Substance Use Guidelines: Buprenorphine
October 2024
Introduction
Role of Buprenorphine in Overdose Prevention
• Buprenorphine is a medication that is used to treat opioid dependence and pain.
• Buprenorphine has been available in the United States since 2002 and is one of three medications currently approved by the FDA for the treatment of opioid use disorder; the other two medications are methadone and extended-release injectable naltrexone.
• Accidental drug overdose remains the leading cause of death for people experiencing homelessness (PEH) in the U.S.1 Multiple community-level studies have demonstrated increasing rates of accidental drug overdose deaths among PEH in recent years, the majority of which involve opioids.2,3
• Treatment with buprenorphine is associated with a significantly reduced risk of opioid overdose among people who use opioids.4,5
• Increased access to buprenorphine has the potential to impact overdose risk and rates, yet in 2022 only 25% of people with opioid use disorder (OUD) received medications to treat their opioid use 6
Taking and Prescribing Buprenorphine
• The ability for primary care providers to prescribe buprenorphine was broadened by the elimination of the X-waiver in 2022. This change removed federal restrictions requiring specialized training and an additional Drug Enforcement Administration (DEA) certification to prescribe buprenorphine.
• Per federal regulations, buprenorphine can now be prescribed in primary care settings by any provider who can prescribe controlled substances.
• However, federal changes to the X-waiver do not supersede state restrictions. Multiple states still have restrictions in place regarding who can prescribe and receive buprenorphine, dosing, and the number of buprenorphine patients an individual prescriber can have at one time.
• Buprenorphine can be taken in two ways: a film or tablet dissolved under the tongue (sublingual) one to three times daily, or as a long-acting (subcutaneous) injection given weekly or monthly.
• Buprenorphine has not been found to have recreational uses; prescribed medication that is diverted into the community is most often used to self-manage treatment and withdrawal.7 Use of nonprescribed buprenorphine (bought on the street) has also been shown to reduce overdose risk.8
Disparities in Access and Health Outcomes:
• Racial and ethnic disparities are present in drug overdose fatalities in the U.S., and these disparities have increased in recent years.9 Currently, age-adjusted overdose rates are highest for American Indian and Alaska Native non-Hispanic populations, followed by Black non-Hispanic populations. 10
• Black non-Hispanic, American Indian/Alaska Native, and Hispanic people are less likely than their white counterparts to be prescribed buprenorphine for opioid use disorder,11,12 and, when prescribed buprenorphine, have a shorter average duration of treatment.13
• People who have a mental health or pain diagnosis, or who are non-English speakers, are less likely to receive buprenorphine from medical providers they encounter in both outpatient and emergency department settings. 14
Key Terms and Definitions
• Harm Reduction: An approach to care that establishes individual agency and self-determination as central to all efforts towards well-being. Harm reduction approaches focus on providing nonjudgmental and non-coercive provision of services and resources to people who use substances with the goal of reducing harms related to their substance use.
• Trauma-informed care (TIC): A patient-centered approach to care that recognizes the impacts of trauma and actively works to prevent re-traumatization and promote recovery. The principles of TIC are grounded in establishing a trusting relationship within a safe physical and psychological space in which to address needs.
• Low-Threshold Programs: Refers generally to an approach to substance use treatment that removes traditional barriers to entering and remaining in treatment. Low-threshold programs typically offer same day admissions/treatment starts, flexible scheduling, ongoing support through relapse events or ongoing use, and care delivery at non-traditional settings in the community.15
• Precipitated Withdrawal: The rapid onset of opioid withdrawal symptoms after the administration of a medication that competitively binds to opioid receptors (pushes opioids off receptors), such as buprenorphine or naloxone.
Clinical Considerations
Physical and Behavioral Health Impacts
• Buprenorphine is a partial opioid agonist, meaning it does not fully activate all the same receptors as full agonists like heroin and methadone. Rather, the medication activates some receptors and blocks others.
• In terms of patient experience, the patrial-agonist property of buprenorphine means that people taking the medication experience relief from withdrawal symptoms and cravings, but do not experience the sedation, respiratory depression, or euphoria associated with full opioid agonists.
