Methadone Users Research Articles

PTU-019 Methadone use is associated with the development of common bile duct dilatation among patients with hepatitis C: results of a retrospective cohort study

IntroductionThe synthetic opioid Methadone is widely used in the treatment of opioid dependence. Opioids are known to induce spasm of the sphincter of Oddi, increase common bile duct (CBD) pressures...

The improvement of adherence to antiretroviral treatment through the pharmaceutical care and the analysis of factors affecting it

BackgroundThe lack of adherence to antiretroviral therapy(ART) is the leading cause of treatment failure. The ART has all the factors to make difficult the adherence. The authors have applied a...

Availability of dopamine and serotonin transporters in opioid-dependent users—a two-isotope SPECT study

The aims of this study were to examine the differences between 32 opioid-dependent users treated with a very low dose of methadone or undergoing methadone-free abstinence and 32 controls. SPECT analysis using [(99m)Tc] TRODAT-1 to assess striatal dopamine transporter (DAT) availability and [(123)I] ADAM to assess midbrain serotonin transporter (SERT) availability were performed. Lower striatal DAT and midbrain SERT availabilities were noted in low-dose methadone users. History of metamphatamine use was associated with the lower striatal DAT. The striatal DAT of methadone-free abstainers was also lower than controls. The midbrain SERT availability tended to be higher in the methadone-free abstainers than the low-dose methadone users. The severity of depressive symptoms was negatively correlated with midbrain SERT availability in the opioid users. The availability of striatal DAT tended to be, and the availability of midbrain SERT was, lower in the opioid users. History of metamphatamine use may confound the difference in straital DAT between controls and opioid users, as midbrain SERT and depressive symptoms are also associated with opioid use and abstinence.

Implicit and Explicit Cognition of Chinese Heroin Abusers

Sixty-five heroin abusers receiving Methadone Maintenance Treatment (MMT), 38 heroin abusers not receiving MMT, and 30 nonusers of drugs participated in this investigation of cognition in heroin and methadone users. Heroin users were measured for both implicit and explicit cognition, while the control group of nonusers was measured only for implicit cognition. The results demonstrate that implicit cognition can influence the development of addictive behaviors, and that implicit and explicit cognition of heroin were separate and independent constructs. Based on the results of Implicit Association Tests (IAT; Greenwald, McGhee, & Schwartz, 1998) MMT appears to be a valid method for opiate withdrawal treatment as it reverses the implicit desire for heroin in heroin abusers.

Benefit Policy and Disenrollment of Adult Medicaid Beneficiaries from the Oregon Health Plan

Oregon's Medicaid program experienced a dramatic decrease in its non-categorically eligible adult members after implementing a new benefit policy in February 2003 for these beneficiaries. The policy included four main elements: premium increases for some enrollees; a more stringent premium payment policy; elimination of some benefits, including mental health and substance abuse treatment; and, the imposition of co-payments. The study compared monthly disenrollment rates eight months before and after the policy change. The new premium payment policy was found to be the main driver of disenrollment, followed by benefit elimination. Premium increases and co-payments had limited impact. Disenrollment was particularly high among vulnerable beneficiary groups, including people with no reported income, those previously obtaining premium waivers, methadone users, and other enrollees with substance abuse conditions. Better understanding of the relationship between benefit design and retention in public health insurance programs could help avoid the unintended policy effects experienced in Oregon.

Assessing the spatial distribution of methadone clinic clients and their access to treatment

Using Geographic Information System (GIS), the spatial distribution of methadone clinic clients and their utilization of a treatment service in Hong Kong was analysed. A majority (93.7%) of the 63 methadone users recruited were residing in the same district, of which 84.1% spent not more than 15 minutes for traveling. Walking (55.6%) was the commonest transport mode followed by cycling (30.2%). There was no distance decay effect on traveling time, but an association between distance and transport selection could be demonstrated. The residence locations displayed a compact distribution, merging with the general population without any evidence of clustering. Though the distribution of methadone users could have been shaped by the location of clinic, it can also be concluded that methadone clinics at convenient locations are needed if maintenance is a key determinant of service effectiveness.

Risk factors which were associated with heroin use during the methadone maintenance treatment among 1301 patients in 9 cities of China.

