Opiate Treatment with Agonists Including Methadone, Buprenorphine, and Suboxone

Related Chapters:

Looking for a referral to, or more information about, mental health or substance use treatment services? The American Board of Preventive Medicine provides this service to locate physicians who are certified in specialists in Addiction Medicine

The federal Substance Abuse and Mental Health Services Administration has a free, confidential National Helpline at 1-800-662-HELP (4357).
"SAMHSA’s National Helpline, 1-800-662-HELP (4357), (also known as the Treatment Referral Routing Service) is a confidential, free, 24-hour-a-day, 365-day-a-year, information service, in English and Spanish, for individuals and family members facing mental and/or substance use disorders. This service provides referrals to local treatment facilities, support groups, and community-based organizations. Callers can also order free publications and other information."
SAMHSA's website also offers a free, confidential Behavioral Health Treatment Services Locator.

21. Comparison of Extended-Release Naltrexone with Buprenorphine-Naloxone

"This large multicentre, randomised, controlled, comparative effectiveness trial had five major findings. First, it was more difficult to start XR-NTX [Extended-release naltrexone] treatment than BUP-NX [sublingual buprenorphine-naloxone] treatment: 28% dropped out of treatment before XR-NTX induction versus only 6% before BUP-NX induction. Second, nearly all induction failures had early relapse. Third, in the intention-to-treat population of all patients who were randomly assigned, XR-NTX had lower relapse-free survival than BUP-NX, directly related to early induction failure. Fourth, for the per-protocol population, who successfully initiated medication, XR-NTX and BUP-NX were similarly effective. Finally, fatal overdose, non-fatal overdose, and other serious adverse events did not differ between treatment groups. Thus, if induction to either medication is successful, XR-NTX and BUP-NX were comparably effective and safe options. These findings afford providers, patients, and families a choice between agonist and antagonist therapies. The risk of XR-NTX induction failure should be considered, and agonist treatments for those individuals unable to complete detoxification should be encouraged."

Lee, J. D., Nunes, E. V., Novo, P., Bachrach, K., Bailey, G. L., et al. (2018). Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet (London, England), 391(10118), 309–318. http://doi.org/...
https://www.ncbi.nlm.nih.gov/p...
https://www.thelancet.com/...

22. Naltrexone

"Originally approved for use in the treatment of opioid dependence by the United States Food and Drug administration (FDA) in 1984, naltrexone is a competitive ?-opioid receptor antagonist with negligible agonist effects, blocking euphoric and physiological effects of opioid agonists.11,12 Naltrexone does not cause the development of dependence or tolerance over time, and dosing cessation does not result in withdrawal.13

"Orally dosed naltrexone is subject to first pass metabolism, where it is converted to active (6-? naltrexol) and inactive metabolites.14 ­First-pass metabolism of orally dosed naltrexone is high, evidenced by the peak dose of naltrexone and its ­metabolites 1 hour after oral dosing.15 Serum ­half-life for chronic oral administration is approximately 10 hours.15 The half-life, when compared to naloxone, another ?-opioid antagonist, is longer, and naltrexone is able to block the agonist effects of other opioids for 48 hours.16 Oral dosing is accomplished by either 50 mg daily dosing or three times weekly dosing with two 100 mg doses and one 150 mg dose."

Kjome, Kimberly L. and Moeller, F. Gerard, "Long-Acting Injectable Naltrexone for the Management of Patients with Opioid Dependence," Substance Abuse: Research and Treatment 2011:5 1–9, doi: 10.4137/SART.S5452
http://www.ncbi.nlm.nih.gov/pm...
http://www.ncbi.nlm.nih.gov/pm...

23. NIH on Methadone and Health Insurance Coverage

"The unnecessary regulations of methadone maintenance therapy and other long-acting opiate agonist treatment programs should be reduced, and coverage for these programs should be a required benefit in public and private insurance programs."

Effective Medical Treatment of Opiate Addiction. NIH Consensus Statement 1997 Nov. 17-19; 15(6): 2.
http://consensus.nih.gov/1997/...

24. Number of Treatment Programs in the US and Types of Treatment Provided

According to SAMHSA, "There was a net increase of 526 responding [substance abuse treatment] facilities between 2015 and 2016, to 14,399 facilities." (p. 11)

"The proportions of facilities offering the major types of care—outpatient, residential (non-hospital), and hospital inpatient—changed little between 2006 and 2016. Opioid treatment programs (OTPs), certified by SAMHSA, provide medication-assisted therapy with methadone, buprenorphine, and extended-release injectable naltrexone (Vivitrol®). Facilities with OTPs can be associated with any type of care. Facilities with OTPs made up 8 to 9 percent of all facilities between 2006 and 2016 [Table 2.4].

