Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies.
Open accessAbstract
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 monthly rate of overdose among individuals treated with transmucosal buprenorphine or extended-release buprenorphine is 2.72 per 1000 people.
“The monthly rate of overdose among individuals treated with transmucosal buprenorphine or extended-release buprenorphine is 2.72 per 1000 people.4,32”
From Economic Evaluation of Extended-Release Buprenorphine for Persons With Opioid Use Disorder (2023) · cites this paper as [4]
The Results section, “Overdose mortality during and after opioid substitution treatment” (page not available), reports fatal overdoses among people receiving buprenorphine. It gives 1.4 per 1000 person-years during treatment, not 2.72 overdoses per 1000 people per month, and does not distinguish transmucosal from extended-release buprenorphine. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMedications for opioid use disorder (MOUD) are a tool that helps reduce opioid-related overdose mortality.
“Evidence shows that medications for opioid use disorder (MOUD) are a tool that helps reduce opioid-related overdose mortality.2,3,4”
From Economic Evaluation of Extended-Release Buprenorphine for Persons With Opioid Use Disorder (2023) · cites this paper as [4]
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Global patterns of opioid use and dependence: harms to populations, interventions, and future action
Degenhardt, L. J., Grebely, J., Stone, J., Hickman, M., Vickerman, P. T., Marshall, B. D. L., Bruneau, J., Altice, F. L., Henderson, G., Rahimi‐Movaghar, A., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(19)32229-9 · Cited by 853 · see citing works
Lee, J. D., Nunes, E. V., Novo, P., Bachrach, K., Bailey, G. L., Bhatt, S., Farkas, S., Fishman, M., Gauthier, P., Hodgkins, C. C., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(17)32812-x · Cited by 700 · see citing works
Strang, J., Volkow, N. D., Degenhardt, L., Hickman, M., Johnson, K., Koob, G. F., Marshall, B. D. L., Tyndall, M., & Walsh, S. L. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0137-5 · Cited by 639 · see citing works
Santo, T., Clark, B., Hickman, M., Grebely, J., Campbell, G., Sordo, L., Chen, A. B., Tran, L. T., Bharat, C., Padmanathan, P., et al. (2021) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2021.0976 · Cited by 614 · see citing works
The changing opioid crisis: development, challenges and opportunities
Volkow, N. D., & Blanco, C. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0661-4 · Cited by 564 · see citing works
Stigma as a fundamental hindrance to the United States opioid overdose crisis response
Tsai, A. C., Kiang, M. V., Barnett, M. L., Beletsky, L. A., Keyes, K. M., McGinty, E. E., Smith, L. R., Strathdee, S. A., Wakeman, S. E., & Venkataramani, A. S. (2019) · PLoS Medicine · doi:10.1371/journal.pmed.1002969 · Cited by 446 · see citing works
“This underuse represents a missed public health opportunity, given the well-established effectiveness of opioid agonist treatment in reducing mortality [55,57].”
BackgroundManagement of opioid use disorders: a national clinical practice guideline
Bruneau, J., Ahamad, K., Goyer, M.-È., Poulin, G., Selby, P. L., Fischer, B., Wild, T. C., & Wood, E. (2018) · Canadian Medical Association Journal · doi:10.1503/cmaj.170958 · Cited by 412 · see citing works
Ma, J., Bao, Y., Wang, R., Su, M.-F., Liu, M.-X., Li, J., Degenhardt, L. J., Farrell, M., Blow, F. C., Ilgen, M. A., et al. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0094-5 · Cited by 397 · see citing works
“In addition to OST including methadone and buprenorphine, we firstly pooled the mortality estimate of antagonist treatment with naltrexone among individual with OUDs.”
InfluentialManagement of opioid use disorder in the USA: present status and future directions
Blanco, C., & Volkow, N. D. (2019) · The Lancet · doi:10.1016/s0140-6736(18)33078-2 · Cited by 407 · see citing works
Development of a Cascade of Care for responding to the opioid epidemic.
