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The United States is facing an epidemic of prescription opioid and heroin use, which has been linked to the escalating prescribing of opioid analgesics. Though opioid prescriptions appear to be reaching a plateau, estimates suggest there are at least 900,000 active heroin users in the United States, and this number continues to grow.1 One response to this epidemic (through state legislation and medical society guidelines) has been a move to reduce opioid prescribing in order to diminish the potential for diversion and misuse.2 However, the treatment of pain is not the sole driver of heroin epidemiology, and new strategies are also needed to better engage patients with existing opioid use disorders (OUDs) to begin treatment. These patients are increasingly hospitalized for infectious comorbidities of injection drug use, trauma, or pregnancy, and this may present a unique opportunity to initiate these patients on maintenance opioid agonist therapy, the most effective option for medication-assisted treatment (MAT) for addiction.
MISSED OPPORTUNITIES
Patients with OUDs comprise an estimated 2% to 4% of hospitalized patients, representing a disproportionately large number of inpatients.3-6 According to a recent analysis of data from the National (Nationwide) Inpatient Sample, the estimated annual number of hospitalizations associated with OUDs in the United States increased from approximately 300,000 to more than 500,000 in the decade from 2002 to 2012.7 Severe bacterial infections associated with intravenous administration of opioids (including endocarditis, osteomyelitis, septic arthritis, and epidural abscess) increased substantially at an estimated cost of more than $700 million in 2012.7 Over a similar period, the prevalence of opioid use among women in labor increased from 13.7 to 22.0 per 10,000 live births,8 and there was a corresponding rise in admissions to neonatal intensive care units for neonatal abstinence syndrome.9 As the prevalence of prescription drug and heroin dependence continues to rise across the United States, hospitals and clinicians find themselves on the front lines of this epidemic, creating potential opportunities to engage patients in recovery, a “treatable moment” for this vulnerable population.10
Currently, a common approach in the hospitalized patient is to attempt medically assisted withdrawal using a rapid taper of long-acting opioids. This process may appeal to healthcare providers who hope to guide their patients in transitioning to opioid abstinence. However, tapering an opioid regimen, even over a period of months, results in unacceptably high rates of relapse (as high as 70% to 90% in some studies), especially when a patient is acutely ill and symptomatic from a concurrent medical issue.11-13 In the hospital setting, this treatment failure can manifest as pain and undertreated withdrawal symptoms (such as agitation, arthralgias, and gastrointestinal distress), which may hinder some patients from completing their treatment or drive some to leave against medical advice.14 Further harm may occur when an inpatient rapid taper is accomplished, putting patients at increased risk of a fatal relapse after discharge due to loss of tolerance.15Maintenance opioid agonist therapy with buprenorphine or methadone, in which a long-acting opioid is titrated until craving and withdrawal symptoms are well controlled, is the first-line modality for MAT among patients with OUDs in outpatient settings and is associated with reduced risk of fatal overdose and all-cause mortality.16 Initiation and dose stabilization of agonist therapy with these agents during acute medical hospitalization has been shown to be feasible in a variety of inpatient settings.17-20 In one trial, patients randomized to buprenorphine induction and linkage to office-based therapy during their inpatient stay were more than 5 times as likely to enter and remain in treatment after discharge when compared with those in whom buprenorphine was tapered.20 International guidelines support the use of maintenance agonist therapy in this context, but this remains an underutilized strategy in recent efforts to treat OUDs in the United States.21,22 A few key barriers currently prevent this strategy from being applied broadly within our healthcare system.
TOWARD EVIDENCE-BASED INPATIENT MANAGEMENT
First, there is a common misconception that regulations prohibit the use of methadone and buprenorphine for opioid agonist therapy by inpatient medical providers without special certification. Title 42 of the Code of Federal Regulations (CFR) provides extensive guidance regarding the use of opioid medications by registered outpatient opioid treatment programs. However, it also contains an exemption from these rules for hospitals treating patients with emergent medical needs (21 CFR § 1306.07[c]) allowing hospital-based clinicians “to maintain or detoxify a person as an incidental adjunct to medical or surgical treatment of conditions other than addiction” without restriction. According to guidelines from the Substance Abuse and Mental Health Services Administration, this exemption applies to the use of both methadone and buprenorphine.23
Many clinicians and hospital pharmacy departments interpret this law to limit the use of maintenance therapy in patients already enrolled in outpatient programs or to require a rapid taper over the first 3 days of hospitalization. However, these interpretations may in part be rooted in confusion with an adjacent section of the regulations (21 CFR § 1306.07[b]) directed at outpatient physicians providing time-limited, emergency treatment for withdrawal in an office setting. The application of this time limit to hospitalized patients has not been supported by communication from the Drug Enforcement Agency.24 There is no case law or other regulation requiring an opioid regimen to be time limited for patients during medical hospitalization, and hospital policies need not place undue constraints on the ability of clinicians to stabilize patients on maintenance therapy and transition them to outpatient treatment.
Second, the limited capacity of existing opioid maintenance programs can lead to a gap in treatment upon hospital discharge for patients in whom methadone or buprenorphine is initiated. Health delivery systems can play a role in mitigating the impact of this resource gap. Integrating the model of screening, brief intervention, and referral to treatment into hospital admission processes and engaging social workers, addiction consult services (where available), and other supports early in the course of hospitalization can help facilitate appropriate follow-up care.25,26 Hospitals may also be eligible for federal funding to strengthen local referral networks for outpatient MAT programs under Section 103 of the Comprehensive Addiction and Recovery Act passed into law in July 2016. Innovative delivery models designed to enhance integration across community stakeholders in healthcare, social services, and criminal justice have recently been developed, such as Vermont’s “Hub and Spoke” model,27 Boston Medical Center’s Faster Paths opioid urgent care center,28 and the police-led Angel Program in Gloucester, Massachusetts.29 Implementation science studies will be needed to identify the most effective ways to engage inpatient medical teams in such efforts.
Currently, individual providers can already play a central role in providing a bridge for patients in whom a delay in beginning MAT cannot be avoided upon discharge. Interim buprenorphine maintenance treatment has been shown to dramatically decrease the use of illicit opioids among those awaiting initiation of comprehensive MAT programs and substantially increase retention in long-term treatment.20,30,31 With the recent expansion of the limits on buprenorphine prescriptions to 275 patients per provider (part of the waiver required under the Drug Addiction Treatment Act [DATA] of 2000 to provide outpatient buprenorphine treatment, also known as a DATA waiver), this may be an increasingly promising option for hospital discharge.
