Substance Use Guidelines: Methadone
September 2023
Introduction
• Methadone is a long-acting opioid that is taken orally and acts on the same neural receptors as other opioids such as oxycodone, fentanyl , or heroin. It differs from other opioids in that it has a longer half-life (15-55 hours), meaning it acts on the receptors for a longer period of time. The slower onset of effect and longer half-life also mean methadone does not generate the same feelings of immediate reward of euphoria like other faster-acting opioids. It is also the reason methadone can be taken only once a day and still control withdrawal symptoms and cravings.
• Methadone has been used to treat Opioid Use Disorder (OUD) in the United States since the 1960s, through federal and state-licensed Opioid Treatment Programs (OTPs) and its use is highly regulated at the federal and state level .
• This medication is dispensed in liquid form or by dispersible tablet and is “dosed” daily from the OTP in the initial stages of treatment and beyond for people who continue to use other opioids or drugs. Take-home doses are allowed after sobriety, diversion prevention, and safety milestones are met, which vary by state law. i
• Methadone is also utilized illicitly because of its pain relief and sedative qualities, and to prevent withdrawal While methadone has a lower risk of overdose compared to drugs like fentanyl, due largely to its long half-life, it also remains in the body for a longer time for the same reason. Especially when taken with other opioids or sedating medications, methadone can still cause overdose.
• Methadone dosing starts at 10 -30mg daily and is titrated to higher doses every 2-3 days during the first 1-3 weeks of treatment. This titration schedule avoids “stacking” of methadone in the body related to its long half-life, which can lead to toxicity and overdose. ii A person’s dose is titrated up until a “blocking” dose is reached. A blocking dose is one in which symptoms of withdrawal and cravings are minimal or non-existent. It can be harder to reach blocking doses when the person is using fentanyl.
• When taken orally, methadone’s onset of action is slower than other methods of use, avoiding reinforcing behavior and subsequent addiction, and it is administered orally in the treatment of OUD.
• The most common side effects of methadone include sedation and constipation. Sedation is overcome with time and tolerance. Constipation can occur regardless of dose or length of time in treatment. Dose adjustments and other medication can be given to counteract these common symptoms so that individuals on methadone treatment can function appropriately in their daily lives.
• When used to treat OUD, methadone use is associated with decreased mortality, increased retention in OUD treatment, decreased recidivism, and decreased high-risk behavior that can lead to
HIV or Hepatitis transmission in individuals with OUD compared with individuals who are not on continuous medication for the treatment of OUD. iii
• People experiencing homelessness (PEH) face high barriers to treatment, are less likely to engage in methadone treatment, and experience poorer treatment retention and earlier recurrence of OUD with methadone treatment iv, v Methadone regulations may be partly culpable for this treatment disparity, as federal law requires at least a six day/week attendance in clinic for the first 90 days of treatment.
Key Terms and Definitions
• Trauma-informed care: 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 and a safe physical and psychological space in which to address needs.
• Harm reduction: A philosophical approach to care that establishes individual agency and selfdetermination as central to all efforts toward well -being. Harm reduction approaches call for the non-judgmental, non-coercive provision of services and resources to people who use substances to assist them in reducing harms related to their substance use or other health behaviors. Harm reduction-based care is collaborative, provides education on available interventions, and centers the goals of the individual in care planning.
• Opioid Treatment Programs (OTPs): Clinics that directly provide medication like methadone and buprenorphine for opioid use disorder. These clinics are licensed through the Substance Abuse and Mental Health Services Administration, the Drug Enforcement Agency, and their respective State Opioid Treatment Authorities. In the United States, these clinics must provide medical treatment and substance use disorder counseling at the level of the state guidelines, should they be more restrictive than federal guidelines.
• Take-Home Doses: Medication for OUD packaged by individual dose and date and given to a patient to take on a day they are not required to dose in clinic. The amount of earned take-home doses allowable after a certain amount of time in treatment varies by state regulations.
• Overdose Prevention Sites/Supervised Consumption Services: Locations where individuals can use previously acquired illicit substances under the care and observation of trained professionals to prevent overdose These centers also offer medical, behavioral health, case management, housing referrals, and other supportive services.
