Diacetylmorphine versus Methadone for the Treatment of Opioid Addiction

School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
New England Journal of Medicine (Impact Factor: 55.87). 08/2009; 361(8):777-86. DOI: 10.1056/NEJMoa0810635
Source: PubMed


Studies in Europe have suggested that injectable diacetylmorphine, the active ingredient in heroin, can be an effective adjunctive treatment for chronic, relapsing opioid dependence.
In an open-label, phase 3, randomized, controlled trial in Canada, we compared injectable diacetylmorphine with oral methadone maintenance therapy in patients with opioid dependence that was refractory to treatment. Long-term users of injectable heroin who had not benefited from at least two previous attempts at treatment for addiction (including at least one methadone treatment) were randomly assigned to receive methadone (111 patients) or diacetylmorphine (115 patients). The primary outcomes, assessed at 12 months, were retention in addiction treatment or drug-free status and a reduction in illicit-drug use or other illegal activity according to the European Addiction Severity Index.
The primary outcomes were determined in 95.2% of the participants. On the basis of an intention-to-treat analysis, the rate of retention in addiction treatment in the diacetylmorphine group was 87.8%, as compared with 54.1% in the methadone group (rate ratio for retention, 1.62; 95% confidence interval [CI], 1.35 to 1.95; P<0.001). The reduction in rates of illicit-drug use or other illegal activity was 67.0% in the diacetylmorphine group and 47.7% in the methadone group (rate ratio, 1.40; 95% CI, 1.11 to 1.77; P=0.004). The most common serious adverse events associated with diacetylmorphine injections were overdoses (in 10 patients) and seizures (in 6 patients).
Injectable diacetylmorphine was more effective than oral methadone. Because of a risk of overdoses and seizures, diacetylmorphine maintenance therapy should be delivered in settings where prompt medical intervention is available. ( number, NCT00175357.)

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    • "The prescription of pharmaceutical heroin has repeatedly been found to be an effective treatment for severe heroin addiction (van den Brink et al., 2003; Haasen et al., 2007; Oviedo-Joekes et al., 2009) and for heroin addicts who have failed to benefit from methadone maintenance treatment (Blanken et al., 2010), although methadone maintenance failures may often be due to low dosing levels (Strain et al., 1993; Farré et al., 2002). Compared with healthy control subjects, chronic heroin users exhibit increased functional connectivity between the right amygdala and the OFC during resting state (Ma et al., 2010). "
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    ABSTRACT: Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treat-ment. Furthermore, this study suggests that the assessment of amygdala-related connectivity during fear processing may provide a prognostic tool to assess stress levels in heroin-dependent patients and to quantify the efficacy of maintenance treatments in drug addiction.
    Full-text · Article · Nov 2014 · Brain
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    • "Participants were aged 25 or older, with at least 5 years of opioid dependence, current daily injection of illicit opioids, a minimum of two previous treatments for opioid dependence, including at least one opioid substitution treatment (OST) attempt, and no enrollment in OST within the prior 6 months. A full description and discussion of the participants’ profiles, study design, methodology, and main results have been published elsewhere [12,23,24]. Briefly, a total of 251 individuals were randomized to receive oral methadone (n = 111), injectable DAM (n = 115), or injectable hydromorphone (HDM) (n = 25); the latter two on a double-blind basis. "
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    ABSTRACT: Background: The North American Opiate Medication Initiative (NAOMI) clinical trial compared the effectiveness of injectable diacetylmorphine (DAM) or hydromorphone (HDM) to oral methadone maintenance treatment (MMT). This study aimed to determine participants' perceptions of treatment delivered in NAOMI. Methods: A qualitative sub-study was conducted with 29 participants (12 female): 18 (62.1%) received injectable DAM or HDM and 11 (37.9%) received MMT. A phenomenological theoretical framework was used. Semi-structured interviews were audio-recorded and transcribed verbatim. A thematic analysis was used over successive phases and was driven by the semantic meanings of the data. Results: Participants receiving injectable medications suggested that the supervised delivery model was stringent but provided valuable stability to their lives. Females discussed the adjustment required for the clinical setting, while males focused on the challenging clinic schedule and its impact on employment abilities. Participants receiving MMT described disappointment with being randomized to this treatment; however, positive aspects, including the quick titration time and availability of auxiliary services, were also discussed. Conclusion: Treatment with injectable DAM (or HDM) is preferred by participants and considered effective in reducing the burden of opioid dependency. Engaging patients in research regarding their perceptions of treatment provides a comprehensive assessment of treatment needs and barriers. Clinical trial registration: NCT00175357
    Full-text · Article · Sep 2014 · Addiction science & clinical practice
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    • "This systematic review will compare methadone, buprenorphine/naloxone, naltrexone, and HAT among other substitute opioid therapies in terms of retention and response to treatment (as measured through continued opioid use). Retention in treatment has multiple definitions and measurements across studies, where some chose to define retention as a continuous value such as the number of days a patient continued in treatment until the last day of receiving an intervention receipt [46]; other studies chose to measure retention as a binary outcome such as the percentage of patients who completed their treatment course [47]; and lastly, some studies chose to report the number of patients who received the treatment for a predefined number of treatment days [39]. Due to the numerous ways retention is defined, measured, and reported, we will collect any information the articles offer on patient retention. "
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    ABSTRACT: Background Opioids are psychoactive analgesic drugs prescribed for pain relief and palliative care. Due to their addictive potential, effort and vigilance in controlling prescriptions is needed to avoid misuse and dependence. Despite the effort, the prevalence of opioid use disorder continues to rise. Opioid substitution therapies are commonly used to treat opioid dependence; however, there is minimal consensus as to which therapy is most effective. Available treatments include methadone, heroin, buprenorphine, as well as naltrexone. This systematic review aims to assess and compare the effect of all available opioid substitution therapies on the treatment of opioid dependence. Methods/Design The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. The title, abstract, and full-text screening will be completed in duplicate. When appropriate, multiple treatment comparison Bayesian meta-analytic methods will be performed to deduce summary statistics estimating the effectiveness of all opioid substitution therapies in terms of retention and response to treatment (as measured through continued opioid abuse). Discussion Using evidence gained from this systematic review, we anticipate disseminating an objective review of the current available literature on the effectiveness of all opioid substitution therapies for the treatment of opioid use disorder. The results of this systematic review are imperative to the further enhancement of clinical practice in addiction medicine. Systematic review registration PROSPERO CRD42013006507.
    Full-text · Article · Sep 2014 · Systematic Reviews
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