Obtaining a waiver to prescribe buprenorphine is not required for the inpatient initiation of buprenorphine therapy. However, doing so is relatively simple (requiring an online, 8-hour training [https://www.samhsa.gov/medication-assisted-treatment/training-resources/buprenorphine-physician-training]) and allows hospital-based providers not only to ensure optimal management of OUDs during hospitalization but also to help their patients with the next steps toward recovery after discharge. The use of buprenorphine may be challenging in some patients with significant pain as a component of their medical condition. For these patients, methadone will likely be better tolerated.
Additional funding is also urgently needed to expand the capacity of existing opioid treatment programs and create specialized discharge-transition clinics that can provide structured interim opioid therapy while patients are on waitlists for traditional MAT programs. Requiring patients who are not ready or able to begin long-term maintenance agonist therapy to rapidly taper an inpatient opioid regimen unnecessarily puts them at risk for overdose after discharge.15 Regardless of the available resources for long-term treatment within the community, hospital discharge planning should include a naloxone prescription and brief training for patients and their loved ones.32 The long-acting opioid antagonist, depot naltrexone, is another effective, alternative MAT option and is increasingly used in community settings among patients who are motivated to achieve opioid abstinence.33,34 It has not yet been studied among hospitalized patients, and further research is needed to determine if it could be a viable option for discharge. However, the requirement that a patient be abstinent from opioids for 7 to 10 days prior to administering the first dose of depot naltrexone may serve as a significant barrier to its use for most hospitalized patients.
Finally, healthcare providers must be trained in the appropriate use of opioid agonist therapy. Medical schools, residency programs, and schools of pharmacy and nursing should develop curricula to expand the capacity of nonspecialists to care for patients with OUDs and to focus on judicious analgesic prescribing to prevent chronic opioid use. This curriculum should address the appropriate titration of methadone and buprenorphine for agonist therapy and address the stigma faced by patients with substance use disorders. Other important topics include the management of overdose and withdrawal symptoms, structured approaches to pain management in patients with OUDs, harm-reduction methods, and multidisciplinary care for the psychosocial and psychiatric comorbidities of addiction. Though international guidelines have been developed for the inpatient management of patients with OUDs,21,22 hospitals and professional societies should take a leadership role in facilitating continuing education to disseminate them among current medical providers.
There is great potential for the leadership and front-line staff of hospital systems, with a few key changes in policy and practice, to become advocates for patients with OUDs to access treatment. As perspectives about opioid prescribing change amid efforts to limit the escalation of the current heroin epidemic, it is vital to identify opportunities to reduce opioid exposure for opioid-naïve patients and enhance the engagement of patients diagnosed with OUDs in treatment.
Disclosure
The authors have no conflicts of interest to declare.
1. Longo DL, Compton WM, Jones CM, Baldwin GT. Relationship between Nonmedical Prescription-Opioid Use and Heroin Use. N Engl J Med. 2016;374(2):154-163. doi:10.1056/NEJMra1508490. PubMed
2. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. MMWR Recomm Rep. 2016;65(1):1-49. doi:10.15585/mmwr.rr6501e1. PubMed
3. Dans PE, Matricciani RM, Otter SE, Reuland DS. Intravenous drug abuse and one academic health center. JAMA. 1990;263(23):3173-3176. PubMed
4. Stein MD, Wilkinson J, Berglas N, O’Sullivan P. Prevalence and detection of illicit drug disorders among hospitalized patients. Am J Drug Alcohol Abuse. 1996;22(3):463-471. PubMed
5. Brown RL, Leonard T, Saunders LA, Papasouliotis O. The prevalence and detection of substance use disorders among inpatients ages 18 to 49: an opportunity for prevention. Prev Med. 1998;27(1):101-110. doi:10.1006/pmed.1997.0250. PubMed
6. McNeely J, Gourevitch MN, Paone D, Shah S, Wright S, Heller D. Estimating the prevalence of illicit opioid use in New York City using multiple data sources. BMC Public Health. 2012;12:443. doi:10.1186/1471-2458-12-443. PubMed
7. Ronan MV, Herzig SJ. Hospitalizations Related To Opioid Abuse/Dependence And Associated Serious Infections Increased Sharply, 2002-12. Health Aff. 2016;35(5):832-837. doi:10.1377/hlthaff.2015.1424. PubMed
8. Pan I-J, Yi H. Prevalence of hospitalized live births affected by alcohol and drugs and parturient women diagnosed with substance abuse at liveborn delivery: United States, 1999-2008. Matern Child Health J. 2013;17(4):667-676. doi:10.1007/s10995-012-1046-3. PubMed
9. Tolia VN, Patrick SW, Bennett MM, et al. Increasing incidence of the neonatal abstinence syndrome in U.S. neonatal ICUs. N Engl J Med. 2015;372(22):2118-2126. doi:10.1056/NEJMsa1500439. PubMed
10. O’Toole TP, Pollini RA, Ford DE, Bigelow G. The health encounter as a treatable moment for homeless substance-using adults: the role of homelessness, health seeking behavior, readiness for behavior change and motivation for treatment. Addict Behav. 2008;33(9):1239-1243. doi:10.1016/j.addbeh.2008.04.015. PubMed
11. Nielsen S, Larance B, Degenhardt L, Gowing L, Kehler C, Lintzeris N. Opioid agonist treatment for pharmaceutical opioid dependent people. Cochrane Database Syst Rev. 2016;(5):CD011117. doi:10.1002/14651858.CD011117.pub2. PubMed
12. Gossop M, Green L, Phillips G, Bradley B. Lapse, relapse and survival among opiate addicts after treatment. A prospective follow-up study. Br J Psychiatry. 1989;154:348-353. PubMed
13. Smyth BP, Barry J, Keenan E, Ducray K. Lapse and relapse following inpatient treatment of opiate dependence. Ir Med J. 2010;103(6):176-179. PubMed
14. McNeil R, Small W, Wood E, Kerr T. Hospitals as a “risk environment”: an ethno-epidemiological study of voluntary and involuntary discharge from hospital against medical advice among people who inject drugs. Soc Sci Med. 2014;105:59-66. doi:10.1016/j.socscimed.2014.01.010. PubMed
15. Strang J. Loss of tolerance and overdose mortality after inpatient opiate detoxification: follow up study. BMJ. 2003;326(7396):959-960. doi:10.1136/bmj.326.7396.959. PubMed
16. Sordo L, Barrio G, Bravo MJ, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017;357:j1550. PubMed
17. Persico AM, Di Giannantonio M, Tempesta E. A prospective assessment of opiate addiction treatment protocols for inpatients with HIV-related syndromes. Drug Alcohol Depend. 1991;27(1):79-86. PubMed
18. Shanahan CW, Beers D, Alford DP, Brigandi E, Samet JH. A transitional opioid program to engage hospitalized drug users. J Gen Intern Med. 2010;25(8):803-808. doi:10.1007/s11606-010-1311-3. PubMed
19. Morozova O, Dvoryak S, Altice FL. Methadone treatment improves tuberculosis treatment among hospitalized opioid dependent patients in Ukraine. Int J Drug Policy. 2013;24(6):e91-e98. doi:10.1016/j.drugpo.2013.09.001. PubMed
20. Liebschutz JM, Crooks D, Herman D, et al. Buprenorphine Treatment for Hospitalized, Opioid-Dependent Patients: A Randomized Clinical Trial. JAMA Intern Med. 2014;174(8):1369. doi:10.1001/jamainternmed.2014.2556. PubMed
21. Haber PS, Demirkol A, Lange K, Murnion B. Management of injecting drug users admitted to hospital. Lancet. 2009;374(9697):1284-1293. doi:10.1016/S0140-6736(09)61036-9. PubMed
22. Donroe JH, Holt SR, Tetrault JM. Caring for patients with opioid use disorder in the hospital. CMAJ. 2016;188(17-18):1232-1239. doi:10.1503/cmaj.160290. PubMed
23. Substance Abuse and Mental Health Services Administration. Special Circumstances for Providing Buprenorphine. https://www.samhsa.gov/medication-assisted-treatment/legislation-regulations-guidelines/special-circumstances-providing-buprenorphine. Accessed October 8, 2016.
