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

      research-article
      , MD, MPH, , MPH, , PhD, , PhD, MHS, , MA, , ScD, SM, , MD, MSc, , MD, MPH, , MD, MSc
      Annals of internal medicine

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          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.

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          Most cited references16

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          Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial.

          Opioid-dependent patients often use the emergency department (ED) for medical care.
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            Is Open Access

            Treatment utilization among persons with opioid use disorder in the United States

            Background The United States is experiencing an opioid overdose epidemic. Treatment use data from diverse racial/ethnic groups with opioid use disorder (OUD) are needed to inform treatment expansion efforts. Methods We examined demographic characteristics and behavioral health of persons aged ≥12 years that met criteria for past-year OUD (n=6,125) in the 2005–2013 National Surveys on Drug Use and Health (N=503,101). We determined the prevalence and correlates of past-year use of alcohol/drug use treatment and opioid-specific treatment to inform efforts for improving OUD treatment. Results Among persons with OUD, 81.93% had prescription (Rx) OUD only, 9.75% had heroin use disorder (HUD) only, and 8.32% had Rx OUD+HUD. Persons with Rx OUD+HUD tended to be white, adults aged 18–49, males, or uninsured. The majority (80.09%) of persons with OUD had another substance use disorder (SUD), and major depressive episode (MDE) was common (28.74%). Of persons with OUD, 26.19% used any alcohol or drug use treatment, and 19.44% used opioid-specific treatment. Adolescents, the uninsured, blacks, native-Hawaiians/Pacific-Islanders/Asian-Americans, persons with Rx OUD only, and persons without MDE or SUD particularly underutilized opioid-specific treatment. Among alcohol/drug use treatment users, self-help group and outpatient rehabilitation treatment were commonly used services. Conclusions Most people with OUD report no use of OUD treatment. Multifaceted interventions, including efforts to access insurance coverage, are required to change attitudes and knowledge towards addiction treatment in order to develop a supportive culture and infrastructure to enable treatment-seeking. Outreach efforts could target adolescents, minority groups, and the uninsured to improve access to treatment.
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              Injectable naltrexone, oral naltrexone, and buprenorphine utilization and discontinuation among individuals treated for opioid use disorder in a United States commercially insured population

              We investigated prescribing patterns for five opioid use disorder (OUD) medications: 1) injectable naltrexone, 2) oral naltrexone, 3) sublingual or oromucosal buprenorphine/naloxone, 4) sublingual buprenorphine, and 5) transdermal buprenorphine in a nationally representative claims-based database (Truven Health MarketScan®) of commercially insured individuals in the United States. We calculated the prevalence of OUD in the database for each year from 2010 to 2014 and the proportion of diagnosed patient months on OUD medication. We compared characteristics of individuals diagnosed with OUD who did and did not receive OUD medications with bivariate descriptive statistics. Finally, we fit a Cox proportional hazards model of time to discontinuation of therapy as a function of therapy type, controlling for relevant confounders. From 2010 to 2014, the proportion of commercially insured individuals diagnosed with OUD grew by fourfold (0.12% to 0.48%), but the proportion of diagnosed patient-months on OUD medication decreased from 25% in 2010 (0.05% injectable naltrexone, 0.4% oral naltrexone, 23.1% sublingual or oromucosal buprenorphine/naloxone, 1.5% sublingual buprenorphine, and 0% transdermal buprenorphine) to 16% in 2014 (0.2% injectable naltrexone, 0.4% oral naltrexone, 13.8% sublingual or oromucosal buprenorphine/naloxone, 1.4% sublingual buprenorphine, and 0.3% transdermal buprenorphine). Individuals who received medication therapy were more likely to be male, younger, and have an additional substance use disorder compared with those diagnosed with OUD who did not receive medication therapy. Those prescribed injectable naltrexone were more often male, younger, and diagnosed with additional substance use disorders compared with those prescribed other medications for opioid use disorder (MOUDs). The proportion discontinuing MOUD 30 days or less after initiation was 52% for individuals treated with injectable naltrexone, 70% for individuals treated with oral naltrexone, 31% for individuals treated with sublingual or oromucosal buprenorphine/naloxone, 58% for individuals treated with sublingual buprenorphine, and 51% for individuals treated with transdermal buprenorphine. In the Cox proportional hazard model, use of injectable naltrexone, oral naltrexone, sublingual buprenorphine, and transdermal buprenorphine were all associated with significantly greater hazard of discontinuing therapy beginning more than 30 days after MOUD initiation (HR=2.17, 2.54, 1.15, and 2.21, respectively, 95% CIs 2.04–2.30, 2.45–2.64, 1.10–1.19, and 2.11–2.33), compared with the use of sublingual or oromucosal buprenorphine/naloxone. This analysis demonstrates that the use of evidence-based medication therapies has not kept pace with increases in OUD diagnoses in commercially insured populations in the United States. Among those who have been treated, discontinuation rates more than 30 days after initiation are high. The proportion treated with injectable naltrexone, oral naltrexone, and transdermal buprenorphine grew over time but remains small, and the discontinuation rates are higher among those treated with these medications compared with those treated with sublingual or oromucosal buprenorphine/naloxone. In the face of the opioid overdose and addiction crisis, new efforts are needed at the provider, health system, and policy levels so that MOUD availability and uptake keep pace with new OUD diagnoses and OUD treatment discontinuation is minimized.
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                Author and article information

                Contributors
                Journal
                0372351
                596
                Ann Intern Med
                Ann. Intern. Med.
                Annals of internal medicine
                0003-4819
                1539-3704
                28 January 2019
                19 June 2018
                07 August 2018
                24 February 2019
                : 169
                : 3
                : 137-145
                Affiliations
                Clinical Addiction Research and Education Unit at Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts
                Office of Special Analytic Projects, Office of Population Health, Massachusetts Department of Public Health, Boston, Massachusetts
                Office of Special Analytic Projects, Office of Population Health, Massachusetts Department of Public Health, Boston, Massachusetts
                Tufts University School of Medicine, Boston, Massachusetts
                Biostatistics and Epidemiology Data Analytics Center, Boston University School of Public Health, Boston, Massachusetts
                Biostatistics and Epidemiology Data Analytics Center, Boston University School of Public Health, Boston, Massachusetts
                Clinical Addiction Research and Education Unit at Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts
                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
                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
                Author notes

                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.

                Corresponding Author: Marc R. Larochelle, MD, MPH, Boston Medical Center, 801 Massachusetts Avenue, 2nd Floor, Boston, MA 02118; marc.larochelle@ 123456bmc.org .
                Article
                PMC6387681 PMC6387681 6387681 nihpa1002372
                10.7326/M17-3107
                6387681
                29913516
                1e458351-a900-4c38-bf93-d864f4cc4d4a
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