• One of the opioid receptor types that buprenorphine has a high affinity, or ability to bind to, is the mu receptor. Because of this affinity, buprenorphine can displace other full opioid agonists, like methadone or heroin, that are bound to these receptors This means that buprenorphine can cause precipitated withdrawal in those who take the medication when they have recently used opioids. There are a number of ways to initiate treatment with buprenorphine that aim to avoid precipitated withdrawal.
• Like other medications used to manage chronic disease, individuals can remain on buprenorphine indefinitely, and certainly for the long term. Those who choose to stop treatment should work with their prescriber to plan a taper and to address relapse and overdose risk.16,17
• The abrupt cessation of treatment with buprenorphine can result in withdrawal symptoms and also increases one’s risk of relapse and overdose. 18,19
Use of Buprenorphine and Experiences of Homelessness
• Multiple factors put people experiencing homelessness at high risk for opioid overdose and other medical and mental health challenges related to drug use. Risk factors can include physical and
social isolation, the ongoing requirement to prioritize safety and basic needs over other health goals, other co-occurring medical and mental health conditions, exposure to the elements putting additional stress on the body, poor access to adequate hygiene, hydration and nutrition, and difficulty accessing treatment and recovery services.
• Accessing treatment can be challenging for people experiencing homelessness, in particular meeting the requirements of traditional, or higher barrier, program models. Transportation concerns, ongoing efforts to meet basic needs taking priority, insurance challenges, theft of medications, and keeping track of appointments can make getting to appointments, obtaining prescriptions, and filling them very difficult.
• High barrier buprenorphine programs, for example programs that require abstinence from all substances except those prescribed, or programs that have strict appointment schedules and late policies, frequently do not meet the needs and realities of people experiencing homelessness. Low threshold programs, for example walk-in or outreach-based models, can prevent program discharges and associated increased overdose risk
• Experiences of homelessness can make it much more likely that people will lose medications, have medications stolen, or feel compelled to sell a portion or all of their medications to meet basic needs. Depending on location, replacement buprenorphine can require a police report documenting theft and/or prior authorization from one’s insurance company and may be limited to once per rolling 12-month calendar. These restrictions can lead to lapses in buprenorphine treatment.
• Flexible approaches and patient-centered solutions, including switching to an injectable form of buprenorphine, shorter duration prescriptions, and partnerships with pharmacies or programs that support individuals in medication management, can be helpful
Harm Reduction Strategies
• The use of buprenorphine is a harm reduction intervention in itself, as the medication has been shown to significantly decrease the risk of opioid overdose and of all-cause mortality among people who use opioids and are opting for treatment.20,21
• Both the sublingual and long-acting injectable versions of buprenorphine decrease opioid overdose risk.22,23
• Substance use goals fall along a continuum, may or may not include abstinence, and change over time Open communication about a person’s goals for their substance use and what is and isn’t working, is vital. It is also important to note that while someone may have a goal of abstinence from one substance, their goals around other substances may differ.
• Relapses and periods of increased use are a normal part of recovery Explore how best to support someone who has re-started or increased their use, or who has stopped using their buprenorphine. Interventions like shorter duration prescriptions, switching to an injectable buprenorphine, referrals to other behavioral health supports, or trying another treatment modality, such as inpatient treatment or methadone, are all appropriate options.
• People who are prescribed buprenorphine should always have access to naloxone as well as to safer use supplies.
• In addition to having access to clean supplies, safer injection techniques can reduce the risk of injection related infections like abscesses.
Treatment and Supportive Services
• There are a number of strategies for initiating treatment with buprenorphine that minimize the risk of precipitated withdrawal or seek to quickly diminish withdrawal symptoms in those already experiencing them. The approaches for starting sublingual therapy fall into three general categories:
o Standard induction: Buprenorphine is initiated when a person is in moderate withdrawal (based on the COWS assessment), starting with a low dose of either 2mg or 4mg. If the person experiences no change or a reduction in withdrawal symptoms, another dose is given 2 to 4 hours later. If withdrawal symptoms increase after the initial dose, induction is attempted again the following day.
o Microdosing or microinduction: Buprenorphine is initiated by taking small amounts (starting with 0.5mg) of the medication over several days to slowly replace opioids on receptors with buprenorphine. The purpose of this approach is to avoid withdrawal symptoms. Some clinicians have also utilized buprenorphine transdermal patches as a way to initiate microdosing, followed by incremental sublingual dosing.
o Macrodosing or macroinduction: Buprenorphine is started with a 16mg dose for people who are already in withdrawal (either due to not using or after naloxone administration), who have a need to initiate treatment quickly, and who have the ability to receive withdrawal symptom support. This is more common in hospital settings.
