• Home
  • Medication-Assisted Treatment with Buprenorphine for Opioid Use Disorder in Emergency Departments

Medication-Assisted Treatment with Buprenorphine for Opioid Use Disorder in Emergency Departments

01 Jun 2021 2:21 PM | Anonymous

By: Sarah Cook, PharmD, BCPS; Clinical Pharmacy Specialist, SSM Health St. Joseph Hospital – St. Charles

Opioid Use Disorder (OUD) is defined as “a problematic pattern of opioid use leading to problems and distress” according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition.1 Per the American Medical Association, approximately 3-19% of people who take an opioid pain medication will develop OUD, and 45% of those who use heroin first started abusing prescription opioids. Dependence to opioids can develop in as little as 4-8 weeks, and in patients who use opioids chronically, the absence of opioids can lead to withdrawal symptoms (generalized pain, nausea/vomiting, diarrhea, dilated pupils, restlessness, anxiety, insomnia, chills, cravings) which promotes further opioid use to avoid such discomfort.2 Due in part to the significance of withdrawal symptoms, many patients with OUD are unable to effectively cease using opioids without additional assistance. Medication-assisted treatment (MAT) for OUD is a strategy that can increase the likelihood of individuals abstaining from inappropriate opioid use, which can translate into reduced mortality, decreased rates of blood borne illnesses, and other clinical benefits.3

Since 1999, overdose deaths due to opioids in the United States have increased by approximately 6 times, with over 47,000 deaths due to opioid overdoses occurring in 2018.4 It is estimated that approximately 10.3 million people misused prescription opioids and 2 million people had an OUD in 2018.5 In response to this alarming trend, the U.S. Department of Health and Human Services declared the opioid crisis a public health emergency in 2017 and outlined 5 priorities, two of which were to “improve access to prevention, treatment, and recovery support services” and to “target the availability and distribution of overdose-reversing drugs.”6 One area that has been a focus of these efforts has been emergency departments, as they are often the location where people engage with the medical system following an overdose or when in opioid withdrawal. Although harm-reduction strategies such as distribution of naloxone, an opioid reversal agent, have become more common in emergency departments, initiation of MAT for OUD is far less common and has faced significant barriers and resistance to implementation.7

Medications for OUD

Medications that are FDA-approved for the treatment of OUD include methadone, naltrexone, and buprenorphine. Naltrexone is a competitive antagonist of the mu opioid receptor, which is the primary receptor responsible for the pain relieving, euphoric, and respiratory depression effects of opioids. By blocking this receptor, naltrexone prevents patients from experiencing the effects of opioids when they are used (unless they are used in especially high quantities), which may discourage use over time; it may also somewhat decrease cravings for opioids, although the exact mechanism for this is unknown. Naltrexone does not have restrictions on what providers are able to prescribe it, but patients must abstain from opioids for 7-10 day prior to initiating naltrexone therapy to avoid precipitating significant opioid withdrawal symptoms, which makes this medication generally inappropriate for initiation in the emergency department. Methadone, on the other hand, is a long-acting full agonist of the mu opioid receptor with a moderate binding affinity. It effectively reduces cravings, prevents withdrawal symptoms, and does not cause euphoric effects in patients tolerant to it. Unfortunately, however, methadone is quite dangerous if used to overdose, and due to a propensity for inappropriate use, it is only able to be dispensed for OUD in specially designated clinics in the United States. Since it only has moderate binding affinity, it does not effectively block the binding of more potent opioids, such as fentanyl. Due to some of the downfalls of naltrexone and methadone, buprenorphine is the ideal medication to use to initiate MAT for OUD in emergency departments.8