24. Noska A, Mohan A, Wakeman S, Rich J, Boutwell A. Managing Opioid Use Disorder During and After Acute Hospitalization: A Case-Based Review Clarifying Methadone Regulation for Acute Care Settings. J Addict Behav Ther Rehabil. 2015;4(2). pii: 1000138. doi:10.4172/2324-9005.1000138. PubMed
25. InSight Project Research Group. SBIRT outcomes in Houston: final report on InSight, a hospital district-based program for patients at risk for alcohol or drug use problems. Alcohol Clin Exp Res. 2009;33(8):1374-1381. doi:10.1111/j.1530-0277.2009.00967.x. PubMed
26. Estee S, Wickizer T, He L, Shah MF, Mancuso D. Evaluation of the Washington state screening, brief intervention, and referral to treatment project: cost outcomes for Medicaid patients screened in hospital emergency departments. Med Care. 2010;48(1):18-24. doi:10.1097/MLR.0b013e3181bd498f. PubMed
27. Simpatico TA. Vermont responds to its opioid crisis. Prev Med. 2015;80:10-11. doi:10.1016/j.ypmed.2015.04.002. PubMed
28. Boston University Medical Center. Boston medical center launches new opioid urgent care center. https://www.eurekalert.org/pub_releases/2016-10/bumc-bmc101716.php. Published on October 17, 2016. Accessed December 29, 2016.
29. Schiff DM, Drainoni M-L, Bair-Merritt M, Weinstein Z, Rosenbloom D. A Police-Led Addiction Treatment Referral Program in Massachusetts. N Engl J Med. 2016;375(25):2502-2503. doi:10.1056/NEJMc1611640. PubMed
30. D’Onofrio G, O’Connor PG, Pantalon MV, et al. Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial. JAMA. 2015;313(16):1636-1644. doi:10.1001/jama.2015.3474. PubMed
31. Sigmon SC, Ochalek TA, Meyer AC, et al. Interim Buprenorphine vs. Waiting List for Opioid Dependence. N Engl J Med. 2016;375(25):2504-2505. doi:10.1056/NEJMc1610047. PubMed
32. McDonald R, Strang J. Are take-home naloxone programmes effective? Systematic review utilizing application of the Bradford Hill criteria. Addiction. 2016;111(7):1177-1187. doi:10.1111/add.13326. . 2015;9(3):238-243. doi:10.1097/ADM.0000000000000125.J Addict Med PubMed
34. Nunes EV, Krupitsky E, Ling W, et al. Treating Opioid Dependence With Injectable Extended-Release Naltrexone (XR-NTX): Who Will Respond? . 2011;377(9776):1506-1513. doi:10.1016/S0140-6736(11)60358-9.Lancet PubMed
33. Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. PubMed
The United States is facing an epidemic of prescription opioid and heroin use, which has been linked to the escalating prescribing of opioid analgesics. Though opioid prescriptions appear to be reaching a plateau, estimates suggest there are at least 900,000 active heroin users in the United States, and this number continues to grow.1 One response to this epidemic (through state legislation and medical society guidelines) has been a move to reduce opioid prescribing in order to diminish the potential for diversion and misuse.2 However, the treatment of pain is not the sole driver of heroin epidemiology, and new strategies are also needed to better engage patients with existing opioid use disorders (OUDs) to begin treatment. These patients are increasingly hospitalized for infectious comorbidities of injection drug use, trauma, or pregnancy, and this may present a unique opportunity to initiate these patients on maintenance opioid agonist therapy, the most effective option for medication-assisted treatment (MAT) for addiction.
MISSED OPPORTUNITIES
Patients with OUDs comprise an estimated 2% to 4% of hospitalized patients, representing a disproportionately large number of inpatients.3-6 According to a recent analysis of data from the National (Nationwide) Inpatient Sample, the estimated annual number of hospitalizations associated with OUDs in the United States increased from approximately 300,000 to more than 500,000 in the decade from 2002 to 2012.7 Severe bacterial infections associated with intravenous administration of opioids (including endocarditis, osteomyelitis, septic arthritis, and epidural abscess) increased substantially at an estimated cost of more than $700 million in 2012.7 Over a similar period, the prevalence of opioid use among women in labor increased from 13.7 to 22.0 per 10,000 live births,8 and there was a corresponding rise in admissions to neonatal intensive care units for neonatal abstinence syndrome.9 As the prevalence of prescription drug and heroin dependence continues to rise across the United States, hospitals and clinicians find themselves on the front lines of this epidemic, creating potential opportunities to engage patients in recovery, a “treatable moment” for this vulnerable population.10
Currently, a common approach in the hospitalized patient is to attempt medically assisted withdrawal using a rapid taper of long-acting opioids. This process may appeal to healthcare providers who hope to guide their patients in transitioning to opioid abstinence. However, tapering an opioid regimen, even over a period of months, results in unacceptably high rates of relapse (as high as 70% to 90% in some studies), especially when a patient is acutely ill and symptomatic from a concurrent medical issue.11-13 In the hospital setting, this treatment failure can manifest as pain and undertreated withdrawal symptoms (such as agitation, arthralgias, and gastrointestinal distress), which may hinder some patients from completing their treatment or drive some to leave against medical advice.14 Further harm may occur when an inpatient rapid taper is accomplished, putting patients at increased risk of a fatal relapse after discharge due to loss of tolerance.15Maintenance opioid agonist therapy with buprenorphine or methadone, in which a long-acting opioid is titrated until craving and withdrawal symptoms are well controlled, is the first-line modality for MAT among patients with OUDs in outpatient settings and is associated with reduced risk of fatal overdose and all-cause mortality.16 Initiation and dose stabilization of agonist therapy with these agents during acute medical hospitalization has been shown to be feasible in a variety of inpatient settings.17-20 In one trial, patients randomized to buprenorphine induction and linkage to office-based therapy during their inpatient stay were more than 5 times as likely to enter and remain in treatment after discharge when compared with those in whom buprenorphine was tapered.20 International guidelines support the use of maintenance agonist therapy in this context, but this remains an underutilized strategy in recent efforts to treat OUDs in the United States.21,22 A few key barriers currently prevent this strategy from being applied broadly within our healthcare system.
