Predictors of methadone maintenance treatment utilization in a multisite cohort of illicit opioid users (OPICAN)

Although methadone maintenance treatment (MMT) has been a primary treatment response to illicit opioid use in Canada for decades, analytical treatment data are scarce. Using data from the multisite OPICAN cohort of illicit opioid and other drug users repeatedly assessed between 2002 (baseline) and 2005 (last follow-up [FU]), we (1) longitudinally examined characteristics associated with MMT uptake between baseline and FU and (2) cross-sectionally compared drug use patterns between cohort participants in MMT (n = 133) and those not in MMT (n = 400) at the last FU through bivariate and multivariate analyses (stepwise logistic regression). Significant baseline predictors of MMT uptake emerging in the logistic regression model included injection drug, heroin, as well as alcohol use, housing status, and Quebec City as a site. Furthermore, lower prevalence levels of opioid (e.g., morphine and OxyContin) and nonopioid (e.g., cocaine and crack) drug use as well as lower frequency of heroin use days were observed among MMT users. This study highlights potential factors relevant for improved MMT uptake and illustrates possible reductions of drug use related to MMT.     

Abnormal frontal activations related to decision-making in current and former amphetamine and opiate dependent individuals

Rationale There is converging evidence for impairments in decision-making in chronic substance users. In the light of findings that substance abuse is associated with disruptions of the functioning of the striato–thalamo–orbitofrontal circuits, it has been suggested that decision-making impairments are linked to frontal lobe dysfunction. We sought to investigate this possibility using functional neuroimaging. Methods Decision-making was investigated using the Cambridge Risk Task during H₂ ¹⁵O PET scans. A specific feature of the Risk Task is the decisional conflict between an unlikely high reward option and a likely low reward option. Four groups, each consisting of 15 participants, were compared: chronic amphetamine users, chronic opiate users, ex-drug users who had been long-term amphetamine/opiate users but are abstinent from all drugs of abuse for at least 1 year and healthy matched controls without a drug-taking history. Results During decision-making, control participants showed relatively greater activation in the right dorsolateral prefrontal cortex, whereas participants engaged in current or previous drug use showed relatively greater activation in the left orbitofrontal cortex. Conclusion Our results indicate a disturbance in the mediation by the prefrontal cortex of a risky decision-making task associated with amphetamine and opiate abuse. Moreover, this disturbance was observed in a group of former drug users who had been abstinent for at least 1 year. This revised version was published online in April 2005 with corrections to the article title and to Tables 5 and 6.     

PET imaging of dopamine transporter and drug craving during methadone maintenance treatment and after prolonged abstinence in heroin users

It has been documented that methadone maintenance treatment is effective in reducing drug craving and relevant risk behaviors in heroin users. However, it is not understood whether methadone maintenance treatment impairs the dopamine transporter in the striatum. To establish whether chronic opiate use might impair brain dopamine neurons in humans, we assessed dopamine transporter (DAT) uptake function in the striatum (caudate and putamen), and analyzed the correlation between DAT in the striatum and heroin craving and subjective anxiety in former heroin users with prolonged abstinence and in patients receiving methadone maintenance treatment. Binding of [(11)C]-2beta-carbomethoxy-3beta-aryltropane ([(11)C] CFT) as a brain dopamine transporter ligand was measured with positron emission tomography (PET) in eleven former heroin users with prolonged abstinence, ten patients receiving methadone maintenance treatment and ten healthy control subjects. Heroin craving and subjective anxiety in prolonged abstinence and methadone maintenance treatment groups were assessed and the correlations between DAT of striatum and heroin craving or subjective anxiety were determined. In comparison with healthy control subjects, methadone maintenance treatment subjects had lower DAT uptake function in the bilateral caudate and putamen and prolonged abstinence subjects showed significantly lower DAT uptake function in the bilateral caudate. Moreover, in comparison to the prolonged abstinence subjects, the methadone maintenance treatment subjects showed significant decreases of DAT uptake in the bilateral putamen. DAT uptake function in bilateral striatum was not associated with heroin craving in prolonged abstinence or in methadone maintenance treatment subjects; however, DAT uptake function in the bilateral caudate was significantly correlated with subjective anxiety in methadone maintenance treatment subjects. Our findings suggest that chronic opioid use induces long-lasting striatum dopamine neuron impairment, and prolonged withdrawal from opioids can benefit the recovery of impaired dopamine neurons in the brain.     

