A randomized controlled trial of interim methadone maintenance

CONTEXT: Effective alternatives to long waiting lists for entry into methadone hydrochloride maintenance treatment are needed to reduce the complications of continuing heroin dependence and to increase methadone treatment entry. OBJECTIVE: To compare the effectiveness of interim methadone maintenance with that of the usual waiting list condition in facilitating methadone treatment entry and reducing heroin and cocaine use and criminal behavior. DESIGN: Randomized, controlled, clinical trial using 2 conditions, with treatment assignment on a 3:2 basis to interim maintenance-waiting list control. SETTING: A methadone treatment program in Baltimore. PARTICIPANTS: A total of 319 individuals meeting the criteria for current heroin dependence and methadone maintenance treatment. INTERVENTIONS: Participants were randomly assigned to either interim methadone maintenance, consisting of an individually determined methadone dose and emergency counseling only for up to 120 days, or referral to community-based methadone treatment programs. MAIN OUTCOME MEASURES: Entry into comprehensive methadone maintenance therapy at 4 months from baseline; self-reported days of heroin use, cocaine use, and criminal behavior; and number of urine drug test results positive for heroin and cocaine at the follow-up interview conducted at time of entry into comprehensive methadone treatment (or at 4 months from baseline for participants who did not enter regular treatment). RESULTS: Significantly more participants assigned to the interim methadone maintenance condition entered comprehensive methadone maintenance treatment by the 120th day from baseline (75.9%) than those assigned to the waiting list control condition (20.8%) (P<.001). Overall, in the past 30 days at follow-up, interim participants reported significantly fewer days of heroin use (P<.001), had a significant reduction in heroin-positive drug test results (P<.001), reported spending less money on drugs (P<.001), and received less illegal income (P<.02) than the waiting list participants. CONCLUSION: Interim methadone maintenance results in a substantial increase in the likelihood of entry into comprehensive treatment, and is an effective means of reducing heroin use and criminal behavior among opioid-dependent individuals awaiting entry into a comprehensive methadone treatment program.     

Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone

BACKGROUND: Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and effective pharmacotherapies are needed for this combined dependence. METHODS: This 13-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of desipramine hydrochloride (0 or 150 mg/d) plus buprenorphine hydrochloride (12 mg/d) or methadone hydrochloride (65 mg/d) in 180 opioid-dependent cocaine abusers (124 men, 56 women). Supervised urine samples were obtained thrice weekly, and self-reported cocaine and heroin use was reported once weekly. Desipramine plasma levels were determined at weeks 4 and 10. RESULTS: In men, opioid abstinence was increased more rapidly over time when treated with methadone than with buprenorphine, whereas cocaine abstinence was increased more with buprenorphine than with methadone. In women, opioid abstinence was increased the least rapidly when treated with buprenorphine plus placebo, while cocaine abstinence was increased more rapidly over time when treated with methadone than with buprenorphine. Regardless of sex or opioid medication, desipramine increased opioid and cocaine abstinence more rapidly over time than placebo. Self-reported opioid use confirmed these findings. Desipramine plasma levels were higher in women than in men, particularly those on buprenorphine maintenance. Higher desipramine plasma levels were associated with greater opioid, but not cocaine, abstinence. CONCLUSIONS: Desipramine may be a useful adjunctive medication in facilitating opioid and cocaine abstinence in opioid-maintained patients. The efficacy of opioid medications to treat opioid or cocaine dependence may differ by sex. These findings highlight the importance of including sex as a factor when examining treatment outcome in these types of trials.     

