Life expectancy of people who are dependent on opioids: A cohort study in New South Wales, Australia

doi:10.1016/j.jpsychires.2020.08.013

Journal of Psychiatric Research

Volume 130, November 2020, Pages 435-440

https://doi.org/10.1016/j.jpsychires.2020.08.013 Get rights and content

Abstract

Background

People who are dependent on opioids have increased risk of premature death, but there are few estimates of life expectancy.

Methods

We calculated age-specific mortality rates in a cohort of people who had at least one prescription of an opioid agonist (methadone or buprenorphine) between 2001 and 2018 in New South Wales, Australia. We used life tables to estimate life expectancy at age 18. We also estimated the potential years of life lost before age 75, decomposed by cause of death.

Results

The cohort included 47,197 people, with a median of 9.8 years of follow-up. 5097 participants died, and the standardised mortality ratio (compared to the general population of New South Wales) was 6.06 (95% CI 5.90–6.23). Life expectancy at age 18 was an additional 47.5 years (95% CI 42.9–50.5) for men and 50.7 years (95% CI 45.4–54.8) for women; deficits of 14.7 and 15.8 years respectively when compared to the general population. The largest cause of death was non-communicable physical diseases, which accounted for 47% of deaths in life tables for men and 42% for women. Drug-related deaths accounted for 16% of deaths for men and 19% for women, but due to the young age at which these deaths occur, they contributed approximately one third of potential years of life lost.

Conclusion

In common with people with serious mental illnesses, people who are dependent on opioids have substantially reduced life expectancy. In both populations most excess deaths relate to non-communicable physical diseases.

Introduction

People who use opioids such as heroin often use these drugs for many years, which can have a profound impact on health and social wellbeing. A large number of cohort studies have measured the relative mortality risk associated with opioid dependence. Systematic reviews of such studies have found that the risk of death for people who inject drugs (Mathers et al., 2013) and people who regularly use heroin and other opioids (Degenhardt et al., 2011) is typically 15 times the general population, though this varies widely by setting. These relative risks can be difficult to interpret. In particular, the ratio between mortality risk in the general population and the mortality risk for people who use illicit drugs tends to be greater for younger samples than for older samples, even if the absolute difference is smaller for younger samples. Cause-specific mortality risk can also be difficult to interpret. The risk of death due to drug overdoses, suicides, or blood-borne viral infections is many times that of the general population, but long-term conditions such as cardiovascular and respiratory diseases may cause more deaths despite having lower risk ratios (Lewer et al., 2019).

Some studies of other marginalised groups, particularly people with serious mental health problems, have addressed these issues by estimating life expectancy deficits rather than relative risks (Erlangsen et al., 2017; Hjorthøj et al., 2017; Lawrence et al., 2013; Plana-Ripoll et al., 2019). Life expectancy is the average age at which people of a specific age would die if current mortality rates in a population remain unchanged. A systematic review of studies into the life expectancy of people with schizophrenia found an average deficit of 15 years when compared to the general population (Hjorthøj et al., 2017). As a measure of mortality risk, life expectancy has the benefits of being (i) independent from the study sample's age structure, (ii) intuitive because it relates to a usual lifespan of around 80 years, and (iii) decomposable by cause of death. Despite the large number of studies reporting relative mortality risks for people who use illicit drugs, there are few estimates of the life expectancy of this population.

We aimed to estimate the life expectancy of people who have been prescribed opioid agonist treatment in New South Wales, Australia. Opioid agonists are essential medicines prescribed to people who are dependent on opioids. They aim to prevent withdrawal, reduce the need to use illicit opioids, and reduce health and social harms associated with illicit drugs (Degenhardt et al., 2019). A large proportion of people who use illicit opioids have been prescribed opioid agonists either currently or historically. We also aimed to calculate the contribution of different causes of death to the years of life lost in this population.

