Nonfatal opioid overdose represents an opportunity to engage young adults into using medication for opioid use disorder. We seek to describe characteristics of young adults who experience nonfatal overdose and estimate rates of and time to medication for opioid use disorder for young adults relative to those aged 26 to 45 years.
We conducted a cohort study using retrospective administrative data of 15,281 individuals aged 18 to 45 years who survived an opioid-related overdose in Massachusetts between 2012 and 2014, using deidentified, individual-level, linked data sets from Massachusetts government agencies. We described patient characteristics stratified by age (18 to 21, 22 to 25, and 26 to 45 years) and evaluated multivariable Cox proportional hazards models to compare rates of medication for opioid use disorder receipt, controlling for age, sex, history of mental health disorders, and addiction treatment.
Among 4,268 young adults in the year after nonfatal overdose, 28% (n=336/1,209) of those aged 18 to 21, 36% (n=1,097/3,059) of those aged 22 to 25 years, and 36% (n=3,916/11,013) of those aged 26 to 45 years received medication for opioid use disorder. For individuals aged 18 to 21 and 22 to 25 years, median time to buprenorphine treatment was 4 months (interquartile range 1.7 to 1.8 months); to methadone treatment, 4 months (interquartile range 2.8 to 2.9 months); and to naltrexone treatment, 1 month (interquartile range 1 to 1 month). Individuals aged 18 to 21 years were less likely (adjusted hazard ratio 0.60 [95% confidence interval 0.45 to 0.70]) to receive methadone than those aged 22 to 25 and 26 to 45 years. Individuals aged 18 to 21 years and those aged 22 to 25 years were more likely to receive naltrexone (adjusted hazard ratio 1.65 [95% confidence interval 1.36 to 2.00] and 1.41 [95% confidence interval 1.23 to 1.61], respectively) than those aged 26 to 45 years.
One in 3 young adults received medication for opioid use disorder in the 12 months after surviving an overdose. Type of medication for opioid use disorder received appeared to be age associated. Future research should focus on how medication choice is made and how to optimize the emergency department for medication for opioid use disorder initiation after nonfatal overdose.
Materials and Methods
We conducted a retrospective cohort study of individuals in Massachusetts, aged 18 to 45 years, who had a nonfatal overdose between January 1, 2012, and December 31, 2014.
Data Collection and Processing
Chapter 55 of the Acts of 2015 mandated that the Massachusetts Department of Public Health analyze data from several Massachusetts government agencies and allowed the linkage of these data sets to identify and report on trends among persons who experienced fatal and nonfatal opioid overdose.
The General Court of the Commonwealth of Massachusetts. Chapter 55: an act requiring certain reports for opiate overdoses.
The Chapter 55 database includes Massachusetts residents aged 11 years and older who have public or private insurance.
Data from disparate agencies were linked through a 10-level match protocol and subsequently deidentified at the Massachusetts Department of Public Health, allowing this study to examine the full course of patients during the study period, from 2011 to 2015. The 10 levels of matches were tested between the data sets in Chapter 55 data sets and identifiers in the All Payers Claim Database. Data linkage was conducted by the Center for Health Information and Analysis in consultation with the Massachusetts Department of Public Health. All matches were deterministic. To improve accuracy, no close matches were used. The matching procedure produced matching from 71% to 100%. To obtain access to the data, our team submitted a proposal to the Massachusetts Department of Public Health for approval; all analyses occurred on site at the department.
To construct the set of variables needed for this study, we used data from the All Payers Claim Database, Massachusetts Department of Public Health Bureau of Substance Addiction Services, the Massachusetts Prescription Monitoring Program, Massachusetts Ambulance Trip Record Information System, and Massachusetts Acute Hospital Case Mix.
- Baker C.D.
- Polito K.E.
- Sudders M.
- et al.
An Assessment of Fatal and Nonfatal Opioid Overdoses in Massachusetts (2011-2015).