Williams, A. R., Nunes, E. V., Bisaga, A., Levin, F. R., & Olfson, M. (2019) · The American Journal of Drug and Alcohol Abuse · doi:10.1080/00952990.2018.1546862 · Cited by 332 · see citing works
“on MOUD (compared to being off of medication), irrespective of whether they intermittently use opioids (23) and all efforts should be made to successfully retain”
BackgroundFatal and nonfatal overdose among pregnant and postpartum women in Massachusetts
Schiff, D. M., Nielsen, T., Terplan, M., Hood, M., Bernson, D., Diop, H., Bharel, M., Wilens, T. E., LaRochelle, M., Walley, A. Y., et al. (2018) · Obstetrics & Gynecology · doi:10.1097/aog.0000000000002734 · Cited by 327 · see citing works
Understanding Links among Opioid Use, Overdose, and Suicide
Bohnert, A. S. B., & Ilgen, M. A. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1802148 · Cited by 321 · see citing works
Retention of patients in opioid substitution treatment: A systematic review
O’Connor, A. M., Cousins, G., Durand, L., Barry, J., & Boland, F. (2020) · PLOS ONE · doi:10.1371/journal.pone.0232086 · Cited by 298 · see citing works
“Given that OST is first-line treatment for opioid dependence [5, 6], and retention in OST is associated with substantial reductions in the risk for all cause and overdose mortality [15], a comprehensive assessment of retention in OST is warranted.”
BackgroundInfluentialTreatment for Opioid Use Disorder: Population Estimates — United States, 2022
Dowell, D., Brown, S., Gyawali, S., Hoenig, J. M., Ko, J. Y., Mikosz, C. A., Ussery, E. N., Baldwin, G. T., Jones, C. M., Olsen, Y. K., et al. (2024) · MMWR Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm7325a1 · Cited by 268 · see citing works
Haffajee, R. L., Lin, L. A., Bohnert, A. S. B., & Goldstick, J. E. (2019) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.6373 · Cited by 266 · see citing works
Policy Pathways to Address Provider Workforce Barriers to Buprenorphine Treatment
Haffajee, R. L., Bohnert, A. S. B., & Lagisetty, P. (2018) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2017.12.022 · Cited by 252 · see citing works
The United States opioid epidemic
Lyden, J. R., & Binswanger, I. A. (2019) · Seminars in Perinatology · doi:10.1053/j.semperi.2019.01.001 · Cited by 249 · see citing works
“the British Medical Journal in 2017 found that patients who received maintenance buprenorphine or methadone had substantially reduced all-cause and overdose mortality rates when compared to patients who did not receive opioid agonist medications.(102) A Cochrane review by Mattick et al in 2009 and 2014 also showed tha…”
BackgroundEnglander, H., Dobbertin, K., Lind, B. K., Nicolaidis, C., Graven, P., Dorfman, C., & Korthuis, P. T. (2019) · Journal of General Internal Medicine · doi:10.1007/s11606-019-05251-9 · Cited by 234 · see citing works
Madras, B. K., Ahmad, N. J., Wen, J., Sharfstein, J., & Prevention, T. (2020) · NAM Perspectives · doi:10.31478/202004b · Cited by 241 · see citing works
“Treatment with methadone and buprenorphine has additional, well-established benefi ts. Methadone and buprenorphine substantially decrease the risk of overdose, opioid-related and all-cause mortality, and the spread of infectious diseases such as human immunodefi ciency virus (HIV) and hepatitis C virus (HCV)[6,7].”
BackgroundIrvine, M. A., Kuo, M. E., Buxton, J. A., Balshaw, R. F., Otterstatter, M. C., MacDougall, L., Milloy, M., Bharmal, A., Henry, B., TYNDALL, M. W., et al. (2019) · Addiction · doi:10.1111/add.14664 · Cited by 233 · see citing works
Hadland, S. E., Bagley, S. M., Rodean, J., Silverstein, M., Levy, S., Larochelle, M. R., Samet, J. H., & Zima, B. T. (2018) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2018.2143 · Cited by 220 · see citing works
“The advantage of this approach is supported by a recent, large meta-analysis, which found that, among adults, remaining in treatment is associated with substantially reduced all-cause mortality and mortality from overdose.(15) Our findings reveal a critical gap in quality of care for youths, with only a minority who s…”
InfluentialWitkiewitz, K., & Vowles, K. E. (2018) · Alcoholism: Clinical and Experimental Research · doi:10.1111/acer.13594 · Cited by 248 · see citing works
“The risk of all-cause mortality from the combination of alcohol and opioids has not been studied, and most research on opioid mortality has focused on opioid overdose risk, with few studies examining all-cause mortality (Sordo et al., 2017).”