TOWARD EVIDENCE-BASED INPATIENT MANAGEMENT
First, there is a common misconception that regulations prohibit the use of methadone and buprenorphine for opioid agonist therapy by inpatient medical providers without special certification. Title 42 of the Code of Federal Regulations (CFR) provides extensive guidance regarding the use of opioid medications by registered outpatient opioid treatment programs. However, it also contains an exemption from these rules for hospitals treating patients with emergent medical needs (21 CFR § 1306.07[c]) allowing hospital-based clinicians “to maintain or detoxify a person as an incidental adjunct to medical or surgical treatment of conditions other than addiction” without restriction. According to guidelines from the Substance Abuse and Mental Health Services Administration, this exemption applies to the use of both methadone and buprenorphine.23
Many clinicians and hospital pharmacy departments interpret this law to limit the use of maintenance therapy in patients already enrolled in outpatient programs or to require a rapid taper over the first 3 days of hospitalization. However, these interpretations may in part be rooted in confusion with an adjacent section of the regulations (21 CFR § 1306.07[b]) directed at outpatient physicians providing time-limited, emergency treatment for withdrawal in an office setting. The application of this time limit to hospitalized patients has not been supported by communication from the Drug Enforcement Agency.24 There is no case law or other regulation requiring an opioid regimen to be time limited for patients during medical hospitalization, and hospital policies need not place undue constraints on the ability of clinicians to stabilize patients on maintenance therapy and transition them to outpatient treatment.
Second, the limited capacity of existing opioid maintenance programs can lead to a gap in treatment upon hospital discharge for patients in whom methadone or buprenorphine is initiated. Health delivery systems can play a role in mitigating the impact of this resource gap. Integrating the model of screening, brief intervention, and referral to treatment into hospital admission processes and engaging social workers, addiction consult services (where available), and other supports early in the course of hospitalization can help facilitate appropriate follow-up care.25,26 Hospitals may also be eligible for federal funding to strengthen local referral networks for outpatient MAT programs under Section 103 of the Comprehensive Addiction and Recovery Act passed into law in July 2016. Innovative delivery models designed to enhance integration across community stakeholders in healthcare, social services, and criminal justice have recently been developed, such as Vermont’s “Hub and Spoke” model,27 Boston Medical Center’s Faster Paths opioid urgent care center,28 and the police-led Angel Program in Gloucester, Massachusetts.29 Implementation science studies will be needed to identify the most effective ways to engage inpatient medical teams in such efforts.
Currently, individual providers can already play a central role in providing a bridge for patients in whom a delay in beginning MAT cannot be avoided upon discharge. Interim buprenorphine maintenance treatment has been shown to dramatically decrease the use of illicit opioids among those awaiting initiation of comprehensive MAT programs and substantially increase retention in long-term treatment.20,30,31 With the recent expansion of the limits on buprenorphine prescriptions to 275 patients per provider (part of the waiver required under the Drug Addiction Treatment Act [DATA] of 2000 to provide outpatient buprenorphine treatment, also known as a DATA waiver), this may be an increasingly promising option for hospital discharge.
Obtaining a waiver to prescribe buprenorphine is not required for the inpatient initiation of buprenorphine therapy. However, doing so is relatively simple (requiring an online, 8-hour training [https://www.samhsa.gov/medication-assisted-treatment/training-resources/buprenorphine-physician-training]) and allows hospital-based providers not only to ensure optimal management of OUDs during hospitalization but also to help their patients with the next steps toward recovery after discharge. The use of buprenorphine may be challenging in some patients with significant pain as a component of their medical condition. For these patients, methadone will likely be better tolerated.
Additional funding is also urgently needed to expand the capacity of existing opioid treatment programs and create specialized discharge-transition clinics that can provide structured interim opioid therapy while patients are on waitlists for traditional MAT programs. Requiring patients who are not ready or able to begin long-term maintenance agonist therapy to rapidly taper an inpatient opioid regimen unnecessarily puts them at risk for overdose after discharge.15 Regardless of the available resources for long-term treatment within the community, hospital discharge planning should include a naloxone prescription and brief training for patients and their loved ones.32 The long-acting opioid antagonist, depot naltrexone, is another effective, alternative MAT option and is increasingly used in community settings among patients who are motivated to achieve opioid abstinence.33,34 It has not yet been studied among hospitalized patients, and further research is needed to determine if it could be a viable option for discharge. However, the requirement that a patient be abstinent from opioids for 7 to 10 days prior to administering the first dose of depot naltrexone may serve as a significant barrier to its use for most hospitalized patients.
Finally, healthcare providers must be trained in the appropriate use of opioid agonist therapy. Medical schools, residency programs, and schools of pharmacy and nursing should develop curricula to expand the capacity of nonspecialists to care for patients with OUDs and to focus on judicious analgesic prescribing to prevent chronic opioid use. This curriculum should address the appropriate titration of methadone and buprenorphine for agonist therapy and address the stigma faced by patients with substance use disorders. Other important topics include the management of overdose and withdrawal symptoms, structured approaches to pain management in patients with OUDs, harm-reduction methods, and multidisciplinary care for the psychosocial and psychiatric comorbidities of addiction. Though international guidelines have been developed for the inpatient management of patients with OUDs,21,22 hospitals and professional societies should take a leadership role in facilitating continuing education to disseminate them among current medical providers.