Section snippets

Study population

We included all patients prescribed an opioid agonist (methadone or buprenorphine) in New South Wales between August 1, 2001 and September 19, 2018. The data were drawn from the Opioid Agonist Treatment Safety (OATS) Study, a resource of linked electronic healthcare databases that includes all permits to prescribe opioid agonists and probabilistic linkage to mortality information from the Cause of Death Unit Record File held by the NSW Ministry of Health Secure Analytics for Population Health

Results

The cohort included 47,197 participants, of which 32,048 (68%) were male and the median age at cohort entry was 32.8 (IQR 26.6–40.4). Table 1 provides descriptive information. A large proportion of participants entered the cohort in 2001–2006 as individuals with previous opioid agonist prescriptions joined the study at the start of follow-up (i.e. prevalent cases). Participants had a median of 9.8 years (range 0–17.1, IQR 3.7–15.4) of follow-up and 5097 (11%) died. The median age of death was

Discussion

People who are dependent on opioids have substantially raised risk of death. Our results show that life expectancy in people with opioid use disorders this population is approximately 15 years shorter than the general population; similar to studies of life expectancy among people with serious mental illnesses (Hjorthøj et al., 2017; Lawrence et al., 2013). These large health inequalities are related to multiple causes of death, with drug-related deaths contributing most at younger ages and

Contributions

Conceptualisation: DL. Study design: DL, NJ, MH, SN & LD. Data curation: NJ and DL. Formal analysis: DL and NJ. Original draft preparation: DL. Review and editing: DL, NJ, MH, SN & LD.

Funding

DL is funded by the National Institute of Health Research (NIHR) [DRF-2018-11-ST2016]. This paper presents independent research. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The OATS study is funded by the National Institutes of Health (R01 DA144740 PI: Degenhardt). LD is supported by an Australian National Health and Medical Research Council Senior Principal Research Fellowship. The National Drug and

Author statement

Conceptualisation: DL. Study design: DL, NJ, MH, SN & LD. Data curation: NJ and DL. Formal analysis: DL and NJ. Original draft preparation: DL. Review and editing: DL, NJ, MH, SN & LD.

Declarations of competing interest

MH reports honoraria for speaking at meetings from Gilead, Abbvie, and MSD. SN reports research funding (untied educational grants) from Indivior and Seqirus, and her institution has received honoraria from Indivior for delivery of training on opioid dependence. LD reports untied educational grant funding to conduct studies of new opioid medications in Australia from Indivior, Mundipharma, Seqirus and Reckitt Benckiser.

Acknowledgements

This research article was reviewed by the OATS Aboriginal reference group, including Alan Bennett, Doug James, Kim Sullivan, and Craig Vaughan. Record linkage was conducted by the NSW Ministry of Health and the Centre for Health Record Linkage. The Cause of Death Unit Record File (COD URF) is provided by the Australian Coordinating Registry for the COD URF on behalf of the NSW Registry of Births Deaths and Marriages, NSW Coroner and the National Coronial Information System.

References (29)

M.-L. Brecht et al.
Substance use pathways to methamphetamine use among treated users
Addict. Behav.
(2007)
L. Degenhardt et al.
Global patterns of opioid use and dependence: Harms to populations, interventions, and future action
Lancet
(2019)
A. Erlangsen et al.
Cause-specific life-years lost in people with mental disorders: A nationwide, register-based cohort study
The Lancet Psychiatry
(2017)
R.D. Hayes et al.
Associations between substance use disorder sub-groups, life expectancy and all-cause mortality in a large British specialist mental healthcare service
Drug Alcohol Depend.
(2011)
C. Hjorthøj et al.
Years of potential life lost and life expectancy in schizophrenia: A systematic review and meta-analysis
The Lancet Psychiatry
(2017)
S.F. Nielsen et al.
Psychiatric disorders and mortality among people in homeless shelters in Denmark: A nationwide register-based cohort study
Lancet
(2011)
O. Plana-Ripoll et al.
A comprehensive analysis of mortality-related health metrics associated with mental disorders: A nationwide, register-based cohort study
Lancet
(2019)
S. Slavova et al.
Heroin and fentanyl overdoses in Kentucky: Epidemiology and surveillance
Int. J. Drug Pol.
(2017)
B. Smyth et al.
Years of potential life lost among heroin addicts 33 years after treatment
Prev. Med.
(2007)
Australian Bureau of Statistics
ABS.Stat
(2019)

M.T. Brugal et al.