Buprenorphine differs from other prescription and non-prescription opioids as it is a partial agonist of the mu opioid receptor rather than a full agonist. As a partial agonist, buprenorphine does have pain-relieving effects, but unlike other opioids, it has a ceiling effect in relation to respiratory depression and euphoria which makes buprenorphine much safer to use. In addition, buprenorphine has much higher affinity for the mu opioid receptor than most other opioids, making it significantly more difficult to overdose with other opioids if buprenorphine is in a person’s system as it will be unable to be displaced from the receptor; however, this high affinity also causes buprenorphine to displace other opioids currently in a person’s system from the receptor which can at times precipitate withdrawal symptoms. Buprenorphine is indicated for use in both acute and chronic pain as well as OUD, and it comes in a variety of formulations, including oral and sublingual tablets, sublingual films, transdermal patches, long-acting injections, and subcutaneous implants. Some of these formulations also contain naloxone, the opioid reversal agent, which is only activated if the medication is not taken via the intended route – this is included to deter patients from abusing buprenorphine.9 In order to prescribe buprenorphine for OUD, providers have to obtain a Drug Addiction Treatment Act 2000 waiver (also known as an X-waiver) – although this is not nearly as restrictive as prescribing methadone, it historically required 8 hours of training for physicians (or 24 hours of training for mid-level providers) and currently restricts providers to having 30 active prescriptions for buprenorphine at a time during the first year, with increased capacity in subsequent years. However, a rule by the DEA also allows buprenorphine to be administered in an emergency department for up to three consecutive days by providers who do not have an X-waiver.10 (Recent changes to X-waiver requirements will be discussed later in this article.)

Buprenorphine in the Emergency Department

Although evidence existed for using buprenorphine maintenance therapy for OUD that showed benefits including decreased cravings, reduced all-cause mortality, decreased overdose mortality, improved quality-of-life, and reduced incidence of blood borne illnesses such as HIV and hepatitis C,11 evidence for its use in the emergency department setting did not start accumulating significantly until the past decade. One clinical trial showed that buprenorphine could be safely used in the emergency department for opioid withdrawal and resulted in a fewer emergency department visits when compared to symptomatic treatment alone.12 The ground-breaking study that drew significant attention to buprenorphine’s use in the emergency medicine setting was published by D’Onofrio and colleagues at Yale in 2015. In this study, patients with opioid dependence who reported non-medical use of prescription opioids or heroin use in the last 30 days were randomized into three treatment groups. The first group (“referral group”), which contained 104 patients, received a screening and referral to treatment using a handout containing information on addiction treatment providers arranged according to insurance coverage. The second group (“brief intervention group”), containing 111 patients, received a screening, a 10-15 minute manual-driven brief negotiation interview (BNI), and a coordinated referral including review of insurance eligibility and transportation assistance. The third group (“buprenorphine group”) contained 114 patients who received a screening, a BNI, treatment with buprenorphine if they exhibited moderate-to-severe opioid withdrawal, and a referral to the hospital’s primary care center with an appointment made within 72 hours. A sufficient supply of buprenorphine was prescribed to patients to continue their treatment until follow up. The primary outcome of this study was engagement in addiction treatment at 30 days, with 37% of patients in the referral group, 45% of patients in the brief intervention group, and 78% of patients in the buprenorphine group being engaged in treatment for OUD at 30 days, which was statistically significant. The buprenorphine group also showed a statistically significant reduction in the mean number of days of illicit opioid use per week. The results of this study, with almost double the amount of patients receiving buprenorphine maintained in treatment at 30 days, highlighted the potential for emergency-department initiated buprenorphine to play a key role in improving outcomes for patients struggling with OUD.13

Since the study by D’Onofrio and colleagues was published, a number of protocols for emergency-department initiated buprenorphine for OUD have been developed and shared. The Yale protocol, which is based off of the treatment strategy for the buprenorphine group in the study led by D’Onofrio, can be seen in Figure 1.14 The CA Bridge initiative which was inspired by the work being done at Yale15 has an extensive library of resources and protocols. This initiative has expanded upon the Yale protocol by expanding the treatment options for patients to include higher total doses of buprenorphine to be given in the emergency department, which has the potential to allow for a longer period of relief from opioid withdrawal symptoms and cravings when an X-waivered provider is not available to write a prescription to bridge patients to their outpatient follow-up appointment. See the Figure 2 for more details.16 Both protocols, as well as others that have been developed, involve screening for inappropriate opioid use as well as an assessment for opioid withdrawal, such as the Clinical Opioid Withdrawal Scale (COWS). If an individual does not yet have notable withdrawal symptoms, buprenorphine should not be administered at that time as it may cause precipitation of worse withdrawal symptoms by displacing other opioids that are bound to the mu opioid receptor. Additionally, naloxone distribution is included as a part of these protocols as a harm-reduction strategy in the event that an individual would continue to use illicit opioids after emergency department discharge. Finally, these protocols are primarily intended to be used by X-waivered providers who will be able to prescribe buprenorphine to be used as an outpatient to bridge patients until their follow-up appointment, but they are written in such a way that they could also be used by non-X-waivered providers in certain situations.14,16 By improving engagement in treatment and therefore increasing the likelihood of long-term abstinence from illicit opioid use, MAT with buprenorphine for OUD being initiated in emergency departments is a key strategy to combating the opioid crisis.