Buprenorphine and methadone maintenance treatment of heroin addicts preserves immune function

Opiate addiction influences many physiological functions including immune responses. The objective of this study was to investigate the immune system function in heroin addicted patients submitted to methadone or buprenorphine maintenance treatment compared to untreated heroin addicts and healthy controls. Four groups were studied: group A included nine heroin addicted subjects, who were still injecting heroin; groups B and C were composed of 12 patients previously addicted to heroin, being treated with methadone (mean dosage 58+/-12.7 mg/day) or buprenorphine (mean dose 9.3+/-2.3mg/day) since at least 6 months; group D was composed of 15 sex and age matched healthy controls. Lymphoproliferation and peripheral mononuclear cell cultures production of the Th1 cytokines IL-2 and IFN-gamma, the Th2 cytokine IL-4, and of the pro-inflammatory cytokine TNF-alpha were evaluated in all the patients and controls. PHA-lymphoproliferation was lower in untreated heroin addicts than in controls, while it was normal in methadone and buprenorphine treated patients. An altered Th1/Th2 balance, characterized by reduced IL-4, IFN-gamma and TNF-alpha but normal IL-2 levels, was present in untreated heroin addicted subjects, while the Th1/Th2 balance was well conserved in the methadone and buprenorphine groups. These findings suggest that the immune system abnormalities in heroin addicted patients can be restored to almost normal values by controlled treatment with methadone and buprenorphine.     

Thrice-weekly versus daily buprenorphine maintenance.

BACKGROUND: Buprenorphine is a promising alternative to methadone or levo-acetyl alpha methadol for opioid agonist maintenance treatment, and thrice-weekly dosing would facilitate its use for this purpose. METHODS: After a 3-day induction, opioid-dependent patients (n = 92) were randomly assigned to daily clinic attendance and 12-weeks maintenance treatment with sublingual buprenorphine administered double blind either daily (n = 45; 16 mg/70 kg) or thrice weekly (n = 47; 34 mg/70 kg on Fridays and Sundays and 44 mg/70 kg on Tuesdays). Outcome measures include retention, results of 3x/week urine toxicology tests, and weekly self-reported illicit drug use. RESULTS: There were no significant differences at baseline in important social, demographic, and drug-use features. Retention was 71% in the daily and 77% in the 3x/week conditions. The proportion of opioid-positive urine tests decreased significantly from baseline in both groups and averaged 57% (daily) and 58% in 3x/week. There were no significant differences between groups in self-reported number of bags of heroin used for any day of the week, including Thursdays (48-72 hours following the last buprenorphine dose for subjects in the 3x/week condition), or in medication compliance (92%, 91%) and counseling attendance (82%, 82%). CONCLUSIONS: At an equivalent weekly dose of 112 mg/70 kg, thrice-weekly and daily sublingual buprenorphine appear comparable in efficacy with regard to retention and reductions in illicit opioid and other drug use. These findings support the potential for utilizing thrice-weekly buprenorphine dosing in novel settings.     

Acute effect of methadone maintenance dose on brain FMRI response to heroin-related cues

OBJECTIVE: Environmental drug-related cues have been implicated as a cause of illicit heroin use during methadone maintenance treatment of heroin dependence. The authors sought to identify the functional neuroanatomy of the brain response to visual heroin-related stimuli in methadone maintenance patients. METHOD: Event-related functional magnetic resonance imaging was used to compare brain responses to heroin-related stimuli and matched neutral stimuli in 25 patients in methadone maintenance treatment. Patients were studied before and after administration of their regular daily methadone dose. RESULTS: The heightened responses to heroin-related stimuli in the insula, amygdala, and hippocampal complex, but not the orbitofrontal and ventral anterior cingulate cortices, were acutely reduced after administration of the daily methadone dose. CONCLUSIONS: The medial prefrontal cortex and the extended limbic system in methadone maintenance patients with a history of heroin dependence remains responsive to salient drug cues, which suggests a continued vulnerability to relapse. Vulnerability may be highest at the end of the 24-hour interdose interval.     