Extended‐release injectable naltrexone for opioid use disorder: a systematic review
Jarvis, B. P., Holtyn, A. F., Subramaniam, S., Tompkins, D. A., Oga, E. A., Bigelow, G. E., & Silverman, K. (2018) · Addiction · doi:10.1111/add.14180 · Cited by 218 · see citing works
“Given the high dropout rates observed in the reviewed studies and the known overdose risks of stopping agonist treatment [76], it is critical that future studies and real-world evaluations evaluate and report fatal and non-fatal overdoses more rigorously.”
McQueenie, R., Ellis, D. A., McConnachie, A., Wilson, P., & Williamson, A. E. (2019) · BMC Medicine · doi:10.1186/s12916-018-1234-0 · Cited by 216 · see citing works
Williams, A. R., Samples, H., Crystal, S., & Olfson, M. (2019) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2019.19060612 · Cited by 211 · see citing works
“Our study refines this finding, demonstrating that the period following buprenorphine discontinuation is associated with rates of overdose approximately two to three times higher than those observed in a general sample of patients with opioid use disorder (29).”
BackgroundPearce, L. A., Min, J. E., Piske, M., Zhou, H., Homayra, F., Slaunwhite, A., Irvine, M. A., McGowan, G., & Nosyk, B. (2020) · BMJ · doi:10.1136/bmj.m772 · Cited by 208 · see citing works
Defining Low-threshold Buprenorphine Treatment
Jakubowski, A. U., & Fox, A. D. (2019) · Journal of Addiction Medicine · doi:10.1097/adm.0000000000000555 · Cited by 206 · see citing works
“People with OUD need consistent access to these medications, and overdose mortality is far lower during periods of treatment than after medications are stopped (Sordo et al., 2017).”
BackgroundTouchpoints—opportunities to predict and prevent opioid overdose: a cohort study.
Larochelle, M. R., Bernstein, R., Bernson, D., Land, T., Stopka, T. J., Rose, A. J., Bharel, M., Liebschutz, J. M., & Walley, A. Y. (2019) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2019.06.039 · Cited by 189 · see citing works
“Naloxone distribution programs and treatment with medications for opioid use disorder (MOUD) are associated with reduced opioid overdose mortality (McDonald and Strang, 2016; Sordo et al., 2017; Walley et al., 2013).”
BackgroundRacial Inequality in Receipt of Medications for Opioid Use Disorder
Barnett, M. L., Meara, E. R., Lewinson, T., Hardy, B., Chyn, D., Onsando, W. M., Huskamp, H. A., Mehrotra, A., & Morden, N. E. (2023) · New England Journal of Medicine · doi:10.1056/nejmsa2212412 · Cited by 190 · see citing works
Hawk, K. F., D’Onofrio, G., Chawarski, M. C., O’Connor, P. G., Cowan, E. A., Lyons, M. S., Richardson, L. D., Rothman, R. E., Whiteside, L., Owens, P. H., et al. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.4561 · Cited by 182 · see citing works
Frank, D., Mateu‐Gelabert, P., Perlman, D. C., Walters, S. M., Curran, L., & Guarino, H. (2021) · Harm Reduction Journal · doi:10.1186/s12954-021-00535-y · Cited by 183 · see citing works
Krawczyk, N., Mojtabai, R., Stuart, E. A., Fingerhood, M., Agus, D., Lyons, B. C., Weiner, J. P., & Saloner, B. (2020) · Addiction · doi:10.1111/add.14991 · Cited by 177 · see citing works
Lewer, D., Freer, J., King, E., Larney, S., Degenhardt, L. J., Tweed, E., Hope, V. D., Harris, M., Millar, T., Hayward, A. C., et al. (2019) · Addiction · doi:10.1111/add.14892 · Cited by 179 · see citing works
“Despite a body of research into the effectiveness of opiate substitutes to reduce use of street heroin [95], community-distributed naloxone to prevent overdose deaths [96], strategies to reduce transmission of hepatitis C and improve access to hepatitis C treatment [97] and some strategies to improve treatment of soft…”
Primary Care and the Opioid-Overdose Crisis — Buprenorphine Myths and Realities
Wakeman, S. E., & Barnett, M. L. (2018) · New England Journal of Medicine · doi:10.1056/nejmp1802741 · Cited by 174 · see citing works
Developing an opioid use disorder treatment cascade: A review of quality measures
Williams, A. R., Nunes, E. V., Bisaga, A. M., Pincus, H. A., Johnson, K., Campbell, A. N. C., Remien, R. H., Crystal, S., Friedmann, P. D., LEVIN, F. R., et al. (2018) · Journal of Substance Abuse Treatment · doi:10.1016/j.jsat.2018.06.001 · Cited by 172 · see citing works
Malta, M., Varatharajan, T., Russell, C., Pang, M., Bonato, S., & Fischer, B. (2019) · PLoS Medicine · doi:10.1371/journal.pmed.1003002 · Cited by 171 · see citing works
“Among the general population with diagnosed OUD, OAT is highly effective [19].”
