Original Research
19 June 2018

Medication for Opioid Use Disorder After Nonfatal Opioid Overdose and Association With Mortality: A Cohort Study

Publication: Annals of Internal Medicine
Volume 169, Number 3

Abstract

Background:

Opioid overdose survivors have an increased risk for death. Whether use of medications for opioid use disorder (MOUD) after overdose is associated with mortality is not known.

Objective:

To identify MOUD use after opioid overdose and its association with all-cause and opioid-related mortality.

Design:

Retrospective cohort study.

Setting:

7 individually linked data sets from Massachusetts government agencies.

Participants:

17 568 Massachusetts adults without cancer who survived an opioid overdose between 2012 and 2014.

Measurements:

Three types of MOUD were examined: methadone maintenance treatment (MMT), buprenorphine, and naltrexone. Exposure to MOUD was identified at monthly intervals, and persons were considered exposed through the month after last receipt. A multivariable Cox proportional hazards model was used to examine MOUD as a monthly time-varying exposure variable to predict time to all-cause and opioid-related mortality.

Results:

In the 12 months after a nonfatal overdose, 2040 persons (11%) enrolled in MMT for a median of 5 months (interquartile range, 2 to 9 months), 3022 persons (17%) received buprenorphine for a median of 4 months (interquartile range, 2 to 8 months), and 1099 persons (6%) received naltrexone for a median of 1 month (interquartile range, 1 to 2 months). Among the entire cohort, all-cause mortality was 4.7 deaths (95% CI, 4.4 to 5.0 deaths) per 100 person-years and opioid-related mortality was 2.1 deaths (CI, 1.9 to 2.4 deaths) per 100 person-years. Compared with no MOUD, MMT was associated with decreased all-cause mortality (adjusted hazard ratio [AHR], 0.47 [CI, 0.32 to 0.71]) and opioid-related mortality (AHR, 0.41 [CI, 0.24 to 0.70]). Buprenorphine was associated with decreased all-cause mortality (AHR, 0.63 [CI, 0.46 to 0.87]) and opioid-related mortality (AHR, 0.62 [CI, 0.41 to 0.92]). No associations between naltrexone and all-cause mortality (AHR, 1.44 [CI, 0.84 to 2.46]) or opioid-related mortality (AHR, 1.42 [CI, 0.73 to 2.79]) were identified.

Limitation:

Few events among naltrexone recipients preclude confident conclusions.

Conclusion:

A minority of opioid overdose survivors received MOUD. Buprenorphine and MMT were associated with reduced all-cause and opioid-related mortality.

Primary Funding Source:

National Center for Advancing Translational Sciences of the National Institutes of Health.

Get full access to this article

View all available purchase options and get full access to this article.

