Elsevier

Drug and Alcohol Dependence

Volume 156, 1 November 2015, Pages 57-61
Drug and Alcohol Dependence

The impact of low-threshold methadone maintenance treatment on mortality in a Canadian setting

https://doi.org/10.1016/j.drugalcdep.2015.08.037Get rights and content

Highlights

  • 2335 persons who inject drugs (PWID) were followed over a 15 year follow up period.

  • 511 (21.9%) participants died (mortality ratio of 3.4 deaths per 100 person years).

  • Methadone maintenance program (MMT) participation was associated with lower mortality.

  • Enrollment in MMT was also associated with lower rates of non-overdose mortality.

  • Our data support the need for universal, unrestricted access to low-threshold MMT.

Abstract

Background

Methadone maintenance therapy (MMT) is among the most effective treatment modalities available for the management of opioid use disorder. However, the effect of MMT on mortality, and optimal strategies for delivering methadone are less clear. This study sought to estimate the effect of low-threshold MMT and its association with all-cause mortality among persons who inject drugs (PWID) in a setting where methadone is widely available through primary care physicians and community pharmacies at no cost through the setting's universal medical insurance plan.

Methods

Between May, 1996 and December, 2011 data were collected as part of two prospective cohort studies of PWID in Vancouver, Canada, and were linked to the provincial vital statistics database to ascertain rates and causes of death. The association of MMT with all-cause mortality was estimated using multivariable extended Cox regression with time-dependent variables.

Results

Of 2335 PWID providing 15027 person-years of observation, 511 deaths were observed for a mortality rate of 3.4 (95% Confidence Interval [CI]: 3.1–3.7) deaths per 100 person-years. After adjusting for potential confounders including age and HIV seropositivity, MMT enrolment was found to be associated with lower mortality (adjusted hazard ratio [AHR] = 0.73, 95% CI: 0.61–0.88).

Conclusions

While observed all-cause mortality rates among PWID in this setting were high, participation in low-threshold MMT was significantly associated with improved survival. These findings add to the known benefits of providing low-threshold MMT on reducing the harms associated with injection drug use.

Introduction

In North America, the use of prescription and illicit opioids continues to increase with devastating consequences (Goodnough, 2015). Opioid dependence has become a serious public health concern as a result of these growing trends (Fullerton et al., 2014, King et al., 2014). Without treatment, the risk of premature death amongst illicit opioid users is significant with estimates ranging from 13 to 63 times higher than that of the general population (English et al., 1995, Gronbladh et al., 1990, Hulse et al., 1999).

While the benefits of methadone maintenance therapy (MMT) for the reduction of illicit opioid use and retention in treatment are well established, its effect on mortality is less clear. Several randomized controlled trials (Gunne and Gronbladh, 1981, Kinlock et al., 2007, Newman and Whitehill, 1979, Yancovitz et al., 1991) comparing MMT and non-pharmacological options were included in a 2009 Cochrane review; separately or pooled, they showed no significant difference in mortality (Mattick et al., 2009). These results are difficult to interpret, however, as the included studies had small sample sizes and low mortality rates. A number of observational and registry studies have demonstrated an association between methadone use and reduced mortality (Bell et al., 2009, Clausen et al., 2008, Degenhardt et al., 2009, Evans et al., 2015, Gibson et al., 2008). A 2008 Norwegian prospective, cross-registry study (Clausen et al., 2008) following 3789 opioid dependent patients who applied for opioid maintenance therapy (OMT) demonstrated a reduction in mortality using an intention to treat analysis (relative risk = 0.60, p = 0.004). Through data linkage, an Australian study by Degenhardt et al., in 2009 demonstrated an overall 29% reduction in mortality among 42,676 opioid-dependent participants entering OMT between 1985 and 2006. Lastly, a more recent longitudinal study published by Evans et al., in 2015 assessed mortality among opioid dependent individuals accessing MMT in the U.S. between 2006 and 2010 and found a decrease in mortality risk with MMT (hazard ratio = 0.30, 95% confidence interval [CI]: 0.25–0.37).