To determine the proportion of heroin use among patients who were involved in community-based methadone maintenance treatment (MMT) program and to identify the risk factors associated with heroin use. This study was conducted in 9 MMT clinics within 3 provinces. Thirteen hundred and one patients who met the study criteria were selected from each of the five groups with different dosages of methadone users. An administrative questionnaire was applied to explore the demographics, drug abuse-related behaviors and MMT services received by the clients, etc. The prevalence of depression and anxiety among the clients were also collected by SAS and SDS. Urine samples were collected as a biological marker to indicate if heroin had been used. Of the 1301 patients, 76.2% were males. The mean age was (34.6 +/- 6.5) years while 71.7% had an education level of primary school or below. The average daily dosage of methadone was (48.1 +/- 29.4) mg and self-satisfied evaluation score on treatment was 8.6. On average, 27.7% urine samples showed positive opiate evidence. Marital status, employment status, treatment retention, self-satisfied evaluation score on dosage and dropout history were found to be significantly associated with heroin use, while gender, education level and dosage had no significant association with heroin use. It seemed that risk factors that associated with heroin use were different from areas to areas. High quality MMT clinic services, high self-satisfied score, longer treatment retention and low dropout rate seemed to have the effects of reducing the risk of ongoing heroin abuse under the methadone maintenance treatment program.

Retention of Under-represented Minorities in Drug Abuse Treatment Studies

Differential attrition by minority participants can be as limiting to interpreting final results as poor initial recruitment of minority participants. This is especially important in drug abuse treatment studies, as minorities are over-represented in substance abuse clinical treatment programs. The specific aims of this secondary data analysis were to: (1) determine if there are differences in study retention rates by race/ethnicity and age, and (2) explore other client characteristics, as well as protocol and treatment program factors, that could account for differential retention rates. We conducted a secondary analysis using data from 1737 participants in the first six clinical trials whose databases were locked in the NIDA Clinical Trials Network. Protocol level characteristics were also abstracted from these studies, and we used data from a study which assessed characteristics of community treatment programs that participated in these studies. Logistic regression was used to study the effect on retention of: client, protocol, and program characteristics. In the model of client characteristics, a significant age by race/ethnicity interaction term was detected based on a threshold of 0.1, with younger African Americans having the lowest odds of retention. Primary drug of abuse was also a significant factor in determining study retention, with heroin, methadone, and opiate users having the greatest odds of retention and polydrug users the lowest. Similar analyses testing treatment program characteristics found that only the presence of HIV risk screening and decreasing levels of female admissions (as a percent of total admissions) were related to study retention. In our final model, there was an effect of age, but not race/ethnicity, with younger participants having lower odds of retention. A multivariable model including protocol variables could not be developed due to the high correlation among protocol variables. We excluded those of multi-race/ethnicity and those from minority groups other than Hispanic or African American due to small numbers. Additionally, only three therapy types were represented among the six studies. Some potential variables that would influence retention, such as client housing, and client comorbidities, the race/ethnicity and gender of the staff who conducted study follow-up assessments, and reasons for loss to follow-up, were not collected by the CTN. Although in our client model older African Americans and Caucasians had the greatest odds of retention and younger African Americans the lowest, in our final model, only age was significantly related to study retention. Additionally, primary drug of abuse, having HIV risk screening as a program benefit, and lower percentages of female admissions were significantly related to study retention. Efforts should be made to increase the study retention of younger participants to improve the validity and generalizability of drug abuse treatment study results.