Figure 1 - Yale Protocol for Buprenorphine Initiation in the Emergency Department14

(Reprinted from https://medicine.yale.edu/edbup/treatment/.)

Figure 2 - CA Bridge Buprenorphine Hospital Quick-Start Algorithm16

(Reprinted from https://cabridge.org/tools/resources/.)

Addressing Challenges to Buprenorphine Use for OUD

Despite growing evidence on the benefits of initiating buprenorphine in the emergency department and development of evidence-based protocols that can be translated to a variety of different situations, there remains significant resistance to implementation. A large amount of resistance comes from stigma that is held by healthcare providers, the public, and patients themselves.7 Despite evidence to the contrary, some clinicians still do not see addiction as a medical disease but rather as a moral failing of the individual. Additionally, even those who do understand addiction to be a medical disease may view buprenorphine use as simply replacing one addiction for another. However, when used as directed for the indication of opioid use disorder, buprenorphine is being used as a medication with evidence to support its benefits and not as a substance of abuse.11 Also, as previously described, buprenorphine is generally safer than other opioids as it is a partial agonist with ceiling effects on respiratory depression and as it can block the binding of other opioids which may decrease risk of overdose if illicit opioids are used.10 Other concerns with implementing a program in the emergency department stem from clinicians’ lack of formalized training and knowledge regarding the diagnosis and treatment of OUD, false perceptions that starting MAT for OUD is outside the scope of practice for emergency medicine providers, and actual or perceived lack of resources to effectively implement a program.17 As MAT for OUD is most effective when used as maintenance therapy, prompt connection to treatment post-discharge is especially of concern.8 Fortunately, health system resources, grant funding, and government resources can help address some of these concerns.

A variety of strategies can be undertaken by health systems to assist with the implementation of buprenorphine programs in emergency departments. Key to any of these strategies, effective programs will have the support of hospital leadership to allocate both educational and administrative resources to the program.17 By increasing clinician’s understating of the science behind addiction and of the diagnosis and treatment of OUD through educational initiatives and advocacy, stigma may slowly be changed to compassion and motivation for some providers, leading to a culture change in the organization.3,7 A variety of educational resources are openly available online, including from Yale, CA Bridge, Project SHOUT: Supporting Hospital Opioid Use Treatment and others, but development of organization-specific materials regarding community treatment resources is also imperative to success.10 Additionally, clinicians who complete X-waiver training have been shown to be more comfortable in providing treatment with buprenorphine,17 so incentivizing providers to obtain this training and obtain an X-waiver can be an effective strategy to help increase participation and bolster the effectiveness of a buprenorphine program by expanding treatment options.18 Having local clinical experts provide guidance and share their expertise can also increase comfort levels with prescribing buprenorphine in the emergency department and can help drive changes in practice. Development of evidence-based, organization-specific protocols and order sets with clinical decision support also increase provider readiness and comfort in initiating buprenorphine.17 Finally, although access to continued treatment for opioid use disorder is of concern and often is reliant on many factors outside an individual health care organization, taking a multidisciplinary approach in implementing buprenorphine in the emergency department, including recovery coaches if possible, may help improve the likelihood of effectively connecting patients to continued treatment.8,18 As implementation of many of these strategies relies on buy-in and support from hospital leadership, presenting evidence on the research-based financial implications of potential cost savings may be beneficial in garnering support; studies show that multiple programs have been initiated with a cost of only approximately $100 per patient and that emergency department programs for treatment of OUD may save from $2000 to $6000 per patient year for patients covered by Medicaid.10 Funds obtained through both government and non-government grants can also alleviate the initial financial burden of program development and implementation for a health care organization.

