SCIENTIFIC ARTICLE SUMMARIES ON OPIOID USE DISORDER TREATMENT
Assembled and summarized by Stop Stigma Now
Abbreviations:
OUD: Opioid Use Disorder
MOUD: Medications for OUD (methadone, buprenorphine, injectable naltrexone)
OAT: Opioid Agonist Therapy, i.e. methadone and buprenorphine
MMT: Methadone Maintenance Therapy
‘An Effective Treatment for Opioid Addiction Exists. Why Isn’t It Used More?’
“Buprenorphine remains drastically under-prescribed. Only between 10 and27 % of those who could potentially benefit from it are taking it.”
New York Times Published Feb. 16, 2025.
https://www.nytimes.com/2025/02/16/magazine/buprenorphine-opioid-addiction-treatment.html?smid=nytcore-ios-
share&referringSource=articleShare&sgrp=c-cb
Treatment for opioid addiction without medications: worse than no treatment at all?
Yale scientists found that those with OUD receiving treatment without methadone or buprenorphine were 75% more likely to die of an opioid-related overdose than those receiving no treatment at all. But treatment with methadone or buprenorphine reduced fatal overdose by over one third.
Heimer R, et. al. Receipt of opioid use disorder treatments prior to fatal overdoses and comparison to no treatment in Connecticut, 2016–17. Drug and Alcohol
Dependence.
Volume 254, January 2024, 111040.
https://www.sciencedirect.com/science/article/pii/S0376871623012784?via%3Dihub
Long-acting injectable naltrexone (Vivitrol) is not a first-line treatment for most individuals with moderate to severe opioid use disorder.
Methadone and buprenorphine are the only treatments for OUD that reduce overdose deaths. Long-acting injectable naltrexone (‘Vivitrol’) is an important option for some, but with less evidence of effectiveness. Evidence summarized at https://bit.ly/naltrexone_secondline (Feb 2023)
Medication stigma and the rationale for medications for OUD (MOUD):
Adams, Joseph A. Stigma: The Greatest Barrier to Effective Treatment of Opioid Use Disorder.
Maryland Medical Journal. March 2023; Volume 24 (1):7
free: article MMJ Adams
Efforts to expand access to treatment should focus on building capacity for outpatient MOUD treatment, rather than on residential care. (from Oregon State University):
- Residential treatment is often thought of as the highest intensity option for opioid use disorder, but few studies have actually compared it to outpatient care.
- Analysis found that the most important factor for preventing overdose deaths was the use of medications for OUD (MOUD), not the treatment setting.
- Without more compelling evidence, efforts to expand access to treatment should focus on building capacity for outpatient MOUD treatment, rather than on residential care.
Hartung DM, et al. Association between treatment setting and outcomes among Oregon Medicaid patients with opioid use disorder. A retrospective cohort study. Addiction Science & Clinical Practice Aug, 2022; 17:45. https://ascpjournal.biomedcentral.com/articles/10.1186/s13722-022-00318-1 And Commentary: Residential vs. Outpatient Treatment for OUD: Which One Works Best? https://bit.ly/Residential_v_outpatient_OUD_treatment
Methadone & buprenorphine are proven life-savers in clinical trial after clinical trial: According to the Director of the National Institute on Drug Abuse, “methadone … and buprenorphine have proven to be life-savers … enabling [patients] to live healthy and successful lives, and facilitating recovery… The efficacy of MOUD has been supported in clinical trial after clinical trial, and is considered the standard of care in treatment of OUD, whether or not it is accompanied by some form of behavioral therapy.”
Five Areas Where “More Research” Isn’t Needed to Curb the Overdose Crisis. August 31, 2022
By Dr. Nora Volkow, NIDA Director.
https://bit.ly/Volkow-areas-where-more-research-not-needed
Medications for OUD – from the Director of the National Institute on Drug Abuse:
“. . At present, methadone has been available the longest and has the largest evidence of efficacy. (Mattick 2014) (Nielsen 2016). Higher doses of methadone are associated with better retention in treatment, less heroin use during treatment and lower withdrawal symptoms . . . “Studies suggest that longer time in treatment is associated with better outcomes and that the risk of relapse greatly increases after medication discontinuation
“It is also important to know which patients, when and under what circumstances can safely discontinue MOUD. Current evidence indicates that counseling or psychotherapy do not increase retention in buprenorphine treatment or improve abstinence rates (Timko 2016) (Cushman 1978) (Morgan 2018) (Nosyk 2012) (Sordo 2017) and that methadone treatment (Schwartz 2006) and buprenorphine without counseling is vastly superior to no treatment. (Simon 2017)
“It is important to determine whether the potential benefits of concurrent psychotherapy outweigh the barrier to treatment created by requiring provision of psychotherapy when delivering buprenorphine treatment.” (emphasis added)
Volkow, ND & Blanco, C. The Changing Opioid Crisis: development, challenges and opportunities
Mol Psychiatry. 2021 January; 26(1): 218–233.
