Overdose Death Risk Rises Dramatically as Opioid Users Age

Pauline Anderson

January 29, 2015

As users of heroin and other opioids get older, their risk for overdose death increases dramatically, a new study of age trends in excess deaths shows.

Although male users had almost double the rate of drug-related poisoning in early adulthood compared with female drug users, the difference narrowed considerably with age, the study found.

"Our analysis provides the first demonstration of a highly significant, age-related increase in opioid users' drug-related poisoning mortality rate that persists beyond 45 years of age," the authors, led by Matthias Pierce, Institute of Brain Behavior and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, United Kingdom, write.

The study was published in Drug and Alcohol Dependence.

Suicide, Homicide

Researchers extracted data from the Drug Data Warehouse, an anonymous, case-linked collection of secondary datasets about substance users in England and Wales. The Warehouse includes data from drug treatment services, prison and probation services, and criminal justice referrals.

The study cohort included 198,247 men and women actively using or being treated for opioid use in England from April 1, 2005, to March 31, 2009. Their median age at cohort assessment was 32.1 years, and 72% were male. Most (93%) were identified as heroin users.

For the analysis, researchers used crude mortality rate (CMR); a CMR of 73 per 10,000 person-years translates to 73 deaths occurring among 10,000 people during a period of 1 year or to 73 deaths among 20,000 people during a period of 6 months. They also compared observed deaths to sex- and age-appropriate expected mortality to derive standardized mortality ratios (SMRs).

During a median follow-up period of 3.1 years and through linkages with national mortality records, researchers determined that there were 3974 deaths from all causes, more than 5.5 times the number of deaths than would be expected in the age- and sex-appropriate general population.

Drug-related poisonings were the most common cause of mortality, accounting for 43% of deaths. Next were "external causes" (excluding drug-related poisonings), which accounted for 21% of all deaths, notably, suicide (5%) and homicide (2%).

The rate of suicide, when it was not also classified as drug-related poisoning, was 3 times higher (SMR, 2.9) than expected. With drug-related poisonings included, the SMR for suicides was 4.3 (95% confidence interval [CI], 3.9 - 4.8).

Sex Differences

The study uncovered some sex differences. The all-cause CMR for men was higher than that for women, reflecting lower female mortality in the general population. For men, the drug-related poisoning CMR was substantially higher than for women.

And they noted differences across ages. For both sexes, drug-related poisoning CMR increased markedly with age, from 19 (95% CI, 16 - 23) for persons aged 18-34 years to 45 (95% CI, 40 - 50) for persons aged 45-64 years (P < .001) and was higher for those aged 45-64 years than for those aged 35-44 years (P = .04).

The sex difference was considerably more marked among those younger than 35 years. Men had almost double the drug-related poisoning CMR than women at ages 18-34 (29 vs 15), but this difference narrowed considerably with increased age.

"These findings underline the importance for public health policy and treatment providers of delivering effective addiction treatment for older age groups, who are characterised by multiple and complex health problems," the authors write.

National targets need to be adjusted for age to effectively monitor the impact of policies, with the aim of reducing drug related poisoning deaths, they said.

The study also found that other major causes of death, including circulatory, respiratory, and liver diseases, were much more common among opioid users than in the general population.

The analysis may include some misclassifications, and the use of self-reports may lead to underestimations of levels of behavioral risks. Other potential study limitations were that factors contributing to excess mortality that are common in opioid users, for example, high rates of smoking, alcohol consumption, and depression and low socioeconomic status, were not measured, and that treatment effects on mortality risk were not considered.

Tim Millar has received research funding from the UK National Treatment Agency for Substance Misuse and the Home Office. He is a member of the organizing committee for, and chairs, conferences supported by unrestricted educational grants from Reckitt Benckiser, Lundbeck, Martindale Pharma, and Britannia Pharmaceuticals Ltd, for which he receives no personal remuneration. Sheila M. Bird holds GSK shares and is an MRC program leader. She chaired the Home Office's Surveys, Design and Statistics Subcommittee (SDSSC) when SDSSC published its report, 21st Century Drugs and Statistical Science in UK. She has previously served as UK representative on the Scientific Committee for European Monitoring Centre for Drugs and Drug Addiction. She is co–principal investigator for an MRC-funded, prison-based N-ALIVE pilot trial.

Drug Alcohol Depend. 2015;146:17-23. Full text

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