Itraconazole-induced Torsade de Pointes in a patient receiving methadone substitution therapy

Issues. Methadone, a pharmacological agent used to treat heroin dependence is relatively safe, but may cause cardiac arrhythmias in the concurrent presence of other risk factors. Approach and Key Findings. This case report highlights the risk of Torsade de Pointes, a life-threatening cardiac arrhythmia, in a heroin-dependent patient receiving methadone substitution therapy who was prescribed itraconazole for vaginal thrush. The patient presented to the accident and emergency department for chest discomfort and an episode of syncope following two doses of itraconazole (200 mg). Electrocardiogram monitoring at the accident and emergency department showed prolonged rate-corrected QT interval leading to Torsade de Pointes. The patient was admitted for cardiac monitoring, and electrocardiogram returned to normal upon discontinuation of methadone. Implication. This cardiac arrhythmia was most likely as a result of a drug interaction between methadone and itraconazole because the patient presented with no other risk factors. Conclusion. Given the benefits of methadone as a substitution treatment for heroin-dependent individuals, the association between methadone and cardiac arrhythmias is of great concern. Physicians treating heroin-dependent patients on methadone substitution therapy should therefore be cautious of the potential risk of drug interactions that may lead to fatal cardiac arrhythmias

The SUMMIT trial: a field comparison of buprenorphine versus methadone maintenance treatment.

This prospective patient-preference study examined the effectiveness in practice of methadone versus buprenorphine maintenance treatment and the beliefs of subjects regarding these drugs. A total of 361 opiate-dependent individuals (89% of those eligible, presenting for treatment over 2 years at a drug service in England) received rapid titration then flexible dosing with methadone or buprenorphine; 227 patients chose methadone (63%) and 134 buprenorphine (37%). Participants choosing methadone had more severe substance abuse and psychiatric and physical problems but were more likely to remain in treatment. Survival analysis indicated those prescribed methadone were over twice as likely to be retained (hazard ratio for retention was 2.08 and 95% confidence interval [CI] = 1.49-2.94 for methadone vs. buprenorphine), However, those retained on buprenorphine were more likely to suppress illicit opiate use (odds ratio = 2.136, 95% CI = 1.509-3.027, p < .001) and achieve detoxification. Buprenorphine may also recruit more individuals to treatment because 28% of those choosing buprenorphine (10% of the total sample) stated they would not have accessed treatment with methadone

An economic evaluation of the prison methadone program in New South Wales, CHERE Project Report No 22

Objectives - The aim of this study is to evaluate the costs and consequences of the provision of the prison methadone program in NSW, compared with no prison methadone. Methods - This study has measured the costs involved in the provision of the prison methadone program in NSW. The overall cost of the prison methadone program was estimated from a governmental perspective, incorporating the costs associated with the administration of the program, staffing requirements, methadone syrup and consumables. Both bottom-up and top-down costing approaches have been used. Both the total cost of the program and the cost per inmate in treatment are presented. The study is based on a follow-up study of a randomised trial of prison methadone in the NSW prison system (Dolan, Shearer et al. 2003). Although methadone is available to prisoners in many NSW prisons, the aim of the trial was to determine the impact of prison methadone on a range of health and social outcomes. Participants were randomised to receive prison methadone immediately or to be waitlisted. Waitlisted inmates were offered methadone after a four month delay. The cohort recruited by Dolan et al is now the subject of a four year follow-up study. Since all subjects had been offered methadone at the conclusion of the RCT, this could no longer be treated as controlled study. This limits the utility of the study outcome data for the economic evaluation. In the absence of comparative outcome data, a threshold analysis has been performed to determine what magnitude of outcomes is required to render the prison methadone program cost-neutral from a governmental perspective. The threshold analysis assumes that, through the provision of prison methadone, patients will gain from the benefits associated with continuous methadone treatment. Thus future criminal activity will be reduced and re-incarceration may be avoided. The analysis determines how many days of re-incarceration must be avoided to offset the annual cost of the methadone program. Firstly the analysis estimates what additional resources are required in the prison system to deliver prison methadone. Secondly, potential cost savings associated with avoided re-incarceration are estimated. The costs of the prison methadone program are then compared with the cost savings accrued by avoided days of re-incarceration and the level of effectiveness required to equate costs and savings is identified. A second threshold analysis assumes that, in addition to avoiding days of re-incarceration, prison methadone also avoids incident cases of Hepatitis-C. Given the cost of the program and the number of avoided cases of Hepatitis-C, the threshold analysis identifies the level of effectiveness, in terms of avoided re-incarceration, at which methadone treatment becomes cost neutral. Results - The total cost of providing prison methadone to 900 inmates in 21 prisons in NSW is $2.9million per annum. The cost per person year is$3,234. Given that the average daily cost of incarceration is $176, the annual cost of prison methadone is offset by avoiding 20 days of re-incarceration once the inmate is released. If avoided incident cases of hepatitis-C are included in the analysis, the annual cost of prison methadone is offset by avoiding 19 days of re-incarceration once the inmate is released. Conclusions - This analysis shows that, despite significant barriers to efficiency, prison methadone compares favourably to community based methadone on the basis of cost alone. The analyses suggests that, irrespective of whether avoided cases of Hepatitis-C are included, approximately 20 days of reincarceration must be avoided to offset the annual cost of methadone treatment. There appears to be no evidence in the literature to prove or disprove the feasibility of prison methadone maintenance avoiding such a period of re-incarceration.Methadone, eonomic evaluation

