Mortality among regular or dependent users of heroin and other opioids: a systematic review and meta-analysis of cohort studies.
OBJECTIVE
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Studies in Epidemiology (MOOSE) group; grey literature searches; and contact of experts for any additional unpublished data from studies meeting inclusion criteria.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.
National Drug and Alcohol Research Centre, University of New South Wales, Sydney NSW, Australia. louisa@burnet.edu.au
Louisa
L
Degenhardt
Chiara
C
Bucello
Bradley
B
Mathers
Christina
C
Briegleb
Hammad
H
Ali
Matt
M
Hickman
Jennifer
J
McLaren
D000328:Adult; D000701:Analgesics, Opioid / Q000506:poisoning*; D001208:Asia / Q000453:epidemiology; D044362:Australasia / Q000453:epidemiology; D002423:Cause of Death; D062787:Drug Overdose / Q000401:mortality; D005060:Europe / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000401:mortality; D006801:Humans; D008297:Male; D009656:North America / Q000453:epidemiology; D009293:Opioid-Related Disorders / Q000401:mortality* / Q000628:therapy; D012008:Recurrence; D015819:Substance Abuse, Intravenous / Q000401:mortality*; D013997:Time Factors; D055815:Young Adult
D000701:Analgesics, Opioid