There is great potential for the leadership and front-line staff of hospital systems, with a few key changes in policy and practice, to become advocates for patients with OUDs to access treatment. As perspectives about opioid prescribing change amid efforts to limit the escalation of the current heroin epidemic, it is vital to identify opportunities to reduce opioid exposure for opioid-naïve patients and enhance the engagement of patients diagnosed with OUDs in treatment.
Disclosure
The authors have no conflicts of interest to declare.
The United States is facing an epidemic of prescription opioid and heroin use, which has been linked to the escalating prescribing of opioid analgesics. Though opioid prescriptions appear to be reaching a plateau, estimates suggest there are at least 900,000 active heroin users in the United States, and this number continues to grow.1 One response to this epidemic (through state legislation and medical society guidelines) has been a move to reduce opioid prescribing in order to diminish the potential for diversion and misuse.2 However, the treatment of pain is not the sole driver of heroin epidemiology, and new strategies are also needed to better engage patients with existing opioid use disorders (OUDs) to begin treatment. These patients are increasingly hospitalized for infectious comorbidities of injection drug use, trauma, or pregnancy, and this may present a unique opportunity to initiate these patients on maintenance opioid agonist therapy, the most effective option for medication-assisted treatment (MAT) for addiction.
MISSED OPPORTUNITIES
Patients with OUDs comprise an estimated 2% to 4% of hospitalized patients, representing a disproportionately large number of inpatients.3-6 According to a recent analysis of data from the National (Nationwide) Inpatient Sample, the estimated annual number of hospitalizations associated with OUDs in the United States increased from approximately 300,000 to more than 500,000 in the decade from 2002 to 2012.7 Severe bacterial infections associated with intravenous administration of opioids (including endocarditis, osteomyelitis, septic arthritis, and epidural abscess) increased substantially at an estimated cost of more than $700 million in 2012.7 Over a similar period, the prevalence of opioid use among women in labor increased from 13.7 to 22.0 per 10,000 live births,8 and there was a corresponding rise in admissions to neonatal intensive care units for neonatal abstinence syndrome.9 As the prevalence of prescription drug and heroin dependence continues to rise across the United States, hospitals and clinicians find themselves on the front lines of this epidemic, creating potential opportunities to engage patients in recovery, a “treatable moment” for this vulnerable population.10
Currently, a common approach in the hospitalized patient is to attempt medically assisted withdrawal using a rapid taper of long-acting opioids. This process may appeal to healthcare providers who hope to guide their patients in transitioning to opioid abstinence. However, tapering an opioid regimen, even over a period of months, results in unacceptably high rates of relapse (as high as 70% to 90% in some studies), especially when a patient is acutely ill and symptomatic from a concurrent medical issue.11-13 In the hospital setting, this treatment failure can manifest as pain and undertreated withdrawal symptoms (such as agitation, arthralgias, and gastrointestinal distress), which may hinder some patients from completing their treatment or drive some to leave against medical advice.14 Further harm may occur when an inpatient rapid taper is accomplished, putting patients at increased risk of a fatal relapse after discharge due to loss of tolerance.15Maintenance opioid agonist therapy with buprenorphine or methadone, in which a long-acting opioid is titrated until craving and withdrawal symptoms are well controlled, is the first-line modality for MAT among patients with OUDs in outpatient settings and is associated with reduced risk of fatal overdose and all-cause mortality.16 Initiation and dose stabilization of agonist therapy with these agents during acute medical hospitalization has been shown to be feasible in a variety of inpatient settings.17-20 In one trial, patients randomized to buprenorphine induction and linkage to office-based therapy during their inpatient stay were more than 5 times as likely to enter and remain in treatment after discharge when compared with those in whom buprenorphine was tapered.20 International guidelines support the use of maintenance agonist therapy in this context, but this remains an underutilized strategy in recent efforts to treat OUDs in the United States.21,22 A few key barriers currently prevent this strategy from being applied broadly within our healthcare system.
TOWARD EVIDENCE-BASED INPATIENT MANAGEMENT
First, there is a common misconception that regulations prohibit the use of methadone and buprenorphine for opioid agonist therapy by inpatient medical providers without special certification. Title 42 of the Code of Federal Regulations (CFR) provides extensive guidance regarding the use of opioid medications by registered outpatient opioid treatment programs. However, it also contains an exemption from these rules for hospitals treating patients with emergent medical needs (21 CFR § 1306.07[c]) allowing hospital-based clinicians “to maintain or detoxify a person as an incidental adjunct to medical or surgical treatment of conditions other than addiction” without restriction. According to guidelines from the Substance Abuse and Mental Health Services Administration, this exemption applies to the use of both methadone and buprenorphine.23
Many clinicians and hospital pharmacy departments interpret this law to limit the use of maintenance therapy in patients already enrolled in outpatient programs or to require a rapid taper over the first 3 days of hospitalization. However, these interpretations may in part be rooted in confusion with an adjacent section of the regulations (21 CFR § 1306.07[b]) directed at outpatient physicians providing time-limited, emergency treatment for withdrawal in an office setting. The application of this time limit to hospitalized patients has not been supported by communication from the Drug Enforcement Agency.24 There is no case law or other regulation requiring an opioid regimen to be time limited for patients during medical hospitalization, and hospital policies need not place undue constraints on the ability of clinicians to stabilize patients on maintenance therapy and transition them to outpatient treatment.
Second, the limited capacity of existing opioid maintenance programs can lead to a gap in treatment upon hospital discharge for patients in whom methadone or buprenorphine is initiated. Health delivery systems can play a role in mitigating the impact of this resource gap. Integrating the model of screening, brief intervention, and referral to treatment into hospital admission processes and engaging social workers, addiction consult services (where available), and other supports early in the course of hospitalization can help facilitate appropriate follow-up care.25,26 Hospitals may also be eligible for federal funding to strengthen local referral networks for outpatient MAT programs under Section 103 of the Comprehensive Addiction and Recovery Act passed into law in July 2016. Innovative delivery models designed to enhance integration across community stakeholders in healthcare, social services, and criminal justice have recently been developed, such as Vermont’s “Hub and Spoke” model,27 Boston Medical Center’s Faster Paths opioid urgent care center,28 and the police-led Angel Program in Gloucester, Massachusetts.29 Implementation science studies will be needed to identify the most effective ways to engage inpatient medical teams in such efforts.
