Patients In Heroin-assisted Treatment Research Articles

Exploring why patients in heroin-assisted treatment are getting incarcerated\u2014a qualitative study

BackgroundHeroin-assisted treatment has proven effective in reducing criminal offenses in opioid dependent individuals. Few studies attempted to explain the observed crime reduction and the reasons why these patients keep offending and getting incarcerated have to date not been explored.MethodsPatients with a history of incarcerations during the time of participating in heroin-assisted treatment (n = 22) were invited to a semi-structured, narrative interview. Findings were evaluated with Mayring’s qualitative content analysis framework. Additionally, the Montreal Cognitive Assessment test and the multiple-choice vocabulary intelligence test used to assess cognitive impairment and premorbid intelligence levels.ResultsThree main categories emerged in patients’ narratives on their incarcerations: cocaine use, impaired functioning, and financial constraints. Lifetime prevalence of cocaine use disorder was 95.5% and their cocaine use often led to patients getting incarcerated. Impaired functioning mainly constituted the inability to receive and open mail. Financial constraints led to incarcerations in lieu of payment in 16 participants (72.7%). Categories overlapped notably and often occurred in close temporal proximity. A fourth category on the likelihood of getting incarcerated again in the future was inhomogeneous and ranged from the strong conviction to complete rejection of the scenario. Average premorbid intelligence levels were found, whereas the cognitive assessment suggested severe cognitive impairment in our sample.ConclusionParticipants mainly reported to have committed minor offenses and not being able to pay for resulting fines. The resulting prison sentences are an unconvincing practice from a medical and economic perspective alike. Public expenditure and the interruptions of the continuum of care could be reduced by legislatively protecting these marginalised patients.

Heroin-assisted treatment of heroin-addicted patients normalizes regulatory T cells but does not restore CD4+ T cell proliferation.

Heroin dependence may result in suppression of adaptive immune responses. Previously, we demonstrated an increase in relative numbers of inhibitory CD4+ regulatory T cells (Tregs) and impaired proliferative activity of CD4+ T cells from heroin-addicted patients in contrast to patients in opioid maintenance therapy and healthy controls. However, it remains elusive whether heroin has a direct impact on the CD4+ T cell compartment or whether observed effects result from stressful living conditions. Here, we analyzed the frequencies of Tregs and the proliferation as well as the cytokine production of stimulated CD4+ T cells from heroin-addicted patients with use of illicit heroin, patients in heroin-assisted treatment (HAT), and patients in methadone maintenance therapy (MMT). Relative numbers of CD4+ Tregs were significantly enhanced in patients with illicit heroin abuse compared with patients in HAT or MMT. Notably, CD4+ T cells from patients in HAT and from persons using illicit heroin showed significant reduced proliferation and secretion of the pro-inflammatory cytokines IFN-γ and IL-6 upon stimulation in vitro. From these results, we conclude that structured programs such as HAT and MMT dampen elevated frequencies of Tregs in heroin-addicted patients, whereas chronic heroin administration irrespective of using illicit heroin or receiving HAT has a direct impact on the proliferative activity and cytokine production of CD4+ T cells.

Patients with non-substance-related disorders report a similar profile of childhood trauma experiences compared to heroin-dependent patients.

Exposure to traumatic events is common among patients with substance use disorders (SUD). In patients with non-substance-related disorders, especially with gambling disorders (GD) and internet addiction (IA), traumatic childhood experiences have not been investigated extensively. The objective of this study was to compare trauma histories in patients with GD and IA to patients with heroin dependence. Cross-sectional surveys including the childhood trauma questionnaire (CTQ) and clinical data among 107 participants; 59 patients with non-substance-related disorders (GD [n = 39]; IA [n = 20]) were compared to 28 patients prescribed injectable heroin for opioid dependence in heroin-assisted treatment (HAT) and to a healthy control group (HC) (n = 20). The findings revealed a high prevalence of trauma exposure in all three clinical groups, with 74.4% of patients with GD, 80.0% of patients with IA, and 93.0% of patients in HAT compared to 40% in HC. All three groups (GD, IA, HAT) reported significantly higher levels of "emotional neglect" compared to HC. The results provide clinically relevant information suggesting that the burden of childhood traumatic experiences may be as common in patients with GD and IA as in patients with heroin dependence. These findings could pose an important starting-point for treatment. (Am J Addict 2017;26:215-220).