Buprenorphine in pregnancy

The treatment of opioid dependence during pregnancy is a major challenge for doctors, social workers and gynaecologists. Continuous drug abuse during pregnancy can lead to a variety of complications in the mother, fetus and neonate. lt is recommended practice to maintain pregnant opioid-dependent women with synthetic opioids and according to international guidelines, methadone is the recommended substance so far. However, a neonatal abstinence syndrome (NAS) of varying severity is observed in 60 - 80 % of the neonates with even a longer course of duration in comparison to the NAS after heroin consumption during pregnancy. NAS is characterised by tremor, irritability, hypertonicity, vomiting, sneezing, fever, poor suckling, and sometimes convulsions. Recent studies have investigated the safety and efficacy of other synthetic opioids like sublingual buprenorphine for the treatment of pregnant patients. We present a 22 year old opioid-dependent woman, who has been maintained continuously on buprenorphine for 3 years. During the treatment episode she delivered two healthy newborns and both did not show any symptoms of NAS. The maintenance therapy with buprenorphine proved safety and efficacy during pregnancy, the mother was free of continuous heroin abuse, verified through supervised urine-toxicology. The quantitative and qualitative difference in NAS may be explained by the partial mu-receptor agonist and kappa-antagonist receptor profile of buprenorphine compared to pure mu-agonist action of methadone or heroin.     

Methadone versus buprenorphine with contingency management or performance feedback for cocaine and opioid dependence

OBJECTIVE: Physicians may prescribe buprenorphine for opioid agonist maintenance treatment outside of narcotic treatment programs, but treatment guidelines for patients with co-occurring cocaine and opioid dependence are not available. This study compares effects of buprenorphine and methadone and evaluates the efficacy of combining contingency management with maintenance treatment for patients with co-occurring cocaine and opioid dependence. METHOD: Subjects with cocaine and opioid dependence (N=162) were provided manual-guided counseling and randomly assigned in a double-blind design to receive daily sublingual buprenorphine (12-16 mg) or methadone (65-85 mg p.o.) and to contingency management or performance feedback. Contingency management subjects received monetary vouchers for opioid- and cocaine-negative urine tests, which were conducted three times a week; voucher value escalated during the first 12 weeks for consecutive drug-free tests and was reduced to a nominal value in weeks 13-24. Performance feedback subjects received slips of paper indicating the urine test results. The primary outcome measures were the maximum number of consecutive weeks abstinent from illicit opioids and cocaine and the proportion of drug-free tests. Analytic models included two-by-two analysis of variance and mixed-model repeated-measures analysis of variance. RESULTS: Methadone-treated subjects remained in treatment significantly longer and achieved significantly longer periods of sustained abstinence and a greater proportion drug-free tests, compared with subjects who received buprenorphine. Subjects receiving contingency management achieved significantly longer periods of abstinence and a greater proportion drug-free tests during the period of escalating voucher value, compared with those who received performance feedback, but there were no significant differences between groups in these variables during the entire 24-week study. CONCLUSIONS: Methadone may be superior to buprenorphine for maintenance treatment of patients with co-occurring cocaine and opioid dependence. Combining methadone or buprenorphine with contingency management may improve treatment outcome.     

行为列联管理在美沙酮维持治疗者中的疗效:一项随机对照研究(英文)