Currently, individual providers can already play a central role in providing a bridge for patients in whom a delay in beginning MAT cannot be avoided upon discharge. Interim buprenorphine maintenance treatment has been shown to dramatically decrease the use of illicit opioids among those awaiting initiation of comprehensive MAT programs and substantially increase retention in long-term treatment.20,30,31 With the recent expansion of the limits on buprenorphine prescriptions to 275 patients per provider (part of the waiver required under the Drug Addiction Treatment Act [DATA] of 2000 to provide outpatient buprenorphine treatment, also known as a DATA waiver), this may be an increasingly promising option for hospital discharge.
Obtaining a waiver to prescribe buprenorphine is not required for the inpatient initiation of buprenorphine therapy. However, doing so is relatively simple (requiring an online, 8-hour training [https://www.samhsa.gov/medication-assisted-treatment/training-resources/buprenorphine-physician-training]) and allows hospital-based providers not only to ensure optimal management of OUDs during hospitalization but also to help their patients with the next steps toward recovery after discharge. The use of buprenorphine may be challenging in some patients with significant pain as a component of their medical condition. For these patients, methadone will likely be better tolerated.
Additional funding is also urgently needed to expand the capacity of existing opioid treatment programs and create specialized discharge-transition clinics that can provide structured interim opioid therapy while patients are on waitlists for traditional MAT programs. Requiring patients who are not ready or able to begin long-term maintenance agonist therapy to rapidly taper an inpatient opioid regimen unnecessarily puts them at risk for overdose after discharge.15 Regardless of the available resources for long-term treatment within the community, hospital discharge planning should include a naloxone prescription and brief training for patients and their loved ones.32 The long-acting opioid antagonist, depot naltrexone, is another effective, alternative MAT option and is increasingly used in community settings among patients who are motivated to achieve opioid abstinence.33,34 It has not yet been studied among hospitalized patients, and further research is needed to determine if it could be a viable option for discharge. However, the requirement that a patient be abstinent from opioids for 7 to 10 days prior to administering the first dose of depot naltrexone may serve as a significant barrier to its use for most hospitalized patients.
Finally, healthcare providers must be trained in the appropriate use of opioid agonist therapy. Medical schools, residency programs, and schools of pharmacy and nursing should develop curricula to expand the capacity of nonspecialists to care for patients with OUDs and to focus on judicious analgesic prescribing to prevent chronic opioid use. This curriculum should address the appropriate titration of methadone and buprenorphine for agonist therapy and address the stigma faced by patients with substance use disorders. Other important topics include the management of overdose and withdrawal symptoms, structured approaches to pain management in patients with OUDs, harm-reduction methods, and multidisciplinary care for the psychosocial and psychiatric comorbidities of addiction. Though international guidelines have been developed for the inpatient management of patients with OUDs,21,22 hospitals and professional societies should take a leadership role in facilitating continuing education to disseminate them among current medical providers.
There is great potential for the leadership and front-line staff of hospital systems, with a few key changes in policy and practice, to become advocates for patients with OUDs to access treatment. As perspectives about opioid prescribing change amid efforts to limit the escalation of the current heroin epidemic, it is vital to identify opportunities to reduce opioid exposure for opioid-naïve patients and enhance the engagement of patients diagnosed with OUDs in treatment.
Disclosure
The authors have no conflicts of interest to declare.
1. Longo DL, Compton WM, Jones CM, Baldwin GT. Relationship between Nonmedical Prescription-Opioid Use and Heroin Use. N Engl J Med. 2016;374(2):154-163. doi:10.1056/NEJMra1508490. PubMed
2. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. MMWR Recomm Rep. 2016;65(1):1-49. doi:10.15585/mmwr.rr6501e1. PubMed
3. Dans PE, Matricciani RM, Otter SE, Reuland DS. Intravenous drug abuse and one academic health center. JAMA. 1990;263(23):3173-3176. PubMed
4. Stein MD, Wilkinson J, Berglas N, O’Sullivan P. Prevalence and detection of illicit drug disorders among hospitalized patients. Am J Drug Alcohol Abuse. 1996;22(3):463-471. PubMed
5. Brown RL, Leonard T, Saunders LA, Papasouliotis O. The prevalence and detection of substance use disorders among inpatients ages 18 to 49: an opportunity for prevention. Prev Med. 1998;27(1):101-110. doi:10.1006/pmed.1997.0250. PubMed
6. McNeely J, Gourevitch MN, Paone D, Shah S, Wright S, Heller D. Estimating the prevalence of illicit opioid use in New York City using multiple data sources. BMC Public Health. 2012;12:443. doi:10.1186/1471-2458-12-443. PubMed
7. Ronan MV, Herzig SJ. Hospitalizations Related To Opioid Abuse/Dependence And Associated Serious Infections Increased Sharply, 2002-12. Health Aff. 2016;35(5):832-837. doi:10.1377/hlthaff.2015.1424. PubMed
8. Pan I-J, Yi H. Prevalence of hospitalized live births affected by alcohol and drugs and parturient women diagnosed with substance abuse at liveborn delivery: United States, 1999-2008. Matern Child Health J. 2013;17(4):667-676. doi:10.1007/s10995-012-1046-3. PubMed
9. Tolia VN, Patrick SW, Bennett MM, et al. Increasing incidence of the neonatal abstinence syndrome in U.S. neonatal ICUs. N Engl J Med. 2015;372(22):2118-2126. doi:10.1056/NEJMsa1500439. PubMed