Methadone-associated Q-T interval prolongation and torsades de pointes

The association of methadone with Q-T interval prolongation and torsades de pointes (TdP) is reviewed, and recommendations for preventing Q-T interval prolongation in methadone users are provided. Abnormalities in voltage-gated potassium channels have been shown to lead to prolonged action potentials that are expressed as long Q-T intervals, and methadone has been found to interact with the voltage-gated potassium channels of the myocardium. While cardiac arrhythmias in methadone users have been reported for several decades, specific reports of methadone-associated Q-T interval prolongation and TdP did not appear in the literature until the early part of the 21st century. Because not every patient experiences Q-T interval prolongation with methadone, recent research has elucidated risk factors that predispose patients to this adverse effect, including female sex, hypokalemia, high-dose methadone, drug interactions, underlying cardiac conditions, unrecognized congenital long Q-T interval syndrome, and predisposing DNA polymorphisms. Given the high mortality rates seen in untreated illicit opioid users and the clear efficacy of methadone in treating opioid addiction, the risk of using methadone, even in a patient with other risk factors for Q-T interval prolongation, may outweigh the alternative of no pharmacologic treatment. A baseline electrocardiogram (ECG), personal and family history of syncope, and a complete medication history should be obtained before a patient begins treatment with methadone. Given the apparent synergistic effects of parenteral methadone and chlorobutanol, oral methadone should be used whenever possible. Q-T interval prolongation and TdP associated with the use of methadone are potentially fatal adverse effects. A thorough patient history and ECG monitoring are essential for patients treated with this agent, and alterations in treatment options may be necessary.

Methylnaltrexone: the answer to opioid-induced constipation?

Opioid-induced constipation is a significant problem particularly for end stage cancer patients, methadone users, patients suffering from chronic pain as well as surgical patients. Until recently, there were few efficacious treatment options that did not have significant side effects. Methylnaltrexone is a promising drug for the treatment of opioid-induced constipation. It is an opioid-receptor antagonist that blocks the peripheral gastrointestinal opioid receptors responsible for opioid-induced bowel dysfunction. Due to the drug's polarity, it does not cross the blood–brain barrier; therefore, it does not block the central opioid receptors, thus, retaining effective analgesia. Methylnaltrexone has been recently approved by the FDA in the subcutaneous form for the treatment of opioid-induced bowel dysfunction, whereas the intravenous and oral forms remain under investigation.

Feasibility of Promoting Smoking Cessation Among Methadone Users Using Multimedia Computer-Assisted Education

Background The prevalence of smoking is very high among methadone users. As a method of delivering health education, computers can be utilized effectively. However computer-assisted education in methadone users has not been evaluated systematically. Objective This study was aimed at assessing feasibility and patient acceptance of an interactive educational module of a multi-component smoking cessation counseling computer program for former illicit drug users treated in an outpatient methadone clinic.Methods The computer-mediated education for hazards of smoking utilized in this study was driven by major constructs of adult learning theories. The program interface was tailored to individuals with minimal computer experience and was implemented on a touch screen tablet PC. The number of consecutive methadone-treated current smokers enrolled in the study was 35. After providing socio-demographic and smoking profiles, the patients were asked to use the educational program for 40 minutes. The impact of the computer-mediated education was assessed by administering a pre- and post-intervention Hazards of Smoking Knowledge Survey (HSKS). An attitudinal survey and semi-structured qualitative interview were used after the educational session to assess the opinions of participants about their educational experience.Results The computer-mediated education resulted in significant increase of HSKS scores from 60.5 ± 16.3 to 70.4 ± 11.7 with t value 3.69 and P < .001. The majority of the patients (78.8%) felt the tablet PC was easy to use, and most of the patients (91.4%) rated the educational experience as good or excellent. After controlling for patient baseline characteristics, the effect of computer-mediated education remained statistically significant.Conclusions Computer-assisted education using tablet PCs was feasible, well-accepted, and an effective means of providing hazards of smoking education among methadone users.

Approaches to methadone treatment: harm reduction in theory and practice

The paper analyses methadone treatment in Copenhagen -- as it is described by methadone users and staff at different outpatient centres. The starting point is a theoretical model distinguishing between two different approaches to methadone treatment: 'palliative' and 'curative'. Included in the model are three dimensions (1) treatment goals at the methadone centres (abstinence vs. stabilisation) (2) treatment focus (focus on addiction vs. focus on the consequences of addiction) and (3) conceptualisation of methadone (methadone as similar to or different from heroin). The paper shows that there is a discrepancy between the attitudes of the staff and those of the users. While the staff favour an almost clear-cut palliative approach to methadone treatment, defining curative goals as both unrealistic and as belonging to the past, the users prefer an approach that does not exclude the goal of abstinence and does not focus on the consequences of drug use alone but also on their problematic relationship to drugs (legal as well as illegal). Furthermore, the users' attitudes towards methadone are far more ambivalent than the staff's. For the users, methadone is not just medicine; it is also a dependence-producing and 'dangerous' drug.

