Cited by 1,816Opioid Use Disorder TreatmentSubstance Abuse Treatment and OutcomesHIV, Drug Use, Sexual Risk

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Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies.

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Sordo, Luis, Barrio, Gregorio, Bravo, Maria J, Indave, B Iciar, Degenhardt, Louisa, Wiessing, Lucas, Ferri, Marica, Pastor-Barriuso, Roberto·2017·BMJ

DOI 10.1136/bmj.j1550PMC PMC5421454

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Abstract

Objective To compare the risk for all cause and overdose mortality in people with opioid dependence during and after substitution treatment with methadone or buprenorphine and to characterise trends in risk of mortality after initiation and cessation of treatment. Design Systematic review and meta-analysis. Data sources Medline, Embase, PsycINFO, and LILACS to September 2016. Study selection Prospective or retrospective cohort studies in people with opioid dependence that reported deaths from all causes or overdose during follow-up periods in and out of opioid substitution treatment with methadone or buprenorphine. Data extraction and synthesis Two independent reviewers performed data extraction and assessed study quality. Mortality rates in and out of treatment were jointly combined across methadone or buprenorphine cohorts by using multivariate random effects meta-analysis. Results There were 19 eligible cohorts, following 122 885 people treated with methadone over 1.3-13.9 years and 15 831 people treated with buprenorphine over 1.1-4.5 years. Pooled all cause mortality rates were 11.3 and 36.1 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 3.20, 95% confidence interval 2.65 to 3.86) and reduced to 4.3 and 9.5 in and out of buprenorphine treatment (2.20, 1.34 to 3.61). In pooled trend analysis, all cause mortality dropped sharply over the first four weeks of methadone treatment and decreased gradually two weeks after leaving treatment. All cause mortality remained stable during induction and remaining time on buprenorphine treatment. Overdose mortality evolved similarly, with pooled overdose mortality rates of 2.6 and 12.7 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 4.80, 2.90 to 7.96) and 1.4 and 4.6 in and out of buprenorphine treatment. Conclusions Retention in methadone and buprenorphine treatment is associated with substantial reductions in the risk for all cause and overdose mortality in people dependent on opioids. The induction phase onto methadone treatment and the time immediately after leaving treatment with both drugs are periods of particularly increased mortality risk, which should be dealt with by both public health and clinical strategies to mitigate such risk. These findings are potentially important, but further research must be conducted to properly account for potential confounding and selection bias in comparisons of mortality risk between opioid substitution treatments, as well as throughout periods in and out of each treatment.

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“The most common reasons expressed for interest in iOAT were to: ‘stay off other opioids’ (44%, n=80); (2) ‘inject opioids in a more healthy way’ (42%, n=77); (3) ‘stay off injecting illicit drugs’ (40%, n=72); and, (4) ‘avoid trouble with the police’ (40%, n=72).”
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“Although treatment with buprenorphine/ naloxone has been shown to decrease the risk for overdose (11, 12), individuals with an opioid use disorder are still at elevated risk for overdose relative to the general population.”
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Authors: Sordo, L., Barrio, G., Bravo, M. J., Indave, B. I., Degenhardt, L., Wiessing, L., Ferri, M., & Pastor-Barriuso, R.
Affiliations: Universidad Complutense de Madrid (ES)
Instituto de Salud Carlos III (ES)
The University of Melbourne (AU)
European Monitoring Centre for Drugs and Drug Addiction (PT)
Corresponding author: Barrio, Gregorio
ORCID: Sordo, Luis
Barrio, Gregorio
Degenhardt, Louisa
Wiessing, Lucas
Ferri, Marica
Venue: BMJ
Publisher: BMJ
Published: 2017-04-26
Volume: 357
Pages: j1550
ISSN: 1756-1833 (ISSN-L)
0959-8138
DOI: 10.1136/bmj.j1550
PMC: PMC5421454
OpenAlex: W2608446001
Cited by: 1,816
References: 76
Citations by year: 2026: 156 · 2025: 194 · 2024: 201 · 2023: 239 · 2022: 228 · 2021: 261 · 2020: 213 · 2019: 187 · 2018: 99 · 2017: 32
FWCI: 23.58
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
www.bmj.org/licenses/tdm/1.0/terms-and-conditions.html (tdm)
Locations: BMJ (publishedVersion, cc-by-nc)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc)
HighWire Press Open Archive (submittedVersion)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Health Sciences › Medicine › Epidemiology › HIV, Drug Use, Sexual Risk
Keywords: opioid substitution therapy, methadone, buprenorphine, opioid use disorder, all-cause mortality, drug overdose deaths, treatment retention, treatment discontinuation, harm reduction, opioid antagonists
MeSH terms: Buprenorphine, Humans, Methadone, Opioid-Related Disorders, Narcotics, Risk, Opiate Substitution Treatment, Drug Overdose

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Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies.

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