背景为了应对海洛因依赖的严重后果,我国开展了美沙酮维持治疗(methadone maintenance treatment,MMT)项目,但是MMT依从性差。目的评估在美沙酮维持治疗中行为列联管理(contingency management,CM)对阿片类药物依赖者的作用。假设在上海市常规MMT项目基础上结合以奖励机制为基础的CM干预共12周,可提高MMT治疗依从性和增加操守程度。方法来自于3个自愿戒毒MMT门诊的160名海洛因依赖者被随机分入常规治疗组(MMT,n=80)和干预组(MMT+CM,n=80),在前12周每周评估患者的服药行为并进行尿液的毒品检测,随后在第16、20和24周分别进行上述评估检测。结果干预组和常规治疗组完成12周治疗的比例都很高,分别为87.5%和86.2%。12周中,两组服用美沙酮的平均天数差异无统计学意义[70(2.9)d与71(2.7)d],两组未吸海洛因的最长时间(分别为7.4周与6.5周)以及尿检阴性的次数(分别为7.9次与7.6次)也没有明显差异。同样,根据24周的分析提示两组间差异也无统计学意义。用成瘾严重程度指数评估成瘾程度,24周内两组完成随访者的成瘾严重程度都显著下降,但是两组间比较同样无明显差异。结论在我国上海的MMT门诊,以奖励机制为基础的行为列联管理干预并未起到提高治疗依从性和促进保持操守的作用。这与西方研究结果不同。究其原因,一是基线依从性高(86%),二是CM项目提供的奖励相对少。在CM项目中奖励是与场景相关的,因而需要对场景进行仔细的分析,了解在特定场景采用什么特定的奖励措施,以便鼓励目标人群改变行为。     

Opioid maintenance therapy suppresses alcohol intake in heroin addicts with alcohol dependence: preliminary results of an open randomized study

An open randomized study lasting 12 months was performed to evaluate the efficacy of methadone or buprenorphine to suppress alcohol use in two hundred and eighteen heroin addicts with alcohol dependence. Daily maintenance doses of methadone were 80, 120, 160, and 200 mg/day, while doses of buprenorphine were 8, 16, 24, and 32 mg/day.As expected, both treatments were able to reduce both heroin use and addiction severity (measured with ASI interview). However, although both medications were able to suppress alcohol use, the highest dose of buprenorphine was better than the highest dose of methadone, in reducing alcohol craving, ethanol intake (measured as daily number of drinks), and the ASI subscale of alcohol use.The mechanism underlying the effects of the opioid maintenance therapy on the reduction of alcohol intake is still unclear.The results of the present study may represent the first clinical evidence of the potential effective use of the highest doses of buprenorphine for the suppression of ethanol intake in heroin addicts with alcohol dependence.     

Depressive symptoms during buprenorphine vs. methadone maintenance: findings from a randomised, controlled trial in opioid dependence

Research suggests that buprenorphine may possess antidepressant activity. The Beck Depression Inventory was completed at baseline and 3 months by heroin dependent subjects receiving either buprenorphine or methadone maintenance as part of a larger, pre-existing, double blind trial conducted by NDARC (Australia). Depressive symptoms improved in all subjects, with no difference between methadone and buprenorphine groups, suggesting no differential benefit on depressive symptoms for buprenorphine compared to methadone.     

Methadone dose increase and abstinence reinforcement for treatment of continued heroin use during methadone maintenance

BACKGROUND: Although methadone maintenance is an effective therapy for heroin dependence, some patients continue to use heroin and may benefit from therapeutic modifications. This study evaluated a behavioral intervention, a pharmacological intervention, and a combination of both interventions. METHODS: Throughout the study all patients received daily methadone hydrochloride maintenance (initially 50 mg/d orally) and weekly counseling. Following baseline treatment patients who continued to use heroin were randomly assigned to 1 of 4 interventions: (1) contingent vouchers for opiate-negative urine specimens (n = 29 patients); (2) methadone hydrochloride dose increase to 70 mg/d (n = 31 patients); (3) combined contingent vouchers and methadone dose increase (n = 32 patients); and (4) neither intervention (comparison standard; n = 28 patients). Methadone dose increases were double blind. Vouchers had monetary value and were exchangeable for goods and services. Groups not receiving contingent vouchers received matching vouchers independent of urine test results. Primary outcome measure was opiate-negative urine specimens (thrice weekly urinalysis). RESULTS: Contingent vouchers and a methadone dose increase each significantly increased the percentage of opiate-negative urine specimens during intervention. Contingent vouchers, with or without a methadone dose increase, increased the duration of sustained abstinence as assessed by urine screenings. Methadone dose increase, with or without contingent vouchers, reduced self-reported frequency of use and self-reported craving. CONCLUSIONS: In patients enrolled in a methadone-maintainence program who continued to use heroin, abstinence reinforcement and a methadone dose increase were each effective in reducing use. When combined, they did not dramatically enhance each other's effects on any 1 outcome measure, but they did seem to have complementary benefits.     