BackgroundKrawczyk, N., Picher, C. E., Feder, K. A., & Saloner, B. K. (2017) · Health Affairs · doi:10.1377/hlthaff.2017.0890 · Cited by 168 · see citing works
Karlsson, A., & Håkansson, A. (2018) · Journal of Behavioral Addictions · doi:10.1556/2006.7.2018.112 · Cited by 164 · see citing works
“In addition, and compared to the extensive literature of mortality on substance-related addictive disorders, where mortality rates have been shown to be highly elevated (Laramée et al., 2015; Singleton, Degenhardt, Hall, & Zabransky, 2009; Sordo et al., 2017; Whiteford et al., 2013), very little has been published abo…”
BackgroundKeeping Up with Clinical Advances: Opioid Use Disorder
Patel, B., & Kosten, T. R. (2019) · CNS Spectrums · doi:10.1017/s109285291900110x · Cited by 164 · see citing works
All-Cause and Cause-Specific Mortality Among People Using Extramedical Opioids
Larney, S., Tran, L. T., Leung, J., Santo, T., Santomauro, D. F., Hickman, M., Peacock, A., Stockings, E., & Degenhardt, L. J. (2019) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2019.4170 · Cited by 162 · see citing works
Cost-effectiveness of Treatments for Opioid Use Disorder
Fairley, M., Humphreys, K. N., Joyce, V. R., Bounthavong, M., Trafton, J. A., Combs, A., Oliva, E. M., Goldhaber‐Fiebert, J. D., Asch, S. M., Brandeau, M. L., et al. (2021) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2021.0247 · Cited by 163 · see citing works
Medication Treatment For Opioid Use Disorders In Substance Use Treatment Facilities
Mojtabai, R., Mauro, C., Wall, M. M., Barry, C. L., & Olfson, M. (2019) · Health Affairs · doi:10.1377/hlthaff.2018.05162 · Cited by 158 · see citing works
Morgan, J. R., Schackman, B. R., Weinstein, Z. M., Walley, A. Y., & Linas, B. P. (2019) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2019.02.031 · Cited by 159 · see citing works
“For methadone and buprenorphine, a meta-analysis demonstrated substantially elevated mortality risk in the initial four weeks after discontinuation (Sordo et al., 2017).”