Evaluating the impact of methadone maintenance programmes on mortality due to overdose and aids in a cohort of heroin users in Spain

Addiction

(2005)

D. Clayton et al.

Chapter 6: Time

G. Corrao et al.

Independent and combined action of hepatitis C virus infection and alcohol consumption on the risk of symptomatic liver cirrhosis: Independent and combined action of hepatitis C virus infection and alcohol consumption on the risk of symptomatic liver cirrhosis

Hepatology

(1998)

L. Degenhardt et al.

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

Addiction

(2011)

Cited by (19)

Mortality risk and causes of death among people who use opioids in a take-home naloxone cohort
2024, Drug and Alcohol Dependence
People who use opioids (PWUO) have an excess mortality from a range of causes. The cumulative effect of behavioral, social, and health risk factors complicates the interpretation of the effects of suitable interventions. This study explores mortality causes among a cohort of PWUO in the take-home naloxone (THN) program.
This was a prospective cohort study of PWUO who received THN between 2015 and 2023. Participant data was linked with death registry data. Crude mortality rates and standardized mortality ratios (SMRs) were calculated for all causes, internal causes, and accidental opioid overdoses (AOOs). In addition to age and gender, risk factors like main route of administration, polydrug use, self-experienced overdoses, and using while alone were fitted in a Cox Regression model to explore factors associated with mortality.
The 2194 participants had a considerably higher mortality ratio for all causes investigated when compared to the general population (SMR=10.9, 95 % CI = 9.3,12.6). AOOs were the most prevalent cause of death (49 %). Those who reported frequent opioid use while alone had an elevated risk of dying of 2.6 (95 % CI = 1.1,6.4) compared to those who never used while alone.
Frequent opioid use while alone was associated with elevated mortality risk, supporting the importance of overdose prevention education with naloxone distribution, and additional efforts to improve environmental and social areas for safer drug-use practices among PWUO. The variety of mortality causes found in this study illustrates the need for multifaceted and targeted interventions for people at risk of overdosing.
Opioid agonist treatment in transition: A cross-country comparison between Austria, Germany and Switzerland
2024, Drug and Alcohol Dependence
OAT is a well developed and successful treatment strategy for opioid dependent patients in Europe. It has significantly contributed to the fight against the HIV and HCV pandemics, leading to an increased life expectancy in this population. Building on the OAT experiences in Austria, Germany, and Switzerland and their models of care, the objective of this study is to analyse experiences and changes in patient structures to identify necessary adaptations for the system of care.
We analysed national register-based data from patients receiving OAT during the period spanning from 2010 to 2020 in Austria, Germany (cases), and Switzerland. We examined and compared OAT policies and practice at national levels through a review of literature and publicly available policy documents.
Across these three countries, the life expectancy of OAT patients increased substantially. The mean age increased from 33.0 in 2010 to 39.1 in 2020 in Austria, from 35.6 years to 41.5 years in Germany (cases), and from 39.6 to 47.1 in Switzerland, respectively. In all three countries, the percentage of patients/cases aged 60 years and older increased more than tenfold between 2010 and 2020.
Integrated support models, reliable care structures, internationally comparable high treatment coverage, flexible prescribing practices, and a wide range of available OAT medications are successful strategies. The experiences in these countries indicate that it is possible to address the complex and chronic nature of opioid dependence and its concurrent mental and physical health challenges, resulting in an increasing life expectancy of OAT patients.
Life expectancy and years of potential life lost in people with mental disorders: a systematic review and meta-analysis
2023, eClinicalMedicine
