Medications for Opioid Use Disorder (MOUD)


There are three FDA-approved medications used to treat opioid use disorder (OUD) in the United States: methadone, buprenorphine, and extended-release injectable naltrexone (XR-NTX). Each medication differs pharmacologically and is governed by different regulations:

  • Methadone is only provided within Substance Abuse and Mental Health Services Administration (SAMHSA)-certified and Drug Enforcement Administration (DEA)-regulated opioid treatment programs (OTP).
  • Buprenorphine can be prescribed in non-specialty settings if physicians, nurse practitioners and physician assistants obtain a SAMHSA waiver (commonly known as the “x-waiver”) by completing requisite training. The Drug Addiction Treatment Act of 2000 (DATA 2000) established that qualified providers can offer buprenorphine for OUD in various settings, including emergency departments, outpatient offices, and correctional facilities.
  • Extended-release injectable naltrexone (XR-NTX) can be prescribed by any clinician who is licensed to prescribe medication. Unlike methadone and buprenorphine, both opioid agonists, XR-NTX is an opioid antagonist and not a controlled substance.

Medication Effectiveness

Research shows that all three FDA-approved MOUD are effective at reducing return to illicit opioid use; however, some medications have been shown to be more effective than others. Methadone is the most studied medication, followed by buprenorphine. Less research exists studying the effectiveness of XR-NTX. Recent studies show that initiating individuals on XR-NTX is more difficult, compared to buprenorphine, because individuals must abstain from using opioids, including MOUD, for seven to 10 days prior to initiating XR-NTX treatment.

MOUD Studies

Extended-release naltrexone versus buprenorphine-naloxone to treat opioid use disorder among black adults. Haeny, A. M., Montgomery, L., Burlew, A. K., Campbell, A. N. C., Scodes, J., Pavlicova, M., . . . Nunes, E. (2020). Addictive Behaviors, 110, 106514.

“Few studies examine the effectiveness of treatments for opioid use disorder (OUD) among Black individuals despite recent evidence suggesting opioid overdose death rates are, in some cases, highest and increasing at a faster rate among Black people compared to other racial/ethnic groups. This secondary analysis study investigated treatment preference, retention, and relapse rates amongst a subgroup of 73 Black participants with OUD (81% male, mean age 39.05, SD = 11.80) participating in a 24-week multisite randomized clinical trial (“X:BOT”) comparing the effectiveness of extended-release naltrexone (XR-NTX) and sublingual buprenorphine naloxone (BUP-NX) between 2014 and 2017. Chi-square analyses were used to investigate treatment preference assessed at baseline, and logistic regression analyses were used to investigate differences in the odds of retention and relapse assessed over the 24-week course of treatment between treatment groups. Our findings suggest no differences in preference for XR-NTX versus BUP-NX. However, similar to the parent trial, there was an induction hurdle such that only 59.5% of those randomized to XR-NTX successfully initiated medication compared to 91.6% of those randomized to BUP-NX (OR =0.13, 95% CI=0.04, 0.52). No significant differences were found in treatment retention (intention-to-treat: OR = 1.19, 95% CI = 0.43, 3.28; per-protocol [i.e., those who initiated medication]: OR = 0.60, 95% CI = 0.20, 1.82) or relapse rates between treatment groups (intention-to treat: OR = 1.53, 95% CI = 0.57, 4.13; per-protocol: OR = 0.69, 95% CI = 0.23, 2.06). Although there is a significant initiation hurdle with XR-NTX, once inducted, both medications appear similar in effectiveness, but as in the main study, dropout rates were high. Future research is needed on how to improve adherence.”

Medication assisted treatment (MAT) in criminal justice settings as a double-edged sword: balancing novel addiction treatments and voluntary participation. Hyatt, J. M. & Lobmaier, P. P. (2020). Health & Justice. doi: 10.1186/s40352-020-0106-9

“Medication-Assisted Treatment (MAT) provides an opportunity to address opioid addiction among justice-involved individuals, an often difficult to reach population. This potential has been increasingly recognized by agencies, policymakers and pharmaceutical companies. The result has been a marked increase in the number of drug courts, prisons and agencies in which MAT, notably with long-acting injectable medications, is offered. While this is a positive development, ensuring that vulnerable individuals are in a position voluntarily participation within the complex criminal justice environment is necessary. The unequal authority and agency inherent in the nature of these environments should be recognized. Therefore, rigorous protections, mirroring the goals of the consent processes required for medical or sociobehavorial research, should be employed when MAT is offered to protect individual autonomy.”

Comparative Effectiveness of Different Treatment Pathways for Opioid Use Disorder. Wakeman, S. E., Larochelle, M. R., Ameli, O., Chaisson, C. E., McPheeters, J. T., Crown, W. H., Azocar, F., & Sanghavi, D. M. (2020).  JAMA Network Open, 3(2), e1920622.