While these studies do demonstrate an association between MMT participation and improved mortality, the strength of this association may be understated given the comparison group is often in receipt of psychosocial treatments and those receiving no treatment are excluded. Often programmatic barriers such as limiting MMT administration to specialized clinics, long-wait lists for treatment entry and lack of universal medical insurance coverage restrict access to MMT (Peterson et al., 2010). Furthermore even when opioid users have access to MMT, limits on dosing and duration of maintenance may limit its potential (Strain et al., 1999). British Columbia, Canada, is a unique environment that overcomes these challenges as the provision of MMT always occurs through a low-threshold methadone program. Specifically, MMT is widely accessible through the setting's universal no-cost medical insurance plan and through the integration of prescribing and dispensation through community physicians and community pharmacies respectively (Nosyk et al., 2012). Furthermore, low-threshold methadone administration occurs without any restriction on the maximum dose needed for desired efficacy or duration of treatment and while abstinence is the ultimate goal, it is not a prerequisite for continuation with the program. Thus, in this setting we sought to determine the relationship between MMT enrolment and all-cause mortality amongst persons who inject drugs (PWID) over a 15 year follow-up period.

Section snippets

Study population

The present study derived data from the Vancouver Injection Drug Users Study (VIDUS) and the AIDS Care Cohort to Evaluate Access to Survival Services (ACCESS); two open prospective cohort studies of illicit drug users in Vancouver, British Columbia, Canada. Described in detail previously (Palepu et al., 2006, Strathdee et al., 1998), ACCESS and VIDUS comprise of HIV-positive and HIV-negative participants respectively. Beyond this, both cohorts follow identical recruitment and follow up

Results

Between May, 1996 and December, 2011, a total of 2595 PWID were recruited. Overall, 2335 (90.0%) participants were included in the study and 260 (10.0%) were excluded as a result of having no follow-up visit (and no confirmed death date) within 24 months of their baseline visit. Compared to the 260 (10.0%) individuals who were excluded, the participants included in these analyses were more likely to be younger, HIV negative or homeless in the preceding 6 months at baseline and were less likely

Discussion

In the present study, we observed a high mortality rate among PWID in our setting. At the same time, we found that enrollment in a low-threshold MMT program was associated with a protective effect against all-cause mortality, even after adjusting for confounders including age, HIV infection and heroin injection.

Though many previous reports demonstrate the increased mortality risk faced by those with an opioid use disorder (English et al., 1995, Gronbladh et al., 1990, Evans et al., 2015, Hulse

Role of funding source

The study was supported by the US National Institutes of Health (R25DA037756, VIDUS: R01DA011591, U01DA038886; ACCESS: R01DA021525) and the Canadian Institutes of Health Research through the Canadian Research Initiative on Substance Misuse (FMN-139148). This research was undertaken, in part, thanks to funding for a Tier 1 Canada Research Chair in Inner City Medicine, which supports Dr. Evan Wood. Dr. Kanna Hayashi is supported by the Canadian Institutes of Health Research. Dr. Julio Montaner is

Contributors

Seonaid Nolan and Evan Wood designed and prepared the first draft of the manuscript. Vivianne Dias Lima and Huiru Dong conducted the statistical analyses. All coauthors contributed to the drafting of the final manuscript.

Conflict of interest

JSGM has received limited unrestricted funding, paid to his institution, from Abbvie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. VDL has received limited unrestricted funding, paid to her institution, from GlaxoSmithKline. All other authors declare no competing interests.

Acknowledgments

The authors thank the study participants for their contribution to the research, as well as current and past researchers and staff.

References (36)

  • H.U. Wittchen et al.

    Feasibility and outcome of substitution treatment of heroin-dependent patients in specialized substitution centers and primary care facilities in Germany: a naturalistic study in 2694 patients

    Drug Alcohol Depend.

    (2008)
  • L.E. Baxter et al.

    Safe methadone induction and stabilization: a report of an expert panel

    J. Addict. Med.

    (2013)
  • J. Bell et al.

    Comparing retention in treatment and mortality in people after initial entry to methadone and buprenorphine treatment

    Addiction

    (2009)
  • M.C. Buster et al.

    An increase in overdose mortality during the first 2 weeks after entering or re-entering methadone treatment in Amsterdam

    Addiction

    (2002)
  • P.M. Carrieri et al.

    Methadone induction in primary care for opioid dependence: a pragmatic randomized trial (ANRS Methaville)

    PLOS ONE

    (2014)
  • G.P. Daly

    Homeless: Policies, Strategies and Lives on the Street

    (1996)
  • D.R. English et al.

    The Quantification of Drug Caused Morbidity and Mortality in Australia 1995. Part 1. Alcohol

    (1995)
  • E. Evans et al.

    Mortality among individuals accessing pharmacological treatment for opioid dependence in California, 2006–10

    Addiction

    (2015)
  • Cited by (0)

    View full text