A pilot randomized trial of exercise as adjunct therapy in a heroin-assisted treatment setting

BackgroundAlthough the potential of exercise as an adjunct treatment for substance dependence is persuasive in theory, few controlled trials have assessed its effectiveness. Existing research has also largely focused on individuals aiming towards, or having already achieved, abstinence. This study employed a randomized design in a pilot trial to assess the feasibility, acceptance, and effects of an exercise intervention for individuals receiving outpatient heroin-assisted treatment. Method50 individuals receiving heroin-assisted treatment at a clinic in Switzerland were invited to take part in the trial. Participants were randomized to 12weeks of exercise twice per week, or a corresponding duration of non-exercise group activities in a comparison condition. Data on attendance, compliance, and numerous psychological and physiological parameters were gathered. Results24 individuals were willing to take part in the study. 92.3% of the exercise condition (n=13) were compliant or semi-compliant with the protocol; by contrast, only 54.6% of participants in the comparison condition (n=11) were compliant or semi-compliant (χ2=7.049; p=0.029). Participants in the exercise condition significantly increased the number of minutes spent exercising at a high intensity level (F(2,44)=3.794; p=0.046; η2=0.159). No other significant interaction effects were observed. ConclusionsAn exercise intervention is a feasible and accepted supplementary therapy to heroin-assisted treatment. Participation rates were high, particularly given the outpatient setting. No evidence regarding the potential mechanisms of exercise as a therapy modality could be identified. Patients in heroin-assisted treatment may require a longer-term exercise programme, specifically targeting particular health parameters, before measurable improvements can be observed.

Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence

BackgroundHeroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence. MethodsGenetic information from four subject groups was collected: non-dependent opioid users (NOD) [n=163]; opioid-dependent (OD) patients in methadone maintenance treatment (MMT) [n=143]; opioid-dependent MMT-resistant patients in heroin-assisted treatment (HAT) [n=138]; and healthy controls with no history of opioid use (HC) [n=153]. Eighty-two variants in eight opioid system genes were studied. To establish the role of these genes in (a) non-dependent opioid use, and (b) heroin dependence, the following groups were compared: HC vs. NOD; HC vs. OD (MMT+HAT); and NOD vs. OD (MMT+HAT). ResultsFive unique SNPs in four genes showed nominally significant associations with non-dependent opioid use and heroin dependence. The association of the delta opioid receptor (OPRD1) intronic SNP rs2236861 with non-dependent opioid use (HC vs. NOD) remained significant after correction for multiple testing (OR=0.032; pcorrected=0.015). This SNP exhibited a significant gene–gene interaction with prepronociceptin (PNOC) SNP rs2722897 (OR=5.24; pcorrected=0.041) (HC vs. NOD). ConclusionsThis study identifies several new and some previously reported associations of variants with heroin dependence and with non-dependent opioid use, an important and difficult to obtain group not extensively studied previously. Further studies are warranted to confirm and elucidate the potential roles of these variants in the vulnerability to illicit drug use and drug addiction.

Efficacy of cocaine contingency management in heroin-assisted treatment: Results of a randomized controlled trial

