Combination Interventions Needed to Tackle Excess Mortality From Extramedical Opioids

Excess mortality occurred as the result of a number of causes, including overdose, injuries, and both infectious and noncommunicable diseases.

The extramedical use of opioids may cause individuals to experience significant excess mortality, which can be readily prevented, according to a meta-analysis published in JAMA Psychiatry. Fatal opioid overdoses have increased substantially worldwide in recent years with rising extramedical use of these drugs, but overdose is not the only associated risk.

Sarah Larney, PhD, of the National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia, and colleagues performed a systematic review and meta-analysis of 124 studies to determine mortality rates and causes of excess mortality among people who use extramedical opioids. They used MEDLINE, PsycINFO, and Embase to search for studies published from January 1 to October 3, 2019, as well as an earlier systematic review published in 2011.

The investigators pooled the extracted data using random-effects meta-analysis models and assessed heterogeneity using stratified meta-analyses and meta-regression. Outcome measures were all-cause and cause-specific crude-mortality rates (CMRs) and standardized mortality ratios (SMRs) among those using extramedical opioids compared with the general population.

Based on 99 cohorts, the pooled all-cause CMR was 1.59 per 100 person-years, with substantial heterogeneity (I2 = 99.7%), and the pooled all-cause SMR was 10.03 based on 43 cohorts, also with substantial heterogeneity (I2 = 99.9%). Among the cohort of individuals who injected opioids, the pooled all-cause CMR was 2.71 per 100 person-years and the pooled all-cause SMR was 16.37. Heterogeneity was associated with the proportion of the study sample that injected drugs or were infected with HIV or hepatitis C.

Excess mortality occurred as the result of a number of causes, including overdose, injuries, and both infectious and noncommunicable diseases. Smoking was highly prevalent among individuals using extramedical opioids, with cardiovascular disease, respiratory disease, and cancer contributing to excess mortality.

The key limitation reported by the study authors was a “lack of information on how causes of death were defined.” The researchers also noted that their failure to exclude people with infrequent or non-disordered extramedical opioid use may have contributed to heterogeneity.

The investigators noted, “There appears to be an urgent need to scale up combination interventions across myriad health issues.” They called for multiple evidence-based interventions to reduce mortality, including opioid agonist treatment, needle and syringe programs, naloxone, and HIV and hepatitis C treatment.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Larney S, Tran LT, Leung J, et al. All-cause and cause-specific mortality among people using extramedical opioids. A systematic review and meta-analysis. JAMA Psychiatry. 2020;77:493-502.