• Another option for those interested in buprenorphine treatment is one of the long-acting injectable formulations of buprenorphine, Sublocade or Brixadi Long-acting injections provide continuous overdose risk reduction as well as prevent withdrawal symptoms and cravings without the lapses that can occur with oral therapy.
• People need to have trialed sublingual buprenorphine before starting either injection. People who have had a hard time with keeping track of their sublingual buprenorphine may benefit from longacting injectables.
• Sublocade has two strengths, a 300mg injection intended for initiation of treatment, and a 100mg injection intended for maintenance. For people who inject heroin and/or fentanyl, the 300mg dose has been found to better control craving and withdrawal symptoms beyond the initiation phase and can be used as a maintenance dose 24
• Some patients on long-acting injections who are having breakthrough withdrawal symptoms may benefit from supplemental sublingual buprenorphine as they initiate treatment 25,26
• Medications to address withdrawal symptoms can be prescribed so patients have a way to manage any symptoms that occur during induction, including diarrhea, nausea/vomiting, anxiety, and pain/body aches.
• Both primary care and other service providers can work to facilitate transitions to other types of treatment if needed, including to methadone, long-acting buprenorphine, or inpatient treatment.
• Hospitalization can be a challenging time for people who use opioids and can also be an opportunity to try medications like buprenorphine. Clinicians and other service providers can support people’s goals and withdrawal management needs by advocating for adequate withdrawal management, providing supporting clinical information, and supporting people to make their recovery goals known.
Models of Care Delivery
• Low-threshold buprenorphine programs work to make it easy to enter and easy to continue treatment. These programs can function as part of primary care and are characterized by the ability
to start buprenorphine treatment on the day the client first presents, varied options for buprenorphine induction, and locations and hours that accommodate clients’ location and access needs. Low-threshold programs utilize protocols that facilitate communication around goals and increase supports when clients are struggling with ongoing use; they do typically have standards that require demonstration of some buprenorphine use, and will help those who need to transfer to other treatment methods, such as inpatient treatment or methadone. Patients who chose to take a break from treatment can easily return.
• Health centers serve a vital role in providing buprenorphine treatment as part of primary care, and in serving as a link between integrated primary and behavioral health care and other services, such as shelter, housing, respite, and other care providers.
• Outreach and street medicine teams are another important point of contact for people to initiate treatment with buprenorphine, and prescribing team members can also serve as providers for ongoing care, including via telehealth.
• Emergency departments can play a role in initiating buprenorphine and bridging people into community outpatient buprenorphine treatment. Initiating buprenorphine in emergency department settings has been found to be an effective entry to treatment, with improved retention (78%) over those who were referred to treatment without starting medication (37%).27 Health centers can partner with emergency departments and hospitals to facilitate warm handoffs into primary care-based treatment.
• Carceral institutions (jails and prisons) can support buprenorphine initiation and ongoing treatment, as well as in liaising with health centers to ensure ongoing treatment after release Initiation of buprenorphine treatment while incarcerated has been shown to increase ongoing treatment postrelease.28
• Medical respite programs may be a helpful support for someone who is beginning induction and experiencing adverse withdrawal symptoms that having access to a bed, bathroom, and medical support staff may help minimize.
Resources
Substance Abuse and Mental Health Services Administration’s (SAMHSA) Buprenorphine Quick Start Guide
Cleveland Clinic’s Practical Guide for Buprenorphine Initiation in Primary Care Settings
National Association of Community Health Centers’ Increasing Equity in Pain Management, Substance Use Treatment, and Linkages to Care
Impact of an Incentive Program on Use of Injectable Buprenorphine in Philadelphia, PA
References
1 Fine DR, Dickins KA, Adams LD, et al. Drug Overdose Mortality Among People Experiencing Homelessness, 2003 to 2018. JAMA Netw Open. 2022;5(1):e2142676. doi:10.1001/jamanetworkopen.2021.42676
2 Los Angeles Department of Public Health. 2023. New public health report shows sharp rise in mortality among people experiencing homelessness - Increase driven by fentanyl-related deaths, traffic deaths, and homicides.