AimsTo determine the efficacy of contingency management (CM), targeting cocaine use, as an add-on intervention for heroin dependent patients in supervised heroin-assisted treatment (HAT) with frequent cocaine use. DesignMulti-center, open-label, parallel group, randomized controlled trial. SettingTwelve specialized addiction treatment centers for HAT in The Netherlands; April 2006–January 2011. Participants214 chronic, treatment-refractory heroin dependent patients in HAT, with frequent cocaine use. InterventionsRoutine, daily supervised diacetylmorphine treatment, co-prescribed with oral methadone (HAT), with and without 6 months contingency management for cocaine use as an add-on intervention; HAT+CM and HAT-only, respectively. MeasurementsPrimary outcome was the longest, uninterrupted duration of cocaine abstinence, based upon laboratory urinalysis. Secondary outcome measures included other cocaine-related measures, treatment retention in HAT, and multi-domain health-related treatment response. FindingsIn an intention-to-treat analysis, HAT+CM was more effective than HAT-only in promoting longer, uninterrupted duration of cocaine abstinence (3.7 weeks versus 1.6 weeks; negative binomial regression: Exp(B)=2.34, 95%-CI: 1.70–3.23; p<0.001). This result remained significant in sensitivity analyses and was supported by all secondary, cocaine-related outcome measures. Treatment retention in HAT was high (91.6%) with no difference between the groups. The improvement in multi-domain health-related treatment response during the trial was numerically higher in HAT+CM (from 37.4% to 53.1%; +15.7%) than in HAT-only (from 44.5% to 46.5%; +2.0%), but this difference was statistically not significant. ConclusionsContingency management is an effective add-on intervention to promote longer, uninterrupted periods of cocaine abstinence in chronic, treatment-refractory heroin dependent patients in heroin-assisted treatment with frequent cocaine use.The trial has been registered in The Netherlands National Trial Register under clinical trial registration number NTR4728.

Sustained-release dexamfetamine in the treatment of chronic cocaine-dependent patients on heroin-assisted treatment: a randomised, double-blind, placebo-controlled trial.

Heroin-assisted treatment is effective for methadone treatment-refractory heroin-dependent patients, but continued comorbid cocaine dependence remains problematic. Sustained-release dexamfetamine is a promising agonist pharmacotherapy for cocaine dependence and we aimed to assess its acceptance, efficacy, and safety. In this multicentre, randomised, double-blind, placebo-controlled trial, patients who were treatment-refractory, as indicated by at least two earlier failed treatments aimed at reducing or abstaining from cocaine use, and who regularly (≥8 days/month) used crack-cocaine were enrolled from four heroin-assisted treatment centres in the Netherlands. Eligible patients were randomly assigned (1:1) to receive either 12 weeks of daily, supervised prescription of 60 mg/day oral sustained-release dexamfetamine or placebo in addition to co-prescribed methadone and diacetylmorphine. Randomisation was done by the collaborating pharmacist, using a computer-generated random number sequence with stratification by treatment centre in blocks of four per stratum. Randomisation was masked to patients, staff, and researchers throughout the study. The primary outcome was the number of self-reported days of cocaine use during study treatment, assessed every 4 weeks. Primary and safety analyses were done in the intention-to-treat population. The study was registered with the European Union Drug Regulating Authorities Clinical Trials (EUdraCT 2013-004024-11) and with The Netherlands Trial Register (NTR2576). Between Aug 8, 2014, and Feb 27, 2015, 111 patients were assessed for eligibility, of whom 73 were enrolled and randomised; 38 patients were assigned to the sustained-release dexamfetamine group and 35 to the placebo group. Sustained-release dexamfetamine treatment resulted in significantly fewer days of cocaine use than placebo treatment (mean 44·9 days [SD 29·4] vs 60·6 days [24·3], respectively [95% CI of difference 3·1-28·4]; p=0·031; Cohen's standardised effect size d=0·58). One or more adverse events were reported by 28 (74%) patients in the dexamfetamine group and by 16 (46%) patients in the placebo group. Most adverse events were transient and well-tolerated. Sustained-release dexamfetamine is a well accepted, effective, and safe agonist pharmacotherapy for comorbid treatment-refractory cocaine dependence in heroin-dependent patients in heroin-assisted treatment. Future research should aim to replicate these findings in chronic cocaine-dependent and other stimulant-dependent patients in more routine treatment settings, including strategies to optimise treatment adherence like medication management interventions and contingency management. Netherlands Organisation for Health Research and Development.