"• Outpatient treatment was provided by 80 to 82 percent of facilities during this period [Table 2.3].
"• Residential (non-hospital) treatment was provided by 28 percent in 2006 and 24 percent of facilities in 2016.
"• Hospital inpatient treatment was provided by 7 percent of facilities in 2006, decreasing to 5 percent of facilities in 2016.
"• Outpatient treatment was provided by 90 to 95 percent of OTP facilities from 2006 to 2016.
"• Residential (non-hospital) treatment was provided by 7 to 12 percent of OTP facilities from 2006 to 2016.
"• Hospital inpatient treatment was provided by 7 to 11 percent of OTP facilities from 2006 to 2016."

Substance Abuse and Mental Health Services Administration, National Survey of Substance Abuse Treatment Services (N-SSATS): 2016. Data on Substance Abuse Treatment Facilities. BHSIS Series S-93, HHS Publication No. (SMA) 17-5039. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2017, p. 11, p. 12.
https://www.samhsa.gov/data/re...
https://www.samhsa.gov/data/si...

25. Number and Characteristics of Patients Receiving Opioid Treatment Programs (OTPs) in the US

"Facilities were asked how many clients in treatment on March 31, 2016, received medication-assisted opioid therapy drugs for detoxification or maintenance purposes. MAT includes the use of methadone and buprenorphine for the treatment of opioid addiction or dependence, and the use of extended-release injectable naltrexone (Vivitrol®) for relapse prevention in opioid addiction. Methadone is available only at OTP facilities that are certified by SAMHSA’s Center for Substance Abuse Treatment. Buprenorphine may be prescribed by physicians who have received DATA 2000 specific training and received a waiver to prescribe the medication for treatment of opioid addiction; some of these physicians are affiliated with facilities (either OTPs or other).22 All physicians or approved medical personnel can prescribe extended-release injectable naltrexone (Vivitrol®).

"• Of the total 1,150,423 clients in treatment, 365,064 (32 percent) received MAT in OTP facilities.
"• There were 345,443 clients receiving methadone in OTP facilities.
" • Of the clients receiving methadone, 215,576 clients (62 percent) were provided treatment at private for-profit OTPs and 109,504 clients (32 percent) were provided treatment at private non-profit OTPs.
"• There were 18,716 clients receiving buprenorphine in OTP facilities and 42,770 clients receiving buprenorphine in non-OTP facilities.
" • Of the clients receiving buprenorphine in OTPs, 12,495 clients (67 percent) were provided treatment at private for-profit OTPs and 4,675 clients (25 percent) were provided treatment at private non-profit OTPs.
" • Of the clients receiving buprenorphine in non-OTP facilities, 19,309 clients (45 percent) were provided treatment at private for-profit non-OTPs and 18,117 clients (42 percent) were provided treatment at private non-profit non-OTPs.

"• There were 905 clients receiving extended-release injectable naltrexone (Vivitrol®) in OTP facilities and 9,223 clients receiving extended-release injectable naltrexone (Vivitrol®) in non-OTP facilities.
" • Of the clients receiving extended-release injectable naltrexone (Vivitrol®) in OTPs, 500 clients (55 percent) were provided treatment at private non-profit OTPs and 251 clients (28 percent) were provided treatment at private for-profit OTPs.
" • Of the clients receiving extended-release injectable naltrexone (Vivitrol®) in non-OTP facilities, 4,464 clients (48 percent) were provided treatment at private non-profit non-OTPs and 3,085 clients (33 percent) were provided treatment at private for-profit non-OTPs."

Substance Abuse and Mental Health Services Administration, National Survey of Substance Abuse Treatment Services (N-SSATS): 2016. Data on Substance Abuse Treatment Facilities. BHSIS Series S-93, HHS Publication No. (SMA) 17-5039. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2017, pp. 30-31.
https://www.samhsa.gov/data/su...
https://www.samhsa.gov/data/si...

26. Trends in Treatment Admissions of People For Whom Their Primary Drug was Heroin or Other Opiates

Heroin
"• Heroin was reported as the primary substance of abuse for 26 percent of TEDS admissions aged 12 and older in 2015 [Table 1.1b].

