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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Quantifying enhanced risk from alcohol and other factors in polysubstance-related deaths
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Lorcaserin treatment for extended-release naltrexone induction and retention for opioid use disorder individuals: A pilot, placebo-controlled randomized trial
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“Repeatedly, data have demonstrated that maintenance treatment with buprenorphine and methadone reduces overdose risk by 70–80% (Kakko et al., 2003; Lee et al., 2018; Sordo et al., 2017).”
Health economic analyses of the justice community opioid innovation network (JCOIN)
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“Undoubtedly this ‘ harm minimisation approach ’ using OST with psychosocial support has been highly effective in improving health and social functioning in opiate addiction (Lingford-Hughes 2012; Schuckit 2016; Sordo 2017).”
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Opioid maintenance treatment in the Czech Republic, Norway and Denmark: a study protocol of a comparative registry linkage study
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“Evidence supports opioid agonist treatment (OAT) in terms of reduced illicit opioid use as well as mortality and crime [10, 11]; however, the treatment-seeking behaviour of those with OUD is low.”
Background
Opioid agonist treatment uptake within provincial correctional facilities in British Columbia, Canada
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Comparison Between Preoperative Methadone and Buprenorphine Use on Postoperative Opioid Requirement
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“Patients were excluded from the study if they: (1) received intravenous patient-controlled analgesia or epidural analgesia containing opioids during the first 48 postoperative hours (as opioid doses administered through those routes were not documented in our electronic medical record and are not retrievable with manu…”
BackgroundMethod
A pilot implementation study to scale-up methadone in incarcerated persons with opioid use disorder and retain them on treatment after release in Moldova
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The Potential of Methocinnamox as a Future Treatment for Opioid Use Disorder: A Narrative Review
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The Feasibility and Utility of Harnessing Digital Health to Understand Clinical Trajectories in Medication Treatment for Opioid Use Disorder: D-TECT Study Design and Methodological Considerations
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Rapid Low-dose Buprenorphine Initiation for Hospitalized Patients With Opioid Use Disorder
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“our interviews of selected practices and from national practice data sets (sources listed in Tables 1-3) and then simulated costs as well as gross and net revenues per full-time physician for each of the following 4 practice subgroups: (1) FQHCs and FQHC look-alikes, (2) non-FQHC practices in high-poverty urban areas…”
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Rural and urban differences in undersupply of buprenorphine provider availability in the United States, 2018
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Association of polysubstance use disorder with treatment quality among Medicaid beneficiaries with opioid use disorder
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“Table 3 presents results for continuity of MOUD treatment, which we consider a proxy indicator for treatment quality given the welldocumented relationship between longer treatment duration and better patient outcomes (Samples et al., 2020; Sordo et al., 2017).”
Background
Trajectories of drug treatment and illicit opioid use in the AIDS Linked to the IntraVenous Experience cohort, 2014–2019
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A Guide to Expanding the Use of Buprenorphine Beyond Standard Initiations for Opioid Use Disorder
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BackgroundMethodResultInfluential
Initiation and rapid titration of methadone and slow-release oral morphine (SROM) in an acute care, inpatient setting: a case series
Rodger, L., Nader, M., Turner, S., & Lurie, E. (2023) · European journal of medical research · doi:10.1186/s40001-023-01538-0 · Cited by 10
“Retention in treatment to an opioid agonist therapy reduce in mortality for those with opioid use disorder [18].”
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Providing medication for opioid use disorder and HIV pre-exposure prophylaxis at syringe services programs via telemedicine: a pilot study
McKellar, M., Marais, A. C. D., Chen, H., Choi, Y., Lilly, R., Ayers, D., Bennett, J., Kestner, L., Perry, B., Poley, S., et al. (2024) · Harm Reduction Journal · doi:10.1186/s12954-024-00983-2 · Cited by 10
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Background
Reducing overdose deaths among persons with opioid use disorder in connecticut
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Background
Risk of drug-related death associated with co-prescribing of gabapentinoids and Z-drugs among people receiving opioid-agonist treatment: A national retrospective cohort study
Glancy, M., Palmateer, N. E., Yeung, A., Hickman, M., Macleod, J., Bishop, J., Barnsdale, L. R., Trayner, K. M. A., Priyadarshi, S., Wallace, J., et al. (2024) · Psychiatry Research · doi:10.1016/j.psychres.2024.116028 · Cited by 10
“There is strong evidence demonstrating the protective effect of opioid-agonist treatment (OAT) in preventing DRDs (Santo et al., 2021), notwithstanding elevated DRD risk in periods immediately after OAT onset and cessation (Sordo et al., 2017; Lim et al., 2022).”
Background
Effect of a peer‐led emergency department behavioral intervention on non‐fatal opioid overdose: 18‐month outcome in the Navigator randomized controlled trial
Chambers, L. C., Li, Y., Hallowell, B. D., Langdon, K. J., Samuels, E. A., Mahoney, L., Beaudoin, F. L., & Marshall, B. D. L. (2024) · Addiction · doi:10.1111/add.16581 · Cited by 10
Harm Reduction in the Field: First Responders’ Perceptions of Opioid Overdose Interventions
Fockele, C. E., Frohe, T. M., McBride, O., Perlmutter, D. L., Goh, B. Y., Williams, G., Wettemann, C., Holland, N., Finegood, B., Oliphant-Wells, T., et al. (2024) · Western Journal of Emergency Medicine · doi:10.5811/westjem.18033 · Cited by 10

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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