Supplemental Material

Supplement. Supplementary Material

References

1.
Rudd RASeth PDavid FScholl L. Increases in drug and opioid-involved overdose deaths—United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016;65:1445-52. [PMID: 28033313]  doi: 10.15585/mmwr.mm655051e1
2.
Volkow NDFrieden TRHyde PSCha SS. Medication-assisted therapies—tackling the opioid-overdose epidemic. N Engl J Med. 2014;370:2063-6. [PMID: 24758595]  doi: 10.1056/NEJMp1402780
3.
Caudarella ADong HMilloy MJKerr TWood EHayashi K. Non-fatal overdose as a risk factor for subsequent fatal overdose among people who inject drugs. Drug Alcohol Depend. 2016;162:51-5. [PMID: 26993373]  doi: 10.1016/j.drugalcdep.2016.02.024
4.
Stoové MADietze PMJolley D. Overdose deaths following previous non-fatal heroin overdose: record linkage of ambulance attendance and death registry data. Drug Alcohol Rev. 2009;28:347-52. [PMID: 19594787]  doi: 10.1111/j.1465-3362.2009.00057.x
5.
Darke SMills KLRoss JTeesson M. Rates and correlates of mortality amongst heroin users: findings from the Australian Treatment Outcome Study (ATOS), 2001-2009. Drug Alcohol Depend. 2011;115:190-5. [PMID: 21130585]  doi: 10.1016/j.drugalcdep.2010.10.021
6.
Coffin POTracy MBucciarelli AOmpad DVlahov DGalea S. Identifying injection drug users at risk of nonfatal overdose. Acad Emerg Med. 2007;14:616-23. [PMID: 17554010]
7.
Darke SWilliamson ARoss JMills KLHavard ATeesson M. Patterns of nonfatal heroin overdose over a 3-year period: findings from the Australian Treatment Outcome Study. J Urban Health. 2007;84:283-91. [PMID: 17265131]
8.
Krupitsky ENunes EVLing WIlleperuma AGastfriend DRSilverman BL. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. Lancet. 2011;377:1506-13. [PMID: 21529928]  doi: 10.1016/S0140-6736(11)60358-9
9.
Mattick RPBreen CKimber JDavoli M. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database Syst Rev. 2009:CD002209. [PMID: 19588333]  doi: 10.1002/14651858.CD002209.pub2
10.
Mattick RPBreen CKimber JDavoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014:CD002207. [PMID: 24500948]  doi: 10.1002/14651858.CD002207.pub4
11.
Sordo LBarrio GBravo MJIndave BIDegenhardt LWiessing Let al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017;357:j1550. [PMID: 28446428]  doi: 10.1136/bmj.j1550
12.
Lincoln TJohnson BDMcCarthy PAlexander E. Extended-release naltrexone for opioid use disorder started during or following incarceration. J Subst Abuse Treat. 2018;85:97-100. [PMID: 28479011]  doi: 10.1016/j.jsat.2017.04.002
13.
Lee JDFriedmann PDKinlock TWNunes EVBoney TYHoskinson RA Jret al. Extended-release naltrexone to prevent opioid relapse in criminal justice offenders. N Engl J Med. 2016;374:1232-42. [PMID: 27028913]  doi: 10.1056/NEJMoa1505409
14.
Kelty EHulse G. Examination of mortality rates in a retrospective cohort of patients treated with oral or implant naltrexone for problematic opiate use. Addiction. 2012;107:1817-24. [PMID: 22487087]  doi: 10.1111/j.1360-0443.2012.03910.x
15.
Gibson AEDegenhardt LJ. Mortality related to pharmacotherapies for opioid dependence: a comparative analysis of coronial records. Drug Alcohol Rev. 2007;26:405-10. [PMID: 17564876]
16.
The Commonwealth of Massachusetts. Data brief: opioid-related overdose deaths among Massachusetts residents. Massachusetts Department of Public Health. 2018. Accessed at www.mass.gov/files/documents/2018/02/14/data-brief-overdose-deaths-february-2018.pdf on 28 March 2018.
17.
The Commonwealth of Massachusetts. An assessment of opioid-related deaths in Massachusetts (2013-2014). Massachusetts Department of Public Health. 2016. Accessed at www.mass.gov/eohhs/docs/dph/stop-addiction/dph-legislative-report-chapter-55-opioid-overdose-study-9-15-2016.pdf on 9 August 2017.
18.
The Commonwealth of Massachusetts. An assessment of fatal and nonfatal opioid overdoses in Massachusetts (2011-2015). Massachusetts Department of Public Health. 2017. Accessed at https://pilot.mass.gov/files/documents/2017/08/31/legislative-report-chapter-55-aug-2017.pdf on 25 May 2018.
19.
