INTRODUCTION: Among people receiving current or previous opioid maintenance treatment (OMT), the leading cause of premature death is an opioid overdose. However, other causes of mortality remain high in this group. An understanding of causes of deaths across multiple settings can be useful in informing more comprehensive prevention responses. The aim of this study was to describe all non-overdose causes of death in three national cohorts (Czechia, Denmark, and Norway) among OMT patients and to explore associations of non-overdose mortality with age and gender. METHODS: This prospective comparative cohort study used national mortality registry databases for OMT patients from Czechia (2000-2019), Denmark (2000-2018), and Norway (2010-2019). Crude mortality rates and age-standardized mortality rates (ASMRs) were calculated as deaths per 1,000 person years for cause-specific mortality. RESULTS: In total, 29,486 patients were included, with 5,322 deaths recorded (18%). We found variations in causes of death among the cohorts and within gender and age groups. The leading non-overdose causes of death were accidents in Czechia and Denmark, and neoplasms in Norway. Cardiovascular deaths were highest in Czechia, particularly for women in OMT (ASMR 3.59 vs. 1.24 in Norway and 1.87 in Denmark). CONCLUSION: This study found high rates of preventable death among both genders and all age groups. Different demographic structures, variations in risk exposure, as well as variations in coding practices can explain the differences. The findings support increased efforts towards screening and preventative health initiatives among OMT patients specific to the demographic characteristics in different settings.

Centre for Alcohol and Drug Research Aarhus University Aarhus Denmark

Department of Addictology 1st Faculty of Medicine Charles University Prague Czechia

Department of Addictology General University Hospital Prague Prague Czechia

Norwegian Centre for Addiction Research University of Oslo Oslo Norway

Norwegian Institute of Public Health Oslo Norway

Zobrazit více v PubMed

Degenhardt L, Randall D, Hall W, Law M, Butler T, Burns L. Mortality among clients of a state-wide opioid pharmacotherapy program over 20 years: risk factors and lives saved. Drug Alcohol Depend. 2009;105(1–2):9–15. 10.1016/j.drugalcdep.2009.05.021. PubMed DOI

Havnes I, Bukten A, Gossop M, Waal H, Stangeland P, Clausen T. Reductions in convictions for violent crime during opioid maintenance treatment: a longitudinal national cohort study. Drug Alcohol Depend. 2012;124(3):307–10. 10.1016/j.drugalcdep.2012.02.005. PubMed DOI

Bukten A, Skurtveit S, Gossop M, Waal H, Stangeland P, Havnes I, et al. . Engagement with opioid maintenance treatment and reductions in crime: a longitudinal national cohort study. Addiction. 2012;107(2):393–9. 10.1111/j.1360-0443.2011.03637.x. PubMed DOI

Platt L, Minozzi S, Reed J, Vickerman P, Hagan H, French C, et al. . Needle and syringe programmes and opioid substitution therapy for preventing HCV transmission among people who inject drugs: findings from a Cochrane Review and meta-analysis. Addiction. 2018;113(3):545–63. 10.1111/add.14012. PubMed DOI PMC

Larney S, Grebely J, Falster M, Swart A, Amin J, Degenhardt L, et al. . Opioid substitution therapy is associated with increased detection of hepatitis C virus infection: a 15-year observational cohort study. Drug Alcohol Depend. 2015;148:213–6. 10.1016/j.drugalcdep.2014.12.027. PubMed DOI

Model list of essential medicines-22nd list. World Health Organization; 2021.

Degenhardt L, Bucello C, Mathers B, Briegleb C, Ali H, Hickman M, et al. . Mortality among regular or dependent users of heroin and other opioids: a systematic review and meta-analysis of cohort studies. Addiction. 2011;106(1):32–51. 10.1111/j.1360-0443.2010.03140.x. PubMed DOI

Larney S, Tran LT, Leung J, Santo T Jr, Santomauro D, Hickman M, et al. . All-cause and cause-specific mortality among people using extramedical opioids: a systematic review and meta-analysis. JAMA Psychiatry. 2020;77(5):493–502. 10.1001/jamapsychiatry.2019.4170. PubMed DOI PMC

Degenhardt L, Larney S, Randall D, Burns L, Hall W. Causes of death in a cohort treated for opioid dependence between 1985 and 2005. Addiction. 2014;109(1):90–9. 10.1111/add.12337. PubMed DOI