An evaluation of a methadone treatment programme : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Psychology at Massey University

The evaluation of a methadone treatment programme was the main focus of this study. A posttest-only design, with a nonequivalent comparison group was used to evaluate both summative and formative aspects of the programme. Participants were 21 opiate abusers (methadone group) and 22 alcohol and polydrug abusers (alcohol and polydrug group) who completed a questionnaire designed to assess demographic and treatment variables, alcohol and drug usage, employment, criminal activity, health, and interpersonal relationships, in the before, during, and after treatment periods. The outcome measures revealed that the methadone programme was effective in reducing opiate, nonopiate analgesic, tranquillizer and stimulant use; decreasing high alcohol consumption to a level considered nonabusive, and decreasing the number of marijuana related criminal convictions. Unanticipated findings were a deterioration in rating of health and no change in the number of days spent sick in bed, friendship satisfaction, or number of friends out of the drug scene. No predictors of treatment outcomes were established, and there were no major differences between the methadone group, and the alcohol and polydrug group in terms of treatment effects. Recommendations for the methadone programme included detailed and procedural steps of how to cope when withdrawing from methadone treatment; health and nutrition education; and social skills and assertiveness training. These are considered essential if the philosophy and goals of the programme are to be attained

Does Maternal Methadone Dose Correlate with Severity of Intrauterine Growth Restriction in Infants with Neonatal Abstinence Syndrome?

Introduction : Previous studies demonstrate a relationship between maternal opioid use during pregnancy and smaller head circumference of infants with neonatal abstinence syndrome (NAS). The goal of this study is to correlate maternal methadone dose and severity of growth restriction in infants with NAS admitted to the neonatal intensive care unit (NICU). Methods: This is a retrospective analysis of infants (≥35 weeks gestation) exposed to in utero methadone, born between August 2006 and May 2018, and admitted to a Philadelphia NICU for medical therapy for NAS. Growth parameters (birth weight, birth length, and birth head circumference) were compared between infants exposed various doses of methadone. The groups were compared using ANOVA, Post-Hoc Tukey, Chi-square and extended Fisher exact tests. Results: A total of 686 infants met the study criteria; 109 in the High dose group, 359 in the Intermediate dose group, and 218 in the Low dose group. There was no significant difference in the use of other drugs or smoking during the pregnancy. Infants exposed to higher doses of methadone displayed significantly smaller head circumferences and lengths at birth. The mean birth weight was similar between the three groups. Discussion: There may be a danger in prescribing high doses of methadone to pregnant mothers, as they may hinder the growth of the infant. We need to conduct more studies investigating how low head circumference and length affect long term developmental outcomes. These findings may help guide physicians toward the optimum dose of methadone for mothers

Methadone ameliorates multiple-low-dose streptozotocin-induced type 1 diabetes in mice

Type 1 diabetes is an autoimmune disease characterized by inflammation of pancreatic islets and destruction of β cells by the immune system. Opioids have been shown to modulate a number of immune functions, including T helper 1 (Th1) and T helper 2 (Th2) cytokines. The immunosuppressive effect of long-term administration of opioids has been demonstrated both in animal models and humans. The aim of this study was to determine the effect of methadone, a μ-opioid receptor agonist, on type 1 diabetes. Administration of multiple low doses of streptozotocin (STZ) (MLDS) (40mg/kg intraperitoneally for 5 consecutive days) to mice resulted in autoimmune diabetes. Mice were treated with methadone (10mg/kg/day subcutaneously) for 24days. Blood glucose, insulin and pancreatic cytokine levels were measured. Chronic methadone treatment significantly reduced hyperglycemia and incidence of diabetes, and restored pancreatic insulin secretion in the MLDS model. The protective effect of methadone can be overcome by pretreatment with naltrexone, an opioid receptor antagonist. Also, methadone treatment decreased the proinflammatory Th1 cytokines [interleukin (IL)-1β, tumor necrosis factor-α and interferon-γ] and increased anti-inflammatory Th2 cytokines (IL-4 and IL-10). Histopathological observations indicated that STZ-mediated destruction of β cells was attenuated by methadone treatment. It seems that methadone as an opioid agonist may have a protective effect against destruction of β cells and insulitis in the MLDS model of type 1 diabete

Is the promise of methadone Kenya's solution to managing HIV and addiction? A mixed-method mathematical modelling and qualitative study.