Wu LTZhu HSwartz MS. Treatment utilization among persons with opioid use disorder in the United States. Drug Alcohol Depend. 2016;169:117-27. [PMID: 27810654]  doi: 10.1016/j.drugalcdep.2016.10.015
20.
Green CAPerrin NAJanoff SLCampbell CIChilcoat HDCoplan PM. Assessing the accuracy of opioid overdose and poisoning codes in diagnostic information from electronic health records, claims data, and death records. Pharmacoepidemiol Drug Saf. 2017;26:509-17. [PMID: 28074520]  doi: 10.1002/pds.4157
21.
Davoli MBargagli AMPerucci CASchifano PBelleudi VHickman Met alVEdeTTE Study Group. Risk of fatal overdose during and after specialist drug treatment: the VEdeTTE study, a national multi-site prospective cohort study. Addiction. 2007;102:1954-9. [PMID: 18031430]
22.
Snapinn SMJiang QIglewicz B. Illustrating the impact of a time-varying covariate with an extended Kaplan-Meier estimator. Am Stat. 2005;59:301-7.
23.
VanderWeele TJDing P. Sensitivity analysis in observational research: introducing the E-value. Ann Intern Med. 2017;167:268-74. [PMID: 28693043].  doi: 10.7326/M16-2607
24.
Larochelle MRLiebschutz JMZhang FRoss-Degnan DWharam JF. Opioid prescribing after nonfatal overdose and association with repeated overdose: a cohort study. Ann Intern Med. 2016;164:1-9. [PMID: 26720742].  doi: 10.7326/M15-0038
25.
Frazier WCochran GLo-Ciganic WHGellad WFGordon AJChang CHet al. Medication-assisted treatment and opioid use before and after overdose in Pennsylvania Medicaid. JAMA. 2017;318:750-2. [PMID: 28829862]  doi: 10.1001/jama.2017.7818
26.
Cousins SJRadfar SRCrèvecoeur-MacPhail DAng ADarfler KRawson RA. Predictors of continued use of extended-released naltrexone (XR-NTX) for opioid-dependence: an analysis of heroin and non-heroin opioid users in Los Angeles county. J Subst Abuse Treat. 2016;63:66-71. [PMID: 26823295]  doi: 10.1016/j.jsat.2015.12.004
27.
Morgan JRSchackman BRLeff JALinas BPWalley AY. Injectable naltrexone, oral naltrexone, and buprenorphine utilization and discontinuation among individuals treated for opioid use disorder in a United States commercially insured population. J Subst Abuse Treat. 2018;85:90-6. [PMID: 28733097]  doi: 10.1016/j.jsat.2017.07.001
28.
Lee JDNunes EV JrNovo PBachrach KBailey GLBhatt Set al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet. 2018;391:309-18. [PMID: 29150198]  doi: 10.1016/S0140-6736(17)32812-X
29.
Digiusto EShakeshaft ARitter AO’Brien SMattick RPNEPOD Research Group. Serious adverse events in the Australian national evaluation of pharmacotherapies for opioid dependence (NEPOD). Addiction. 2004;99:450-60. [PMID: 15049745]
30.
Hulse GKMorris NArnold-Reed DTait RJ. Improving clinical outcomes in treating heroin dependence: randomized, controlled trial of oral or implant naltrexone. Arch Gen Psychiatry. 2009;66:1108-15. [PMID: 19805701]  doi: 10.1001/archgenpsychiatry.2009.130
31.
Krupitsky EZvartau EBlokhina EVerbitskaya EWahlgren VTsoy-Podosenin Met al. Randomized trial of long-acting sustained-release naltrexone implant vs oral naltrexone or placebo for preventing relapse to opioid dependence. Arch Gen Psychiatry. 2012;69:973-81. [PMID: 22945623]  doi: 10.1001/archgenpsychiatry.2012.1a
32.
Pollini RAMcCall LMehta SHVlahov DStrathdee SA. Non-fatal overdose and subsequent drug treatment among injection drug users. Drug Alcohol Depend. 2006;83:104-10. [PMID: 16310322]
33.
D'Onofrio GChawarski MCO'Connor PGPantalon MVBusch SHOwens PHet al. Emergency department-initiated buprenorphine for opioid dependence with continuation in primary care: outcomes during and after intervention. J Gen Intern Med. 2017;32:660-6. [PMID: 28194688]  doi: 10.1007/s11606-017-3993-2
34.
D'Onofrio GO'Connor PGPantalon MVChawarski MCBusch SHOwens PHet al. Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial. JAMA. 2015;313:1636-44. [PMID: 25919527]  doi: 10.1001/jama.2015.3474
35.
Liebschutz JMCrooks DHerman DAnderson BTsui JMeshesha LZet al. Buprenorphine treatment for hospitalized, opioid-dependent patients: a randomized clinical trial. JAMA Intern Med. 2014;174:1369-76. [PMID: 25090173]  doi: 10.1001/jamainternmed.2014.2556

Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 169Number 37 August 2018
Pages: 137 - 145

History

Published online: 19 June 2018
Published in issue: 7 August 2018

Keywords

Authors

Affiliations

Marc R. Larochelle, MD, MPH
Clinical Addiction Research and Education Unit at Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts (M.R.L., S.M.B.)
Dana Bernson, MPH
Office of Special Analytic Projects, Office of Population Health, Massachusetts Department of Public Health, Boston, Massachusetts (D.B., T.L.)
Thomas Land, PhD
Office of Special Analytic Projects, Office of Population Health, Massachusetts Department of Public Health, Boston, Massachusetts (D.B., T.L.)
Thomas J. Stopka, PhD, MHS
Tufts University School of Medicine, Boston, Massachusetts (T.J.S.)
Na Wang, MA
Biostatistics and Epidemiology Data Analytics Center, Boston University School of Public Health, Boston, Massachusetts (N.W.)
Ziming Xuan, ScD, SM
Boston University School of Public Health, Boston, Massachusetts (Z.X.)
Sarah M. Bagley, MD, MSc
Clinical Addiction Research and Education Unit at Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts (M.R.L., S.M.B.)
Jane M. Liebschutz, MD, MPH
Clinical Addiction Research and Education Unit at Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, and Center for Research on Health Care, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (J.M.L.)
Alexander Y. Walley, MD, MSc
Clinical Addiction Research and Education Unit at Boston University School of Medicine and Boston Medical Center and Bureau of Substance Addiction Services, Massachusetts Department of Public Health, Boston, Massachusetts (A.Y.W.)
Financial Support: By grant 1UL1TR001430 from the National Center for Advancing Translational Sciences of the National Institutes of Health. Dr. Larochelle was supported by award K23 DA042168 from the National Institute on Drug Abuse and a Boston University School of Medicine Department of Medicine Career Investment Award. Dr. Stopka was supported by award 33924399 from the GE Foundation.
Disclosures: Dr. Larochelle reports grants from the National Center for Advancing Translational Sciences, National Institute on Drug Abuse, and Boston University School of Medicine Department of Medicine during the conduct of the study. Dr. Stopka reports grants from the GE Foundation during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-3107.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement: Study protocol and data set: Not available. Statistical code: Available from Dr. Larochelle (e-mail, [email protected]).
Corresponding Author: Marc R. Larochelle, MD, MPH, Boston Medical Center, 801 Massachusetts Avenue, 2nd Floor, Boston, MA 02118; e-mail, [email protected].
Current Author Addresses: Drs. Larochelle, Bagley, and Walley: Boston Medical Center, 801 Massachusetts Avenue, 2nd Floor, Boston, MA 02118.
Ms. Bernson and Dr. Land: Massachusetts Department of Public Health, 250 Washington Street, 6th Floor, Boston, MA 02108.
Dr. Stopka: Tufts University School of Medicine, 136 Harrison Avenue, MV244, Boston, MA 02111.
Ms. Wang and Dr. Xuan: Boston University School of Public Health, 801 Massachusetts Avenue, 3rd Floor, Boston, MA 02118.
Dr. Liebschutz: University of Pittsburgh School of Medicine Center for Research on Health Care, 200 Lothrop Street, Suite 933W, Pittsburgh, PA 15213.
Author Contributions: Conception and design: M.R. Larochelle, T. Land, S.M. Bagley, A.Y. Walley.
Analysis and interpretation of the data: M.R. Larochelle, D. Bernson, T. Land, T.J. Stopka, N. Wang, Z. Xuan, S.M. Bagley, J.M. Liebschutz, A.Y. Walley.
Drafting of the article: M.R. Larochelle, T. Land, A.Y. Walley.
Critical revision of the article for important intellectual content: M.R. Larochelle, D. Bernson, T. Land, T.J. Stopka, Z. Xuan, S.M. Bagley, J.M. Liebschutz, A.Y. Walley.
Final approval of the article: M.R. Larochelle, D. Bernson, T. Land, T.J. Stopka, N. Wang, Z. Xuan, S.M. Bagley, J.M. Liebschutz, A.Y. Walley.
Statistical expertise: T. Land, Z. Xuan.
Obtaining of funding: M.R. Larochelle, T.J. Stopka, A.Y. Walley.
Administrative, technical, or logistic support: M.R. Larochelle, D. Bernson, T. Land, A.Y. Walley.
Collection and assembly of data: M.R. Larochelle, D. Bernson, T. Land.
This article was published at Annals.org on 19 June 2018.

Metrics & Citations

Metrics

Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. For an editable text file, please select Medlars format which will download as a .txt file. Simply select your manager software from the list below and click Download.

For more information or tips please see 'Downloading to a citation manager' in the Help menu.

Format





Download article citation data for:
Marc R. Larochelle, Dana Bernson, Thomas Land, et al. Medication for Opioid Use Disorder After Nonfatal Opioid Overdose and Association With Mortality: A Cohort Study. Ann Intern Med.2018;169:137-145. [Epub 19 June 2018]. doi:10.7326/M17-3107

View More

Get Access

Login Options:
Purchase

You will be redirected to acponline.org to sign-in to Annals to complete your purchase.

Create your Free Account

You will be redirected to acponline.org to create an account that will provide access to Annals.

View options

PDF/ePub

View PDF/ePub

Related in ACP Journals

Full Text

View Full Text

Media

Figures

Other

Tables

Share

Share

Copy the content Link

Share on social media