Hesse M, Thylstrup B, Seid AK, Skogen JC. Suicide among people treated for drug use disorders: a Danish national record-linkage study. BMC Public Health. 2020;20(1):146. 10.1186/s12889-020-8261-4. PubMed DOI PMC

GBD 2019 Diseases and Injuries Collaborators . Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1204–22. 10.1016/S0140-6736(20)30925-9. PubMed DOI PMC

Carew AM, Comiskey C. Treatment for opioid use and outcomes in older adults: a systematic literature review. Drug Alcohol Depend. 2018;182:48–57. 10.1016/j.drugalcdep.2017.10.007. PubMed DOI

Han B, Polydorou S, Ferris R, Blaum CS, Ross S, McNeely J. Demographic trends of adults in New York city opioid treatment programs: an aging population. Subst Use Misuse. 2015;50(13):1660–7. 10.3109/10826084.2015.1027929. PubMed DOI

Lofwall MR, Brooner RK, Bigelow GE, Kindbom K, Strain EC. Characteristics of older opioid maintenance patients. J Subst Abuse Treat. 2005;28(3):265–72. 10.1016/j.jsat.2005.01.007. PubMed DOI

Medved D, Clausen T, Bukten A, Bjørnestad R, Muller AE. Large and non-specific somatic disease burdens among ageing, long-term opioid maintenance treatment patients. Subst Abuse Treat Prev Pol. 2020;15(1):87. 10.1186/s13011-020-00311-4. PubMed DOI PMC

Sharif B, Nosyk B, Sun H, Marsh DC, Anis A. Changes in the characteristics and levels of comorbidity among new patients into methadone maintenance treatment program in British Columbia during its expansion period from 1998–2006. Subst Use Misuse. 2013;48(8):671–82. 10.3109/10826084.2013.800119. PubMed DOI PMC

Gao L, Dimitropoulou P, Robertson JR, McTaggart S, Bennie M, Bird SM. Risk-factors for methadone-specific deaths in Scotland’s methadone-prescription clients between 2009 and 2013. Drug Alcohol Depend. 2016;167:214–23. 10.1016/j.drugalcdep.2016.08.627. PubMed DOI PMC

Pierce M, Millar T, Robertson JR, Bird SM. Ageing opioid users’ increased risk of methadone-specific death in the UK. Int J Drug Policy. 2018;55:121–7. 10.1016/j.drugpo.2018.02.005. PubMed DOI PMC

Arnold-Reed DE, Brett T, Troeung L, O’Neill J, Backhouse R, Bulsara MK. Multimorbidity in patients enrolled in a community-based methadone maintenance treatment programme delivered through primary care. J Comorb. 2014;4:46–54. 10.15256/joc.2014.4.42. PubMed DOI PMC

Tjagvad C, Skurtveit S, Linnet K, Andersen LV, Christoffersen DJ, Clausen T. Methadone-related overdose deaths in a liberal opioid maintenance treatment programme. Eur Addict Res. 2016;22(5):249–58. 10.1159/000446429. PubMed DOI

Guidance for doctors who treat patients with opioid use disorder on substitution medication. (Vejledning til læger, der behandler opioidafhængige patienter med substitutionsmedicin). Copenhagen; 2017.

Waal H. Merits and problems in high-threshold methadone maintenance treatment. Evaluation of medication-assisted rehabilitation in Norway 1998-2004. Eur Addict Res. 2007;13(2):66–73. 10.1159/000097935. PubMed DOI

National evidence-based guidelines for medication-assisted treatment for opioid addiction (Nasjonal faglig retningslinje for legemmiddelassistert rehabilitering ved opioidavhengighet). Oslo: Norwegian Directorate of health; 2022.

Gabrhelík R, Handal M, Mravčík V, Nechanská B, Tjagvad C, Thylstrup B, et al. . Opioid maintenance treatment in the Czech Republic, Norway and Denmark: a study protocol of a comparative registry linkage study. BMJ Open. 2021;11(5):e047028. 10.1136/bmjopen-2020-047028. PubMed DOI PMC

Helweg-Larsen K. The Danish register of causes of death. Scand J Public Health. 2011;39(7 Suppl):26–9. 10.1177/1403494811399958. PubMed DOI

Furu K. Establishment of the nationwide Norwegian PrescriptionDatabase (NorPD): new opportunities for research inpharmacoepidemiology in Norway. Norsk Epidemiologi. 2018;18(2):129–36.