Methadone: Dental Risks and Preventive Action

For some time dentists have successfully promoted the benefits of sugar-free medications. There are now over 180 sugar-free medicines manufactured and prescribed. Methadone, used in the rehabilitation of drug-users, is available as a sugar-free preparation; however, the sugar-based version is most often used. This article examines the content of methadone, explains some of the reasons for prescribing patterns and explores how a multi-disciplinary approach can be used to help methadone users with their rehabilitation and minimize risks to oral health. The wider public health and health policy implications of methadone use are discussed and the available literature reviewed. Dentists are most likely to encounter patients on methadone as a dental emergency and they need to be aware that methadone users are at greater risk of decay and erosion from methadone sugar syrup, as well as perhaps their lifestyle. For dental practitioners, addressing the oral health needs of methadone users can contribute to their general well-being.

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Achieving a high coverage--the challenge of controlling HIV spread in heroin users.

In China, the national plan to open 1000 methadone clinics over a five-year period provides a unique opportunity to assess the impacts of harm reduction in a country with concentrated HIV epidemic amongst heroin users. To track the progress of this public health response, data were collected from the first methadone clinic in Liuzhou, Guangxi, a province with a high HIV prevalence. In the first 15 months of its operation, a cumulative total of 488 heroin users, 86% of which male, had joined the programme. The first dose of methadone was given efficiently at a median of 2 days after registration. Of the 240 heroin users attending the clinic in August 2006, 61% took methadone for four days or more each week. The number of active methadone users, however, leveled off at around 170 after the first two months, despite the availability of capacity to deliver more services. The reasons for this observation are: firstly, the provision of one single service that may not be convenient to all heroin users; and secondly, concerns of heroin users who may feel insecure to come forward. As broad coverage is essential in ultimately reducing HIV risk, a low threshold approach is crucial, which should be supported by the removal of social obstacles and a refinement of the administrative procedures.

Differences in orbitofrontal activation during decision-making between methadone-maintained opiate users, heroin users and healthy volunteers

Previously, we reported that opiate users enrolled in methadone treatment made 'risky' choices on a decision-making task following a loss of points compared with heroin users and healthy volunteers. One possible explanation for this behaviour is that methadone users were less sensitive to punishment on immediately preceding unsuccessful trials. We sought to explore this finding from a neural perspective by performing a post hoc analysis of data from a previous [see text] positron emission tomography study. We restricted the analysis to the opiate groups and controls, assessing differences between opiate users on methadone and those on heroin. We found significant over-activation in the lateral orbitofrontal cortex (OFC) in methadone users compared with both heroin users and controls concomitant with the greatest overall tendency to 'play risky'. Heroin users showed significant under-activation in this area compared with the other two groups whilst exhibiting the greatest overall tendency to 'play safe'. Correlational analysis revealed that abnormal task-related activation of the left OFC was associated with the dose of methadone in methadone users and with the duration of intravenous heroin use in heroin users. 'Playing safe' following a loss of points was also negatively correlated with the activation of pregenual anterior cingulate and insula cortex in controls, but not in opiate users. Our findings suggest that the interplay between processes involved in integrating penalty information for the purpose of response selection may be altered in opiate users. This change was reflected differentially in task-related pattern of OFC activation depending on the opiate used.

Pharmacokinetic interaction of nelfinavir and methadone in intravenous drug users

The effect of nelfinavir 1250 mg twice daily (b.i.d.) on the pharmacokinetics of methadone was determined in 14 HIV-negative methadone users. The methadone dose (20-140 mg/day) was stabilized and fixed for at least 1 month before nelfinavir (1250 mg b.i.d. for 8 days) was added to the regimen. The concentrations of methadone enantiomers were measured before and during nelfinavir treatment, and the concentrations of nelfinavir and its active metabolite, AG1402, were measured during nelfinavir treatment. Adverse events and withdrawal/intoxication symptoms were monitored throughout the study. Nelfinavir reduced the area under the concentration-time curve of R-methadone, and S-methadone by 43% and 51%, respectively. Nelfinavir and AG1402 concentrations were within the normal range of historical data, and no subject experienced withdrawal symptoms during the study or required dose adjustment during or after the study. Although nelfinavir reduced the plasma concentrations of both R- and S-methadone, it seems to have no impact on the maintenance dose of methadone. A routine reduction of methadone dose is not recommended when coadministered with nelfinavir.