Free: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398847/
Medication Treatments Led to 80 Percent Lower Risk of Fatal Overdose
In this Retrospective cohort study, subjects experienced 371 opioid overdose deaths overall. Periods in medication treatment were associated with substantially reduced hazard of opioid overdose death compared with periods in non-medication treatment [adjusted hazard ratio (aHR) = 0.18, 95% confidence interval (CI) = 0.08–0.40].
Krawczyk N, et al. Opioid agonist treatment and fatal overdose risk in a state-wide US population receiving opioid use disorder services.
Addiction. February 2020. https://onlinelibrary.wiley.com/doi/10.1111/add.14991
Medication Treatments Led to 80 Percent Lower Risk of Fatal Overdose for Patients with Opioid Use Disorder:
Press Release on the above publication by Krawczyk, et al.
“People with opioid use disorder (OUD) receiving treatment with opioid agonists (medications such as methadone or buprenorphine) had an 80 percent lower risk of dying from an opioid overdose compared with people in treatment without the use of medications.” …
“This is one of the first U.S. population-based studies, the researchers say, to compare overdose risk among two patient populations across an entire state—one whose treatment includes agonist medications and a control group receiving psychosocial interventions without agonist medication.” (i.e. methadone or buprenorphine).
Press Release, NYU Langone Health February 25, 2020
https://nyulangone.org/news/medication-treatments-led-80-percent-lower-risk-fatal-overdose-patients-opioid-use-disorder
Buprenorphine or methadone were the only treatments that reduced the risk of OD:
In a study of over 40,000 individuals with OUD, only treatment with buprenorphine or methadone reduced the risk of overdose and serious opioid-related acute care use, compared with no treatment, during 3 and 12 months of follow-up. Neither inpatient detoxification, residential services, intensive behavioral health, or naltrexone treatment resulted in a reduction in overdose deaths.
Wakeman, Sarah E. et al. Comparative Effectiveness of Different Treatment Pathways for Opioid
Use Disorder JAMA Netw Open. February 2020; 3(2).
free: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2760032
Most residential treatment facilities offer no maintenance medications for opioid addiction:
Huhn, AS, et al. Differences in Availability and Use of Medications for Opioid Use Disorder in Residential Treatment Settings in the United States. JAMA Netw Open. Feb 7,2020; 3(2): e1920843 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2760443
“Patients who discontinue OUD medication generally return to illicit opioid use.”:
“Arbitrary time limits are inadvisable.”
SAMHSA, Treatment Improvement Protocol 63 2020 Substance Abuse & Mental Health Services
Administration.
https://store.samhsa.gov/product/TIP-63-Medications-for-Opioid-Use-Disorder-Full-Document/PEP21-02-01-002
“All studies of tapering and discontinuation demonstrate very high rates of relapse”:
pg. 40, ‘Medications for opioid use disorder save lives.’ National Academies of Sciences,
Engineering, and Medicine. 2019. Washington, DC. The National Academies Press
www.ncbi.nlm.nih.gov/books/NBK541390
Methadone and buprenorphine are the most effective treatments for opioid use disorder:
“There is consensus in the scientific literature that the opioid agonist medications methadone and buprenorphine are the most effective treatments for opioid use disorder. . . these medications remain substantially underutilized. For no other medical conditions for which an effective treatment exists is that treatment used so infrequently . . . We offer pragmatic public health solutions to reduce stigma and expand access to these effective treatments.”
