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.
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Author, Article, and Disclosure Information
Clinical Addiction Research and Education Unit at Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts (M.R.L., S.M.B.)
Office of Special Analytic Projects, Office of Population Health, Massachusetts Department of Public Health, Boston, Massachusetts (D.B., T.L.)
Tufts University School of Medicine, Boston, Massachusetts (T.J.S.)
Biostatistics and Epidemiology Data Analytics Center, Boston University School of Public Health, Boston, Massachusetts (N.W.)
Boston University School of Public Health, Boston, Massachusetts (Z.X.)
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.)
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, marc.
Corresponding Author: Marc R. Larochelle, MD, MPH, Boston Medical Center, 801 Massachusetts Avenue, 2nd Floor, Boston, MA 02118; e-mail, marc.
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.
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