Clinical Considerations
Physical
and Behavioral Health Impacts
• Methadone as a treatment for OUD is known to help reduce high-risk behaviors, such as injection drug use (IDU) and high-risk sexual behaviors. Adherence to treatment leads to decreases in overall health care costs, including decreases in the occurrence of injection-related illnesses such as skin infections, heart infections like endocarditis, and bone infections like osteomyelitis. vi, vii
• Methadone, while a highly effective treatment for OUD, carries risks of cardiac toxicity and has significant drug-drug interactions. Methadone can prolong the QT interval (part of the electrical
impulse that causes the heart to beat) increasing the risk of an abnormal heart rhythm, and should be used cautiously in individuals with a pre-existing prolonged QT or who are on other medications that prolong QT. Electrocardiograms (ECGs) are recommended for individuals with coronary artery disease prior to methadone initiation, and they should be periodically rechecked to ensure no electrical abnormalities have developed that could put an individual at risk for Torsades-DesPointes, a potentially fatal arrhythmia. A careful review of medications to avoid these interactions is necessary prior to treatment initiation.
• Methadone can be additive with other opioids, and overdose is still possible. The goal of treatment with methadone is identifying the dose of methadone that effectively extinguishes withdrawal symptoms and cravings to use illicit opioids. For some individuals, inpatient treatment may be considered for methadone dose titration to optimize symptom management during initial treatment and increase the likelihood of cessation of other opioids.
• Polysubstance use, particularly with alcohol, benzodiazepines, or related sedatives, can cause accidental poisonings or facilitate intentional overdoses. Methadone clinics utilize random urine drug screens and breathalyzer tests to reduce the risk of unintentional overdose. Some programs may decrease methadone dosing significantly if breathalyzer or urine drug screens demonstrate use of alcohol or benzodiazepines.
Use of Methadone and Experiences of Homelessness
• Unhoused individuals on methadone treatment are known to have higher rates of pain and trauma, including physical assault, as well as psychiatric distress. As a result, there may be a higher likelihood of polysubstance use, medical comorbidity, and psychiatric comorbidity which should be addressed upon accessing treatment. viii, ix, x
• Daily transportation to methadone clinics presents a significant barrier to treatment for people experiencing homelessness and strict scheduling may be difficult to adhere to, so identifying an OTP with flexibility and ability to provide or pay for transportation is important
• There are still eight states that require a government-issued identification in order to access methadone treatment. This is a significant barrier to treatment for people experiencing homelessness in those states
Harm Reduction Strategies
• Methadone is considered a harm reduction intervention to decrease high-risk injection drug use, and its ability to prevent overdoses. Given the licensing constraints in the United States, however, it is rare to find OTPs associated with Syringe Service Programs (SSPs), wound care clinics, or other medical services. For PEH, low-barrier methadone treatment and mobile treatment options are preferable but can be difficult to obtain due to regulations around methadone treatment.
• It is important to talk with people on methadone treatment about other substance use, including substances that might be favored because they are not routinely checked on urine drug screens, such as synthetic cannabinoids (K2 or spice) or prescription drugs like clonidine. Clonidine can significantly increase sedation and may contribute to bradycardia and hypotension when combined with methadone or other opioids. Other sedating additives in the drug supply, such as xylazine, should be discussed with clients as well.
• It can be difficult to transition from fentanyl to methadone and people may need additional withdrawal support, especially if starting in an outpatient program at a methadone dose of 30mg. Many people in this situation will need to continue to use fentanyl while their methadone dose is increased. With heavy fentanyl use, some people may prefer inpatient treatment for methadone initiation and titration. Open dialogue about symptoms, ongoing use, interest in inpatient treatment to manage withdrawal, and overdose risk and prevention measures are a vital part of treatment.
• It is important to recognize that people’s recovery goals vary widely, from not wanting to stop using , to wanting to avoid sedation associated with use but also withdrawal, to wanting to decrease or stop use altogether. Continued use should not be cause to discharge people out of methadone treatment but rather viewed as an opportunity to engage further and discuss treatment goals.
• Supervised Consumption Services (SCS) may also be beneficial for PEH not wanting to stop use. These programs allow for previously obtained illicit drugs to be used under the care and observation of trained professionals. These services reduce overdose deaths, provide safe syringe access and disposal, and enable medical and behavioral treatment xi, xii
• Receiving methadone while in an inpatient medical setting can be challenging, as hospital providers must first verify the client’s dose with their methadone program before administering methadone at their current dose. Health Care for the Homeless service providers can support this process by making patients aware of the risk of delayed dosing, especially if admitted after hours or on a weekend, and facilitate communication by alerting the methadone program of the hospitalization and the hospital of the methadone program counselor’s name and contact information.
