David C. Marsh

Diacetylmorphine versus Methadone for the Treatment of Opioid Addiction

BACKGROUND Studies in Europe have suggested that injectable diacetylmorphine, the active ingredient in heroin, can be an effective adjunctive treatment for chronic, relapsing opioid dependence. METHODS 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. RESULTS 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). CONCLUSIONS 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. (ClinicalTrials.gov number, NCT00175357.)

Changes in public order after the opening of a medically supervised safer injecting facility for illicit injection drug users

Background: North Americas first medically supervised safer injecting facility for illicit injection drug users was opened in Vancouver on Sept. 22, 2003. Although similar facilities exist in a number of European cities and in Sydney, Australia, no standardized evaluations of their impact have been presented in the scientific literature. Methods: Using a standardized prospective data collection protocol, we measured injection-related public order problems during the 6 weeks before and the 12 weeks after the opening of the safer injecting facility in Vancouver. We measured changes in the number of drug users injecting in public, publicly discarded syringes and injection-related litter. We used Poisson log-linear regression models to evaluate changes in these public order indicators while considering potential confounding variables such as police presence and rainfall. Results: In stratified linear regression models, the 12-week period after the facilitys opening was independently associated with reductions in the number of drug users injecting in public (p < 0.001), publicly discarded syringes (p < 0.001) and injection-related litter (p < 0.001). The predicted mean daily number of drug users injecting in public was 4.3 (95% confidence interval [CI] 3.5–5.4) during the period before the facilitys opening and 2.4 (95% CI 1.9–3.0) after the opening; the corresponding predicted mean daily numbers of publicly discarded syringes were 11.5 (95% CI 10.0–13.2) and 5.4 (95% CI 4.7–6.2). Externally compiled statistics from the city of Vancouver on the number of syringes discarded in outdoor safe disposal boxes were consistent with our findings. Interpretation: The opening of the safer injecting facility was independently associated with improvements in several measures of public order, including reduced public injection drug use and public syringe disposal.

Methadone maintenance therapy promotes initiation of antiretroviral therapy among injection drug users

AIMS Despite proven benefits of antiretroviral therapy (ART), many human immunodeficiency virus (HIV)-infected injection drug users (IDU) do not access treatment even in settings with free health care. We examined whether methadone maintenance therapy (MMT) increased initiation and adherence to ART among an IDU population with free health care. DESIGN We examined prospectively a cohort of opioid-using antiretroviral-naive HIV-infected IDU and investigated factors associated with initiation of antiretroviral therapy as well as subsequent adherence. Factors associated independently with time to first initiation of antiretroviral therapy were modelled using Cox proportional hazards regression. FINDINGS Between May 1996 and April 2008, 231 antiretroviral-naive HIV-infected opioid-using IDU were enrolled, among whom 152 (65.8%) initiated ART, for an incidence density of 30.5 [95% confidence interval (CI): 25.9-35.6] per 100 person-years. After adjustment for time-updated clinical characteristics and other potential confounders, use of MMT was associated independently with more rapid uptake of antiretroviral therapy [relative hazard = 1.62 (95% CI: 1.15-2.28); P = 0.006]. Those prescribed methadone also had higher rates of ART adherence after first antiretroviral initiation [odds ratio = 1.49 (95% CI: 1.07-2.08); P = 0.019]. CONCLUSION These results demonstrate that MMT contributes to more rapid initiation and subsequent adherence to ART among opioid-using HIV-infected IDU. Addressing international barriers to the use and availability of methadone may increase dramatically uptake of HIV treatment among this population.

Methodology for evaluating Insite: Canada's first medically supervised safer injection facility for injection drug users.