BACKGROUND AND OBJECTIVES: Promoted globally as an evidence-based intervention in the prevention of HIV and treatment of heroin addiction among people who inject drugs (PWID), opioid substitution treatment (OST) can help control emerging HIV epidemics among PWID. With implementation in December 2014, Kenya is the third Sub-Saharan African country to have introduced OST. We combine dynamic mathematical modelling with qualitative sociological research to examine the 'promise of methadone' to Kenya. METHODS, SETTING AND PARTICIPANTS: We model the HIV prevention impact of OST in Nairobi, Kenya, at different levels of intervention coverage. We draw on thematic analyses of 109 qualitative interviews with PWID, and 43 with stakeholders, to chart their narratives of expectation in relation to the promise of methadone. RESULTS: The modelled impact of OST shows relatively slight reductions in HIV incidence (5-10%) and prevalence (2-4%) over 5 years at coverage levels (around 10%) anticipated in the planned roll-out of OST. However, there is a higher impact with increased coverage, with 40% coverage producing a 20% reduction in HIV incidence, even when accounting for relatively high sexual transmissions. Qualitative findings emphasise a culture of 'rationed expectation' in relation to access to care and a 'poverty of drug treatment opportunity'. In this context, the promise of methadone may be narrated as a symbol of hope-both for individuals and community-in relation to addiction recovery. CONCLUSIONS: Methadone offers HIV prevention potential, but there is a need to better model the effects of sexual HIV transmission in mediating the impact of OST among PWID in settings characterised by a combination of generalised and concentrated epidemics. We find that individual and community narratives of methadone as hope for recovery coexist with policy narratives positioning methadone primarily in relation to HIV prevention. Our analyses show the value of mixed methods approaches to investigating newly-introduced interventions

Alcohol consumption in heroin users, methadone-substituted and codeine-substituted patients - Frequency and correlates of use

This retrospective study aims to determine whether there is a difference in the additional consumption of alcohol between addicts treated with methadone or dihydrocodeine (DHC) and untreated addicts injecting heroin. 1,685 patients admitted for opioid withdrawal between 1991 and 1997 were reviewed. Cross-reference tables and multiple logistic regression analyses were carried out. 28% of patients take more than 40 g of alcohol daily (on average 176 g). We found that patients who are treated with methadone or DHC drink alcohol significantly more often daily than the heroin-dependent patients (p<0.01). Using multiple regression analyses, the results were confirmed. Additionally, we found that co-abuse of alcohol was predicted by male gender, longer duration of drug use, additional daily consumption of tetrahydrocannabinol and daily consumption of benzodiazepines. Alcohol consumption by opioid-addicted patients treated with methadone or DHC presents a serious medical problem. Co-abuse of alcohol will receive more attention Copyright (C) 2003 S. Karger AG, Basel

Maternal methadone use in pregnancy : factors associated with the development of neonatal abstinence syndrome and implications for healthcare resources

The objectives of this study were to investigate factors associated with the development of neonatal abstinence syndrome (NAS) and to assess the implications for healthcare resources of infants born to drug-misusing women. Design. Retrospective cohort study from 1 January 2004 to 31 December 2006. Setting. Inner-city maternity hospital providing dedicated multidisciplinary care to drug-misusing women. Four hundred and fifty singleton pregnancies of drugmisusing women prescribed substitute methadone in pregnancy. Development of NAS and duration of infant hospital stay. 45.5% of infants developed NAS requiring pharmacological treatment. The odds ratio of the infant developing NAS was independently related to prescribed maternal methadone dose rather than associated polydrug misuse. Breastfeeding was associated with reduced odds of requiring treatment for NAS (OR 0.55, 95% CI 0.34-0.88). Preterm birth did not influence the odds of the infant receiving treatment for NAS. 48.4% infants were admitted to the neonatal unit (NNU) 40% of these primarily for treatment of NAS. The median total hospital stay for all infants was 10 days (interquartile range 7-17 days). Infants born to methadone-prescribed drug-misusing mothers represented 2.9% of hospital births, but used 18.2% of NNU cot days. Higher maternal methadone dose is associated with a higher incidence of NAS. Pregnant drug-misusing women should be encouraged and supported to breastfeed. Their infants are extremely vulnerable and draw heavily on healthcare resources