"• Sixty-seven percent of primary heroin admissions were non-Hispanic White (41 percent were males and 26 percent were females). Non-Hispanic Blacks made up 14 percent (9 percent were males and 5 percent were females). Admissions of Puerto Rican origin made up 7 percent of primary heroin admissions (6 percent were males and 1 percent were females) [Table 2.3b]. See Chapter 3 for additional data on heroin admissions.

"• Injection was reported as the usual route of administration by 68 percent of primary heroin admissions; inhalation was reported by 25 percent. Daily heroin use was reported by 63 percent of primary heroin admissions [Table 2.4b].

"• Twenty-two percent of primary heroin admissions had no prior treatment episode, and 25 percent had been in treatment five or more times previously [Table 2.5b].

"• Primary heroin admissions were less likely than all admissions combined to be referred to treatment by the court/criminal justice system (14 vs. 30 percent) and more likely to be self or individually referred (61 vs. 41 percent) [Table 2.6b].

"• Medication-assisted opioid therapy was planned for 37 percent of heroin admissions [Table 2.7b].

"• Only 17 percent of primary heroin admissions aged 16 and older were employed (vs. 25 percent of all admissions that age); 45 percent were not in labor force (vs. 39 percent of all admissions that age) [Table 2.8b].

"• Sixty-one percent of primary heroin admissions reported abuse of additional substances. Marijuana/hashish was reported by 18 percent, alcohol by 14 percent, and non-smoked cocaine by 13 percent [Table 3.8].

Opiates Other than Heroin
"• Opiates other than heroin were reported as the primary substance of abuse for 8 percent of TEDS admissions aged 12 and older in 2015 [Table 1.1b]. These drugs include methadone, buprenorphine, codeine, hydrocodone, hydromorphone, meperidine, morphine, opium, oxycodone, pentazocine, propoxyphene, tramadol, and any other drug with morphine-like effects.

"• Admissions for primary opiates other than heroin were more likely than all admissions combined to be aged 20 to 39 (74 vs. 58 percent) [Table 2.1b].

"• Non-Hispanic Whites made up approximately 82 percent of admissions for primary opiates other than heroin (43 percent were males and 39 percent were females) [Table 2.3b].

"• The usual route of administration most frequently reported by admissions of primary opiates other than heroin was oral (61 percent); next were inhalation (18 percent) and injection (16 percent) [Table 2.4b].

"• Admissions for primary opiates other than heroin were more likely than all admissions combined to report first use after age 18 (66 vs. 39 percent) [Table 2.5b].

"• Medication-assisted opioid therapy was planned for 31 percent of admissions for primary opiates other than heroin [Table 2.7b].

"• Fifty-eight percent of admissions for primary opiates other than heroin reported abuse of other substances. The most commonly reported secondary substances of abuse were marijuana/hashish (22 percent), alcohol (16 percent), and tranquilizers (12 percent) [Table 3.8]."

Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. Treatment Episode Data Set (TEDS): 2005-2015. National Admissions to Substance Abuse Treatment Services. BHSIS Series S-91, HHS Publication No. (SMA) 17-5037. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2017, Table 1.1A, pp. 17-19.
https://www.samhsa.gov/data/si...

27. Availability of Treatment for Opioid Dependence and the "Treatment Gap"

"Nationally, in 2012, the rate of opioid abuse or dependence was 891.8 per 100,000 people aged 12 years or older compared with national rates of maximum potential buprenorphine treatment capacity and patients receiving methadone in OTPs of, respectively, 420.3 and 119.9. Among states and the District of Columbia, 96% had opioid abuse or dependence rates higher than their buprenorphine treatment capacity rates; 37% had a gap of at least 5 per 1000 people. Thirty-eight states (77.6%) reported at least 75% of their OTPs were operating at 80% capacity or more."

Christopher M. Jones, Melinda Campopiano, Grant Baldwin, and Elinore McCance-Katz. National and State Treatment Need and Capacity for Opioid Agonist Medication-Assisted Treatment. American Journal of Public Health: August 2015, Vol. 105, No. 8, pp. e55-e63.
doi: 10.2105/AJPH.2015.302664
aphapublications.org/...

