Introduction to SSN’s Research Articles on MAT
SCIENTIFIC ARTICLES
Abbreviations:
OUD: Opioid Use Disorder;
MOUD: Medications for OUD
OAT: Opioid Agonist Therapy, i.e. methadone and buprenorphine
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
(This is an EXCERPT from an article by Volkow & Blanco, January 2021, ‘The Changing Opioid Crisis: development, challenges and opportunities’ full citation below)
“. . . At present, MOUD constitutes the standard of care for most patients with OUD. 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 . . . It can lead to overdoses if it is used at doses above the patient’s tolerance or combined with other central nervous depressants such as alcohol, benzodiazepines or other opioids. To minimize the risk of intoxication or overdose, methadone should be started at low doses and increased gradually with daily monitoring over several weeks. At present, limited data are available regarding the comparative effectiveness of MOUD or about which patients will respond better to each medication. 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/
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
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
“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 Admin’n.
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
The term “Opioid Substitution Treatment or Therapy,” “(OST)” is still used to describe opioid agonist therapies (OAT, i.e. methadone, suboxone) despite its stigmatizing effects and fundamental inaccuracy. ‘Medication Assisted Treatment (MAT) was an earlier, ca. 2000, which, in turn, has been superseded by ‘medications for opioid use disorder’ (MOUD). Yet the term ‘substitution’ is still in significant use.
This essay explores how the discredited term ‘substitution’ fails to describe OAT on linguistic and psychopharmacological grounds, its sometimes intentional stigmatizing effects, and indirect fatal consequences. Federal and state government agencies, non-MOUD treatment systems and support groups, treatment accrediting agencies, academics, journals, health services training institutions, international health agencies, and the media, should screen for this term, and replace it with ‘MOUD.’ The goal is to increase the willingness to welcome and implement programs employing agonist medications for OUD as essential to public health and individual recovery, and to view MOUD programs as a key support for the communities where patients are treated.
Appel, P. Despite repeated criticism, medications (methadone, suboxone) for opioid use disorder continue being called “substitution” treatments. Heroin Addict Relat Clin Probl. 2020.
“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
On a population level, 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. Abstract: https://psycnet.apa.org/record/2018-01971-018
(This article describes the past and present treatment of OUD)
Methadone treatment began as research in the 1960s. Initial work in New York City (Dole, Nyswander 1965, see below) (Dole, Nyswander & Kreek 1966) documented that methadone administered orally 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 and integrate with physical and mental health 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/
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)
Abstract: Abstract: https://pubmed.ncbi.nlm.nih.gov/25747921/
“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/
“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/
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.
https://facesandvoicesofrecovery.org/resource/medication-assisted-recovery-from-opioid-addiction-historical-and-contemporary-perspectives/
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.
Abstract: www.tandfonline.com/doi/abs/10.3109/10826084.2012.680172?journalCode=isum20
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, participants were asked to read a vignette containing one of the two terms and to rate their agreement with a number of related statements. Clinicians (N=516) attending two mental health conferences completed the study (71% response rate).
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. Conclusions: Even among highly trained mental health professionals, exposure to these two commonly used terms evokes systematically different judgments. The commonly used “substance abuser” term may perpetuate stigmatizing attitudes.
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.
This article reviews the pharmacological differences between long-acting opioids, such as methadone or buprenorphine, and short-acting opioids such as heroin, in terms of reinforcing properties, endocrine and immune effects, etc. 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.
Abstract: https://www.tandfonline.com/doi/abs/10.1080/10826080902810251?journalCode=isum20
“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 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
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. Abstract: https://pubmed.ncbi.nlm.nih.gov/11135508/
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 was 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.
Abstract: https://jamanetwork.com/journals/jama/article-abstract/656315