Regulatory Issues and the Future of the X-waiver

Government resources and regulatory changes are also imperative to expansion of MAT programs for OUD in emergency departments. Since the opioid crisis was declared a public health emergency, a large amount of federal grant funding has been made available to states and health organizations to improve access to OUD treatment and services.6 Additionally, it has been shown that Medicaid expansion resulting from the Affordable Care Act of 2008 increased access to care and treatment utilization for OUD,7 with better access to MAT and a 6% decrease in the rate of opioid overdose deaths in expansion states compared to non-expansion states.19,20

The federal government is currently considering changing the regulatory requirement for providers to have an X-waiver to prescribe buprenorphine. In the meantime, as of April 2021, federal guidelines have been updated to remove the educational requirements for practitioners to obtain an X-waiver if they only desire to treat up to 30 patients at a time. Practitioners still must have a valid DEA registration to prescribe buprenorphine and need to file a Notice of Intent to obtain an X-waiver, but the barrier of completing training has been removed if clinicians do not intend to treat large numbers of patients.21 Further information regarding these changes and answers to frequently asked questions in regards to the new federal guidelines are available on the Substance Abuse and Mental Health Services Administration website.22

In the future, government agencies will need to continue to consider the implications and efficacy of requiring an X-waiver for prescription of buprenorphine for OUD. Replacing the X-waiver with broad requirements for the inclusion of education regarding diagnosis and treatment for substance use disorders in medical training programs and continuing education requirements for licensure to further improve access to MAT for OUD may be more effective in providing safe, widely-available OUD treatment.7,23 In France, where restrictions on buprenorphine prescribing were removed in 1995, increased use of buprenorphine for treatment of OUD was seen and opioid overdose deaths decreased by 79% within 3 years, which supports the concept of decreased government regulation of buprenorphine.24 Additionally, states and insurance payers that require coverage of buprenorphine to be contingent on concomitant counseling therapy should consider removing this requirement, as it limits access to care and the benefits of buprenorphine can be seen even in the absence of counseling; these restrictions especially impact rural areas where counseling services are less common.7,8


It is as important as ever for health systems and government agencies to dedicate resources to effectively implement buprenorphine programs in emergency departments, thereby improving outcomes for individuals struggling with OUD by increasing engagement in treatment. The emergency department is an ideal location to focus resources on as it is a common place for patients to present to following opioid overdose or in opioid withdrawal, and buprenorphine has been shown to be a safe and effective treatment option in this setting as well as for maintenance treatment of OUD. Although there are many barriers to implementation of buprenorphine programs in emergency departments, there are multiple evidence-based strategies to overcoming these barriers, and easing of training requirements to obtain an X-waiver will hopefully ease some of these barriers as well. Especially considering that provisional data from the CDC indicates that overdose deaths increased by over 25% from the previous year as of August 2020,21 there is an urgent need to expand this evidence-based treatment with buprenorphine in emergency departments nationwide.


