Cause-specific opioid mortality research reveals need for combination interventions

Individuals who use illicitly manufactured opioids or pharmaceutical opioids outside the bounds of a medical prescription experience significant yet preventable excess mortality, according to results of a systematic review and meta-analysis published in JAMA Psychiatry.

“Extramedical opioid use is a significant public health problem, with use and related harms escalating across many high-income countries,” Sarah Larney, PhD, of the National Drug and Alcohol Research Centre at the University of New South Wales in Australia, and colleagues wrote. “In the United States, HIV and hepatitis C virus infection outbreaks associated with opioid injecting have been observed, and fatal opioid overdoses have increased markedly, exceeding 47,000 deaths in 2018. Increased fatal opioid overdoses have also been observed in Canada, the United Kingdom, Australia and Europe.”

Larney and colleagues conducted the present study to estimate all-cause and cause-specific crude mortality rates, standardized mortality ratios and relative risks with age- and sex-specific estimates when possible among people using extramedical opioids. They identified 8,683 cohort studies that reported mortality outcomes for people using extramedical opioids and included 124 in their analysis, with 100 primary studies and 24 that provided additional data for primary studies.

Based on 99 cohorts of 1,262,592 people, the researchers reported a pooled all-cause crude mortality rate of 1.6 per 100 person-years (95% CI, 1.4-1.8 per 100 person-years). This outcome had substantial heterogeneity (I² = 99.7%), which was associated with the proportion of the study sample that lived with HIV infection or hepatitis C or injected opioids. Based on 43 cohorts, they reported a pooled all-cause standardized mortality ratio of 10 (95% CI, 7.6-13.2). They observed excess mortality across numerous causes, including infectious and noncommunicable diseases, overdose and injuries.

“Combinations of opioid agonist treatment, needle and syringe programs and naloxone, as well as treatment for HIV and HCV infections, may be associated with reduced overdose, disease incidence and mortality from multiple adverse health outcomes,” the researchers wrote. “There appears to be an urgent need to scale up combination interventions across myriad health issues to ensure that people who use opioids no longer face elevated mortality risks for health outcomes for which evidence-based interventions (such as nicotine-replacement therapy for smoking cessation) are easily available to the wider community.” – by Joe Gramigna

Disclosures: Larney reports grants from the National Health and Medical Research Council and the NIH during the conduct of the study, as well as grants from Indivior outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.