Accessed from: http://publichealth.lacounty.gov/phcommon/public/media/mediapubhpdetail.cfm?prid=438
3 Cawley C, Kanzaria HK, Zevin B, Doran KM, Kushel M, Raven MC. Mortality Among People Experiencing Homelessness in San Francisco During the COVID-19 Pandemic. JAMA Netw Open. 2022;5(3):e221870. doi:10.1001/jamanetworkopen.2022.1870
4 Morgan, J. R., Schackman, B. R., Weinstein, Z. M., Walley, A. Y., & Linas, B. P. (2019). Overdose following initiation of naltrexone and buprenorphine medication treatment for opioid use disorder in a United States commercially insured cohort. Drug and Alcohol Dependence, 200, 34–39. https://doi.org/10.1016/j.drugalcdep.2019.02.031
5 Samples, H., Nowels, M. A., Williams, A. R., Olfson, M., & Crystal, S. (2023). Buprenorphine after nonfatal opioid overdose: Reduced mortality risk in Medicare disability beneficiaries. American Journal of Preventive Medicine, 65(1), 19–29. https://doi.org/10.1016/j.amepre.2023.01.037
6 Dowell D, Brown S, Gyawali S, et al. Treatment for Opioid Use Disorder: Population Estimates United States, 2022. MMWR Morb Mortal Wkly Rep 2024;73:567–574. DOI: http://dx.doi.org/10.15585/mmwr.mm7325a1
7 Grande, L. A., Cundiff, D., Greenwald, M. K., Murray, M., Wright, T. E., & Martin, S. A. (2023). Evidence on Buprenorphine Dose Limits: A Review. Journal of addiction medicine, 17(5), 509–516. https://doi.org/10.1097/ADM.0000000000001189
8 Carlson, R. G., Daniulaityte, R., Silverstein, S. M., Nahhas, R. W., & Martins, S. S. (2020). Unintentional drug overdose: Is more frequent use of non-prescribed buprenorphine associated with lower risk of overdose?
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9 Britz, J. B., O'Loughlin, K. M., Henry, T. L., Richards, A., Sabo, R. T., Saunders, H. G., Tong, S. T., Brooks, E. M., Lowe, J., Harrell, A., Bethune, C., Moeller, F. G., & Krist, A. H. (2023). Rising Racial Disparities in Opioid Mortality and Undertreatment of Opioid Use Disorder and Mental Health Comorbidities in Virginia. AJPM focus, 2(3), 100102. https://doi.org/10.1016/j.focus.2023.100102
10 Centers for Disease Control. 2024. Drug overdose deaths in the United States: 2002 to 2022. Accessed from: https://www.cdc.gov/nchs/products/databriefs/db491.htm
11 Miles, J., Treitler, P., Lloyd, J., Samples, H., Mahone, A., Hermida, R., Gupta, S., Duncan, A., Baaklini, V., Simon, K. I., & Crystal, S. (2023). Racial and ethnic disparities in buprenorphine receipt among Medicare beneficiaries, 2015–19. Health Affairs, 42(10), 1431–1438. https://doi.org/10.1377/hlthaff.2023.0020 5
12 Dunphy, C. C., Zhang, K., Xu, L., & Guy, G. P., Jr (2022). Racial‒Ethnic Disparities of Buprenorphine and Vivitrol Receipt in Medicaid. American journal of preventive medicine, 63(5), 717–725. https://doi.org/10.1016/j.amepre.2022.05.006
13 Dong, H., Stringfellow, E. J., Russell, W. A., & Jalali, M. S. (2023). Racial and Ethnic Disparities in Buprenorphine Treatment Duration in the US. JAMA psychiatry, 80(1), 93–95. https://doi.org/10.1001/jamapsychiatry.2022.3673
14 Sordo, L., Barrio, G., Bravo, M. J., Indave, B. I., Degenhardt, L., Wiessing, L., Ferri, M., & Pastor-Barriuso, R. (2017). Mortality risk during and after opioid substitution treatment: Systematic review and meta-analysis of Cohort studies. BMJ. https://doi.org/10.1136/bmj.j1550
15 Jakubowski, A., & Fox, A. (2020). Defining low-threshold buprenorphine treatment. Journal of Addiction Medicine, 14(2), 95–98. https://doi.org/10.1097/adm.0000000000000555