Symptom complaints of patients prescribed either oral methadone or injectable heroin

Many methadone patients and untreated heroin users have an ambivalent attitude toward methadone maintenance. This may be a result of the widespread belief that methadone produces various side effects not found with heroin. This study compared the symptom complaints of patients on oral methadone maintenance (MMT) with those of patients prescribed injectable heroin (IHT). A convenience sample of 117 (63 MMT, 54 IHT) patients was recruited from two maintenance clinics. With the use of a self-completion questionnaire, patients were interviewed about a range of symptoms they had experienced and which, in their view, were due to maintenance substance immediately after the last 10 opioid administrations, during the previous week and previous year. The complaints of the two groups overlapped considerably with only few significant differences; these appeared related to the route of administration. IHT patients reported a larger number of complications experienced immediately after administration than MMT patients (p = .007). From the patients' view, methadone does not produce many more or side effects very different from heroin and thus seems at least as tolerable as heroin for maintenance treatment.     

Factors associated with mortality among heroin users after seeking treatment with methadone: A population-based cohort study in Taiwan

Data concerning factors associated with mortality among heroin users under methadone maintenance treatment (MMT) in the Han Chinese population are limited. This study examined mortality risk among heroin users after seeking treatment with methadone in a catchment area using a cohort of 1616 Taiwanese heroin users between October 2006 and December 2008. During the study period, 26 (1.6%) people died, with an all-cause mortality rate per 100 person years of 3.42. The primary cause of death among our patients was accidents, followed by suicide and drug overdose. Older age, HIV infection, psychiatric treatment history, and alcohol abuse/dependence were risk factors for all-cause mortality; remaining on MMT was protective for survival. Our findings suggest that although mortality is mainly associated with medical and psychiatric comorbidities, continuing with the MMT program is still an important predictor for survival.     

Unintended impacts of regulatory changes to British Columbia Methadone Maintenance Program on addiction and HIV-related outcomes: An interrupted time series analysis

BackgroundIn February 2014, several regulatory reforms were introduced to the methadone maintenance treatment (MMT) program in British Columbia, Canada, including a switch to a ten-times more concentrated methadone formulation and restrictions in pharmacy delivery services. We evaluated possible unintended effects of these changes on illicit drug use patterns and HIV treatment outcomes among HIV-positive opioid users.MethodsData was drawn from ACCESS, a prospective community-recruited cohort of HIV-positive people who use illicit drugs in Vancouver, Canada. Interrupted Time Series Analyses were used to evaluate impacts of the policy change on monthly rates of MMT enrolment, illicit heroin injection, antiretroviral therapy (ART) adherence, and HIV viral suppression among HIV-positive opioid users between November 2012 and May 2015.ResultsA total of 331 HIV-positive opioid users were included. The MMT policy change led to a significant immediate 11.5% increase in heroin injection, and 15.9% drop in optimal ART adherence. A gradual increase in the prevalence of MMT enrolment after the policy change was also documented (0.9% per month). No changes in viral suppression rates were observed.ConclusionWe observed immediate increases in illicit heroin injection and decreases in ART adherence in the wake of regulatory changes to the local MMT program. These findings underscore the need to consider potential unintended effects of altering health programmes for vulnerable populations, the need to develop appropriate mitigation strategies, as well as to involve all relevant stakeholders in the planning and implementations of new policies.     

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

Objective 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.Methods We sought to explore this finding from a neural perspective by performing a post hoc analysis of data from a previous 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.Results 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.Conclusion 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.     

Heroin use and HIV risk-taking behaviour among women injecting drug users

This study compares drug use, injecting and sexual risk-taking behaviour among pregnant injecting drug users (IDUs) enrolled in methadone maintenance treatment (MMT), non-pregnant women IDUs enrolled in MMT and women IDUs not enrolled in treatment. There was no significant difference between pregnant IDUs enrolled in MMT and women IDUs not enrolled in treatment in terms of their injecting risk-taking behaviour. Both groups reported significantly higher levels of injecting risk-taking behaviour compared to (non-pregnant) women enrolled in MMT. Pregnant women enrolled in MMT reported a significantly lower methadone dose compared to non-pregnant women in MMT. There was a trend for pregnant women enrolled in MMT to report a higher level of heroin use compared to non-pregnant women in MMT. The lack of evidence for a difference in level of injecting risk-taking behaviour between pregnant IDUs enrolled in MMT and women IDUs not enrolled in treatment suggests the need for additional strategies among pregnant IDUs to reduce IDU and injecting risk-taking behaviour. Possible strategies include maintenance on higher doses of methadone and the application of relapse prevention strategies.     