28. Growth in Availability and Utilization of Opioid Treatment Programs in the US

"In 2011, 9 percent of all substance treatment facilities had OTPs (Figure 1). This percentage has consistently been between 8 and 9 percent since 2001, when the Substance Abuse and Mental Health Services Administration began certifying OTPs. While the number of facilities with OTPs has remained constant at around 1,100 to 1,200 since 2003, the number of clients receiving methadone on the survey reference date5 increased from about 227,000 in 2003 to over 306,000 in 2011 (Figure 2). Clients receiving treatment with methadone accounted for approximately 21 to 25 percent of all substance abuse treatment clients each year. The increase in the number of clients receiving methadone treatment coupled with the stability of the proportion of clients receiving this treatment suggest that the overall availability of methadone treatment has increased over time."

Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. (April 23, 2013). The N-SSATS Report: Trends in the Use of Methadone and Buprenorphine at Substance Abuse Treatment Facilities: 2003 to 2011. Rockville, MD, p. 2.
http://www.samhsa.gov/data/2k1...

29. OST and Rates of Abstinence

"As compared with patients taking low-dose methadone, those taking levomethadyl acetate had a significantly higher rate of continuous abstinence from opioids, and those taking high-dose methadone and buprenorphine had a trend toward a higher rate of continuous abstinence."

Johnson, Rolley E., Pharm. D., Mary Ann Chutuape, PhD, Eric C. Strain, MD, Sharon L. Walsh, PhD, Maxine L. Stitzer, PhD, and George E. Bigelow, PhD, "A Comparison of Levomethadyl Acetate, Buprenorphine, and Methadone for Opioid Dependence," New England Journal of Medicine (Boston, MA: Massachusetts Medical Society, Nov. 2, 2000), Vol. 343, No. 18, p. 1295.
http://content.nejm.org/cgi/re...

30. OST and Reductions in Drug Use

Effectiveness of Opioid Substitution Treatment (OST)

"In summary, levomethadyl acetate, buprenorphine, and high-dose methadone were more effective than low-dose methadone in reducing the use of illicit opioids. As compared with low-dose methadone, levomethadyl acetate produced the longest duration of continuous abstinence; buprenorphine administered three times weekly was similar to levomethadyl acetate in terms of study retention and was similar to high-dose methadone in terms of abstinence."

Johnson, Rolley E., Pharm. D., Mary Ann Chutuape, PhD, Eric C. Strain, MD, Sharon L. Walsh, PhD, Maxine L. Stitzer, PhD, and George E. Bigelow, PhD, "A Comparison of Levomethadyl Acetate, Buprenorphine, and Methadone for Opioid Dependence," New England Journal of Medicine (Boston, MA: Massachusetts Medical Society, Nov. 2, 2000), Vol. 343, No. 18, p. 1296.
http://content.nejm.org/cgi/re...

31. Opioid Substitution Treatment and Risk of New HIV Infection Among IDUs

"There is evidence from published and unpublished observational studies that opiate substitution treatment is associated with an average 54% reduction in the risk of new HIV infection among people who inject drugs. There is weak evidence to suggest that greater benefit might be associated with longer measured duration of exposure to opiate substitution treatment. All of the eligible studies examined the impact of methadone maintenance treatment, indicating that there are few data regarding the impact of buprenorphine or other forms of non-methadone opiate substitution treatment in relation to HIV transmission. We found no evidence that methadone detoxification is associated with a reduction in the risk of HIV transmission."

MacArthur, Georgie J., et al., "Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis," BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.... (Published 4 October 2012).
http://www.bmj.com/content/345...

32. Opioid Substitution Treatment and Prevention of HIV Transmission

"The unparalleled international epidemic of injection drug use as a major cause of global HIV transmission, coupled with the research evidence supporting the efficacy of methadone treatment in decreasing drug injection and HIV transmission, and the unique pharmacological properties and potential acceptance of buprenorphine and the buprenorphine/naloxone combination, mean that the world is poised for implementation and evaluation of these treatments as a method to stem the spread of HIV."

Sullivan, Lynn, David S. Metzger, Paul J. Fudala & David A. Fiellin, "Decreasing International HIV Transmission: The Role of Expanding Access to Opioid Agonist Therapies for Injection Drug Users," Addiction, February 2005, Vol. 100, No. 2, p. 153.
http://www.ncbi.nlm.nih.gov/pu...

33. OST and Reductions in HIV-Risk Behaviors

A study reported in the March 8, 2000 edition of the Journal of the American Medical Association showed that traditional methadone maintenance therapy (MMT) is superior to both short-term and long-term detoxification treatment as a method to treat heroin dependence, concluding, "Our results confirm the usefulness of MMT in reducing heroin use and HIV risk behaviors. Illicit opioid use continued in both groups, but frequency was reduced. Results do not provide support for diverting resources from MMT into longterm detoxification."