BackgroundMethadone Matters: What the United States Can Learn from the Global Effort to Treat Opioid Addiction
Calcaterra, S. L., Bach, P., Chadi, A., Chadi, N., Kimmel, S. D., Morford, K. L., Roy, P. J., & Samet, J. H. (2019) · Journal of General Internal Medicine · doi:10.1007/s11606-018-4801-3 · Cited by 151 · see citing works
Recommendations for buprenorphine and methadone therapy in opioid use disorder: a European consensus
Dematteis, M., Auriacombe, M., D’Agnone, O., Somaini, L., Szerman, N., Littlewood, R., Alam, F., Alho, H., Benyamina, A., Bobes, J., et al. (2017) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2017.1409722 · Cited by 141 · see citing works
“including opioid agonist medication, is associated with important social and clinical benefits, reduces overdose deaths and crime, increases quality of life [6,7], and enables patients to”
BackgroundAddictions in the COVID-19 era: Current evidence, future perspectives a comprehensive review
Mallet, J., Dubertret, C., & Strat, Y. L. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110070 · Cited by 167 · see citing works
Hall, N. Y., Le, L. K., Majmudar, I. K., & Mihalopoulos, C. (2021) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2021.108651 · Cited by 141 · see citing works
The Future of Fentanyl and Other Synthetic Opioids
Pardo, B., Taylor, J., Caulkins, J. P., Kilmer, B., Reuter, P. H., & Stein, B. D. (2019) · RAND Corporation eBooks · doi:10.7249/rr3117 · Cited by 139 · see citing works
Kohan, L. R., Potru, S., Barreveld, A. M., Sprintz, M., Lane, O. P., Aryal, A., Emerick, T. D., Dopp, A., Chhay, S., & Viscusi, E. R. (2021) · Regional Anesthesia & Pain Medicine · doi:10.1136/rapm-2021-103007 · Cited by 146 · see citing works
Hickman, M., Steer, C. D., Tilling, K. M., Lim, A. G., Marsden, J., Millar, T., Strang, J., Telfer, M., Vickerman, P. T., & Macleod, J. (2018) · Addiction · doi:10.1111/add.14188 · Cited by 134 · see citing works
“Mortality risk is reduced during treatment, as shown in reviews that compare mortality rates in and out of OST [43], but our model estimates suggest that the overall treatment duration, at least in UK primary care, is too short to have a population bene fi t.”
BackgroundMethodResultInfluentialWinhusen, T. M., Walley, A. Y., Fanucchi, L. C., Hunt, T., Lyons, M., Lofwall, M. R., Brown, J. L., Freeman, P. R., Nunes, E. V., Beers, D., et al. (2020) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2020.108325 · Cited by 133 · see citing works
“Methadone and buprenorphine, two of the three FDA-approved medications for treating opioid use disorder (OUD), decrease all-cause and overdose mortality for persons with OUD (Larochelle et al., 2018; Pearce et al., 2020; Sordo et al., 2017).”
Opioid Use Disorders: Perioperative Management of a Special Population
Ward, E. N., Quaye, A., & Wilens, T. E. (2018) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000003477 · Cited by 133 · see citing works
Baddour, L. M., Weimer, M. B., Wurcel, A. G., McElhinney, D. B., Marks, L. R., Fanucchi, L. C., Garrigos, Z. E., Pettersson, G., & DeSimone, D. C. (2022) · Circulation · doi:10.1161/cir.0000000000001090 · Cited by 135 · see citing works
Consensus Recommendations on the Treatment of Opioid Use Disorder in the Emergency Department
Hawk, K. F., Hoppe, J. A., Ketcham, E. M., LaPietra, A. M., Moulin, A. K., Nelson, L. S., Schwarz, E. S., Shahid, S., Stader, D. E., Wilson, M. P., et al. (2021) · Annals of Emergency Medicine · doi:10.1016/j.annemergmed.2021.04.023 · Cited by 125 · see citing works
Expanding access to buprenorphine treatment in rural areas with the use of telemedicine
Weintraub, E., Greenblatt, A. D., Chang, J. W., Himelhoch, S. S., & Welsh, C. (2018) · American Journal on Addictions · doi:10.1111/ajad.12805 · Cited by 124 · see citing works
Krawczyk, N., Buresh, M. E., Gordon, M., Blue, T. R., Fingerhood, M., & Agus, D. (2019) · Journal of Substance Abuse Treatment · doi:10.1016/j.jsat.2019.05.002 · Cited by 124 · see citing works
“, especially in the current state of the opioid crisis, is critical given the high risk of overdose and death among this population (a third of patients had previously overdosed), and the proven effectiveness of buprenorphine in reducing overdose risk (Sordo et al., 2017), even during continued illicit substance use (…”
BackgroundBabu, K. M., Brent, J. A., & Juurlink, D. N. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1807054 · Cited by 123 · see citing works
Chambers, L. C., Hallowell, B. D., Zullo, A. R., Paiva, T. J., Berk, J., Gaither, R., Hampson, A. J., Beaudoin, F. L., & Wightman, R. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.34540 · Cited by 122 · see citing works
“004 Male 3950 (61) 1987 (61) 424 (63) Unknown 115 (2) 95 (3) 5 (1) Health insurance type Medicaid 2153 (33) 1162 (36) 214 (32)”
Magwood, O., Salvalaggio, G., Beder, M., Kendall, C., Kpadé, V., Daghmach, W., Habonimana, G., Marshall, Z., Snyder, E., O'Shea, T., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0227298 · Cited by 112 · see citing works
“Results suggest that buprenorphine and methadone are the most effective pharmaceutical agents to address mortality and morbidity among people who use substances [50,57,60].”
