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
Stigma: The Greatest Barrier to Effective of Opioid Use Disorder. This is a clear and concise summary of the evidence and rationale for medications for OUD (MOUD) as a primary therapy. It points out that current OUD therapy is very often ineffective due to “MOUD stigma.”
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
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Efforts to expand access to treatment should focus on building capacity for outpatient MOUD treatment, rather than on residential care, according to an August 2022 study 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 (buprenorphine, e.g.) – not 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.
Summary: Residential vs. Outpatient Treatment for OUD: Which One Works Best?
based on:
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. free: https://ascpjournal.biomedcentral.com/articles/10.1186/s13722-022-00318-1
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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. free: nida.nih.gov/about-nida/noras-blog/2022/08/five-areas-where-more-research-isnt-needed-to-curb-overdose-crisis
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The Changing Opioid Crisis: development, challenges and opportunities:
Excerpt:
“. . . 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, yet rates of MOUD discontinuation in the first 6 months of treatment remain very high. Thus, there is a need to improve retention in MOUD treatment.
“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 concomitant 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.”
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/
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60% of residential treatment facilities offered no medications for opioid use disorder, and only 1% offered all 3 FDA approved types of medication:
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.
free: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2760443
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Only about 30% of residential addiction treatment programs offer maintenance medication, the gold standard treatment of opioid use disorder:
Beetham T, et al. Therapies Offered at Residential Addiction Treatment Programs in the United States.
Research Letter August 25, 2020. JAMA. 2020; 324(8):804-806
free: https://jamanetwork.com/journals/jama/fullarticle/2769709
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“Patients who discontinue OUD medication generally return to illicit opioid use.”:
“Arbitrary time limits are inadvisable.” free: SAMHSA, Treatment Improvement Protocol 63 2020 Substance Abuse & Mental Health Services Admin’n. https://store.samhsa.gov/product/TIP-63-Medications-for-Opioid-Use-Disorder-Full-Document/PEP21-02-01-002
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Long-acting injectable naltrexone (Vivitrol) is not a first-line treatment for most individuals with moderate to severe opioid use disorder.
Both methadone and buprenorphine are associated with a decrease in overdose deaths, have been clearly demonstrated, for decades, as effective treatments for OUD, and are considered “first line” and “gold standard” treatments. In contrast, long-acting injectable naltrexone (brand name Vivitrol) is a second-line OUD treatment with less evidence of effectiveness. The evidence for this consensus is summarized in a document at https://www.stopstigmanow.org/ssn-policies-2/#Injectable_Naltrexone
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Methadone and buprenorphine are associated with reduced death rates in people who have experienced an opioid overdose.
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 also about 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). This was a large cohort study of the records of over 17,000 people who survived an opioid overdose between 2012 and 2014 in Massachusetts.
To re-state this with more detail, compared with no MOUD, MMT was associated with decreased all-cause mortality (adjusted hazard ratio [AHR] 0.47 [CI, 0.32 to 0.71]) and opioid-related mortality (AHR, 0.41 [CI, 0.24 to 0.70]). Buprenorphine was associated with decreased all-cause mortality (AHR, 0.63 [CI, 0.46 to 0.87]) and opioid-related mortality (AHR, 0.62 [CI, 0.41 to 0.92]). There were no associations between naltrexone and all-cause mortality (AHR, 1.44 [CI, 0.84 to 2.46]) or opioid-related mortality (AHR, 1.42 [CI, 0.73 to 2.79]). Among the entire cohort, all-cause mortality was 4.7 deaths (95% CI, 4.4 to 5.0 deaths) per 100 person-years and opioid-related mortality was 2.1 deaths (CI, 1.9 to 2.4 deaths) per 100 person-years.
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.
Free: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387681/
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Buprenorphine or methadone are the only treatments that reduce the risk of overdose:
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
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“All studies of tapering and discontinuation [of MOUD] 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. free: www.nap.edu/download/25310 Summary: www.ncbi.nlm.nih.gov/books/NBK541390
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Methadone and buprenorphine are the most effective treatments for opioid use disorder.