Sees, Karen, DO, et al., "Methadone Maintenance vs. 180-Day Psychosocially Enriched Detoxification for Treatment of Opiod Dependence: A Randomized Controlled Trial", Journal of the American Medical Association, 2000, 283:1303-1310.
http://jama.jamanetwork.com/ar...

34. Methadone - 3-11-10

"Our results support the hypothesis that harm-reduction-based methadone maintenance treatment decreases the risk of natural-cause and overdose mortality. Furthermore, our data suggest that in harm- reduction-based methadone programs, being in methadone treatment is important in itself, independent of the pharmacologic effect of methadone dosage. To decrease mortality among drug users, prevention measures should be expanded for those who dropout of treatment."

Langendam, Miranda W., PhD, Giel H.A.van Brussel, MD, Roel A. Coutinho, MD, PhD, and Erik J.C. van Ameijden, PhD, "The Impact of Harm-Reduction-Based Methadone Treatment on Mortality Among Heroin Users," American Journal of Public Health (Washington, DC: American Public Health Association, May 2001), Vol. 95, No. 5, p. 779.
http://www.ncbi.nlm.nih.gov/pm...

35. Methadone - 3-12-10

"Methadone maintenance treatment (MMT) has been shown to improve life functioning and decrease heroin use; criminal behavior; drug use practices, such as needle sharing, that increase human immunodeficiency virus (HIV) risk; and HIV infection."

Sees, Karen, DO, et al., "Methadone Maintenance vs. 180-Day Psychosocially Enriched Detoxification for Treatment of Opiod Dependence: A Randomized Controlled Trial", Journal of the American Medical Association, 2000, 283:1303.
http://jama.jamanetwork.com/ar...

36. Methadone - 3-12-10

"MMT [methadone maintenance treatment] facilitates a process of gradual reduction in heroin use, reduction of syringe sharing and HIV risk, and reduction of criminal activities."

Rosenbaum, et al., "Treatment as Harm Reduction, Defunding as Harm Maximization: The Case of Methadone Maintenance," Journal of Psychoactive Drugs, 28: 241-249 (1996).

37. Methadone - 3-11-10

"Over the past two decades, clear and convincing evidence has been collected from multiple studies showing that effective treatment of opiate dependence markedly reduces the rates of criminal activity. Therefore, it is clear that significant amounts of crime perpetrated by opiate dependent persons are a direct consequence of untreated opiate dependence."

National Institutes of Health, Office of the Director, "NIH Consensus Statement: Effective Medical Treatment of Opiate Addiction," (U.S. Department of Health: Bethesda, MD, November 1997) Vol. 15, No. 6., p. 12.
http://consensus.nih.gov/1997/...

38. Methadone - 2-26-10

According to the National Institutes of Health (NIH), "Methadone maintenance treatment is effective in reducing illicit opiate drug use, in reducing crime, in enhancing social productivity, and in reducing the spread of viral diseases such as AIDS and hepatitis."

Effective Medical Treatment of Opiate Addiction. NIH Consensus Statement 1997 Nov. 17-19; 15(6): 4.
http://consensus.nih.gov/1997/...

39. Methadone - 3-11-10

"Although a drug-free state represents an optimal treatment goal, research has demonstrated that this goal cannot be achieved or sustained by the majority of opiate-dependent people. However, other laudable treatment goals, including decreased drug use, reduced criminal activity, and gainful employment can be achieved by most MMT [methadone maintenance treatment] patients."

National Institutes of Health, Office of the Director, "NIH Consensus Statement: Effective Medical Treatment of Opiate Addiction," (U.S. Department of Health: Bethesda, MD, November 1997) Vol. 15, No. 6., p. 4.
http://consensus.nih.gov/1997/...

40. Methadone - 3-12-10

An editorial in the March 8, 2000, edition of The Journal of the American Medical Association states that following the Scottish example and allowing primary care physicians to dispense methadone "can provide a 3- to 5-fold increase in access. It can also reduce the cost per patient, although added access will clearly increase short-term substance abuse treatment costs while reducing long-term costs associated with overdose emergencies, HIV infection, and crime."

Rounsaville, Bruce J., MD, and Kosten, Thomas R., MD, "Treatment for Opioid Dependence: Quality and Access", Journal of the American Medical Association, (Chicago, IL: American Medical Association, March 8, 2000), Vol. 283, No. 10, p. 1338.
http://www.doctordeluca.com/Li...

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