“In this comparative effectiveness research study of 40,885 adults with opioid use disorder that compared 6 different treatment pathways, only treatment with buprenorphine or methadone was associated with reduced risk of overdose and serious opioid-related acute care use compared with no treatment during 3 and 12 months of follow-up.

Effectiveness of medication assisted treatment for opioid use in prison and jail settings: A meta-analysis and systematic review. Moore, K. E., Roberts, W., Reid, H. H., Smith, K. M. Z., Oberleitner, L. M. S., & McKee, S. A. (2019).  Journal of Substance Abuse Treatment, 99, 32-43.

“Data from RCTs involving 807 inmates (treatment n = 407, control n = 400) showed that methadone provided during incarceration increased community treatment engagement (n = 3 studies; OR = 8.69, 95% CI = 2.46; 30.75), reduced illicit opioid use (n = 4 studies; OR = 0.22, 95% CI = 0.15; 0.32) and injection drug use (n = 3 studies; OR = 0.26, 95% CI = 0.12; 0.56), but did not reduce recidivism (n = 4 studies; OR = 0.93, 95% CI = 0.51; 1.68). Data from observational studies of methadone showed consistent findings. Individual review of buprenorphine and naltrexone studies showed these medications were either superior to methadone or to placebo, or were as effective as methadone in reducing illicit opioid use post-release. Results provide the first meta-analytic summary of MATs delivered in correctional settings and support the use of MATs, especially with regard to community substance use treatment engagement and opioid use; additional work is needed to understand the reduction of recidivism and other health risk behaviors.”

Opioid-related treatment, interventions, and outcomes among incarcerated persons: A systemic review. Malta, M., Varatharajan, T., Russell, C., Pang, M., Bonato, S., & Fischer, B. (2019).  PLOS Medicine, 16(12), e1003002.

“In this carefully conducted systematic review, we found that correctional facilities should scale up OAT among incarcerated persons with OUD. The strategy is likely to decrease opioid-related overdose and mortality, reduce opioid use and other risky behaviors during and after incarceration, and improve retention in addiction treatment after prison release. Immediate OAT after prison release and additional preventive strategies such as the distribution of NLX kits to at-risk individuals upon release greatly decrease the occurrence of opioid-related overdose and mortality. In an effort to mitigate the impact of the opioid-related overdose crisis, it is crucial to scale up OAT and opioid-related overdose prevention strategies (e.g., NLX) within a continuum of treatment before, during, and after incarceration.”

The benefits and implementation challenges of the first state-wide comprehensive medication for addictions program in a unified jail and prison setting. Brinkley-Rubinstein, L., Peterson, M., Clarke, J., Macmadu, A., Truong, Pognon, K. . . . Rich, J. D. (2019). Drug and Alcohol Dependence, 205, 107514.

“The prevalence of opioid use disorders among people who are incarcerated is high. People who are released from incarceration are at increased risk for overdose. The current study details the first year of implementation of a state-wide medications for addiction treatment (MAT) program in a unified jail and prison setting at the Rhode Island Department of Corrections in Cranston, Rhode Island. We conducted 40 semi-structured, qualitative interviews with people who were incarcerated and concurrently enrolled in the MAT program. Analysis employed a general, inductive approach in NVivo 12. We found that a majority of participants discussed program benefits such as reduced withdrawal symptoms, decreased prevalence of illicit drug use in the facility, improved general environment at the RIDOC, and increased post-release intentions to continue MAT. Suggested areas of improvement include reducing delays to first dose, increasing access to other recovery services in combination with MAT, improving staff training on stigma, and earlier access to medical discharge planning information prior to release. Our findings suggest that correctional MAT programs are acceptable to targeted populations and are a feasible intervention that may be transferable to other states.”

Extended-release injectable naltrexone for opioid use disorder: a systematic review. Jarvis, B. P., Holtyn, A. F., Subramaniams, S. Tompkins, D. A., Oga, E. A., Bigelow, G. E., & Silverman, K. (2018).  Addiction, 113(7), 1188-1209.

“We identified and included 34 studies. Pooled estimates showed that XR-NTX induction success was lower in studies that included individuals that required opioid detoxification [62.6%, 95% confidence interval (CI) = 54.5-70.0%] compared with studies that included individuals already detoxified from opioids (85.0%, 95% CI = 78.0-90.1%); 44.2% (95% CI = 33.1-55.9%) of individuals took all scheduled injections of XR-NTX, which were usually six or fewer. Adherence was higher in prospective investigational studies (i.e. studies conducted in a research context according to a study protocol) compared to retrospective studies of medical records taken from routine care (6-month rates: 46.7%, 95% CI = 34.5-59.2% versus 10.5%, 95% CI = 4.6-22.4%, respectively). Compared with referral to treatment, XR-NTX reduced opioid use in adults under criminal justice supervision and when administered to inmates before release. XR-NTX reduced opioid use compared with placebo in Russian adults, but this effect was confounded by differential retention between study groups. XR-NTX showed similar efficacy to buprenorphine when randomization occurred after detoxification, but was inferior to buprenorphine when randomization occurred prior to detoxification.”