10. O’Toole TP, Pollini RA, Ford DE, Bigelow G. The health encounter as a treatable moment for homeless substance-using adults: the role of homelessness, health seeking behavior, readiness for behavior change and motivation for treatment. Addict Behav. 2008;33(9):1239-1243. doi:10.1016/j.addbeh.2008.04.015. PubMed
11. Nielsen S, Larance B, Degenhardt L, Gowing L, Kehler C, Lintzeris N. Opioid agonist treatment for pharmaceutical opioid dependent people. Cochrane Database Syst Rev. 2016;(5):CD011117. doi:10.1002/14651858.CD011117.pub2. PubMed
12. Gossop M, Green L, Phillips G, Bradley B. Lapse, relapse and survival among opiate addicts after treatment. A prospective follow-up study. Br J Psychiatry. 1989;154:348-353. PubMed
13. Smyth BP, Barry J, Keenan E, Ducray K. Lapse and relapse following inpatient treatment of opiate dependence. Ir Med J. 2010;103(6):176-179. PubMed
14. McNeil R, Small W, Wood E, Kerr T. Hospitals as a “risk environment”: an ethno-epidemiological study of voluntary and involuntary discharge from hospital against medical advice among people who inject drugs. Soc Sci Med. 2014;105:59-66. doi:10.1016/j.socscimed.2014.01.010. PubMed
15. Strang J. Loss of tolerance and overdose mortality after inpatient opiate detoxification: follow up study. BMJ. 2003;326(7396):959-960. doi:10.1136/bmj.326.7396.959. PubMed
16. Sordo L, Barrio G, Bravo MJ, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017;357:j1550. PubMed
17. Persico AM, Di Giannantonio M, Tempesta E. A prospective assessment of opiate addiction treatment protocols for inpatients with HIV-related syndromes. Drug Alcohol Depend. 1991;27(1):79-86. PubMed
18. Shanahan CW, Beers D, Alford DP, Brigandi E, Samet JH. A transitional opioid program to engage hospitalized drug users. J Gen Intern Med. 2010;25(8):803-808. doi:10.1007/s11606-010-1311-3. PubMed
19. Morozova O, Dvoryak S, Altice FL. Methadone treatment improves tuberculosis treatment among hospitalized opioid dependent patients in Ukraine. Int J Drug Policy. 2013;24(6):e91-e98. doi:10.1016/j.drugpo.2013.09.001. PubMed
20. Liebschutz JM, Crooks D, Herman D, et al. Buprenorphine Treatment for Hospitalized, Opioid-Dependent Patients: A Randomized Clinical Trial. JAMA Intern Med. 2014;174(8):1369. doi:10.1001/jamainternmed.2014.2556. PubMed
21. Haber PS, Demirkol A, Lange K, Murnion B. Management of injecting drug users admitted to hospital. Lancet. 2009;374(9697):1284-1293. doi:10.1016/S0140-6736(09)61036-9. PubMed
22. Donroe JH, Holt SR, Tetrault JM. Caring for patients with opioid use disorder in the hospital. CMAJ. 2016;188(17-18):1232-1239. doi:10.1503/cmaj.160290. PubMed
23. Substance Abuse and Mental Health Services Administration. Special Circumstances for Providing Buprenorphine. https://www.samhsa.gov/medication-assisted-treatment/legislation-regulations-guidelines/special-circumstances-providing-buprenorphine. Accessed October 8, 2016.
24. Noska A, Mohan A, Wakeman S, Rich J, Boutwell A. Managing Opioid Use Disorder During and After Acute Hospitalization: A Case-Based Review Clarifying Methadone Regulation for Acute Care Settings. J Addict Behav Ther Rehabil. 2015;4(2). pii: 1000138. doi:10.4172/2324-9005.1000138. PubMed
25. InSight Project Research Group. SBIRT outcomes in Houston: final report on InSight, a hospital district-based program for patients at risk for alcohol or drug use problems. Alcohol Clin Exp Res. 2009;33(8):1374-1381. doi:10.1111/j.1530-0277.2009.00967.x. PubMed
26. Estee S, Wickizer T, He L, Shah MF, Mancuso D. Evaluation of the Washington state screening, brief intervention, and referral to treatment project: cost outcomes for Medicaid patients screened in hospital emergency departments. Med Care. 2010;48(1):18-24. doi:10.1097/MLR.0b013e3181bd498f. PubMed
27. Simpatico TA. Vermont responds to its opioid crisis. Prev Med. 2015;80:10-11. doi:10.1016/j.ypmed.2015.04.002. PubMed
28. Boston University Medical Center. Boston medical center launches new opioid urgent care center. https://www.eurekalert.org/pub_releases/2016-10/bumc-bmc101716.php. Published on October 17, 2016. Accessed December 29, 2016.
29. Schiff DM, Drainoni M-L, Bair-Merritt M, Weinstein Z, Rosenbloom D. A Police-Led Addiction Treatment Referral Program in Massachusetts. N Engl J Med. 2016;375(25):2502-2503. doi:10.1056/NEJMc1611640. PubMed
30. D’Onofrio G, O’Connor PG, Pantalon MV, et al. Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial. JAMA. 2015;313(16):1636-1644. doi:10.1001/jama.2015.3474. PubMed
31. Sigmon SC, Ochalek TA, Meyer AC, et al. Interim Buprenorphine vs. Waiting List for Opioid Dependence. N Engl J Med. 2016;375(25):2504-2505. doi:10.1056/NEJMc1610047. PubMed
32. McDonald R, Strang J. Are take-home naloxone programmes effective? Systematic review utilizing application of the Bradford Hill criteria. Addiction. 2016;111(7):1177-1187. doi:10.1111/add.13326. . 2015;9(3):238-243. doi:10.1097/ADM.0000000000000125.J Addict Med PubMed
34. Nunes EV, Krupitsky E, Ling W, et al. Treating Opioid Dependence With Injectable Extended-Release Naltrexone (XR-NTX): Who Will Respond? . 2011;377(9776):1506-1513. doi:10.1016/S0140-6736(11)60358-9.Lancet PubMed
33. Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. PubMed
1. Longo DL, Compton WM, Jones CM, Baldwin GT. Relationship between Nonmedical Prescription-Opioid Use and Heroin Use. N Engl J Med. 2016;374(2):154-163. doi:10.1056/NEJMra1508490. PubMed
2. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. MMWR Recomm Rep. 2016;65(1):1-49. doi:10.15585/mmwr.rr6501e1. PubMed
3. Dans PE, Matricciani RM, Otter SE, Reuland DS. Intravenous drug abuse and one academic health center. JAMA. 1990;263(23):3173-3176. PubMed
4. Stein MD, Wilkinson J, Berglas N, O’Sullivan P. Prevalence and detection of illicit drug disorders among hospitalized patients. Am J Drug Alcohol Abuse. 1996;22(3):463-471. PubMed
5. Brown RL, Leonard T, Saunders LA, Papasouliotis O. The prevalence and detection of substance use disorders among inpatients ages 18 to 49: an opportunity for prevention. Prev Med. 1998;27(1):101-110. doi:10.1006/pmed.1997.0250. PubMed