For no other medical conditions for which an effective treatment exists is that treatment used so infrequently:
There is consensus in the scientific literature that the opioid agonist medications methadone and buprenorphine are the most effective treatments for opioid use disorder. However, these medications remain substantially underutilized. We discuss the potential role of stigma in the underutilization of these medications, outline stigma toward medications for addiction treatment, suggest that structural and policy barriers to methadone and buprenorphine may contribute to this stigma, and offer pragmatic public health solutions to 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/
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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/
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The past and present treatment of OUD:
Dole, Nyswander & Kreek documented that methadone reduced opioid craving and opioid use, and contributed to increased employment, improved health, and reduced criminal activity (Jaffe 1997) (Kreek 2002). When patients complete opioid withdrawal, return to use is often rapid and frequently deadly. US and international authorities recommend opioid agonist therapy (i.e., methadone or buprenorphine). Opioid antagonist therapy (i.e., extended-release naltrexone) may also inhibit return to use. Opioid use disorder prevention and treatment must embrace evidence-based care.
McCarty D at al. Treatment and Prevention of Opioid Use Disorder: Challenges and Opportunities
Annual Review of Public Health. 2018. 39:525–41.
free: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880741/
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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. (Carrieri, 2006; Schwartz, 2013) In addition, maintenance treatment with opioid agonists reduces the risk of recurrence of active opioid use by 50% or more. (Clark, 2015) 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. (Bart, 2012) Globally, less than 10% of those in need of treatment are receiving opioid agonist therapy. A U.K. study demonstrated that prison-based opioid agonist therapy initiation is associated with a 75% reduction in all-cause mortality and an 85% reduction in fatal overdose in the first month after release. (Marsden, 2017) Stigma is a major driver behind the lack of access to opioid agonist therapy. Even the widely adopted terminology to refer to opioid agonist therapy, medication-assisted treatment, implies that medications are an adjunct to treatment rather than lifesaving interventions in and of themselves. Stigma about medications for addiction treatment is common within mutual help organizations and some psychosocial programs, which may not allow individuals receiving opioid agonist therapy to participate. This stigma is also demonstrated in the medical system. A campaign which combines personal narrative from individuals being treated with opioid agonist therapy coupled with science-based education about opioid use disorder and the benefit of medication treatments has been proposed as a useful approach to reduce stigma (‘Recovery Oriented Methadone Maintenance,’ White, 2010; see below). Stop Stigma Now, a nonprofit organization dedicated to eradicating the stigma around opioid agonist therapy, is an example of such a model (www.stopstigmanow.org). 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
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79% drop in overdose deaths with the introduction of buprenorphine in 4 years:
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. During this period, 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–S28.
https://pubmed.ncbi.nlm.nih.gov/15204673/
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Long term follow-up (up to 33 years) of OUD patients:
A review of all 23 published studies with long-term follow-up of OUD patients (3 to 33 years), identified most subjects from methadone treatment programs. 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. Remaining in treatment 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.
Hser Y-I et al. Long-Term Course of Opioid Addiction. Harvard Review of Psychiatry. 2015; Volume 23(2)
https://pubmed.ncbi.nlm.nih.gov/25747921/
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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-related hospitalization within 18 months. These poor outcomes are consistent with the findings of prior analyses.” Those who tapered slowly over 52 weeks had a higher success rate of ~ 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/
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A recovery-oriented approach to medication-assisted treatment:
Recovery is being used as a conceptual fulcrum for the redesign of addiction treatment and related support services in the United States. Efforts by policy, research, and clinical leaders to define recovery and calls for assertive models of long-term recovery management raise critical questions about how transformation efforts of recovery-focused systems will affect the pharmacotherapeutic treatment of opioid addiction and the status of patients participating in such treatment. This article highlights recent work advocating a recovery-oriented approach to medication-assisted treatment.
White WL. Medication-Assisted Recovery from Opioid Addiction: Historical and Contemporary Perspectives.
J Addict Dis. 2012; 31(3):199-206.
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Media messages about MOUD are stigmatizing:
A content analysis of a popular reality television program on addiction treatment was performed. There were no positive messages about methadone or buprenorphine. The two main messages were that they (1) are primarily drugs of abuse, and (2) not acceptable treatment options. These messages reinforce negative stereotypes and may perpetuate stigma. There were multiple missed opportunities to provide evidence-based information.
