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Background: As CRH-binding protein (CRHBP) SNP rs1500 was associated with reduced cocaine abuse after 1 year in methadone maintenance treatment (MMT) for heroin addiction, we evaluated the association of additional 28 selected SNPs, in 17 stress-related genes, with MMT outcome.Methods: The distribution of genotypes of each SNP by cocaine abuse after 1 year in MMT was assessed under the dominant and recessive models using χ2. Cumulative retention (up to 26.5 years) was studied using Kaplan-Meier analyses. Logistic regression and Cox model were used for multivariate analyses.Results: Of a nonselective sample of 404 patients, 25 patients with <50% Europeans/Middle Eastern ancestry were excluded. Of the remaining 379 patients, 330 (87.1%) stayed at least 1 year in treatment. Four SNPs were associated with cocaine abuse after 1 year in MMT. A lower proportion of cocaine abusers was found in the groups of subjects with the following genotypes: arginine vasopressin (AVP) SNP rs2282018 CC, CRHBP rs7728378 TT, galanin rs3136541 TT/TC, and neuropeptide Y receptor Y1 (NPY1R) rs4518200 AA. The following independent variables were associated with lack of cocaine in urine after 1 year (multivariate analyses): CRHBP rs7728378 TT, NPY1R rs4518200 AA, no cocaine in urine on admission, as well as opiate and benzodiazepine use after 1 year in MMT. Cumulative retention (n = 379) was longer in carriers of AVP rs2282018 CC (13.7 years, 95% CI 11.1-16.2) versus TT/TC genotypes (10.5, 95% CI 9.4-11.5) (p = 0.0230) Conclusions: The study suggests that a reduction in cocaine abuse and longer retention among MMT patients is mediated in part by variants in stress-related genes and is a step toward precision medicine. [ABSTRACT FROM AUTHOR]

Background: Animal studies have demonstrated that oxytocin can influence addiction behaviors and might interact with the dopaminergic system, which is a key component of addiction behaviors. However, related evidence from clinical studies is scarce. The aim of our study was to explore the relationship between plasma oxytocin level and heroin craving among patients receiving methadone maintenance treatment, and to ascertain whether this relationship is moderated by novelty-seeking.Methods: The study was conducted in a methadone maintenance therapy clinic of a medical center in Taiwan. Seventy-seven patients with heroin addiction were enrolled. Plasma oxytocin was measured using an ELISA kit. Craving was assessed using an established instrument, the Chinese Craving Scale.Results: A significant negative association was found between the plasma oxytocin level and craving score, which remained robust after controlling the effects of social support and low-density lipoprotein cholesterol. An interaction between oxytocin and novelty-seeking indicated that this relationship was stronger among patients with a lower level of novelty-seeking.Conclusion: This finding may be taken into account in future studies and may provide a basis for the development of potential treatment for addiction. The effect of oxytocin for the treatment of opioid dependence might be modulated by some psychological factors. [ABSTRACT FROM AUTHOR]

Aims: We aimed to improve the retention in treatment and therapeutic outcome of methadone maintenance treatment (MMT) patients by adjusting the oral methadone dose in order to reach a "target" plasma R-methadone level (80-250 ng/mL).Methods: A multicenter randomized controlled trial was organized.Results: The intention-to-treat statistical analysis showed that repeated dose adjustments performed in order to obtain therapeutic plasma R-methadone levels did not improve retention in treatment of heroin-dependent patients. However, patients having plasma methadone levels in the "target range" at the beginning of the study had a better retention in treatment than controls. Furthermore, patients succeeding in keeping plasma R-methadone target levels (per protocol analysis) remained in treatment and improved their social scores better than controls. -Conclusion: Although the primary endpoint of this study was not demonstrated, a post hoc and a per protocol analysis suggested that patients in MMT with plasma R-methadone concentrations in the target range have a better therapeutic outcome than controls. [ABSTRACT FROM AUTHOR]