Treatment and Supportive Services
• For unhoused individuals on methadone treatment, outpatient treatment for comorbid alcohol use and/or anxiolytic (benzodiazepine) dependence disorder must be made with care, as benzodiazepine and alcohol use in combination with methadone can cause respiratory depression, overdose, and death. Inpatient treatment for alcohol or benzodiazepine use should be offered when possible In the absence of inpatient treatment, off-label medications, such as gabapentin, pregabalin, and topiramate can be used to help reduce alcohol use and improve abstinence. xiii, xiv, xv
• Individuals who are experiencing homelessness and opting for treatment with methadone need early and ongoing support with treatment initiation and continuation. The attendance requirements of methadone programs can be a significant challenge for people experiencing homelessness.
• Due to the isolation and poor social support often found among PEH, it is critical to treat social isolation with services such as peer support and group therapy. There is some evidence that they can improve treatment retention and increase relationships with providers. xvi
• Supportive housing is associated with increased initiation into substance use treatment and decreased emergency department visits and hospitalizations. Stable housing makes attending a methadone clinic daily more feasible and also opens the possibility of take-home doses.
• Other non-pharmacologic interventions such as contingency management can benefit all individuals seeking treatment, including people experiencing homelessness, and should be offered wherever possible for as long as possible, as improvements in sobriety diminish once this intervention stops. xvii
Models of Care Delivery
• Leveraging an interdisciplinary care model is vital for supporting people who use methadone Service providers should work to improve care coordination and communication between providers, including referrals to behavioral health and specialty care when appropriate.
• In the United States, methadone can only be dispensed out of federally and state-licensed OTPs, which is a huge challenge in rural areas, where OTPs are scarce. The number of methadone clinics has remained static over the past 20 years despite the exponential increase in overdose deaths in the country during the same period. xviii
• The current model requires evaluation by a physician at the OTP and dose dispensing by nurses in the same facility. An individual must have directly observed dosing on a daily basis at an OTP for at least the first 90 days of treatment before any take-home doses are granted. xix Allowances for takehome doses vary by state, and requirements can be difficult to meet.
• OTPs vary in operation style from “high-threshold” to “ low-barrier.” Low-barrier methadone clinics are designed to reduce logistic and financial hurdles to receiving treatment, utilize a harm reduction approach, and have more flexible attendance policies. They offer methadone initiation on the same day of intake regardless of financial means or housing status and may be more effective at enrolling unhoused individuals, as they acknowledge that many individuals’ lives may be unpredictable, and appointments may not always be able to be attended Conversely, “high-threshold” methadone clinics may involuntarily discharge a participant for any illicit drug use.
• Mobile methadone services have been found to have higher treatment retention rates than their fixed-site counterparts in one study xx Decreased travel time and reduction in transportation costs promoted adherence to treatment and may be more useful for individuals with OUD experiencing homelessness.
• The “72 rule” allows for non-OTP providers to administer methadone for opioid withdrawal for three consecutive days while arranging more definitive care at OTPs. This allows for a “bridge” to treatment but is difficult to find and requires community health centers to forge close relationships with OTPs, which thus far, has not been adequately implemented. xxi
• Interim methadone treatment is when methadone is initiated without the requirement of counseling services when counseling is unavailable and can be offered for a maximum of 120 days with the permission of SAMHSA. This more flexible approach aims to reduce wait times for methadone treatment initiation and can only be used if traditional initiation is not available. When used, it was found to be safe and effective compared to waitlists and had similar outcomes to usual methadone treatment. xxii
Additional Resources
• NHCHC: The Opioid Epidemic & Homelessness: An Action Agenda for the HCH Community
• Center for Addiction and Mental Health: Street Methadone
• National Harm Reduction Coalition: Overview of Supervised Consumption Services in the United States
• Health Affairs: The New Mobile Methadone Rules and What They Mean for Treatment Access
• National Institute on Drug Abuse: Treating Opioid Use Disorder During Pregnancy
References
i Cunningham, C., Edlund, M. J., Fishman, M., Gordon, A. J., Jones, H. E., Langleben, D., & Femino, J. (2020). The ASAM national practice guideline for the treatment of opioid use disorder: 2020 focused update. J Addict Med, 14(2S Suppl 1), 36-39.
ii Substance Abuse and Mental Health Services Administration. Federal guidelines for opioid treatment.
http://www.dpt.samhsa.gov/pdf/FederalGuidelinesforOpioidTreatment5-6-2013revisiondraft_508.pdf. Published 2013
iii National Academies of Sciences, Engineering, and Medicine. (2019). Medications for opioid use disorder save lives. National Academies Press.
iv Corsi, K. F., Kwiatkowski, C. F., & Booth, R. E. (2007). Treatment entry and predictors among opiate-using injection drug users, 2007/01/01 The American Journal of Drug and Alcohol Abuse, 33(1), 121–127.