InfluentialJoudrey, P. J., Chadi, N., Roy, P. J., Morford, K. L., Bach, P., Kimmel, S. D., Wang, E. A., & Calcaterra, S. L. (2020) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2020.107968 · Cited by 117 · see citing works
“Overwhelming evidence demonstrates methadone prevents opioid overdose deaths (Larochelle et al., 2018; Sordo et al., 2017).”
BackgroundColledge‐Frisby, S., Peacock, A., Leung, J., Larney, S., Grebely, J., Hickman, M., Cunningham, E. B., Trickey, A., Stone, J., Vickerman, P. T., et al. (2019) · International Journal of Drug Policy · doi:10.1016/j.drugpo.2019.07.030 · Cited by 115 · see citing works
Frost, M., Bailey, G. L., Lintzeris, N., Strang, J., Dunlop, A. J., Nunes, E. V., Jansen, J. B., Frey, L. C., Weber, B., Haber, P., et al. (2019) · Addiction · doi:10.1111/add.14636 · Cited by 114 · see citing works
Carter, J., Zevin, B., & Lum, P. J. (2019) · Addiction Science & Clinical Practice · doi:10.1186/s13722-019-0149-1 · Cited by 110 · see citing works
The opioid crisis and HIV in the USA: deadly synergies
Hodder, S., Feinberg, J., Strathdee, S. A., SHOPTAW, S. J., Altice, F. L., Ortenzio, L., & Beyrer, C. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00391-3 · Cited by 111 · see citing works
Prevalence and treatment of opioid use disorders among primary care patients in six health systems
Lapham, G. T., Boudreau, D. M., Johnson, E. A., Bobb, J. F., Matthews, A. G., McCormack, J., Liu, D., Samet, J. H., Saxon, A. J., Campbell, C. I., et al. (2019) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2019.107732 · Cited by 106 · see citing works
Access to Office-Based Buprenorphine Treatment in Areas With High Rates of Opioid-Related Mortality
Beetham, T., Saloner, B. K., Wakeman, S. E., Gaye, M., & Barnett, M. L. (2019) · Annals of Internal Medicine · doi:10.7326/m18-3457 · Cited by 105 · see citing works
Brothers, S., Viera, A., & Heimer, R. (2021) · Journal of Substance Abuse Treatment · doi:10.1016/j.jsat.2021.108449 · Cited by 104 · see citing works
“Since methadone treatment reduces mortality for people with OUD (Sordo et al., 2017), and unsupervised take-home dosing is positively associated with treatment retention and improvement in quality of life and employment, and does not differ from supervised in-person dosing in illicit opioid use, diversion, or patient…”
BackgroundMcAuley, A., Matheson, C., & Robertson, J. (2021) · International Journal of Drug Policy · doi:10.1016/j.drugpo.2021.103512 · Cited by 104 · see citing works
Barnett, M. L., Lee, D., & Frank, R. G. (2019) · Health Affairs · doi:10.1377/hlthaff.2019.00859 · Cited by 103 · see citing works
The cascade of care for opioid use disorder: a retrospective study in British Columbia, Canada
Piske, M., Zhou, H., Min, J. E., Hongdilokkul, N., Pearce, L. A., Homayra, F., Socias, M. E., McGowan, G., & Nosyk, B. (2020) · Addiction · doi:10.1111/add.14947 · Cited by 104 · see citing works
“Compared with those never on OAT, those currently engaged in OAT were more likely to be under 45 years of age (adjusted odds ratio: 1.75; 95% confidence interval: 1.64,1.89), male (1.72; 1.64,1.82), with concurrent substance use disorders (2.56; 2.44,2.70), HCV (1.22; 1.14,1.33) and either homeless or receiving income…”
BackgroundInfluentialPottie, K. C., Kendall, C., Aubry, T., Magwood, O., Andermann, A. A. J., Salvalaggio, G., Ponka, D., Bloch, G. C., Brcic, V., Agbata, E. N., et al. (2020) · Canadian Medical Association Journal · doi:10.1503/cmaj.190777 · Cited by 102 · see citing works
Eaton, E., Westfall, A. O., McClesky, B., Paddock, C. S., Lane, P. S., Cropsey, K. L., & Lee, R. A. (2020) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofaa074 · Cited by 102 · see citing works
“In cases of opioid use disorders (OUD), our AM providers prescribe medications for OUD (MOUD), which is associated with reduction in illicit opioid use, overdose, death, and retention in treatment [11, 12].”