Effective drug therapy for cocaine dependence: a milestone.

In The Lancet, Mascha Nuijten and colleagues 1 Nuijten M Blanken P van de Wetering B Nuijen B van den Brink W Hendriks VM Sustained-release dexamfetamine in the treatment of chronic cocaine-dependent patients on heroin-assisted treatment: a randomised, double-blind, placebo-controlled trial. Lancet. 2016; (published online March 22.)http://dx.doi.org/10.1016/S0140-6736(16)00205-1 Google Scholar present the results of a multicentre, randomised, double-blind, placebo-controlled trial assessing the acceptance, safety, and efficacy of sustained-release dexamfetamine in cocaine-dependent patients on heroin-assisted treatment. The study findings showed that 60 mg/day oral sustained-release dexamfetamine over 12 weeks was well accepted, safe, and superior to placebo in terms of days of cocaine use (mean 44·9 days [SD 29·4] in the sustained-release dexamfetamine group vs 60·6 days [24·3] in the placebo group [95% CI of difference 3·1–28·4]; p=0·031; Cohen's standardised effect size d=0·58) and all self-reported and urine-based cocaine use-related outcomes. Cocaine dependence is prevalent throughout the world and causes major morbidity and mortality. 2 Degenhardt L Hall W Extent of illicit drug use and dependence, and their contribution to the global burden of disease. Lancet. 2012; 379: 55-70 Summary Full Text Full Text PDF PubMed Scopus (868) Google Scholar At present, no effective pharmacotherapy exists. Agonist replacement therapy has been successfully applied to opioid and tobacco dependence, 3 Strain EC Bigelow GE Liebson IA Stitzer ML Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial. JAMA. 1999; 281: 1000-1005 Crossref PubMed Scopus (359) Google Scholar , 4 Aubin HJ Luquiens A Berlin I Pharmacotherapy for smoking cessation: pharmacological principles and clinical practice. Br J Clin Pharmacol. 2014; 77: 324-336 Crossref PubMed Scopus (73) Google Scholar but previous studies examining this approach in cocaine dependence failed to find statistically significant benefits in terms of reduced cocaine use, or showed indecisive results. This could be due to limitations in the methods, such as small sample sizes, 5 Shearer J Wodak A van Beek I Mattick RP Lewis J Pilot randomized double blind placebo-controlled study of dexamphetamine for cocaine dependence. Addiction. 2003; 98: 1137-1141 Crossref PubMed Scopus (120) Google Scholar inadequate dosing schemes, 6 Dursteler KM Berger EM Strasser J et al. Clinical potential of methylphenidate in the treatment of cocaine addiction: a review of the current evidence. Subst Abuse Rehabil. 2015; 6: 61-74 Crossref PubMed Google Scholar or large attrition rates. 7 Grabowski J Rhoades H Stotts A et al. Agonist-like or antagonist-like treatment for cocaine dependence with methadone for heroin dependence: two double-blind randomized clinical trials. Neuropsychopharmacology. 2004; 29: 969-981 Crossref PubMed Scopus (168) Google Scholar The study by Nuijten and colleagues 1 Nuijten M Blanken P van de Wetering B Nuijen B van den Brink W Hendriks VM Sustained-release dexamfetamine in the treatment of chronic cocaine-dependent patients on heroin-assisted treatment: a randomised, double-blind, placebo-controlled trial. Lancet. 2016; (published online March 22.)http://dx.doi.org/10.1016/S0140-6736(16)00205-1 Google Scholar overcomes most of these shortcomings. Sustained-release dexamfetamine in the treatment of chronic cocaine-dependent patients on heroin-assisted treatment: a randomised, double-blind, placebo-controlled trialSustained-release dexamfetamine is a well accepted, effective, and safe agonist pharmacotherapy for comorbid treatment-refractory cocaine dependence in heroin-dependent patients in heroin-assisted treatment. Future research should aim to replicate these findings in chronic cocaine-dependent and other stimulant-dependent patients in more routine treatment settings, including strategies to optimise treatment adherence like medication management interventions and contingency management. Full-Text PDF