CANADIAN ILLICIT OPIATE USERS’ VIEWS ON METHADONE AND OTHER OPIATE PRESCRIPTION TREATMENT: AN EXPLORATORY QUALITATIVE STUDY

Although methadone treatment has been available in North America for decades, only a small proportion of opiate addicts (some 25% of estimated opiate users in Canada) are receiving methadone treatment. Many users have tried methadone treatment, often multiple times, but leave treatment prematurely. Others would not consider it as a worthwhile treatment option for themselves. This exploratory study examines regular opiate users’ attitudes towards and experiences with methadone treatment in Canada, primarily setting out to determine what makes methadone an unsuccessful or even an undesirable treatment option for considerably large groups of opiate users. This empirical effort to explore the limitations of existing methadone treatment comes at an appropriate time, when alternative forms of opiate pharmacotherapy treatment are being proposed in Canada as complementary modes of intervention that hope to address the shortcomings of methadone treatment. The rationale for this study were feasibility questions and development efforts for a clinical trial in North America evaluating the effectiveness of using injectable opioids (heroin, dilaudid) in attracting and engaging treatment-resistant opiate users into treatment. Data for this exploratory qualitative study was collected in 1999 through a series of focus groups involving 47 treatment-experienced and treatment-naive opiate users in Vancouver, Montreal, and Toronto, with the objective of identifying key themes and issues on the described topic as a basis for further systematic research.     

Chronic heroin use during methadone treatment: a test of the efficacy of high maintenance doses

A pilot study was conducted at two maintenance programs to test the effect of increasing the methadone dose of clients who continue chronic heroin use after stabilization on methadone. Program 1 subjects (Group 1) received substantial dose increases for a 14-week period; Program 2 subjects (Group 2) received no dose modifications during the same period. Results show Group 1 reported an alleviation of physical and psychological complaints but did not decrease illicit opiate use. Group 2 maintained the low level of complaints reported at baseline and, unexpectedly, decreased opiate abuse. Because the two maintenance programs differed in clinical practices and in enforcement of rules, it was concluded that clients who continue chronic heroin use need not only long-term dosage increases, but also clear, consistently applied program policies.     

Canadian illicit opiate users' views on methadone and other opiate prescription treatment: an exploratory qualitative study

Although methadone treatment has been available in North America for decades, only a small proportion of opiate addicts (some 25% of estimated opiate users in Canada) are receiving methadone treatment. Many users have tried methadone treatment, often multiple times, but leave treatment prematurely. Others would not consider it as a worthwhile treatment option for themselves. This exploratory study examines regular opiate users' attitudes towards and experiences with methadone treatment in Canada, primarily setting out to determine what makes methadone an unsuccessful or even an undesirable treatment option for considerably large groups of opiate users. This empirical effort to explore the limitations of existing methadone treatment comes at an appropriate time, when alternative forms of opiate pharmacotherapy treatment are being proposed in Canada as complementary modes of intervention that hope to address the shortcomings of methadone treatment. The rationale for this study were feasibility questions and development efforts for a clinical trial in North America evaluating the effectiveness of using injectable opioids (heroin, dilaudid) in attracting and engaging treatment-resistant opiate users into treatment. Data for this exploratory qualitative study was collected in 1999 through a series of focus groups involving 47 treatment-experienced and treatment-naive opiate users in Vancouver, Montreal, and Toronto, with the objective of identifying key themes and issues on the described topic as a basis for further systematic research.     

Neuropsychological functioning in opiate-dependent subjects receiving and following methadone maintenance treatment

OBJECTIVE: An accumulating body of research suggests that former heroin abusers in methadone maintenance therapy (MMT) exhibit deficits in cognitive function. Whether these deficits are present in former methadone maintained patients following discontinuation of MMT is unknown. This study tests the hypothesis that former heroin users who have detoxified from methadone maintenance therapy and are drug-free have less pronounced cognitive impairment than patients continuing long-term MMT. METHOD: A series of neuropsychological tests were administered to three groups of subjects: 29 former heroin addicts receiving methadone maintenance treatment, 27 former heroin addicts withdrawn from all opiates, and 29 healthy controls without a history of drug dependence. Testing included Wechsler Adult Intelligence Scale-Revised Vocabulary Test, the Stroop Color-Word Test, the Controlled Oral Word Association Test, the Benton Visual Retention Test, and a Substance Use Inventory. FINDINGS: Both methadone-maintained and abstinent subject groups performed worse than controls on tasks that measured verbal function, visual-spatial analysis and memory, and resistance to distractibility. Abstinent subjects performed worse than their methadone maintained counterparts on tests measuring visual memory and construct formation. Cognitive impairment did not correlate with any index of drug use. CONCLUSIONS: We confirmed previous findings of neuropsychological impairment in long-term MMT recipients. Both patients receiving MMT and former heroin users in prolonged abstinence exhibited a similar degree of cognitive impairment. Cognitive dysfunction in patients receiving methadone maintenance may not resolve following methadone detoxification.     

