Mortality among regular or dependent users of heroin and other opioids: a systematic review and meta-analysis of cohort studies

Addiction. 2011 Jan;106(1):32-51. doi: 10.1111/j.1360-0443.2010.03140.x. Epub 2010 Nov 4.


Aims: To review the literature on mortality among dependent or regular users of opioids across regions, according to specific causes, and related to a number of demographic and clinical variables.

Methods: Multiple search strategies included searches of Medline, EMBASE and PsycINFO, consistent with the methodology recommended by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group; grey literature searches; and contact of experts for any additional unpublished data from studies meeting inclusion criteria. Random-effects meta-analyses were conducted for crude mortality rates (CMRs) and standardized mortality ratios (SMRs), with stratified analyses where possible. Meta-regressions examined potentially important sources of heterogeneity across studies.

Results: Fifty-eight prospective studies reported mortality rates from opioid-dependent samples. Very high heterogeneity across studies was observed; pooled all-cause CMR was 2.09 per 100 person-years (PY; 95% CI; 1.93, 2.26), and the pooled SMR was 14.66 (95% CI: 12.82, 16.50). Males had higher CMRs and lower SMRs than females. Out-of-treatment periods had higher mortality risk than in-treatment periods (pooled RR 2.38 (CI: 1.79, 3.17)). Causes of death varied across studies, but overdose was the most common cause. Multivariable regressions found the following predictors of mortality rates: country of origin; the proportion of sample injecting; the extent to which populations were recruited from an entire country (versus subnational); and year of publication.

Conclusions: Mortality among opioid-dependent users varies across countries and populations. Treatment is clearly protective against mortality even in non-randomized observational studies. Study characteristics predict mortality levels; these should be taken into account in future studies.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Analgesics, Opioid / poisoning*
  • Asia / epidemiology
  • Australasia / epidemiology
  • Cause of Death
  • Drug Overdose / mortality
  • Europe / epidemiology
  • Female
  • HIV Infections / mortality
  • Humans
  • Male
  • North America / epidemiology
  • Opioid-Related Disorders / mortality*
  • Opioid-Related Disorders / therapy
  • Recurrence
  • Substance Abuse, Intravenous / mortality*
  • Time Factors
  • Young Adult


  • Analgesics, Opioid