Acute Effects of Intravenous Heroin on the Hypothalamic-Pituitary-Adrenal Axis Response

Heroin dependence is associated with a stressful environment and with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. The present study examined the acute effects of intravenous heroin versus placebo on the HPA axis response in heroin-dependent patients. Twenty-eight heroin-dependent patients in heroin-assisted treatment and 20 age- and sex-matched healthy participants were included in a controlled trial in which patients were twice administered heroin or saline in a crossover design, and healthy controls were only administered saline. The HPA axis response was measured by adrenocorticotropic hormone (ACTH) levels and by cortisol levels in serum and saliva before and 20 and 60 minutes after substance administration. Craving, withdrawal, and anxiety levels were measured before and 60 minutes after substance application. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography. Heroin administration reduces craving, withdrawal, and anxiety levels and leads to significant decreases in ACTH and cortisol concentrations (P < 0.01). After heroin administration, cortisol concentrations did not differ from healthy controls, and ACTH levels were significantly lower (P < 0.01). In contrast, when patients receive saline, all hormone levels were significantly higher in patients than in healthy controls (P < 0.01). Heroin-dependent patients showed a normalized HPA axis response compared to healthy controls when they receive their regular heroin dose. These findings indicate that regular opioid administration protects addicts from stress and underscore the clinical significance of heroin-assisted treatment for heroin-dependent patients.

Craving and illicit heroin use among patients in heroin-assisted treatment

Aims To investigate in heroin-assisted treatment (HAT) compared to methadone maintenance treatment (MMT): the course of heroin craving and illicit heroin use, their mutual association, and their association with multi-domain treatment response. Design RCTs on the efficacy of 12 months co-prescribed injectable or inhalable HAT compared to 12 months continued oral MMT. Setting Outpatient treatment in MMT- or specialized HAT-centers in the Netherlands. Participants Chronic, treatment-refractory heroin dependent patients ( n = 73). Study parameters General craving for heroin (Obsessive Compulsive Drug Use Scale); self-reported illicit heroin use; multi-domain treatment response in physical, mental and social health and illicit drug use. Findings The course of heroin craving and illicit heroin use differed significantly, with strong reductions in HAT but not in MMT. General heroin craving was significantly related to illicit heroin use. Heroin craving was not and illicit heroin use was marginally related to multi-domain treatment response, but only in MMT and not in HAT. Conclusions Heroin craving and illicit heroin use were significantly associated and both strongly decreased in HAT but not in MMT. Craving was not related to multi-domain treatment response and illicit heroin use was marginally related to treatment response in MMT, but not in HAT. The latter was probably due to the strong reduction in illicit heroin use in most patients in HAT and the small sample size of the sub-study. It is hypothesized that the strong reductions in craving for heroin in HAT are related to the stable availability of prescribed, pharmaceutical grade heroin.

Optimizing heroin-assisted treatment (HAT): Assessment of the contribution of direct ethanol metabolites in identifying hazardous and harmful alcohol use

Heavy alcohol consumption may accelerate the progression of hepatitis C-related liver disease and/or limit efforts at antiviral treatment in opioid-dependent patients receiving heroin-assisted treatment (HAT). Our study aims to assess alcohol intake among HAT patients by self-reports compared to direct ethanol metabolites. Fifty-four patients in HAT were recruited from the centre for HAT at the University of Basel, Switzerland. The patients completed the Alcohol Use Disorder Identification Test (AUDIT), a self-report questionnaire on past-week ethanol intake and provided samples for the determination of ethyl glucuronide (UEtG) and ethyl sulphate (UEtS) in urine and of ethyl glucuronide (HEtG) in hair. Eighteen patients scored above the AUDIT cut-off levels. Twenty-six patients tested positive for UEtG and 29 for UEtS. HEtG identified ethanol intake of more than 20 g/d in 20 additional cases that did not appear in the AUDIT. Using the total score of the AUDIT, HEtG detected 14 additional cases of relevant alcohol intake. The findings of this study, which is the first assessing alcohol intake in HAT patients using direct ethanol metabolites and self reports, suggest the complementary use of both. Improved detection of hazardous or harmful alcohol consumption in the context of HCV and heroin dependence will allow for earlier intervention in this population. This ultimately will contribute to an improvement in quality of life of patients in HAT. Furthermore, a significant reduction of costs can be achieved through a reduction of complications caused by alcohol intake.