Allen B et al. Underutilization of medications to treat opioid use disorder: What role does stigma play? Substance Abuse, 40 (4) (2019), pp. 459-465.
https://pubmed.ncbi.nlm.nih.gov/31550201/
Overdose survivors who do not get methadone or buprenorphineare more likely to die:
In a study of the records of over 17,000 people who survived an opioid overdose, those who were later treated with methadone had about a 50% lower overall death rate and about a 60% lower opioid-related death rate (compared with those who were not treated). Those who were later treated with buprenorphine had about a 40% lower overall death rate and a 40% lower opioid-related death rate (compared with those who were not treated). Of those who were later treated with naltrexone, there was no reduction in death rates (but few events in this group prevented confident conclusions about naltrexone).
Larochelle MR, et al. Medication for opioid use disorder after nonfatal opioid overdose and association with mortality: a cohort study.
Ann Intern Med. 2018;169(3):137-145.
‘Methadone and buprenorphine reduce risk of death after opioid overdose’
National Institutes of Health News Release on the publication of the above article by Larochelle.
News Release June 19, 2018
https://www.nih.gov/news-events/news-releases/methadone-buprenorphine-reduce-risk-death-after-opioid-overdose
Some proven benefits of methadone or buprenorphine; How stigma kills:
Access to opioid agonist therapy has been associated with a 50–79% reduction in heroin overdose death. In addition, maintenance treatment with opioid agonists reduces the risk of recurrence of active opioid use by 50% or more. When dosed adequately, opioid agonist therapy results in treatment retention rates in excess of 60%, with only 15% of those treated using heroin at one year. Stigma is a major driver behind the lack of access to opioid agonist therapy. Expanded access to
medications for addiction treatment, particularly the opioid agonists methadone and buprenorphine, may be the most powerful tool we have to stop the death toll from the current opioid epidemic
Wakeman SE, et al. Barriers to medications for addiction treatment: how stigma kills.
Subst Use Misuse. 2018; 53:330–33. https://psycnet.apa.org/record/2018-01971-018
The past and present treatment of OUD:
Drs. Dole, Nyswander & Kreek documented that methadone reduced opioid cravings, opioid use and criminal activity; while improving employment and health status. (Jaffe 1997) (Kreek 2002). When patients complete opioid withdrawal, return to use is often rapid and frequently deadly. U.S. and international authorities recommend opioid agonist therapy (i.e., methadone or buprenorphine).
McCarty D at al. Treatment and Prevention of Opioid Use Disorder: Challenges and Opportunities.
Annual Review of Public Health. 2018. 39:525–41. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880741/
How are patients with opioid addiction doing after thirty years?
A review of all 23 published studies with long-term follow-up of OUD patients (3 to 33 years).
Most subjects were identified from methadone treatment programs. Remaining in treatment with medication for longer periods was associated with a greater likelihood of abstinence. Maintaining opioid abstinence for at least five years substantially increased the likelihood of stable abstinence. Of those still alive, abstinence rates decreased over time to about 30% or lower after ten years of observation, and remained stable thereafter. Death rates, mostly from overdose, increased over time and were 6 to 20 times that of the general population.
Hser Y-I et al. Long-Term Course of Opioid Addiction. Harvard Review of Psychiatry. 2015; Volume23(2).
https://pubmed.ncbi.nlm.nih.gov/25747921/
Attempts to taper methadone have a poor outcome on average:
“Of over 4,000 patients who started a methadone taper, 13% had a “successful taper” defined as remaining alive, reaching a dose ≤5mg per day, not re-entering treatment, and not having an opioid- prior analyses.” Those who tapered slowly over 52 weeks had a higher success rate of about 22%.”
Nosyk B, et al. Defining dosing pattern characteristics of successful tapers following methadone maintenance treatment: results from a population-based retrospective cohort study.
Addiction. 2012; 107(9):1621
free: www.ncbi.nlm.nih.gov/pmc/articles/PMC3376663/
Maintenance medication for opioid addiction: the Foundation of Recovery:
“Treatment for opiate addiction requires long-term management. Behavioral interventions alone have extremely poor outcomes, with more than 80% of patients returning to drug use. Similarly poor results are seen with medication assisted tapering . . . Longer periods of tapering (1–6 months) with methadone or buprenorphine are also ineffective in promoting abstinence beyond the initial stabilization period . . . maintenance medication provides the best opportunity for patients to achieve recovery from opiate addiction. Extensive literature and systematic reviews show that maintenance treatment with either methadone or buprenorphine is associated with retention in treatment, reduction in illicit opiate use, decreased craving, and improved social function.”