Selection of Participants
Individuals entered the cohort when they experienced a nonfatal overdose between January 1, 2012, and December 31, 2014, in Massachusetts, providing a full 12 months of observation before and after the nonfatal overdose. Each individual contributed only his or her first nonfatal overdose event in the data set window. Recurrent nonfatal overdose events were excluded. Nonfatal overdose was identified in 2 ways. First, any individual who had an ambulance encounter related to opioid overdose was included. The algorithm used to identify opioid-related overdoses in the emergency medical services data resulted from a collaboration between the Massachusetts Department of Public Health and the Centers for Disease Control and Prevention.
- Green C.A.
- Perrin N.A.
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- et al.
Assessing the accuracy of opioid overdose and poisoning codes in diagnostic information from electronic health records, claims data, and death records.
The second was an ED, observation, or hospital encounter with an International Classification of Diseases, Ninth Revision (ICD-9)
code containing a diagnosis code for opioid poisoning (965.00 to 965.02, 965.09, and E85.00 to E85.02).
- MacArthur G.J.
- Minozzi S.
- Martin N.
- et al.
Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis.
Visits to Veterans Administration hospitals were not included. There were 558 events that were removed from the analysis because death occurred within 30 days of the overdose.
The primary independent variable was age group, categorized as aged 18 to 21, 22 to 25, and 26 to 45 years. Young adulthood is a transitional period in which changes in brain function, social capital, and individual responsibility are greater than in other periods. Therefore, we subcategorized the age group to understand whether the characteristics and medication experience were consistent throughout the period. This has been shown in previous work that has revealed differences between aged 18 to 21 and 22 to 25 years. We chose to use the age group of 26 to 45 years as the comparison group because at aged 26 years, brain myelination of the frontal lobe has matured. This is also the age when young adults are no longer eligible to be on their parents’ health insurance. We capped the age group at 45 years so that our observations were not affected by the increasing onset of the chronic illnesses of aging, such as chronic obstructive pulmonary disease, chronic liver disease from hepatitis C infection, and alcohol and cardiovascular disease.
We included in the multivariable models the following covariates: sex (from the All Payers Claim Database), anxiety, and depression. Anxiety and depression were identified through ICD-9 and -10 diagnosis codes (anxiety 300.X and F41.X; depression 296.2X, 296.3X, 296.99, 300.4, 311, 625.4, F32.X, F33.X, F34.1, and F34.8X) and defined as having a claim for these conditions any time between 2011 and 2015. Homelessness was identified with ICD-9 diagnosis code V60.0 or ICD-10 diagnosis code Z590 in the All Payers Claim Database. Receipt of opioid prescriptions in the past 12 months was obtained from the Prescription Monitoring Program. We included involuntary commitment to substance use treatment through a special statute specific to Massachusetts because of risk to self or others in the previous 12 months before the nonfatal overdose, from the Bureau of Substance Addiction Services. The other covariates were Bureau of Substance Addiction Services–funded inpatient medical detoxification and residential substance use treatment (defined as any treatment beyond medical detoxification) in the 12 months before nonfatal overdose.
The primary outcome was receipt of medication for opioid use disorder, defined as follows: buprenorphine obtained from the Prescription Monitoring Program; oral or injectable naltrexone, obtained from the All Payers Claim Database; or methadone treatment as identified in Bureau of Substance Addiction Services or All Payers Claim Database data (identified by Healthcare Common Procedure Coding System code H0020). Receipt of medication for opioid use disorder was identified in each month, starting with the month of the nonfatal overdose through 12 months afterward.
Primary Data Analysis
We used summary statistics to describe characteristics of the cohort. We examined time to receipt of medication for opioid use disorder after nonfatal overdose by estimating Kaplan-Meier survival curves stratified by age groups (ie, 18 to 21, 22 to 25, and 26 to 45 years). Individuals were censored at 12 months or at death. We chose 12 months so we would have the same amount of follow-up time for all individuals in the cohort. We calculated median time to treatment in months and median duration of medication in months. We developed multivariable Cox proportional hazards models to compare rates of treatment receipt after nonfatal overdose, adjusting for sex, anxiety or depression diagnosis, homelessness, past-year benzodiazepine prescription, past-year opioid use disorder medication treatment, past-year detoxification admission, past-year residential treatment, and past-year involuntary commitment. We used SAS Studio for the analysis (version 3.5; SAS Institute, Inc., Cary, NC).