Background: There is equivocal evidence regarding whether people who use heroin substitute heroin for alcohol upon entry to methadone maintenance therapy (MMT). We aimed to examine the impact of MMT enrolment on the onset of heavy drinking among people who use heroin.Methods: We derived data from prospective, community-based cohorts of people who inject drugs in Vancouver, Canada, between December 1, 2005, and May 31, 2014. Multivariable extended Cox regression analysis examined the effect of MMT enrolment on the onset of heavy drinking among people who used heroin at baseline.Results: In total, 357 people who use heroin were included in this study. Of these, 208 (58%) enrolled in MMT at some point during follow-up, and 115 (32%) reported initiating heavy drinking during follow-up for an incidence density of 7.8 events (95% CI 6.4-9.5) per 100 person-years. The incidence density of heavy drinking was significantly lower among those enrolled in MMT at some point during follow-up compared to those who did not (4.6 vs. 16.2; p < 0.001). MMT enrolment was not significantly associated with time to initiate heavy drinking (adjusted relative hazard (ARH) 1.27; 95% CI 0.78-2.07) after adjustment for relevant demographic and substance-use characteristics. Age and cannabis use were the only variables that were independently associated with the time to onset of heavy drinking (ARH 0.74; 95% CI 0.58-0.94 and ARH 2.06; 95% CI 1.32-3.19, respectively).Conclusion: In this study, MMT enrolment did not predict heavy drinking and may even appear to decrease the initiation of heavy drinking. Our findings suggest younger age and cannabis use may predict heavy drinking. These findings could help inform on-going discussions about the effects of opioid agonist therapy on alcohol consumption among people who use heroin. [ABSTRACT FROM AUTHOR]

Background/Aims: Heroin-assisted treatment (HAT) can improve the condition of heroin addicts still using street heroin after a methadone treatment. In Belgium, a new trial compared the efficacy of a HAT to existing methadone maintenance treatment. Methods: In this randomised controlled trial, HAT was limited to 12 months. Participants were assessed every 3 months. They were responders if they showed improvement on the level of street heroin use, health or criminal involvement. Results: 74 participants were randomised in the trial. The experimental group (n = 36) counted 30% of responders more than the control group (n = 38) at each assessment point (p < 0.05), except at 12 months where the difference (11%) was no longer significant (p = 0.35). Still, after 12 months, participants in the experimental group reported significantly greater improvements (p < 0.05) than the control group on the level of street heroin use and on the level of physical and mental health. Both groups reported significantly less criminal acts after 12 months (p < 0.001), but with no significant difference between the groups. Conclusions: This trial confirms the short-term efficacy of HAT for severe heroin addicts, who already failed methadone treatment. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The effect of intake procedures on treatment entry and retention was examined in a natural experiment, in which a methadone maintenance clinic in Israel admitted 127 clients by employing a rapid intake procedure (maximum of 3 days before the initiation of treatment was offered). Using information gathered from patient files, these clients were retrospectively compared to a control group (n = 121) who underwent the clinic's regular intake procedure (between 3 weeks and 3 months). Outcome measures included entry into treatment and subsequent retention in treatment (at 3, 6 and 12 months). Results show that 81% of clients from the rapid intake group entered treatment compared to only 57% from the regular intake group. Treatment retention was similar for both groups. In addition, Jewish clients were more likely to enter treatment via the rapid intake procedure than clients from other religions, and women were retained in treatment longer than men, regardless of the type of intake procedure. Results of this single-site study lend support to the effectiveness of rapid intake procedures as a way to engage clients in treatment and carry significant implications for improving access into treatment. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Oxytocin interacts with the dopaminergic system, which plays a role in addiction behaviors. The association between oxytocin and addiction was confirmed in animal studies. Novelty seeking is one of the predictors and indicators of drug addiction. The aim of the present study was to probe the association between oxytocin and novelty seeking. Methods: The study was conducted in a methadone maintenance therapy clinic of a medical center in Taiwan; 77 patients with heroin dependency were enrolled. Plasma oxytocin was measured using an ELISA kit. Novelty seeking was measured using an established instrument (the novelty seeking subscale of the Tridimensional Personality Questionnaire). Results: A significant negative association (ρ = -0.27, p = 0.02; r = -0.34, p = 0.003) between the blood level of plasma oxytocin and novelty seeking was found. This association was significant after controlling the effects of perceived social support and the dosage of methadone (r = -0.32, p = 0.006). Conclusion: The negative association between oxytocin and novelty seeking may provide insight into future treatments for addiction. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Drug - including opioid - dependence is common in correctional populations, however little research exists on interventions for women offenders. Based on retrospective administrative data, we examined rates of return to custody (RTC) among three samples of Canadian federal women offenders with problematic opioid use (total n = 137): (1) a group initiated on MMT during incarceration who continued MMT post-release (MMT-C; n = 25); (2) a group initiated on MMT but who terminated treatment post-release (MMT-T; n = 67), and (3) a non-MMT control group (MMT-N; n = 45). Study groups were similar regarding socio-demographic, drug use and criminogenic indicators. Based on an unadjusted Cox proportional hazards model, the MMT-C group had a 65% lower risk of RTC than the MMT-N (reference) group (HR 0.35, CI 0.13-0.90); RTC risk was not different between the MMT-T and the reference group. Most RTCs were for technical revocations (e.g. violation of a legal condition of their release). Continuous MMT following release from corrections appears to be effective in reducing recidivism in women offenders with opioid problems; barriers to MMT in the study population should be better understood and ameliorated. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aim: To inform understanding of the experience of long-term opiate maintenance and identify barriers to recovery. Methods: A qualitative systematic review. Results: 14 studies in 17 papers, mainly from the USA (65%), met inclusion criteria, involving 1,088 participants. Studies focused on methadone prescribing. Participants reported stability; however, many disliked methadone. Barriers to full recovery were primarily 'inward focused'. Conclusion: This is the first review of qualitative literature on long-term maintenance, finding that universal service improvements could be made to address reported barriers to recovery, including involving ex-users as positive role models, and increasing access to psychological support. Treatment policies combining harm minimisation and abstinence-orientated approaches may best support individualised recovery. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the prevalence of childhood and adulthood attention deficit hyperactivity disorder (ADHD) and clinical obsessive-compulsive disorder (OCD) among adult patients in methadone maintenance treatment (MMT) and to characterize possible risk factors. Sampling andMethods: A random sample of 154 current MMT patients was studied for childhood ADHD (Wender Utah Rating Scale), current clinical OCD (Yale-Brown Obsessive Compulsive Scale), lifetime trauma history and modified Addiction Severity Index for demographics, as well as any lifetime DSM-IV-TR psychiatric diagnosis. Results: Fifty-one patients (33.1%) had childhood ADHD, and more of this group currently had clinical OCD compared to patients who did not have childhood ADHD (55.3 vs. 30.1%). The two groups did not differ with regard to gender and age of admission to MMT. Logistic regression found that the childhood ADHD group had a higher risk of having OCD [odds ratio (OR) 3.8, 95% confidence interval (CI) 1.6-8.8], more severe nicotine smoking (OR 1.4, 95% CI 1.1-1.7) and fewer years of education (OR 0.8, 95% CI 0.6-1) and were more likely to have a DSM-IV-TR axis II disorder (OR 4.3, 95% CI 1.4-13.4) and a history of falls (OR 4.3, 95% CI 1.4-12.9). Conclusions: Although ADHD is more prevalent among males in the general population, the rates in our MMT population were similar in each gender. One third of our sample had suffered from ADHD during childhood, which may have led them to self-medicate with drugs and thus to addiction. Childhood ADHD was associated with current OCD, and both conditions were highly prevalent among our MMT patients. The reason for a history of repeated falls warrants further study. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Methadone maintenance treatment is a chronic treatment for opiate addicts. After having reached full capacity, new admissions to our clinic were delayed (through a waiting list) for all but opiate addicts with HIV and pregnant women. We compared characteristics and outcomes between patients admitted without delay (1993-2002) and those admitted through a waiting list (2003-2009). All 704 patients admitted between June 1993 and June 2009 were followed up until June 2010. There were 470 patients in the early period and 234 in the late period (56 patients were admitted immediately and 178 after 1.1 ± 0.8 years of waiting). Predictors for 1-year retention in treatment (logistic regression model) were if a patient self-referred during the late period, on a waiting list. The waiting list patient group was characterized by older age and self-referral - two known independent predictors of better retention that were attributed to their superior retention rate. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: Studies on determinants of quality of life (QoL) among opiate-dependent individuals are scarce. Moreover, findings concerning the role of severity of drug use are inconsistent. This exploratory study investigates the association between domain-specific QoL and demographic, social, person, health and drug-related variables, and potential indirect effects of current heroin use on opiate-dependent individuals' QoL. Methods: A cohort of opiate-dependent individuals who started outpatient methadone treatment at least 5 years previously (n = 159) were interviewed about their current QoL, psychological distress, satisfaction with methadone treatment and the severity of drug-related problems using the Lancashire Quality of Life Profile, the Brief Symptom Inventory, the Verona Service Satisfaction Scale for Methadone Treatment and the EuropASI. Results: None of the QoL domains were defined by the same compilation of determinants. No direct effect of current heroin use on QoL was retained, but path analyses demonstrated its indirect effects on the domains of 'living situation', 'finances' and 'leisure and social participation'. Conclusion: These findings illustrate the particularity of each QoL domain and the need for a multidimensional approach to the concept. The relationship between current heroin use and various domains of opiate-dependent individuals' QoL is complex, indirect and mediated by psychosocial and treatment-related variables. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Methadone maintenance treatment (MMT) has been shown to dramatically reduce illicit opioid use and criminal activity among injection drug users (IDU). However, questions remain concerning the effect of MMT in reducing rates of incarceration among IDU. We therefore sought to investigate the long-term effect of MMT on rates of incarceration. Methods: We performed a generalized estimating equation longitudinal analysis of factors associated with incarceration among participants in the Vancouver Injection Drug Users Study (VIDUS). We also recorded whether participants reported having difficulty accessing drug treatment during the study period. Results: Among 1,247 active IDU, 624 (50.0%) reported being incarcerated at least once during the 6-year study period. In multivariate analysis, there was a strong negative association between methadone treatment and incarceration (adjusted odds ratio = 0.64, 95% CI: 0.54–0.76, p < 0.001) despite intensive covariate adjustment. Conclusions: Given our findings concerning the strong negative association between MMT and incarceration, and the reported high-risk injection practices of incarcerated IDU, limiting the availability of MMT has the potential to further exacerbate the high levels of HIV transmission found among IDU who are in need of treatment both in their communities and in correctional facilities. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This article assesses changes over 10 years in the role of pharmacies in the care of drug misusers – needle/syringe provision and methadone treatment supervision – in the Swiss French-speaking Canton of Vaud (636,000 inhabitants, 238 pharmacies). A review of data collected in four surveys (1991, 1994, 1996, 2003) on the provision of sterile material (and methadone treatment supervision in 2003) including all the pharmacists of the Canton of Vaud was conducted, as well as a review of data of the monitoring of needle exchange programmes introduced since 1996 in this canton, and of methadone treatment statistics. In 2003, interviews with pharmacists complemented the survey. Pharmacies play an important role in the ‘frontline’ services to drug misusers: the provision of needles/syringes to drug users by pharmacies remains important in spite of a decrease in the provision of sterile material by them since the advent of needle exchange programmes, and they are included in the supervision of two thirds of the methadone treatments. However, they do not feel integrated enough in the network of care to drug misusers and ask for more training and better recognition of their role. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A controlled trial was conducted evaluating cognitive-behavioural group psychotherapy as a measure to reduce concomitant drug use in methadone maintenance treatment (MMT). 