Many Canadian cities are experiencing ongoing infectious disease and overdose epidemics among injection drug users (IDUs). In particular, Human Immunodeficiency Virus (HIV) and hepatitis C Virus (HCV) have become endemic in many settings and bacterial and viral infections, such as endocarditis and cellulitis, have become extremely common among this population. In an effort to reduce these public health concerns and the public order problems associated with public injection drug use, in September 2003, Vancouver, Canada opened a pilot medically supervised safer injecting facility (SIF), where IDUs can inject pre-obtained illicit drugs under the supervision of medical staff. The SIF was granted a legal exemption to operate on the condition that its impacts be rigorously evaluated. In order to ensure that the evaluation is appropriately open to scrutiny among the public health community, the present article was prepared to outline the methodology for evaluating the SIF and report on some preliminary observations. The evaluation is primarily structured around a prospective cohort of SIF users, that will examine risk behavior, blood-borne infection transmission, overdose, and health service use. These analyses will be augmented with process data from within the SIF, as well as surveys of local residents and qualitative interviews with users, staff, and key stakeholders, and standardised evaluations of public order changes. Preliminary observations suggest that the site has been successful in attracting IDUs into its programs and in turn helped to reduce public drug use. However, each of the indicators described above is the subject of a rigorous scientific evaluation that is attempting to quantify the overall impacts of the site and identify both benefits and potentially harmful consequences and it will take several years before the SIFs impacts can be appropriately examined.

The impact of benzodiazepine use on methadone maintenance treatment outcomes

ABSTRACT The purposes of this study were to examine predictors of benzodiazepine use among methadone maintenance treatment patients, to determine whether baseline benzodiazepine use influenced ongoing use during methadone maintenance treatment, and to assess the effect of ongoing benzodiazepine use on treatment outcomes (i.e., opioid and cocaine use and treatment retention). A retrospective chart review of 172 methadone maintenance treatment patients (mean age = 34.6 years; standard deviation = 8.5 years; 64% male) from January 1997 to December 1999 was conducted. At baseline, 29% were “non-users” (past year) of benzodiazepine, 36% were “occasional users,” and 35% were “regular/problem users.” Regular/problem users were more likely to have started opioid use with prescription opioids, experienced more overdoses, and reported psychiatric comorbidity. Being female, more years of opioid use, and a history of psychiatric treatment were significant predictors of baseline benzodiazepine use. Ongoing benzodiazepine users were more likely to have opioid-positive and cocaine-positive urine screens during methadone maintenance treatment. Only ongoing cocaine use was negatively related to retention. Benzodiazepine use by methadone maintenance treatment patients is associated with a more complex clinical picture and may negatively influence treatment outcomes.

A Call For Evidence-Based Medical Treatment Of Opioid Dependence In The United States And Canada

Despite decades of experience treating heroin or prescription opioid dependence with methadone or buprenorphine--two forms of opioid substitution therapy--gaps remain between current practices and evidence-based standards in both Canada and the United States. This is largely because of regulatory constraints and pervasive suboptimal clinical practices. Fewer than 10 percent of all people dependent on opioids in the United States are receiving substitution treatment, although the proportion may increase with expanded health insurance coverage as a result of the Affordable Care Act. In light of the accumulated evidence, we recommend eliminating restrictions on office-based methadone prescribing in the United States; reducing financial barriers to treatment, such as varying levels of copayment in Canada and the United States; reducing reliance on less effective and potentially unsafe opioid detoxification; and evaluating and creating mechanisms to integrate emerging treatments. Taking these steps can greatly reduce the harms of opioid dependence by maximizing the individual and public health benefits of treatment.

Trends in methadone maintenance treatment participation, retention, and compliance to dosing guidelines in British Columbia, Canada: 1996-2006.

Aspects of methadone maintenance treatment (MMT) delivery, particularly daily dosing practices, are associated with longer retention in treatment. Our objective was to identify trends in compliance to MMT dosing guidelines at the population level in British Columbia, Canada, from 1996 to 2006. Analysis of a provincial drug dispensation database identified 31,724 MMT episodes initiated during the study period. The number of patients in treatment increased from 2,827 in 1996 to 9,601 in 2006. Long-term retention (>36 months) was achieved in 20%-25% of all episodes. Compliance to minimally effective dose guidelines, which is independently associated with retention, fell from 2001 to 2006. Accordingly, this decline was mirrored by 12-month retention figures, which fell from 45.9% in 2001 to 40.5% in 2005. Our evaluation has both highlighted the successes of the British Columbia Methadone program and identified aspects that may be improved to ensure safety and maximize the benefits of MMT.