Patterns of heroin, cocaine, and alcohol abuse during long-term methadone maintenance treatment

Individuals' use of heroin, cocaine, and alcohol during long-term methadone maintenance treatment (MMT) was studied. Prospectively collected data from 103 heroin-addicted individuals who were consecutively admitted for MMT and remained 2 years in treatment were evaluated. The patients were assessed every 6 months with a standardized interview. Three longitudinal patterns of drug abuse were identified. A proportion of patients abstained fully from their particular drug use (26% from heroin, 39% from cocaine, and 19% from alcohol); a proportion (39%, 32%, and 47%, respectively) switched between periods of abuse and nonuse of these drugs; and chronic drug users (34%, 28%, and 33%, respectively) continued use, including periods of daily abuse throughout MMT. Different therapeutic interventions may be needed in patients with different longitudinal patterns of additional substance use during MMT.     

Predictors for Dropping-Out From Methadone Maintenance Therapy Programs Among Heroin Users in Southern Taiwan

This study examined the methadone maintenance therapy (MMT) retention rates of heroin users in Taiwan and the predictors for dropout in the 18-month period after starting MMT. We consecutively recruited 368 intravenous heroin users receiving MMT in 2007–2008 and applied Cox proportional hazards regression analysis to determine the predictive effect of pre- and in-treatment variables on early discontinuation of MMT. The retention rate at 18 months was 32.3%. High heroin expenses, more severe harm caused by heroin use, perceived lower family support, and lower methadone dosage at 3 months after starting MMT increased the risk of dropout in the follow-up period.     

Lifetime multiple substance use pattern among heroin users before entering methadone maintenance treatment clinic in Yunnan,China

Introduction and Aims. Multiple substance use leads to greater levels of psycho‐behavioural problems, unsafe sex, and therefore a high risk of contracting sexually transmitted diseases, and is also more difficult to treat. This study aims to determine pattern of lifetime multiple substance use among Chinese heroin users before entering methadone maintenance treatment clinic. Design and Methods. A survey to obtain retrospective longitudinal data on lifetime multiple substance use was conducted among 203 heroin users in two of the biggest methadone maintenance clinics in Kunming City, Yunnan province. Results. All participants used more than one substance in their lifetime. Most of them used four or more substance groups (range two to seven groups). The most common substance patterns in lifetime use were alcohol, tobacco, opiates and depressants. Approximately 80% of them had a history of simultaneous substance use (co‐use). The most common combination of co‐use pattern was heroin with depressant. Common reasons for co‐use were to get high, to experiment, to sleep and to increase the potency of other drugs. Determinants of co‐use were education, marital status and family relationship. Discussion and Conclusions. Multiple substance use is highly prevalent among Chinese heroin users. Depressants are the most common substances used in combination with heroin.[Li L, Sangthong R, Chongsuvivatwong V, McNeil E, Li J. Lifetime multiple substance use pattern among heroin users before entering methadone maintenance treatment clinic in Yunnan, China. Drug Alcohol Rev 2010]     

Effect of methadone maintenance treatment on heroin craving, a literature review

Despite agreement that methadone maintenance treatment (MMT) is an effective and safe option for treatment of heroin dependence, there have been controversies about its effect on heroin craving. A systematic literature review of the PubMed database was used to find studies eligible for inclusion in the study. The authors present the results of 16 articles that met all inclusion criteria. Overall, 7 studies reported that methadone could reduce heroin craving, 4 studies reported that patients in MMT are still at risk of having heroin craving, 1 study reported that methadone could increase heroin craving, and 4 studies reported that methadone has a neutral effect on heroin craving. One may speculate from these data that methadone may help with heroin craving, but patients in MMT may still be at risk of cue-induced heroin cravings. Methadone provides a helpful tool for reducing some components of craving and risk of relapse for patient receiving MMT.     