BackgroundHulme, S., Bright, D. A., & Nielsen, S. (2018) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2018.02.010 · Cited by 104 · see citing works
Association of Medicaid Expansion With Opioid Overdose Mortality in the United States
Kravitz‐Wirtz, N., Davis, C. S., Ponicki, W. R., Rivera‐Aguirre, A., Marshall, B. D. L., Martins, S. S., & Cerdá, M. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.19066 · Cited by 101 · see citing works
Impact Of Long-Term Buprenorphine Treatment On Adverse Health Care Outcomes In Medicaid
Samples, H., Williams, A. R., Crystal, S., & Olfson, M. (2020) · Health Affairs · doi:10.1377/hlthaff.2019.01085 · Cited by 100 · see citing works
Methadone in Primary Care — One Small Step for Congress, One Giant Leap for Addiction Treatment
Samet, J. H., Botticelli, M. P., & Bharel, M. (2018) · New England Journal of Medicine · doi:10.1056/nejmp1803982 · Cited by 99 · see citing works
Pharmacological and Behavioral Treatment of Opioid Use Disorder
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“1 per 1,000 person-years in and out of methadone treatment, respectively) (32).”
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“Though mortality rates are highest amongst users not in treatment, deaths during treatment and following the end of treatment are still observed [6,7].”
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“The evaluation of policy efforts to address the current opioid crisis has focused on reducing the risk of overdose and death, that fortunately affect relatively small numbers of people, while treatment trials have focused on abstinence or days of drug use, both salient indicators of disease severity (Gowing et al., 20…”
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“Patients randomized to placebo withdrawal, compared with methadone or buprenorphine maintenance treatment, are 2 times to 4 times more likely to be dead at a year.(3,8) A Cochrane meta-analysis of oral naltrexone showed no difference compared with”
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Addressing Racial And Ethnic Disparities In The Use Of Medications For Opioid Use Disorder
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“OUD was defined using the diagnostic criteria for OUD as defined in the Diagnostic and Statistical Manual (DSM)-IV, DSM-V, or International Statistical Classification of Diseases and Related Health Problems (ICD)-10 manuals.”
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“The first 4 weeks after initiation of methadone treatment and following cessation of buprenorphine or methadone treatment are the periods of greatest mortality risk, and should be the main focus of efforts for the prevention of drug-related deaths (Sordo et al., 2017).”
BackgroundThe Pharmacology of Buprenorphine Microinduction for Opioid Use Disorder
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“Further, as the risk of overdose is greater during the start and cessation of opioid pharmacotherapies, this approach may offer a safer way to transition from full opioid agonists to BUP, reducing the mortality associated with OUD [11].”
BackgroundStructural Racism and the Opioid Overdose Epidemic: The Need for Antiracist Public Health Practice
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“A strong body of evidence indicates that the MOUDs methadone and buprenorphine are highly effective first-line treatments of opioid use disorder that reduce the risk of overdose.(17,18) Both medications are tightly regulated, although buprenorphine can be prescribed by outpatient providers of any specialty following a…”
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“While data are limited in surgical patients, failure to initiate treatment for OUD increases morbidity and mortality in nonsurgical populations.(84) Evaluation for OUD should be nonjudgmental, and providers should be conscious of potential stigma and implicit bias.”
Background
- 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
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2017-04-26
- Volume
- 357
- Pages
- j1550
- ISSN
- 1756-1833 (ISSN-L)
- 0959-8138
- 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 · 2013: 1 · 2012: 1
- FWCI
- 23.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- 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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