73 opiate addicts were randomly assigned to local routine MMT or to routine MMT plus group psychotherapy (20 sessions over 20 weeks). Psychotherapy was delivered by therapists according to a manual. Drug use (urine screen) was compared at onset of psychotherapy, end of intervention period (6 months after study onset), and 6 months later. Data analysis was done according to intention-to-treat principles. Results indicated that patients in the psychotherapy group (n = 41) showed less drug use than control subjects (n = 32). This group difference was statistically significant at 6-month follow-up (p = 0.02). These findings underscore the usefulness of group psychotherapy in MMT. The delayed effect is comparable to other studies evaluating cognitive-behavioural psychotherapy. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Using data from the Public Health Service, we studied the demographic and clinical characteristics of 1,782 patients enrolled in methadone maintenance treatment (MMT) during 2001 in the Swiss Canton of Vaud, comparing our findings with the results of a previous study from 1976 to 1986. In 2001, most patients (76.9%) were treated in general practice. Mortality is low in this MMT population (1%/year). While patient age and sex profiles were similar to those found in the earlier study, we did observe a substantial increase in the number of patients and the number of practitioners treating MMT patients, probably reflecting the low-threshold governmental policies and the creation of specialized centers. In conclusion, easier access to MMT enhances the number of patients, but new concerns about the quality of management emerge: benzodiazepine as a concomitant prescription; low rates of screening for hepatitis B, C and HIV, and social and psychiatric preoccupations. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Methadone maintenance treatment (MMT) has been the ‘gold standard’ pharmacotherapy treatment for illicit opioid dependence for over 30 years. It has been widely evaluated, and is generally claimed to be ‘effective’. Methods: The objective of this paper is to review the rationale of MMT as an intervention for a biomedical disorder with primary social objectives as well as the methodological quality and evidence of MMT outcome research. Data sources included opioid dependence treatment practice, review and outcome research literature (1965–2001) in the form of peer-reviewed articles, books, monographs and reports that are preeminently cited and reviewed international studies on MMT. Results/Data Synthesis: Rigorous and appropriate evaluation (i.e., RCTs, intent-to-treat, patient-centered) methods in MMT evaluations are rare. Evidence of MMT’s effectiveness on primary treatment objectives is mixed and appears to be largely partial and short-term. Positive outcomes may be the result of selection effects of compliant patients and loss in proportion when more rigorous standards of analysis are applied. Conclusions: The quality of existing MMT research, and evidence for its general effectiveness are limited. Key concepts of self-medication and psychiatric comorbidity are largely ignored in MMT treatment and research frameworks, although they may serve to explain MMT’s limited treatment success. Emerging new opioid pharmacotherapies require the fundamental review of the existing MMT paradigm as well as the application of rigorous and appropriate evaluation methods for future treatment. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Although factors associated with successful termination of methadone maintenance treatment (MMT) have been well studied, the question of why certain methadone patients try to taper off methadone while others do not is still unanswered. Those patients who wish to continue MMT should of course be allowed to stay in treatment. However, even if only a small portion of the MMT patients wish to quit maintenance treatment, they should be offered all possible support by the treatment staff to maximize the possibility of a successful outcome. In the present study, we compared two groups of well-functioning MMT patients with respect to background factors, methadone-related factors, drug-related factors and psychological characteristics: one group consisted of patients who were trying to terminate their MMT (group 1) and the other group consisted of patients who were not trying (group 2). Each of the groups contained 25 well-rehabilitated subjects matched by age, gender and the number of years in MMT. The results show that the patients who were not trying to terminate MMT (in comparison to group 1) were not influenced by others to try to quit methadone, had a long history of opiate use as well as mixed drug use prior to MMT, had a higher methadone dose and reported a lower degree of anticipated abstinence symptoms. According to the statements of the subjects in group 2, the most important reason for not quitting treatment was the belief that they needed the methadone. The fact that they knew others who had failed to quit MMT and low confidence in succeeding were other common answers. Further, our results suggest that patients who were satisfied with their overall drug situation were less inclined to make a withdrawal attempt.