Mental disorders are associated with premature mortality. There is increasing research examining life expectancy and years-of-potential-life-lost (YPLL) to quantify the disease impact on survival in people with mental disorders. We aimed to systematically synthesize studies to estimate life expectancy and YPLL in people with any and specific mental disorders across a broad spectrum of diagnoses.
In this systematic review and meta-analysis, we searched Embase, MEDLINE, PsychINFO, WOS from inception to July 31, 2023, for published studies reporting life expectancy and/or YPLL for mental disorders. Criteria for study inclusion were: patients of all ages with any mental disorders; reported data on life expectancy and/or YPLL of a mental-disorder cohort relative to the general population or a comparison group without mental disorders; and cohort studies. We excluded non-cohort studies, publications containing non-peer-reviewed data or those restricted to population subgroups. Survival estimates, i.e., life expectancy and YPLL, were pooled (based on summary data extracted from the included studies) using random-effects models. Subgroup analyses and random-effects meta-regression analyses were performed to explore sources of heterogeneity. Risk-of-bias assessment was evaluated using the Newcastle–Ottawa Scale. This study is registered with PROSPERO (CRD42022321190).
Of 35,865 studies identified in our research, 109 studies from 24 countries or regions including 12,171,909 patients with mental disorders were eligible for analysis (54 for life expectancy and 109 for YPLL). Pooled life expectancy for mental disorders was 63.85 years (95% CI 62.63–65.06; I² = 100.0%), and pooled YPLL was 14.66 years (95% CI 13.88–15.98; I² = 100.0%). Disorder-stratified analyses revealed that substance-use disorders had the shortest life expectancy (57.07 years [95% CI 54.47–59.67]), while neurotic disorders had the longest lifespan (69.51 years [95% CI 67.26–71.76]). Substance-use disorders exhibited the greatest YPLL (20.38 years [95% CI 18.65–22.11]), followed by eating disorders (16.64 years [95% CI 7.45–25.82]), schizophrenia-spectrum disorders (15.37 years [95% CI 14.18–16.55]), and personality disorders (15.35 years [95% CI 12.80–17.89]). YPLLs attributable to natural and unnatural deaths in mental disorders were 4.38 years (95% CI 3.15–5.61) and 8.11 years (95% CI 6.10–10.13; suicide: 8.31 years [95% CI 6.43–10.19]), respectively. Stratified analyses by study period suggested that the longevity gap persisted over time. Significant cross-study heterogeneity was observed.
Mental disorders are associated with substantially reduced life expectancy, which is transdiagnostic in nature, encompassing a wide range of diagnoses. Implementation of comprehensive and multilevel intervention approaches is urgently needed to rectify lifespan inequalities for people with mental disorders.
None.
Long-acting injectable buprenorphine for opioid use disorder: A systematic review of impact of use on social determinants of health
2022, Journal of Substance Abuse Treatment
Citation Excerpt :
The well-recognized global burden of OUD includes significant physical, economic, and social consequences, amounting to 16.6 million disability-adjusted life-years (DALYs) (Degenhardt et al., 2019). People with OUD have worse hospital outcomes, are more likely to die of noncommunicable diseases, and have significantly reduced life expectancies compared to the general population (Lewer, Jones, Hickman, Nielsen, & Degenhardt, 2020; Nordeck et al., 2018). Causation and course of OUD are complex, with research increasingly recognizing the interplay between individual and social factors in the development and perpetuation of OUD (Gowing et al., 2014).
This systematic review synthesizes evidence on both the effects and perspectives of the use of novel long-acting injectable buprenorphine (LAIB) as part of medication-assisted treatment (MAT) and its impact on social determinants of health (SDH), specifically abstinence, accessibility, employment, forensic matters, and gender and social relationships via a framework approach.