16 Zweben, Joan E. PhD; Sorensen, James L. PhD; Shingle, Mallory BA; Blazes, Christopher K. MD. 2021. Discontinuing methadone and buprenorphine: A review and clinical challenges. Journal of Addiction Medicine 15(6):p 454-460. doi 10.1097/ADM.0000000000000789
17 Epland C, Pals H, Hayden J. 2024. Buprenorphine enhanced taper tolerability evaluation report (BETTER): A case series. Substance Use & Addiction Journal. doi:10.1177/29767342241242242
18 Sordo, L., Barrio, G., Bravo, M. J., Indave, B. I., Degenhardt, L., Wiessing, L., Ferri, M., & Pastor-Barriuso, R. (2017). Mortality risk during and after opioid substitution treatment: Systematic review and meta-analysis of Cohort studies. BMJ. https://doi.org/10.1136/bmj.j1550
19 Gibbons JB, McCullough JS, Zivin K, Brown ZY, Norton EC. Association Between Buprenorphine Treatment Gaps, Opioid Overdose, and Health Care Spending in US Medicare Beneficiaries With Opioid Use Disorder. JAMA Psychiatry. 2022;79(12):1173–1179. doi:10.1001/jamapsychiatry.2022.3118
20 Morgan, J. R., Schackman, B. R., Weinstein, Z. M., Walley, A. Y., & Linas, B. P. (2019a). Overdose following initiation of naltrexone and buprenorphine medication treatment for opioid use disorder in a United States commercially insured cohort. Drug and Alcohol Dependence, 200, 34–39. https://doi.org/10.1016/j.drugalcdep.2019.02.031
21 Larochelle, M. R., Bernson, D., Land, T., Stopka, T. J., Wang, N., Xuan, Z., Bagley, S. M., Liebschutz, J. M., & Walley, A. Y. (2018). Medication for opioid use disorder after nonfatal opioid overdose and association with mortality. Annals of Internal Medicine, 169(3), 137. https://doi.org/10.7326/m17-3107
22 Ochalek, T. A., Ringwood, K. J., Davis, T. T., Gal, T. S., Wills, B. K., Sabo, R. T., Keyser-Marcus, L., Martin, C. E., Polak, K., Cumpston, K. L., & Moeller, F. G. (2023). Rapid induction onto extended-release injectable buprenorphine following opioid overdose: A case series. Drug and Alcohol Dependence Reports, 7, 100144. https://doi.org/10.1016/j.dadr.2023.100144
23 Lee, K., Zhao, Y., Merali, T., Fraser, C., Kozicky, J.-M., Mormont, M.-C., & Conway, B. (2023). Real-world evidence for impact of opioid agonist therapy on nonfatal overdose in patients with opioid use disorder during the COVID-19 pandemic. Journal of Addiction Medicine. https://doi.org/10.1097/adm.0000000000001213
24 Greenwald, M.K., Wiest, K.L., Haight, B.R. et al. Examining the benefit of a higher maintenance dose of extendedrelease buprenorphine in opioid-injecting participants treated for opioid use disorder. Harm Reduct J 20, 173 (2023). https://doi.org/10.1186/s12954-023-00906-7
25 Rutgers University (2022). Using injectable buprenorphine (Sublocade): A guide for providers. Accessed from: https://sites.rutgers.edu/mat-coe/wp-content/uploads/sites/473/2022/05/Sublocade-Guidance-Booklet-4.14.pdf
26 The College of Physicians and Surgeons of Manitoba (2023). Recommendations for Sublocade and considerations for informed consent. Accessed from: https://cpsm.mb.ca/assets/PrescribingPracticesProgram/Buprenorphine%20Specific%20Guidance%20%20Recommendations%20for%20Sublocade%20&%20Considerations%20for%20Informed%20Consent.pdf
27 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. https://doi.org/10.1001/jama.2015.3474
28 Bovell-Ammon, B. J., Yan, S., Dunn, D., Evans, E. A., Friedmann, P. D., Walley, A. Y., & LaRochelle, M. R. (2024). Prison buprenorphine implementation and postrelease opioid use disorder outcomes. JAMA Network Open, 7(3). https://doi.org/10.1001/jamanetworkopen.2024.2732