Innovations in agonist maintenance treatment of opioid-dependent patients

PURPOSE OF REVIEW: To provide an overview of published studies on agonist maintenance treatment options for opioid-dependent patients. RECENT FINDINGS: The recent publication of controlled trials confirms earlier clinical evidence of the efficacy of diamorphine (heroin) in the treatment of opioid dependence. Findings show not only efficacy with respect to improvement of health, reduction of illicit drug use, reduction of criminality and stabilization of social conditions, but also cost effectiveness in the treatment of chronic treatment-resistant heroin addicts. SUMMARY: Agonist maintenance treatment has become the first-line treatment for chronic opioid dependence. High-quality studies demonstrate the effectiveness of a growing number of different agonist maintenance treatments for opioid dependence such as methadone and buprenorphine. In addition, there is new evidence for the effectiveness of other agonists, mainly slow-release morphine, intravenous and inhalable diamorphine and possibly oral diamorphine. Maintenance treatment with intravenous or inhalable diamorphine should be implemented into the healthcare system to treat a group of severely dependent treatment-resistant patients. Furthermore, the opioid-dependent patients not under treatment need to be engaged in maintenance treatments through other harm reduction measures. Agonist maintenance treatment is very effective in stabilizing the health condition and social situation, while also reducing harm, thereby increasing life expectancy and quality of life.     

Differential effects of gestational buprenorphine, naloxone, and methadone on mesolimbic mu opioid and ORL1 receptor G protein coupling

In addition to its use for heroin addiction pharmacotherapy in general, buprenorphine has advantages in treating maternal heroin abuse. To examine the gestational effects of buprenorphine on opioid receptor signaling, the [(35)S]-GTP gamma S in situ binding induced by the mu agonist [D-Ala(2),MePhe(4),Gly(5)-ol] enkephalin (DAMGO) or the nociceptin/orphanin FQ (N/OFQ) agonist was measured in mesolimbic structures of pup brains from pregnant rats administered with buprenorphine +/- naloxone, naloxone, or methadone by osmotic minipump. Drug- and gender-based changes in DAMGO- and N/OFQ-induced GTP gamma S binding were discovered in mesolimbic regions of dam, P2, and P7 brains. Buprenorphine and/or methadone gestational treatment attenuated DAMGO-induced GTP gamma S binding in some dam and male P2 mesolimbic regions. Methadone diminished DAMGO-induced GTP gamma S binding in almost all monitored brain regions of the dam but had few effects on their N/OFQ-induced GTP gamma S binding. Naloxone used in combination with buprenorphine blocked the inhibition by buprenorphine alone on DAMGO-induced GTP gamma S binding. In contrast to its inhibitory effects on DAMGO-induced GTP gamma S binding, buprenorphine stimulated N/OFQ-induced GTP gamma S binding in male P2 nucleus accumbens and lateral septum. Brain region-dependent gender differences in DAMGO-induced GTP gamma S binding were seen in P2 pups, and males showed greater sensitivity to buprenorphine and methadone than females. Our findings on mu opioid receptor (MOR) GTP-binding regulatory protein (G protein) coupling and its gender dependency are consistent with our earlier studies on mu receptor binding adaptation induced by buprenorphine in dams and neonatal rats after in utero treatment regimens, and they extend the gestational effects of this opiate to mu and N/OFQ receptor functionality.     