The study team searched three databases between January 2010 and June 2020 to identify English-language original research published in peer reviewed journals. This search yielded 9253 papers. A comprehensive search followed by 67 full text publication screenings by two independent reviewers yielded 15 papers meeting inclusion criteria. The study included three randomized control trials, one open label safety study, two case series, and six qualitative papers examining patient perspectives toward the LAIB prior to use. The team assessed the quality of studies via standardized quality assessment tools.
The LAIB was positively associated with improvements in abstinence, accessibility, employment, social relationships, and forensic matters. Limited evidence exists on gender equity within the current literature. The qualitative papers highlighted the importance of patients' preferences and individualization of treatment planning to ensure the success of MAT.
The quality of evidence was rated as medium or high risk of bias, which does limit interpretation of the results. Overall, the LAIB was positively associated with SDH and should be offered as part of MAT in alignment with the recovery model. Future research should evaluate the implementation and longitudinal impacts of LAI buprenorphine compared to treatment as usual (TAU).
Highlighting the hidden dangers of a ‘weak’ opioid: Deaths following use of dihydrocodeine in England (2001–2020)
2022, Drug and Alcohol Dependence
Citation Excerpt :
The correlation between DHC prescriptions and deaths suggest a strong link between DHC use and mortality. Even when controlling for life-limiting conditions (e.g. terminal cancer), initiation of opioid therapy is associated with decreased life expectancy (Imtiaz et al., 2018), which is further exacerbated upon development of opioid dependence (Lewer et al., 2020), and the prescribing of DHC can act as a ‘gateway’ to opioid dependence (Conroy and Hill, 2014). Long-term prescribing of opioids is commonplace (Mordecai et al., 2018), despite limited evidence for their effectiveness in treating chronic pain.
Dihydrocodeine (DHC) is considered a ‘weak’ opioid, but there is evidence of its increasing misuse in overdose deaths. This research aims to analyse trends in DHC-related deaths in England relevant to source and dose of DHC, and decedent demographics.
Cases from England reported to the National Programme on Substance Abuse Deaths (NPSAD) where DHC was identified at post-mortem and/or implicated in death between 2001 and 2020 were extracted for analysis.
2071 DHC-related deaths were identified. The greatest number of deaths involved illicitly obtained DHC and a significant increase in these deaths was recorded over time (r = 0.5, p = 0.03). However, there was a concurrent decline in the implication rate of DHC in causing death (r = −0.6, p < 0.01). Fatalities were primarily due to accidental overdose (64.8%) and misuse was highly prevalent in combination with additional central nervous system depressants (95.3%), namely illicit heroin/morphine and diazepam. In contrast, when DHC was obtained over-the-counter (OTC) suicide mortality accounted for almost half of the deaths (42.5%). Differences in polysubstance use were also identified, with less heroin/morphine and benzodiazepine co-detection, but increased OTC codeine co-detection.
DHC misuse in England is increasing. The pharmacological consideration of DHC as a ‘weak’ opioid may be misinterpreted by users, leading to accidental overdosing. There is an urgent need to understand increasing polypharmacy in overdose deaths. Additionally, suicides involving DHC is a potential cause for concern and a review of OTC opioid-paracetamol preparations is necessary to determine whether the benefits of these medications continue to outweigh the risks of intentional overdose.
Causes of death among people who used illicit opioids in England, 2001–18: a matched cohort study
2022, The Lancet Public Health
Citation Excerpt :
Therefore, our results are not generalisable to people who use illicit opioids in countries other than England. The transition in the predominant causes of death from drug poisoning, infections, accidents, and suicides to non-communicable diseases has also been observed among people in opioid agonist therapy in Australia, which is also a population with increasing average age.39,40 Fourth, despite the large sample, our study did not have sufficient power to estimate changes in mortality over time with precision, particularly in cause-specific analyses.