Roose R et al. Messages about methadone and buprenorphine in reality television: a content analysis of
celebrity rehab with Dr. Drew. Subst Use Misuse. 2012 Aug; 47(10):1117-24.
www.tandfonline.com/doi/abs/10.3109/10826084.2012.680172?journalCode=isum20
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Long-acting opioids (like methadone & buprenorphine) are very different than short-acting:
This article reviews the pharmacological differences between long-acting opioids, such as methadone or buprenorphine, and short-acting opioids such as heroin. The specific pharmacological profile of long-acting opioids contributes to their ability to treat addictive behavior, reduce craving and normalize endocrine function. The use of the term “substitution” for methadone or buprenorphine has contributed to the widespread misunderstanding of this treatment approach.
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
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Words cause real-world harm: “substance abuser” vs. “having a substance use disorder”:
The authors sought to determine whether referring to an individual as “a substance abuser” vs. “having a substance use disorder” evokes different judgments about behavioral self-regulation, social threat, and treatment vs. punishment. In this randomized trial, highly trained mental health professionals were asked to read a vignette containing one of the two terms and to rate their agreement with a number of related statements. Compared to those in the “substance use disorder” condition, those in the “substance abuser” condition agreed more with the notion that the character was personally culpable and that punitive measures should be taken.
Kelly JF, Westerhoff CM. Does it Matter How We Refer to Individuals With Substance-Related Conditions? A Randomized Study of Two Commonly Used Terms. Int J Drug Policy. 2010 May; 21(3):202-7.
Abstract: https://pubmed.ncbi.nlm.nih.gov/20005692/
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The term ‘opioid substitution treatment’ should not be used.
The term “Opioid Substitution Treatment or Therapy,” “(OST)” is still used to describe opioid agonist therapies (OAT, i.e. methadone, buprenorphine) despite its stigmatizing effects and lack of accuracy. Agencies, treatment providers, academics, etc. should replace this term with ‘MOUD,’ which may help encourage the acceptance of agonist medications for OUD as being essential to public health.
Appel, P. Despite repeated criticism, medications (methadone, suboxone) for opioid use disorder continue
being called “substitution” treatments. Heroin Addict Relat Clin Probl. 2020.
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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.] . . . Average methadone maintenance doses of 60 to 120 mg or higher have consistently better results than use of lower average doses . . . Most deaths have been from methadone prescribed for pain rather than from methadone treatment programs . . . MMT has been shown not to impair driving ability . . . An Institute of Medicine review concluded that “. . . current policy puts too much emphasis on protecting society from methadone, and not enough on protecting society from the epidemic of addiction, violence, and infections that methadone can help reduce.” . . . 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
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Leaving methadone treatment: lessons learned, lessons forgotten, lessons ignored:
This paper reviews the published research literature on post-discharge outcomes of patients exiting from extended methadone tapering. Virtually all of these studies document high rates of relapse to opioid use after methadone treatment is discontinued. Most of the patients studied left treatment without meeting clinical criteria for tapering, although high relapse rates were also reported for patients who completed treatment in the program. The detrimental consequences of leaving methadone treatment are dramatically indicated by greatly increased death rates following discharge. Until more is learned about how to improve post-methadone outcomes, treatment providers and regulatory/funding agencies should be very cautious about imposing disincentives and structural barriers that discourage or impede 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.
free: https://wmich.edu/sites/default/files/attachments/u372/2015/Leaving%20Methodone%20Treatment.pdf
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The original 1965 publication on methadone for OUD:
This original 1965 peer-reviewed publication on medication treatment for OUD reports that a combination of methadone treatment and a comprehensive program of rehabilitation was associated with marked improvement in patient problems such as jobs, returning to school, and family reconciliation. No adverse effect other than constipation were found. 22 patients, addicted to heroin for 9.5 years (median) were stabilized using methadone and then observed for approximately 1 to 15 months (median 3 months). The medication had 2 main effects: (1) relief of narcotic hunger (craving); and (2) induction of sufficient tolerance to block 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 Feb 6, 2023