Injection drug use cessation and use of North America's first medically supervised safer injecting facility

BACKGROUND Vancouver, Canada has a pilot supervised injecting facility (SIF), where individuals can inject pre-obtained drugs under the supervision of medical staff. There has been concern that the program may facilitate ongoing drug use and delay entry into addiction treatment. METHODS We used Cox regression to examine factors associated with the time to the cessation of injecting, for a minimum of 6 months, among a random sample of individuals recruited from within the Vancouver SIF. In further analyses, we evaluated the time to enrollment in addiction treatment. RESULTS Between December 2003 and June 2006, 1090 participants were recruited. In Cox regression, factors independently associated with drug use cessation included use of methadone maintenance therapy (Adjusted Hazard Ratio [AHR] = 1.57 [95% Confidence Interval [CI]: 1.02-2.40]) and other addiction treatment (AHR = 1.85 [95% CI: 1.06-3.24]). In subsequent analyses, factors independently associated with the initiation of addiction treatment included: regular SIF use at baseline (AHR = 1.33 [95% CI: 1.04-1.72]); having contact with the addiction counselor within the SIF (AHR = 1.54 [95% CI: 1.13-2.08]); and Aboriginal ancestry (AHR = 0.66 [95% CI: 0.47-0.92]). CONCLUSIONS While the role of addiction treatment in promoting injection cessation has been well described, these data indicate a potential role of SIF in promoting increased uptake of addiction treatment and subsequent injection cessation. The finding that Aboriginal persons were less likely to enroll in addiction treatment is consistent with prior reports and demonstrates the need for novel and culturally appropriate drug treatment approaches for this population.

Transforming health professional education through social accountability: Canada's Northern Ontario School of Medicine

Background: The Northern Ontario School of Medicine (NOSM) has a social accountability mandate to contribute to improving the health of the people and communities of Northern Ontario. NOSM recruits students from Northern Ontario or similar backgrounds and provides Distributed Community Engaged Learning in over 70 clinical and community settings located in the region, a vast underserved rural part of Canada. Methods: NOSM and the Centre for Rural and Northern Health Research (CRaNHR) used mixed methods studies to track NOSM medical learners and dietetic interns, and to assess the socioeconomic impact of NOSM. Results: Ninety-one percent of all MD students come from Northern Ontario with substantial inclusion of Aboriginal (7%) and Francophone (22%) students. Sixty-one percent of MD graduates have chosen family practice (predominantly rural) training. The socioeconomic impact of NOSM included new economic activity, more than double the Schools budget; enhanced retention and recruitment for the universities and hospital/health services; and a sense of empowerment among community participants attributable in large part to NOSM. Discussion: There are signs that NOSM is successful in graduating health professionals who have the skills and desire to practice in rural/remote communities and that NOSM is having a largely positive socioeconomic impact on Northern Ontario.

Cost-effectiveness of diacetylmorphine versus methadone for chronic opioid dependence refractory to treatment

Background: Although diacetylmorphine has been proven to be more effective than methadone maintenance treatment for opioid dependence, its direct costs are higher. We compared the cost-effectiveness of diacetylmorphine and methadone maintenance treatment for chronic opioid dependence refractory to treatment. Methods: We constructed a semi-Markov cohort model using data from the North American Opiate Medication Initiative trial, supplemented with administrative data for the province of British Columbia and other published data, to capture the chronic, recurrent nature of opioid dependence. We calculated incremental cost-effectiveness ratios to compare diacetylmorphine and methadone over 1-, 5-, 10-year and lifetime horizons. Results: Diacetylmorphine was found to be a dominant strategy over methadone maintenance treatment in each of the time horizons. Over a lifetime horizon, our model showed that people receiving methadone gained 7.46 discounted quality-adjusted life-years (QALYs) on average (95% credibility interval [CI] 6.91–8.01) and generated a societal cost of