Waal H, Bussesund K, Clausen T, Lillevold P, Skeie I. 20 years of OMT: status, evaluations, and perspectives in 2017 (LAR 20 år. Status, vurderinger og perspektiver 2017). Oslo; 2017.

European Comission . Revision of the European Standard Population: report of Eurostat’s task force: 2013 edition. Luxembourg; 2013. (cited January 25, 2023). Available from: https://data.europa.eu/doi/10.2785/11470 DOI

Causes Eurostat. of death- standardised death rate; 2022. (Updated 2022 Dec 9; cited 2023 Jan 25). Available from: https://ec.europa.eu/eurostat/databrowser/view/HLTH_CD_ASDR2__custom_4089701/default/table?lang=en.

Eurostat. Causes of causes of death statistics. (Updated 2022 Mar; cited 2023 Jan 25). (Available from: https://ec.europa.eu/eurostat/statistics-explained/index.php?title=Causes_of_death_statistics.

European Monitoring Centre for Drugs and Drug Addiction . Treatment and care for older drug users. Luxembourg; 2010.

Carew AM, Comiskey C. Rising incidence of ageing opioid users within the EU wide treatment demand indicator; the Irish opioid epidemic from 1996 to 2014. Drug Alcohol Depend. 2018;192:329–37. 10.1016/j.drugalcdep.2018.08.031. PubMed DOI

Huhn AS, Strain EC, Tompkins DA, Dunn KE. A hidden aspect of the U.S. opioid crisis: rise in first-time treatment admissions for older adults with opioid use disorder. Drug Alcohol Depend. 2018;193:142–7. 10.1016/j.drugalcdep.2018.10.002. PubMed DOI PMC

Lynch A, Arndt S, Acion L. Late- and typical-onset heroin use among older adults seeking treatment for opioid use disorder. Am J Geriatr Psychiatry. 2021;29(5):417–25. 10.1016/j.jagp.2020.12.005. PubMed DOI

Gossop M, Moos R. Substance misuse among older adults: a neglected but treatable problem. Addiction. 2008;103(3):347–8. 10.1111/j.1360-0443.2007.02096.x. PubMed DOI

Wu L-T, Blazer DG. Substance use disorders and psychiatric comorbidity in mid and later life: a review. Int J Epidemiol. 2014;43(2):304–17. 10.1093/ije/dyt173. PubMed DOI PMC

Bech AB, Clausen T, Waal H, Šaltytė Benth J, Skeie I. Mortality and causes of death among patients with opioid use disorder receiving opioid agonist treatment: a national register study. BMC Health Serv Res. 2019;19(1):440. 10.1186/s12913-019-4282-z. PubMed DOI PMC

Clausen T, Waal H, Thoresen M, Gossop M. Mortality among opiate users: opioid maintenance therapy, age and causes of death. Addiction. 2009;104(8):1356–62. 10.1111/j.1360-0443.2009.02570.x. PubMed DOI

Clausen T, Anchersen K, Waal H. Mortality prior to, during and after opioid maintenance treatment (OMT): a national prospective cross-registry study. Drug Alcohol Depend. 2008;94(1–3):151–7. 10.1016/j.drugalcdep.2007.11.003. PubMed DOI

Randall D, Degenhardt L, Vajdic CM, Burns L, Hall WD, Law M, et al. . Increasing cancer mortality among opioid-dependent persons in Australia: a new public health challenge for a disadvantaged population. Aust N Z J Public Health. 2011;35(3):220–5. 10.1111/j.1753-6405.2011.00682.x. PubMed DOI

Santo T Jr, Clark B, Hickman M, Grebely J, Campbell G, Sordo L, et al. . Association of opioid agonist treatment with all-cause mortality and specific causes of death among people with opioid dependence: a systematic review and meta-analysis. JAMA Psychiatry. 2021;78(9):979–93. 10.1001/jamapsychiatry.2021.0976. PubMed DOI PMC

Guydish J, Passalacqua E, Pagano A, Martínez C, Le T, Chun J, et al. . An international systematic review of smoking prevalence in addiction treatment. Addiction. 2016;111(2):220–30. 10.1111/add.13099. PubMed DOI PMC

Soyka M. Alcohol use disorders in opioid maintenance therapy: prevalence, clinical correlates and treatment. Eur Addict Res. 2015;21(2):78–87. 10.1159/000363232. PubMed DOI