Cracks in the glass: polydrug use in rural areas

We have already looked at the emerging crack and heroin problems in inner cities. But are the polydrug using practices catching on in rural areas? In this special research summary, we expose the spreading taste for crack among heroin and methadone users and uncover the familiar inability of services to cope.

A phase III double-blind placebo-controlled trial of methylnaltrexone (MNTX) for opioid-induced constipation (OIC) in advanced medical illness (AMI)

LBA8003 Background: Constipation is a common and distressing side effect of opioid treatment. Patients with AMI commonly experience severe OIC unresponsive to laxatives which can significantly complicate pain management. MNTX is a quaternary derivative of the pure opioid antagonist naltrexone formed by the addition of a methyl group to the ring nitrogen. MNTX does not cross the blood-brain barrier; hence it has the potential to antagonize the peripheral effects of opioids while sparing centrally mediated analgesia. MNTX has been shown to reverse OIC in chronic methadone users and we have previously reported positive results of a phase II trial of MNTX for relief of OIC in hospice patients without evidence of withdrawal or worsened pain (Thomas, et al. ProcASCO, 2003). The present phase III study was initiated to confirm the findings of phase II and assess the safety and efficacy of MNTX in treating OIC in patients with AMI. Methods: This is a multi-center, double-blind, randomized, placebo-controlled study of subcutaneous MNTX for OIC in AMI patients in hospice or palliative care programs. Patients must have a life expectancy of 1 to 6 months, no laxation for 48 hours, on stable opioids for pain and stable laxatives. Patients are randomized to either placebo, MNTX 0.15 mg/kg, or MNTX 0.30 mg/kg. 24 hours after a single subcutaneous dose of study drug, patients may receive open label MNTX, as needed over the next 4 weeks, titrated to effect and tolerability. Total accrual will be approximately 150 patients (50 per group). The primary endpoint is the efficacy of single-dose MNTX (0.15 mg/kg or 0.30 mg/kg vs. placebo) to induce laxation within 4 hours of dosing. We will also measure laxation over 24 hours and adverse events, pain scores, and opioid withdrawal symptoms. The primary analysis will be intent-to-treat and include all randomized patients using a Cochran-Mantel-Haenszel test of placebo against each MNTX dose level. Results: 150 patients have been enrolled as of 12/2/04 and enrollment will be closed on 12/15/04. Analysis of the primary and secondary endpoints and a summary of the demographics will be presented for all patients. Conclusions: To be reached after data becomes available. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Progenics Progenics Progenics

QT prolongation and torsades de pointes among methadone users: reports to the FDA spontaneous reporting system

Recent case series have associated the synthetic opioid, methadone, with QT prolongation and torsades de pointes (TdP) ventricular arrhythmia. To review and analyze adverse events (QT prolongation and TdP) reported to the Food and Drug Administration (FDA) to determine the patient characteristics, dosages of methadone, and outcomes of methadone-treated patients. The study design was a retrieval and retrospective analysis of reports of adverse events associated with methadone voluntarily reported to the FDA MedWatch program from 1969 to October 2002. Reports were accessed via QSCAN (DrugLogic, Reston, VA), a commercially available software interface. In a total of 5,503 reports of adverse events associated with methadone, 43 (0.78%) noted the occurrence of TdP and 16 (0.29%) QT prolongation. Doses were reported in 42/59 (71%) of cases; mean dose was 410 +/- 349 mg/day (median 345, range 29-1680). The dosages for 10 of the 42 cases (29%) were within the recommended range for methadone maintenance treatment, 60-100 mg/day. Female gender, interacting medications, hypokalemia, hypomagnesemia, and structural heart disease, risk factors previously identified with other drugs known to cause TdP, were found in 44 (75%) cases. Most adverse events required hospitalization or resulted in prolonged hospitalization (28/59, 47%) and 5/59 (8%) were fatal. Cases of TdP associated with methadone have been reported to the FDA MedWatch system. Analysis of the cases provides evidence that prolonged QT and TdP can occur over a wide range of dosages including those usually recommended for addiction treatment.