We received a Not Human Subjects Research determination from the Boston University Medical Campus Institutional Review Committee.
This study used data from Chapter 55 of the Acts of 2015 of individuals who experienced a nonfatal opioid-related overdose. This data set could not identify individuals who survived an overdose but did not have an ambulance or hospital encounter. But we were able to include all overdose-related acute hospital discharges and ambulance encounters across all providers in Massachusetts. It is possible that not every individual had a known diagnosis of opioid use disorder before the nonfatal overdose. However, opioid overdose is almost always a qualifying criterion for opioid use disorder, and thus receipt of medication for opioid use disorder. It is not possible to confirm adherence completely to medication according to administrative data, but high concordance between self-report, electronic pharmacy records, and medication lids has been demonstrated in other studies.
- Hansen R.A.
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- et al.
Adherence: comparison of methods to assess medication adherence and classify nonadherence.
Also, data are not clustered by hospital center or provider. It is likely that there are some locations across the state that provide coordination of care and linkage of treatment that others do not. As noted in the “Materials and Methods” section, we excluded individuals who had a death within 30 days of the overdose. Table E1
(available online at http://www.annemergmed.com
) provides age and other demographic data on these individuals. Exclusion of these individuals introduces survivor bias.
The database did not include good indicators for race, HIV, hepatitis C virus, and socioeconomic status. These factors have been previously associated with opioid-related treatment and overdose and should be better characterized in future studies. We did not include insurance status because insurance coverage was between 96% and 97% during the study period.
Kaiser Family Foundation
Health insurance coverage of the total population.
Our data and our analyses are limited to 2011 to 2015, which included the period in Massachusetts when fentanyl emerged as a major driver of overdose deaths. Massachusetts was one of the first states affected by fentanyl, and thus, the 2011 to 2015 timeframe reflects what has happened nationally more recently.
Increases in drug and opioid-involved overdose deaths—United States, 2010-2015.
Furthermore, Massachusetts was an early adopter of near-universal health care coverage, increased access to medication treatment, and naloxone for overdose prevention, which means that the care environment in Massachusetts represents what other states have been adopting.
Massachusetts Department of Public Health
Data brief: opioid-related overdose deaths among Massachusetts residents (2018-11).
Center for Health Information and Analysis
Access to substance use disorder treatment in Massachusetts.
An additional limitation is that we calculated the time in treatment only within the 12-month window of the study. Although the median times were all less than 12 months, it would be interesting to look in future studies beyond 12 months of treatment to identify potential differences by age. Finally, because the data are from Massachusetts residents, the results may not be fully reflective of other populations.
In this study of individuals aged 18 to 45 years who survived opioid overdose in Massachusetts between 2012 and 2014, approximately 1 in 3 young adults received evidence-based, recommended medication treatment with buprenorphine, naltrexone, or methadone in the subsequent 12 months. The median time to all types of medication treatment was between 3 and 5 months for all age groups, with time in treatment highest for those receiving methadone and buprenorphine. Young adults were more likely to receive naltrexone than older ones, and younger young adults (18 to 21 years) were less likely to receive methadone.
These data highlight a missed opportunity to engage all adults, including young adults in treatment after nonfatal overdose. The median time to treatment found in this study was at least 4 months, which underscores substantial room for improvement in the timing required to engage them in care. For young adults, providing timely treatment after a near-fatal event offers a chance for earlier intervention and prevention of the long-term physical and social consequences of ongoing substance use. The stakes are high because the mortality is high: 2% or more of individuals in each age group who survive an opioid overdose die within 12 months.
- Larochelle M.R.
- Bernson D.
- Land T.
- et al.
Medication for opioid use disorder after nonfatal opioid overdose and association with mortality: a cohort study.
Despite the increased efforts to initiate buprenorphine in the ED since the study by D’Onofrio et al
- D’Onofrio G.
- O’Connor P.G.
- Pantalon M.V.
- et al.
Emergency department–initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial.
was published, there is no evidence or clinical guidance for administering buprenorphine in the midst of naloxone-precipitated withdrawal. In that study, only 8% of the participants had presented with an overdose. More work is needed to demonstrate the feasibility and safety of medication for opioid use disorder immediately after an overdose.