Efficacy of maintenance treatment with methadone for opioid dependence: a meta-analytical study

The two aims of this study were to analyse the impact of methadone on outcome, and to confirm the results from previous meta-analyses by using a different methodology. The literature on randomized controlled trials (RCT) of methadone as maintenance treatment for opioid dependence was systematically reviewed. Eight studies involving 1511 patients were included. Both dichotomous and continuous variables were transformed into the standardized effect size (d). Homogeneity was analysed. A random effect model was used in all calculations. The combined analyses for retention, abuse and criminality were all significant: d=0.90, d=0.61, and d=0.35, respectively. A test of heterogeneity was significant for all three outcomes: P<0.01 for all comparisons. The type of study design was a significant moderator in five of nine comparisons: for retention in all three comparisons, concerning abuse in gradual detoxification vs. untreated controls and concerning criminality in placebo vs. untreated controls. In these sub-groups, three of six studies were homogeneous. In one study, methadone maintenance treatment reduced abuse of illegal opioids in prisoners. We conclude that methadone maintenance treatment in opioid dependence shows positive effects on retention, opioid abuse and criminality compared with non-active controlled conditions. Type of study design could explain some of the heterogeneity found. A different meta-analytical approach made it possible to confirm effects of methadone on retention and opioid abuse from previous studies and document effect on criminality.     

The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Substance Use and Related Disorders. Part 2: Opioid dependence

Abstract

Objectives. To develop evidence-based practice guidelines for the pharmacological treatment of opioid abuse and dependence. Methods. An international task force of the World Federation of Societies of Biological Psychiatry (WFSBP) developed these practice guidelines after a systematic review of the available evidence pertaining to the treatment of opioid dependence. On the basis of the evidence, the Task Force reached a consensus on practice recommendations, which are intended to be clinically and scientifically meaningful for physicians who treat adults with opioid dependence. The data used to develop these guidelines were extracted primarily from national treatment guidelines for opioid use disorders, as well as from meta-analyses, reviews, and publications of randomized clinical trials on the efficacy of pharmacological and other biological treatments for these disorders. Publications were identified by searching the MEDLINE database and the Cochrane Library. The literature was evaluated with respect to the strength of evidence for efficacy, which was categorized into one of six levels (A–F). Results. There is an excellent evidence base supporting the efficacy of methadone and buprenorphine or the combination of buprenorphine and naloxone for the treatment of opioid withdrawal, with clonidine and lofexidine as secondary or adjunctive medications. Opioid maintenance with methadone and buprenorphine is the best-studied and most effective treatment for opioid dependence, with heroin and naltrexone as second-line medications. Conclusions. There is enough high quality data to formulate evidence-based guidelines for the treatment of opioid abuse and dependence. This task force report provides evidence for the efficacy of a number of medications to treat opioid abuse and dependence, particularly the opioid agonists methadone or buprenorphine. These medications have great relevance for clinical practice.     

Vergleichsuntersuchung von Buprenorphin und Methadon im Rahmen der Erhaltungstherapie Opiatkranker

The efficacy of buprenorphine in opioid dependent patients (n = 20) was compared to methadone maintained subjects (n = 20) in a randomized comparison trial. Sublingual application of buprenorphine as an alternative synthetical opioid is being compared to methadone during a 24 week study period. A trend (p = 0.06) could be found in the retention rate of investigated patients being maintained on a mean dosage of 63 mg oral applicable methadone (racemat of L- and D-methadone) in comparison to the group on a mean dosage of 7.3 mg buprenorphine (sublingual tablets). The dropout-rate of 11 subjects at the end of the study in the buprenorphine group was higher when compared to the dropout-rate of 5 in the methadone group. There was no significant difference between the two groups over the treatment period in respect to additional consumption of opiates, benzodiazepines and cocaine as evaluated through urine toxicology. The result in regard to compliance over the study period demonstrates that methadone appears to be the more successful oral opioid (p = 0.04). Nevertheless, efficacy of buprenorphine in maintenance could be demonstrated in the remaining subjects, and further studies with higher daily doses and a higher number of subjects have to be performed.     