6. McNeely J, Gourevitch MN, Paone D, Shah S, Wright S, Heller D. Estimating the prevalence of illicit opioid use in New York City using multiple data sources. BMC Public Health. 2012;12:443. doi:10.1186/1471-2458-12-443. PubMed
7. Ronan MV, Herzig SJ. Hospitalizations Related To Opioid Abuse/Dependence And Associated Serious Infections Increased Sharply, 2002-12. Health Aff. 2016;35(5):832-837. doi:10.1377/hlthaff.2015.1424. PubMed
8. Pan I-J, Yi H. Prevalence of hospitalized live births affected by alcohol and drugs and parturient women diagnosed with substance abuse at liveborn delivery: United States, 1999-2008. Matern Child Health J. 2013;17(4):667-676. doi:10.1007/s10995-012-1046-3. PubMed
9. Tolia VN, Patrick SW, Bennett MM, et al. Increasing incidence of the neonatal abstinence syndrome in U.S. neonatal ICUs. N Engl J Med. 2015;372(22):2118-2126. doi:10.1056/NEJMsa1500439. PubMed
10. O’Toole TP, Pollini RA, Ford DE, Bigelow G. The health encounter as a treatable moment for homeless substance-using adults: the role of homelessness, health seeking behavior, readiness for behavior change and motivation for treatment. Addict Behav. 2008;33(9):1239-1243. doi:10.1016/j.addbeh.2008.04.015. PubMed
11. Nielsen S, Larance B, Degenhardt L, Gowing L, Kehler C, Lintzeris N. Opioid agonist treatment for pharmaceutical opioid dependent people. Cochrane Database Syst Rev. 2016;(5):CD011117. doi:10.1002/14651858.CD011117.pub2. PubMed
12. Gossop M, Green L, Phillips G, Bradley B. Lapse, relapse and survival among opiate addicts after treatment. A prospective follow-up study. Br J Psychiatry. 1989;154:348-353. PubMed
13. Smyth BP, Barry J, Keenan E, Ducray K. Lapse and relapse following inpatient treatment of opiate dependence. Ir Med J. 2010;103(6):176-179. PubMed
14. McNeil R, Small W, Wood E, Kerr T. Hospitals as a “risk environment”: an ethno-epidemiological study of voluntary and involuntary discharge from hospital against medical advice among people who inject drugs. Soc Sci Med. 2014;105:59-66. doi:10.1016/j.socscimed.2014.01.010. PubMed
15. Strang J. Loss of tolerance and overdose mortality after inpatient opiate detoxification: follow up study. BMJ. 2003;326(7396):959-960. doi:10.1136/bmj.326.7396.959. PubMed
16. Sordo L, Barrio G, Bravo MJ, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017;357:j1550. PubMed
17. Persico AM, Di Giannantonio M, Tempesta E. A prospective assessment of opiate addiction treatment protocols for inpatients with HIV-related syndromes. Drug Alcohol Depend. 1991;27(1):79-86. PubMed
18. Shanahan CW, Beers D, Alford DP, Brigandi E, Samet JH. A transitional opioid program to engage hospitalized drug users. J Gen Intern Med. 2010;25(8):803-808. doi:10.1007/s11606-010-1311-3. PubMed
19. Morozova O, Dvoryak S, Altice FL. Methadone treatment improves tuberculosis treatment among hospitalized opioid dependent patients in Ukraine. Int J Drug Policy. 2013;24(6):e91-e98. doi:10.1016/j.drugpo.2013.09.001. PubMed
20. Liebschutz JM, Crooks D, Herman D, et al. Buprenorphine Treatment for Hospitalized, Opioid-Dependent Patients: A Randomized Clinical Trial. JAMA Intern Med. 2014;174(8):1369. doi:10.1001/jamainternmed.2014.2556. PubMed
21. Haber PS, Demirkol A, Lange K, Murnion B. Management of injecting drug users admitted to hospital. Lancet. 2009;374(9697):1284-1293. doi:10.1016/S0140-6736(09)61036-9. PubMed
22. Donroe JH, Holt SR, Tetrault JM. Caring for patients with opioid use disorder in the hospital. CMAJ. 2016;188(17-18):1232-1239. doi:10.1503/cmaj.160290. PubMed
23. Substance Abuse and Mental Health Services Administration. Special Circumstances for Providing Buprenorphine. https://www.samhsa.gov/medication-assisted-treatment/legislation-regulations-guidelines/special-circumstances-providing-buprenorphine. Accessed October 8, 2016.
24. Noska A, Mohan A, Wakeman S, Rich J, Boutwell A. Managing Opioid Use Disorder During and After Acute Hospitalization: A Case-Based Review Clarifying Methadone Regulation for Acute Care Settings. J Addict Behav Ther Rehabil. 2015;4(2). pii: 1000138. doi:10.4172/2324-9005.1000138. PubMed
25. InSight Project Research Group. SBIRT outcomes in Houston: final report on InSight, a hospital district-based program for patients at risk for alcohol or drug use problems. Alcohol Clin Exp Res. 2009;33(8):1374-1381. doi:10.1111/j.1530-0277.2009.00967.x. PubMed
26. Estee S, Wickizer T, He L, Shah MF, Mancuso D. Evaluation of the Washington state screening, brief intervention, and referral to treatment project: cost outcomes for Medicaid patients screened in hospital emergency departments. Med Care. 2010;48(1):18-24. doi:10.1097/MLR.0b013e3181bd498f. PubMed
27. Simpatico TA. Vermont responds to its opioid crisis. Prev Med. 2015;80:10-11. doi:10.1016/j.ypmed.2015.04.002. PubMed
28. Boston University Medical Center. Boston medical center launches new opioid urgent care center. https://www.eurekalert.org/pub_releases/2016-10/bumc-bmc101716.php. Published on October 17, 2016. Accessed December 29, 2016.
29. Schiff DM, Drainoni M-L, Bair-Merritt M, Weinstein Z, Rosenbloom D. A Police-Led Addiction Treatment Referral Program in Massachusetts. N Engl J Med. 2016;375(25):2502-2503. doi:10.1056/NEJMc1611640. PubMed
30. D’Onofrio G, O’Connor PG, Pantalon MV, et al. Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial. JAMA. 2015;313(16):1636-1644. doi:10.1001/jama.2015.3474. PubMed
31. Sigmon SC, Ochalek TA, Meyer AC, et al. Interim Buprenorphine vs. Waiting List for Opioid Dependence. N Engl J Med. 2016;375(25):2504-2505. doi:10.1056/NEJMc1610047. PubMed
32. McDonald R, Strang J. Are take-home naloxone programmes effective? Systematic review utilizing application of the Bradford Hill criteria. Addiction. 2016;111(7):1177-1187. doi:10.1111/add.13326. . 2015;9(3):238-243. doi:10.1097/ADM.0000000000000125.J Addict Med PubMed
34. Nunes EV, Krupitsky E, Ling W, et al. Treating Opioid Dependence With Injectable Extended-Release Naltrexone (XR-NTX): Who Will Respond? . 2011;377(9776):1506-1513. doi:10.1016/S0140-6736(11)60358-9.Lancet PubMed
33. Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. PubMed
© 2017 Society of Hospital Medicine