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Alcohol consumption during methadone maintenance treatment (MMT) often becomes a problem. We investigated a group of 68 patients undergoing MMT in our care. Mean duration of MMT was 50 months. A set of risk factors for problematic alcohol use (‘alcohol indicators’) was set up consisting of patients’ account and laboratory parameters. 52% of patients were positive for these ‘alcohol indicators’ and 32% of patients fulfilled more severe criteria for alcohol abuse. There was exactly the same proportion of patients with ‘alcohol indicators’ at the start of MMT as at follow-up examination. In 79% of these patients ‘alcohol indicators’ were found on both occasions, testifying that alcohol problems were a stable trait. While patients without ‘alcohol indicators’ showed an improvement of liver parameters over time, those with ‘alcohol indicators’ suffered a considerable deterioration, indicating that the amount of alcohol consumption had increased.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Fifty-four methadone-maintained patients and 54 healthy controls, matched for age, gender and educational attainment, completed a battery of six cognitive-psychomotor performance tests. Results of previous studies were replicated in four areas. An attention task was performed less well by patients [mean difference more than 0.7 standard deviations (SD)] as was a tachistoscopic perception task (0.3 SD). On a simple-choice reaction test, patients showed higher speed in decision making and motor reaction as well as an increased number of decision errors (0.3 SD each). Performing a tracking test, patients showed less deviations (0.4 SD) combined with more time needed (0.8 SD). Our data go beyond previous (seemingly inconsistent) research findings by showing that patients did less well by more than 0.6 SD when on higher speed levels. Absolving a test on visual structuring, more patients than controls achieved a 100% accuracy level (52 vs. 30%), but at the same time patients were slower (0.6 SD) than controls. An inferior test performance of patients in methadone maintenance treatment has been confirmed in some areas, especially in attention. However, the fairly moderate size of these effects and the fact that in the majority of measures the observed variance was better explained by sociodemographic features than by group membership lead on the conclusion that belonging to the group of methadone patients alone is not necessarily sufficient to predict an impairment in cognitive-psychomotor skills. To conclude, assessment of fitness for certain tasks or occupations should be done individually for each patient and should take into account comorbidity, including the extent of alcohol and other drug use.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The clinical effectiveness of l-methadone maintenance treatment (LMMT) carried out using d,l-methadone or l-methadone have been compared with ambulatory heroin-dependent subjects. A total of 40 heroin-dependent subjects, previously maintained on l-methadone in Frankfurt am Main, were divided into two groups under randomised double-blind conditions and received either an equivalent dose of l-methadone as d,l-methadone or remained on the previous l-methadone treatment. Requests for a change in the dose of d,l-methadone and l-methadone were recorded, urine samples for determination of illicit drug use were collected and the individual level of opiate craving was determined over a 22-day observation period. There was no significant difference between the two groups in the number requests for a dose change (dose increase <10%). However, there was a significant increase in heroin use in the group which continued to receive l-methadone. Although there was less variability in opiate craving in the group receiving d,l-methadone, the mean intensity of opiate craving did not differ between the two groups. The mean l-methadone dose:l-methadone plasma concentration ratio, an index of the bioavailability of l-methadone in individual subjects, showed no significant change when the treatment was changed to d,l-methadone. The mean d-methadone:l-methadone plasma concentration ratio was 1.17. There was no significant difference between these ratios for day 15 and day 22. The mean l-methadone:EDDP plasma concentration ratio in the l-methadone group was 22.2 and the d,l-methadone:EDDP plasma concentration ratio was 18.4 . The plasma EDDP concentration in the d,l-methadone group increased 3-fold after starting treatment with d,l-methadone. These findings suggest that d,l-methadone can be used in methadone maintenance treatment of heroin-dependent subjects but that further studies are required to evaluate pharmacokinetic interactions between methadone enantiomers. [ABSTRACT FROM AUTHOR]