Bart G, Maintenance medication for opioid addiction: the Foundation of Recovery
J Addict Dis. 2012; 31(3):207. free: www.ncbi.nlm.nih.gov/pmc/articles/PMC3411273/
Methadone effective for reducing heroin use and increasing retention n treatment:
All 11 published randomized trials of subjects treated with methadone for opioid use disorder vs. those treated with placebo or non-pharmacological treatment, were reviewed. Methadone showed a statistically significant improvement in retaining patients in treatment and in the suppression of heroin use.
Mattick RP, et al. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database of Systematic reviews. July 2009
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002209.pub2/full
Methadone & buprenorphine are not “substitutes” for heroin or fentanyl:
The specific pharmacological profile of the long-acting opioids methadone or buprenorphine is very different from that of heroin or fentanyl, and contributes to their ability to treat addictions, reduce craving and normalize endocrine function. Referring to these medications as “substitution therapy” has contributed to widespread misunderstanding.
Gerra G et al. Long-Acting Opioid-Agonists in the Treatment of Heroin Addiction: Why Should We Call Them “Substitution”? Subst Use Misuse. 2009; 44(5):663-71.
https://www.tandfonline.com/doi/abs/10.1080/10826080902810251?journalCode=isum20
Methadone Maintenance 4 Decades Later: Thousands of Lives Saved:
“Numerous studies have demonstrated the effectiveness of methadone maintenance therapy (MMT) for reducing illicit opioid use, morbidity and mortality, risk of human immunodeficiency virus (HIV) infection, illegal activities, and improving overall functioning. Patients in MMT had a 1-year mortality rate of 1% compared with 8% among patients who discontinued treatment . . . Risk is decreased in relation to length of time continuously receiving methadone maintenance; risk of hepatitis B and hepatitis C also was reduced . . . In a 1991 study, crime days per year among individuals addicted to narcotics decreased more than 70% while receiving MMT. [In a randomized study, there were marked reductions in illicit opioid use, and improvements in overall functioning.] . . . Doses of 60 to 120 mg or higher have consistently better results than use of lower average doses . . . MMT has been shown not to impair driving ability . . . An Institute of Medicine review concluded that ‘. . .two years of MMT appears to be the minimum duration before attempting withdrawal. Patients . . . often relapse after leaving treatment, and death rates are much higher than for individuals who remain in treatment. For many patients, therefore, years or even lifetime maintenance may be needed. . .”
Methadone Maintenance 4 Decades Later: Thousands of Lives Saved But Still Controversial.
Kleber HD. JAMA. 2008; 300, No. 19, 2303-2305.
free: https://jamanetwork.com/journals/jama/fullarticle/182898
79% drop in overdose deaths after the introduction of buprenorphine:
Starting in 1995, the French government successfully introduced and encouraged buprenorphine treatment for OUD, reimbursing physicians for this nationwide, so that by 1999 an estimated 80% of individuals with OUD were treated with buprenorphine. From 1995 to 1999, the number of overdose deaths declined by 79%.
Auriacombe M, et al. French field experience with buprenorphine. Am J Addict. 2004;13 (suppl 1):S17
https://pubmed.ncbi.nlm.nih.gov/15204673/
Leaving methadone treatment: lessons learned, lessons forgotten, lessons ignored:
In a review of the post-discharge outcomes of patients exiting from extended methadone tapering, virtually all studies document high rates of relapse to opioid use and greatly increased death rates following discharge, even when patients met “clinical criteria” for tapering. Treatment providers and regulatory agencies should avoid disincentives and barriers to long-term opiate agonist therapy.
Magura S & Rosenblum A. Leaving methadone treatment: lessons learned, lessons forgotten, lessons ignored. Mt Sinai J Med. 2001 Jan;68(1):62-74.
The original 1965 publication on methadone for OUD:
Methadone with rehabilitation led to marked improvement in employment, returning to school, and family reconciliation, with no adverse effect other than constipation. 22 patients, addicted to heroin for a median of 9.5 years were stabilized with methadone and then observed for up to 15 months (median of 3 months). Methadone relieved craving and blocked the average illegal dose of heroin.
Dole VP, Nyswander M. A Medical Treatment for Diacetylmorphine (Heroin) Addiction, A Clinical Trial With Methadone Hydrochloride JAMA. 1965;193(8):646-650.
https://jamanetwork.com/journals/jama/article-abstract/656315
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Updated October 24, 2025