Deuterodiacetylmorphine as a Marker for Use of Illicit Heroin by Addicts in a Heroin-Assisted Treatment Program

In preparation for a treatment program concerning the medical coprescription of heroin and methadone to treatment-resistant addicts in the Netherlands, we studied a novel strategy for monitoring co-use of illicit (nonprescribed) heroin. A deuterated analogue of heroin was added (1:20) to pharmaceutical, smokable heroin (a powder mixture of 75% w/w diacetylmorphine base and 25% w/w caffeine anhydrate), to be used by inhalation after volatilization ("chasing the dragon"). Plasma and urine samples were collected from nine male patients who had used pharmaceutical, smokable heroin during a four-day stay in a closed clinical research unit, and these samples were analyzed by liquid chromatography coupled with tandem mass spectrometry. Ratios of deuterated and undeuterated diacetylmorphine and 6-acetylmorphine (MAM/MAM-d3) in plasma and urine were calculated from peak areas of these substances in the respective chromatograms. The MAM/MAM-d3 ratios in plasma and urine were normally distributed (with small standard deviations) and independent from concentrations of 6-acetylmorphine and from time after use of pharmaceutical heroin. A MAM/MAM-d3 ratio in urine above 32.8 was considered indicative of co-use of illicit heroin, and this value was associated with a false-positive rate of only 1% (95% confidence interval: -1 to 3%). The MAM/MAM-d3 ratio was detectable in urine for 4-9.5 h after use of pharmaceutical, smokable heroin. Addition of stable, isotopically labelled heroin to pharmaceutical, smokable heroin is considered to be a feasible strategy for the detection of co-use of illicit heroin by patients in heroin-assisted treatment.

Mortality in heroin-assisted treatment in Switzerland 1994–2000

Background: A major goal of heroin-assisted treatment in Switzerland has been to reduce the drug-related mortality of heroin users. Therefore, a continuous monitoring of deaths under treatment is essential. Aims: To assess mortality of participants in heroin-assisted treatment in Switzerland over a 7-year period from 1994 to 2000, and to compare this mortality to the general population and to other populations of opioid users, as reported in the literature. Method: Estimation of person years under heroin-assisted treatment from the complete case registry of heroin-assisted treatment in Switzerland. Estimation of standardized mortality ratios comparing the population in treatment to the Swiss population (standardized to the year 2000). Results: Over the 7-year period, the crude death rate of patients in heroin-assisted treatment, and including one month after discharge from treatment, was 1% per year. The standardized mortality ratio for the entire observation period was 9.7 (95% C.I. 7.3–12.8), with females having higher standardized mortality ratios (SMR 17.2) than males (SMR 8.4). There was no clear time trend. Conclusion: Mortality in heroin-assisted treatment was low compared to the mortality rate of Swiss opioid users 1990s (estimated to be between 2.5 and 3%). It was also low compared to mortality rates of opioid users in other maintenance treatments in other countries as reported in the literature. The SMR was also lower than that reported in the only meta-analysis in the literature: 13.2 (95% C.I. 12.3–14.1). The low mortality rate is all the more noteworthy as heroin-assisted treatment in Switzerland included only refractory opioid addicts with existing severe somatic and/or mental problems. Declaration of interest: No conflicts of interest declared

S.25.04 Matching treatment to patients in heroin assisted treatment of methadone resistant heroin dependent patients: Results of two randomised controlled trials

S.25.04 Matching treatment to patients in heroin assisted treatment of methadone resistant heroin dependent patients: Results of two randomised controlled trials