The tridimensional personality of male heroin users treated with methadone in Taiwan

It was our assumption that male heroin users have the personality traits of high impulsivity and low social interaction. Compliance regarding methadone maintenance therapy (MMT) is hypothesized to be related to personality features. We recruited 43 patients that had been receiving MMT and 43 healthy volunteers. All participants completed a Tridimensional Personality Questionnaire (TPQ). Information related to the Opiate Treatment Index (OTI) was gathered from the heroin group. The personality dimensions in the heroin user group and the control group were compared. We further investigated the association between TPQ and OTI. The heroin group presented with lower reward dependence than the control group. Regarding sub-dimensions, heroin users showed higher impulsivity and fatigability, and lower exploratory excitability and social dependence. The explosive (borderline) pattern was more common among the heroin users. The odds ratio of explosive pattern developing to heroin dependence was 4.19. Q scores of heroin use and the maximal methadone dose were associated with persistence.     

Differential regional effects of methadone maintenance compared to heroin dependence on mu-opioid receptor desensitization in rat brain

Methadone maintenance therapy has been the mainstay of treatment for heroin addiction since the 1970s. Recent studies indicate that methadone is of greater relative intrinsic efficacy than the active metabolites of heroin at mu-opioid receptors and that the extent of mu-opioid receptor desensitization is dependent upon agonist efficacy. Regional differences have been found for mu-opioid receptor desensitization with chronic heroin self-administration, and a similar paradigm was employed to compare regional differences between the effects of heroin and methadone. Rats were trained to self-administer heroin i.v., and the dose available was increased incrementally to a terminal value of 6 mg/kg for each infusion. Half of these rats were allowed to continue to self-administer heroin, while dependence was maintained in the others by hourly infusions of 3 mg/kg of methadone. A separate group of animals was kept on a low dose of heroin. Activation of G-proteins by the high efficacy agonist DAMGO was decreased to a greater extent in animals treated chronically with methadone compared with those allowed to self-administer heroin in amygdala, periaqueductal gray, and subicular nucleus. Activation of G-proteins by the partial agonist endomorphin was decreased in striatum, thalamus, and amygdala in rats from all drug treatment groups, but to a greater extent in the striatum in methadone treated rats compared with the heroin groups. Elucidating the mechanisms by which methadone induces differential desensitization of mu-opioid receptors across brain regions compared with heroin could provide insights to improve the pharmacotherapy of heroin addiction.     

Patients’ Perceptions of Opioid Replacement Therapy: a Comparison of Diamorphine and Methadone/Levomethadone

Diamorphine was first legalized as a novel treatment option for heroin dependence in Germany in 2009. Today, specialized clinics in ten German cities provide diamorphine to heavily addicted patients. As the medical and societal context of diamorphine-assisted therapy is evolving, continued research into patients’ perceptions of opioid replacement therapy remains important. From February 2018 to June 2018, we conducted a survey study of outpatients on maintenance treatment with either diamorphine (n = 85) or methadone/levomethadone (n = 126). Patients were asked to complete a self-report questionnaire querying, besides socio-demographic information, the study participant’s satisfaction with the substitute drug, relapse with illicit drugs, patterns of craving, and alcohol consumption. Duration of opioid dependence did not differ significantly between groups. Patients on diamorphine were approximately 3 years younger than patients on methadone/levomethadone. They also had a higher frequency of daily intake of their substitute drug and had had their dosage adjusted more often during the preceding 6 months. Still, diamorphine patients reported greater satisfaction with their substitute drug in tandem with significant reductions in relapse-related behaviors and cravings. While the most common relapse reported by patients on methadone replacement was heroin relapse (68%), most instances of illicit drug use in the diamorphine group involved cocaine (48%). Although self-reported alcohol consumption did not differ significantly between groups, a higher percentage of diamorphine patients than methadone patients endorsed decreased alcohol consumption since entering therapy. Taken together, these findings point to meaningful differences between diamorphine and methadone/levomethadone in opioid replacement therapy.