In addition, we found variation in type of medication received by age group, and the consequences of that variation may have important implications. Young adults aged 18 to 21 years were less likely than the older young adults (ie, 22 to 25 years) to receive methadone after a nonfatal overdose, even though the evidence for methadone treatment is the best established among all 3 Food and Drug Administration–approved medications. Methadone has been shown to improve retention, decrease risk for HIV, and, most important, decrease risk for death.
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- et al.
Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies.
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- et al.
A retrospective study of retention of opioid-dependent adolescents and young adults in an outpatient buprenorphine/naloxone clinic.
There are potential barriers to treating young adults with methadone; it is associated with significant stigma, and also federal rules that severely limit access to methadone to individuals younger than 18 years may make methadone a less recognized option for young adults. However, in this study, similar to other studies, methadone had the best retention in treatment for all age groups.
Confronting the stigma of opioid use disorder—and its treatment.
There was no significant difference in receipt of buprenorphine among young adults. Nonetheless, the overall proportion of people receiving buprenorphine was still less than 20%. Expansion of medication for opioid use disorder is a critical component of federal and state responses to the increasing opioid-related overdose rate in the United States, and this study demonstrates that for all age groups, there continues to be a wide treatment gap that must be bridged.
We also found that young adults had a higher probability of receiving naltrexone in the 12 months after nonfatal overdose than older adults. However, the median time receiving it was only 1 month. The effectiveness of a medication is limited to the time people receive it; therefore, improving medication retention is a crucial challenge for individuals prescribed naltrexone. Naltrexone is the least studied of the 3 medications indicated for opioid use disorder. Further studies should examine how young adult patients and their providers make decisions in regard to which medication for opioid use disorder to use, including what structural factors (eg, state regulations, insurance coverage) contribute to medication for opioid use disorder selection. These findings further underscore the need for a more nuanced understanding of how medication choices are being made by patients and providers.
In summary, this study documents low proportions of young adults who receive medication for opioid use disorder after a nonfatal overdose and further advances the evidence base of the types of, time to, and duration of medication treatment received by young adults compared with older adult groups. Knowing that young adults respond to interventions and treatment differently than older adults
- Satre D.D.
- Mertens J.
- Areán P.A.
- et al.
Contrasting outcomes of older versus middle-aged and younger adult chemical dependency patients in a managed care program.
is an important step in improving care for this population. The differences in rate of treatment receipt, types of medication treatment, and duration of medication treatment between individuals aged 18 to 21 and 22 to 25 years suggest that even within the young adult population, tailored interventions for each age group may be required to best engage them.
Future studies should seek to understand how young adults and providers choose medication for opioid use disorder and demonstrate the safety and feasibility of medication for opioid use disorder initiation postoverdose in the ED. Because the United States continues to experience increasing opioid-related deaths, strategies to ensure that all medications are available to all people regardless of age are needed, and the ED can be a critical link in identification and engagement for this highest-risk population.
Published online: October 04, 2019
Received in revised form:
Received in revised form:
Please see page 30 for the Editor’s Capsule Summary of this article.
Supervising editor: Donald M. Yealy, MD. Specific detailed information about possible conflict of interest for individual editors is available at https://www.annemergmed.com/editors.
Author contributions: SMB conceived of the study and wrote the first draft of the article. MRL, ZX, DB, and TL contributed to the development of the analytic plan. MRL, ZX, DB, MS, SEH, TL, and AYW provided feedback on the article. NW conducted the analysis. NW, MS, and SEH reviewed the final draft of the article. MS and SEH conceived the results. SMB, MRL, MS, SEH, JHS, and AYW interpreted the results. MRL, JHS, and AYW reviewed the article. SMB takes responsibility for the paper as a whole.
All authors attest to meeting the four ICMJE.org authorship criteria: (1) Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND (2) Drafting the work or revising it critically for important intellectual content; AND (3) Final approval of the version to be published; AND (4) Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist. Dr. Bagley reports receiving salary support through a Career Development Award ( NIDA 1K23DA044324 ).
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© 2019 by the American College of Emergency Physicians.