贵州美沙酮维持治疗受治者间隔服药特点的观察

目的:了解贵州省8家美沙酮维持治疗(MMT)门诊的受治者间隔服药特点。方法:采用队列研究设计,从2006年6月到2007年6月,对1003名贵州省8家MMT门诊受治者进行服药情况调查。结果:有87.1%、74.9%、60.6%和50.3%受治者分别有过连续3d、7d、15d和30d间隔不到门诊服药情况。结论:MMT受治者间隔服药现象十分普遍。     

Incarcerated intravenous heroin users: Predictors of post-release utilization of methadone maintenance treatment

Incarcerated intravenous heroin users have more problematic patterns of heroin use, but are less likely to access methadone maintenance treatment by their own initiative than heroin users in the community. The present study examined predictors for receiving methadone maintenance treatment post-release among incarcerated intravenous heroin users within a 24-month period. This cohort study recruited 315 incarcerated intravenous heroin users detained in 4 prisons in southern Taiwan and followed up within the 24-month period post-release. Cox proportional hazards regression analysis was applied to determine the predictive effects of sociodemographic and drug-use characteristics, attitude toward methadone maintenance treatment, human immunodeficiency virus serostatus, perceived family support, and depression for access to methadone maintenance treatment after release. There were 295 (93.7%) incarcerated intravenous heroin users released that entered the follow-up phase of the study. During the 24-month follow-up period, 50.8% of them received methadone maintenance treatment. After controlling for the effects of the detainment period before and after recruitment by Cox proportional hazards regression analysis, incarcerated intravenous heroin users who had positive human immunodeficiency virus serostatus (HR = 2.85, 95% CI = 1.80–4.52, p < .001) and had ever received methadone maintenance treatment before committal (HR = 1.94, 95% CI = 1.23–3.05, p < .01) were more likely to enter methadone maintenance treatment within the 24-month follow-up period. Positive human immunodeficiency virus serostatus with fully subsidized treatment and previous methadone maintenance treatment experiences predicted access of methadone maintenance treatment post-release. Strategies for getting familiar with methadone maintenance treatment during detainment, including providing methadone maintenance treatment prior to release and lowering the economic burden of receiving treatment, may facilitate entry of methadone maintenance treatment for incarcerated intravenous heroin users.     

Antiretroviral adherence and HIV treatment outcomes among HIV/HCV co-infected injection drug users: the role of methadone maintenance therapy

OBJECTIVE: We examined the association of methadone maintenance therapy (MMT) with highly active antiretroviral therapy (HAART) adherence and HIV treatment outcomes among a cohort of HIV/HCV co-infected injection drug users (IDUs). METHODS: We obtained demographic, drug use, and addiction care history from the Vancouver Injection Drug User Study (VIDUS), which is an open cohort study of IDUs. The questionnaires were longitudinally linked to the British Columbia HIV/AIDS Drug Treatment Program to obtain HAART adherence and HIV treatment outcome data. There were 278 VIDUS participants who accessed HAART from August 1, 1996 to November 24, 2003. We constructed longitudinal logistic models using generalized estimating equations to examine the independent associations between methadone maintenance therapy and the following outcomes: HAART adherence; plasma HIV-1 RNA suppression; and CD4 cell rise of 100cells/mm(3). RESULTS: Among participants who reported at least weekly heroin use, MMT was independently associated with lower odds of subsequent weekly heroin use during the follow-up period (adjusted odds ratio; 95% confidence interval [AOR; 95% CI]: 0.24; 0.14-0.40). We also found that MMT was positively associated with adherence (AOR 1.52; 95% CI 1.16-2.00), HIV-1 RNA suppression (AOR 1.34; 95% CI 1.00-1.79), and CD4 cell count rise (AOR 1.58; 95% CI 1.26-1.99). CONCLUSIONS: Among HIV/HCV co-infected IDUs on HAART, enrollment in MMT was associated with reduced heroin use, and improved adherence, HIV-1 RNA suppression and CD4 cell count response. Integrating opiate addiction care and HIV care may provide improved health outcomes for this vulnerable population and should be further explored.     

Family history influence on drug abuse severity and treatment outcome

Influence of parental alcohol/substance abuse on methadone maintenance therapy (MMT) outcome was examined in 164 DSM-III-R opioid dependent adults with no other current DSM Axis I disorder. Family history positive patients had more DSM-III-R opioid dependence symptoms and were more likely to be classified as severely dependent. However, when placed on identical daily doses of methadone (50 mg), they had lower rates of illicit opioid use but higher rates of cocaine use than family history negative patients. Both effects remained significant after adjusting for gender and race. These results suggest that common genetic factors may underlie both susceptibility to heroin dependence and response to therapeutic methadone treatment.