In many countries, the average age of people who use illicit opioids, such as heroin, is increasing. This has been suggested to be a reason for increasing numbers of opioid-related deaths seen in surveillance data. We aimed to describe causes of death among people who use illicit opioids in England, how causes of death have changed over time, and how they change with age.
In this matched cohort study, we studied patients in the Clinical Practice Research Datalink with recorded illicit opioid use (defined as aged 18–64 years, with prescriptions or clinical observations that indicate use of illicit opioids) in England between Jan 1, 2001, and Oct 30, 2018. We also included a comparison group, matched (1:3) for age, sex, and general practice with no records of illicit opioid use before cohort entry. Dates and causes of death were obtained from the UK Office for National Statistics. The cohort exit date was the earliest of date of death or Oct 30, 2018. We described rates of death and calculated cause-specific standardised mortality ratios. We used Poisson regression to estimate associations between age, calendar year, and cause-specific death.
We collected data for 106 789 participants with a history of illicit opioid use, with a median follow-up of 8·7 years (IQR 4·3–13·5), and 320 367 matched controls with a median follow-up of 9·5 years (5·0–14·4). 13 209 (12·4%) of 106 789 participants in the exposed cohort had died, with a standardised mortality ratio of 7·72 (95% CI 7·47–7·97). The most common causes of death were drug poisoning (4375 [33·1%] of 13 209), liver disease (1272 [9·6%]), chronic obstructive pulmonary disease (COPD; 681 [5·2%]), and suicide (645 [4·9%]). Participants with a history of illicit opioid use had higher mortality rates than the comparison group for all causes of death analysed, with highest standardised mortality ratios being seen for viral hepatitis (103·5 [95% CI 61·7–242·6]), HIV (16·7 [9·5–34·9]), and COPD (14·8 [12·6–17·6]). In the exposed cohort, at age 20 years, the rate of fatal drug poisonings was 271 (95% CI 230–313) per 100 000 person-years, accounting for 59·9% of deaths at this age, whereas the mortality rate due to non-communicable diseases was 31 (16–45) per 100 000 person-years, accounting for 6·8% of deaths at this age. Deaths due to non-communicable diseases increased more rapidly with age (1155 [95% CI 880–1431] deaths per 100 000 person-years at age 50 years; accounting for 52·0% of deaths at this age) than did deaths due to drug poisoning (507 (95% CI 452–562) per 100 000 person-years at age 50 years; accounting for 22·8% of deaths at this age). Mirroring national surveillance data, the rate of fatal drug poisonings in the exposed cohort increased from 345 (95% CI 299–391) deaths per 100 000 person-years in 2010–12 to 534 (468–600) per 100 000 person-years in 2016–18; an increase of 55%, a trend that was not explained by ageing of participants.
People who use illicit opioids have excess risk of death across all major causes of death we analysed. Our findings suggest that population ageing is unlikely to explain the increasing number of fatal drug poisonings seen in surveillance data, but is associated with many more deaths due to non-communicable diseases.
National Institute for Health Research.

View all citing articles on Scopus

View full text

Life expectancy of people who are dependent on opioids: A cohort study in New South Wales, Australia

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Study population

Results

Discussion

Contributions

Funding

Author statement

Declarations of competing interest

Acknowledgements

Addict. Behav.

Lancet

The Lancet Psychiatry

Drug Alcohol Depend.

The Lancet Psychiatry

Lancet

Lancet

Int. J. Drug Pol.

Prev. Med.

ABS.Stat

Evaluating the impact of methadone maintenance programmes on mortality due to overdose and aids in a cohort of heroin users in Spain

Addiction

Chapter 6: Time

Independent and combined action of hepatitis C virus infection and alcohol consumption on the risk of symptomatic liver cirrhosis: Independent and combined action of hepatitis C virus infection and alcohol consumption on the risk of symptomatic liver cirrhosis

Hepatology

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

Addiction