  1. American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders, 5th Edition: DSM-5 (5th ed.). American Psychiatric Publishing.
  2. American Psychiatric Association. (2018, November). Opioid Use Disorder. American Psychiatric Association (APA). https://www.psychiatry.org/patients-families/addiction/opioid-use-disorder/opioid-use-disorder#:~:text=The%20Diagnostic%20and%20Statistical%20Manual,a%20longer%20period%20than%20intended.
  3. Strugar-Fritsch, D. (2019, August). MAT for Opioid Use Disorder: Overcoming Objections. California Health Care Foundation. https://www.chcf.org/wp-content/uploads/2019/06/MATOpioidOvercomingObjections.pdf
  4. Centers for Disease Control and Prevention. (2020, March 19). Data Overview | Drug Overdose | CDC Injury Center. Centers for Disease Control and Prevention (CDC). https://www.cdc.gov/drugoverdose/data/index.html
  5. Assistant Secretary of Public Affairs (ASPA). (2019, September 4). About the Epidemic. HHS.Gov. https://www.hhs.gov/opioids/about-the-epidemic/index.html
  6. U.S. Department of Health and Human Services. (2018, May 23). HHS Acting Secretary Declares Public Health Emergency to Address. HHS.Gov. https://www.hhs.gov/about/news/2017/10/26/hhs-acting-secretary-declares-public-health-emergency-address-national-opioid-crisis.html
  7. Madras, B. K., Ahmad, N. J., Wen, J., Sharfstein, J., & Prevention, Treatment, and Recovery Working Group of the Action Collaborative on Countering the U.S. Opioid Epidemic. (2020). Improving Access to Evidence-Based Medical Treatment for Opioid Use Disorder: Strategies to Address Key Barriers Within the Treatment System. NAM Perspectives, 1–37.
  8. Strayer, R. J., Hawk, K., Hayes, B. D., Herring, A. A., Ketcham, E., LaPietra, A. M., Lynch, J. J., Motov, S., Repanshek, Z., Weiner, S. G., & Nelson, L. S. (2020). Management of Opioid Use Disorder in the Emergency Department: A White Paper Prepared for the American Academy of Emergency Medicine. The Journal of Emergency Medicine, 58(3), 522–546.
  9. Ling, W. (2012). Buprenorphine for opioid addiction. Pain Management, 2(4), 345–350.
  10. Cisewski, D. H., Santos, C., Koyfman, A., & Long, B. (2019). Approach to buprenorphine use for opioid withdrawal treatment in the emergency setting. The American Journal of Emergency Medicine, 37(1), 143–150.
  11. Velander, J. R. (2018). Suboxone: Rationale, Science, Misconceptions. The Oschner Journal, 18(1), 23–29.
  12. Berg, M. L., Idrees, U., Ding, R., Nesbit, S. A., Liang, H. K., & McCarthy, M. L. (2007). Evaluation of the use of buprenorphine for opioid withdrawal in an emergency department. Drug and Alcohol Dependence, 86(2–3), 239–244.
  13. D’Onofrio, G., O’Connor, P. G., Pantalon, M. V., Chawarski, M. C., Busch, S. H., Owens, P. H., Bernstein, S. L., & Fiellin, D. A. (2015). Emergency Department–Initiated Buprenorphine/Naloxone Treatment for Opioid Dependence. JAMA, 313(16), 1636.
  14. Yale School of Medicine. (2018, September 24). ED-Initiated Buprenorphine. https://medicine.yale.edu/edbup/treatment/
  15. Goodnough, A. (2018, August 20). This E.R. Treats Opioid Addiction on Demand. That’s Very Rare. New York Times. https://www.nytimes.com/2018/08/18/health/opioid-addiction-treatment.html
  16. CA Bridge. (2021, May). Resources to Treat Substance Use Disorders. https://cabridge.org/tools/resources/
  17. Hawk, K. F., D’Onofrio, G., Chawarski, M. C., O’Connor, P. G., Cowan, E., Lyons, M. S., Richardson, L., Rothman, R. E., Whiteside, L. K., Owens, P. H., Martel, S. H., Coupet, E., Pantalon, M., Curry, L., Fiellin, D. A., & Edelman, E. J. (2020). Barriers and Facilitators to Clinician Readiness to Provide Emergency Department–Initiated Buprenorphine. JAMA Network Open, 3(5), e204561.
  18. Lowenstein, M. (2019, March 13). Starting Opioid Use Disorder Treatment in the Emergency Department. Leonard Davis Institute of Health Economics at the University of Pennsylvania. https://ldi.upenn.edu/healthpolicysense/starting-opioid-use-disorder-treatment-emergency-department
  19. Kravitz-Wirtz, N., Davis, C. S., Ponicki, W. R., Rivera-Aguirre, A., Marshall, B. D. L., Martins, S. S., & Cerdá, M. (2020). Association of Medicaid Expansion With Opioid Overdose Mortality in the United States. JAMA Network Open, 3(1), e1919066.
  20. Sharp, A., Jones, A., Sherwood, J., Kutsa, O., Honermann, B., & Millett, G. (2018). Impact of Medicaid Expansion on Access to Opioid Analgesic Medications and Medication-Assisted Treatment. American Journal of Public Health, 108(5), 642–648.
  21. Practice Guidelines for the Administration of Buprenorphine for Treating Opioid Use Disorder. Federal Register. (2021, April 28). https://www.federalregister.gov/documents/2021/04/28/2021-08961/practice-guidelines-for-the-administration-of-buprenorphine-for-treating-opioid-use-disorder.
  22. Become a Buprenorphine Waivered Practitioner. SAMHSA. (2021, May 5). https://www.samhsa.gov/medication-assisted-treatment/become-buprenorphine-waivered-practitioner.
  23. Fiscella, K., Wakeman, S. E., & Beletsky, L. (2019). Buprenorphine Deregulation and Mainstreaming Treatment for Opioid Use Disorder. JAMA Psychiatry, 76(3), 229.
  24. Auriacombe, M., Fatséas, M., Dubernet, J., Daulouède, J.-P., & Tignol, J. (2004). French Field Experience with Buprenorphine. American Journal on Addictions, 13(s1), S17–S28.

Upcoming events

Copyright 2020, Missouri Society of Health-System Pharmacists
501(c)6 non-profit organization. 2650 S. Hanley Rd., Suite 100, St. Louis, MO 63144 
p: (314) 416-2246, f: (314) 845-1891, www.moshp.org
Powered by Wild Apricot Membership Software