistently maintain reversal of respiratory depression but not precipitate withdrawal.Trial registration numberIRCT2015011020624N1. Registered 30 September 2015.

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Transferring Patients From Methadone to Buprenorphine: The Feasibility and Evaluation of Practice Guidelines.

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Transferring Patients From Methadone to Buprenorphine: The Feasibility and Evaluation of Practice Guidelines.

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