Grebely J, Larney S, Peacock A, Colledge S, Leung J, Hickman M, et al. . Global, regional, and country-level estimates of hepatitis C infection among people who have recently injected drugs. Addiction. 2019;114(1):150–66. 10.1111/add.14393. PubMed DOI PMC

Aceijas C, Rhodes T. Global estimates of prevalence of HCV infection among injecting drug users. Int J Drug Policy. 2007;18(5):352–8. 10.1016/j.drugpo.2007.04.004. PubMed DOI

Eurostat. Cancer statistics. (Updated 2022 Apr; cited 2022 Nov). Available from: https://ec.europa.eu/eurostat/statistics-explained/index.php?title=Cancer_statistics#Deaths_from_cancer.

Hser YI, Mooney LJ, Saxon AJ, Miotto K, Bell DS, Zhu Y, et al. . High mortality among patients with opioid use disorder in a large healthcare system. J Addict Med. 2017;11(4):315–9. 10.1097/ADM.0000000000000312. PubMed DOI PMC

Kůrková S. Cardiovascular mortality in the Czech republic. Prague: University of Economics; 2018.

Masoudkabir F, Sarrafzadegan N, Eisenberg MJ. Effects of opium consumption on cardiometabolic diseases. Nat Rev Cardiol. 2013;10(12):733–40. 10.1038/nrcardio.2013.159. PubMed DOI

Ebdali RT, Tabaee SS, Tabaei S. Cardiovascular complications and related risk factors underlying opium consumption. J Cell Physiol. 2019;234(6):8487–95. 10.1002/jcp.27780. PubMed DOI

Thylstrup B, Clausen T, Hesse M. Cardiovascular disease among people with drug use disorders. Int J Public Health. 2015;60(6):659–68. 10.1007/s00038-015-0698-3. PubMed DOI

Gao L, Robertson JR, Bird SM. Non drug-related and opioid-specific causes of 3,262 deaths in Scotland’s methadone-prescription clients, 2009-2015. Drug Alcohol Depend. 2019;197:262–70. 10.1016/j.drugalcdep.2019.01.019. PubMed DOI PMC

Vallecillo G, Pedro-Botet J, Fernandez S, Román I, Elosua R, Camps A, et al. . High cardiovascular risk in older patients with opioid use disorder: differences with the general population. Drug Alcohol Rev. 2022;41(5):1078–84. PubMed

Rockett IR, Hobbs G, De Leo D, Stack S, Frost JL, Ducatman AM, et al. . Suicide and unintentional poisoning mortality trends in the United States, 1987-2006: two unrelated phenomena? BMC Public Health. 2010;10:705. 10.1186/1471-2458-10-705. PubMed DOI PMC

Zhong BL, Xie WX, Zhu JH, Lu J, Chen H. Prevalence and correlates of suicide attempt among Chinese individuals receiving methadone maintenance treatment for heroin dependence. Sci Rep. 2019;9(1):15859. 10.1038/s41598-019-52440-x. PubMed DOI PMC

Darke S, Ross J. Suicide among heroin users: rates, risk factors and methods. Addiction. 2002;97(11):1383–94. 10.1046/j.1360-0443.2002.00214.x. PubMed DOI

Bohnert AS, Roeder K, Ilgen MA. Unintentional overdose and suicide among substance users: a review of overlap and risk factors. Drug Alcohol Depend. 2010;110(3):183–92. 10.1016/j.drugalcdep.2010.03.010. PubMed DOI

Molero Y, Zetterqvist J, Binswanger IA, Hellner C, Larsson H, Fazel S. Medications for alcohol and opioid use disorders and risk of suicidal behavior, accidental overdoses, and crime. Am J Psychiatry. 2018;175(10):970–8. 10.1176/appi.ajp.2018.17101112. PubMed DOI PMC

Petruželka B, Mravčík V, Barták M, Babor TF. The identification of artefacts in reporting of drug-induced deaths using structural breaks analysis of time series statistics. Drug Alcohol Rev. 2021;40(7):1207–18. 10.1111/dar.13296. PubMed DOI

Bukten A, Stavseth MR, Clasuen T. From restrictive to more liberal: variations in mortality among patients in opioid maintenance treament over a 12-year period. BMC Health Serv Res. 2019;19(1):553. 10.1186/s12913-019-4382-9. PubMed DOI PMC

Exploring dual diagnosis in opioid agonist treatment patients: a registry-linkage study in Czechia and Norway