https://doi.org/10.1080/00952990601091093
v Huissoud, T., Rousson, V., & Dubois-Arber, F. (2012). Methadone treatments in a Swiss Region, 2001–2008: a registry-based analysis. BMC psychiatry, 12, 1-11.
vi Karki, P., Shrestha, R., Huedo-Medina, T. B., & Copenhaver, M. (2016). The impact of methadone maintenance treatment on HIV risk behaviors among high-risk injection drug users: a systematic review. Evidence-based medicine & public health, 2
vii McCarty, D., Perrin, N. A., Green, C. A., Polen, M. R., Leo, M. C., & Lynch, F. (2010). Methadone maintenance and the cost and utilization of health care among individuals dependent on opioids in a commercial health plan. Drug and alcohol dependence, 111(3), 235-240.
viii Sundin, E. C., & Baguley, T. (2015, Feb). Prevalence of childhood abuse among people who are homeless in Western countries: A systematic review and meta-analysis. Social Psychiatry and Psychiatric Epidemiology, 50(2), 183–194. https://doi.org/10.1007/s00127-014-0937-6
ix Taylor, K. M., & Sharpe, L. (2008, Mar). Trauma and post-traumatic stress disorder among homeless adults in Sydney. Australian and New Zealand Journal of Psychiatry, 42(3), 206–213.
https://doi.org/10.1080/00048670701827218
x Fisher, R., Ewing, J., Garrett, A., Harrison, E. K., Lwin, K. K., & Wheeler, D. W. (2013). The nature and prevalence of chronic pain in homeless persons: An observational study. F1000Res, 2, 164.
https://doi.org/10.12688/f1000research.2-164.v1
xi Milloy M-JS, Kerr T, Tyndall M, Montaner J, Wood E. Estimated drug overdose deaths averted by North America’s first medically-supervised safer injection facility. PLoS One 2008;3(10):e3351-e3351
xii Salmon AM, van Beek I, Amin J, Grulich A, Maher L. High HIV testing and low HIV prevalence among injecting drug users attending the Sydney Medically Supervised Injecting Centre. Aust N Z J Public Health 2009;33:280-283
xiii Mason, B. J., Quello, S., Goodell, V., Shadan, F., Kyle, M., & Begovic, A. (2014). Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA internal medicine, 174(1), 70-77.
xiv Johnson, B. A., Rosenthal, N., Capece, J. A., Wiegand, F., Mao, L., Beyers, K., ... & Swift, R. M. (2007). Topiramate for treating alcohol dependence: a randomized controlled trial. Jama, 298(14), 1641-1651.
xv Guglielmo, R., Martinotti, G., Clerici, M., & Janiri, L. (2012). Pregabalin for alcohol dependence: a critical review of the literature. Advances in therapy, 29, 947-957.
xvi Gazzola, M. G., Carmichael, I. D., Madden, L. M., Dasgupta, N., Beitel, M., Zheng, X., ... & Barry, D. T. (2022). A cohort study examining the relationship among housing status, patient characteristics, and retention among individuals enrolled in low-barrier-to-treatment-access methadone maintenance treatment. Journal of Substance Abuse Treatment, 138, 108753.
xvii Schumacher, J. E., Milby, J. B., McNamara, C. L., Wallace, D., Michael, M., Popkin, S., & Usdan, S. (1999). Effective treatment of homeless substance abusers: The role of contingency management.
xviii Yang, J. C., Roman-Urrestarazu, A., & Brayne, C. (2020). Responses among substance abuse treatment providers to the opioid epidemic in the USA: Variations in buprenorphine and methadone treatment by geography, operational, and payment characteristics, 2007-16. Plos one, 15(3), e0229787.
xix Substance Abuse and Mental Health Services Administration (SAMHSA). (2018). Medications for Opioid Use Disorder. Treatment Improvement Protocol (TIP) Series 63, full document.
xx Greenfield, L., Brady, J. V., Besteman, K. J., & De Smet, A. (1996). Patient retention in mobile and fixed-site methadone maintenance treatment. Drug and Alcohol Dependence, 42(2), 125-131.
xxi Laks, J., Kehoe, J., Farrell, N. M., Komaromy, M., Kolodziej, J., Walley, A. Y., & Taylor, J. L. (2021). Methadone initiation in a bridge clinic for opioid withdrawal and opioid treatment program linkage: a case report applying the 72-hour rule. Addiction Science & Clinical Practice, 16, 1-5.
xxii McCarty, D., Chan, B., Bougatsos, C., Grusing, S., & Chou, R. (2021). Interim methadone–Effective but underutilized: A scoping review. Drug and Alcohol Dependence, 225, 108766.