Opiate Treatment with Agonists Including Methadone, Buprenorphine, and Suboxone

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The federal Substance Abuse and Mental Health Services Administration has a free, confidential National Helpline at 1-800-662-HELP (4357).
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41. OST and Patient Retention

The New England Journal of Medicine published a study comparing methadone with LAAM and buprenorphine. The authors concluded that "Levomethadyl acetate, buprenorphine, and high-dose methadone were all effective in treating opioid dependence and were were superior on multiple measures to low-dose methadone. The percentage of patients retained at 17 weeks compared favorably with rates reported elsewhere for these medications."

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...

42. Risk of Death and Other Adverse Events from Anesthesia-Assisted Rapid Opioid Detoxification (AAROD)

"Government agencies and professional societies,* including the American Society of Addiction Medicine, have recommended against using AAROD in clinical settings (9). There is insufficient knowledge regarding how widely AAROD is used in the United States and the frequency of AAROD-associated adverse events in community practice settings. At least seven deaths occurred following AAROD among 2,350 procedures performed in one practice during 1995–1999.†
"The New York City clinic investigation revealed that AAROD was performed on 75 patients during January–September 2012 and was associated with two deaths and five additional adverse events requiring hospitalization, a serious adverse event rate of 9.3%. No standard protocol exists for AAROD; however, the clinic’s practice was consistent with AAROD use described elsewhere (7). All events occurred after and in close temporal proximity to AAROD. Although a common mechanism linking these events to AAROD is not evident, the events are consistent with previously proposed mechanisms of AAROD-associated adverse events, including electrolyte disturbance, catecholamine release, altered cardiopulmonary functioning, acute lung injury, and other physiologic effects associated with administration of high doses of opioid antagonists under general anesthesia (10). Given the ongoing epidemic of prescription opioid dependence, further increases in the demand for substance use disorder services are to be expected. AAROD has substantial risks, including a risk for death, and little to no evidence to support its use. Safe, evidence-based treatments of opioid dependence (e.g., MAT [Medication-Assisted Treatment]) exist and are preferred (2)."


* Additional information available at http://www.nice.org.uk/. Care Med 2000;28:969–76.
† Additional information available at http://njlaw.rutgers.edu/colle....

"Deaths and Severe Adverse Events Associated With Anesthesia-Assisted Rapid Opioid Detoxification - New York City, 2012," Mortality and Morbidity Weekly Report (Atlanta, GA: Centers for Disease Control, Sept. 27, 2013), Vol. 62, No. 38, p. 780.
http://www.cdc.gov/...
http://www.cdc.gov/mmwr/pdf/wk...

43. Feasibility of OBOT

Office-Based Opioid Substitution Treatment (OBOT)

"This study has implications for future treatment of opioid dependence. First, the results support the feasibility of transferring stable patients from NTPs to the offices of trained primary care physicians and extends prior research in this field. These findings, along with recent trials demonstrating the effectiveness of buprenorphine for untreated opioid-dependent patients in primary care settings, offer encouragement regarding the use of primary care offices to help expand access to treatment for opioid dependence."

Fiellin, David A., MD, Patrick G. O'Connor, MD, MPH, Marek Chawarski, PhD, Juliana P. Pakes, MEd, Michael V. Pantalon, PhD, and Richard S. Schottenfeld, MD, "Methadone Maintenance in Primary Care: A Randomized Controlled Trial," Journal of the American Medical Association (Chicago, IL: American Medical Association, Oct. 10, 2001), Vol. 286, No. 14, p. 1730.
http://jama.jamanetwork.com/ar...

44. Feasibility of OBOT

"Our results demonstrate that methadone maintenance using weekly physician office-based dispensing is feasible, that treatment retention and patient and clinician satisfaction are high, and that illicit drug use does not differ significantly compared with continued treatment in an NTP [narcotic treatment program]. Stable patients demonstrated high functional status and low levels of health and social service use on transfer from an NTP to office-based care. The high level of patient and clinician satisfaction with office-based care and the outcomes observed with office-based treatment run counter to concerns regarding the potential quality of this type of care and the ability to identify a group of physicians interested in providing treatment for opioid-dependent patients."

Fiellin, David A., MD, Patrick G. O'Connor, MD, MPH, Marek Chawarski, PhD, Juliana P. Pakes, MEd, Michael V. Pantalon, PhD, and Richard S. Schottenfeld, MD, "Methadone Maintenance in Primary Care: A Randomized Controlled Trial," Journal of the American Medical Association (Chicago, IL: American Medical Association, Oct. 10, 2001), Vol. 286, No. 14, p. 1729.
http://jama.jamanetwork.com/ar...

45. Benefits from OBOT

"Office-based methadone maintenance administered by appropriately trained primary care and specialist physicians has the potential to provide an alternative for selected patients to the current narcotic treatment system that would allow for greater physician involvement and perhaps increased quality of care. Potential benefits from this type of care include increased attention to comorbid medical and psychiatric conditions, decreased stigma associated with the diagnosis and treatment, decreased contact with active heroin users, and increased access to treatment. These benefits may increase patient satisfaction and enhance clinical outcomes."

Fiellin, David A., MD, Patrick G. O'Connor, MD, MPH, Marek Chawarski, PhD, Juliana P. Pakes, MEd, Michael V. Pantalon, PhD, and Richard S. Schottenfeld, MD, "Methadone Maintenance in Primary Care: A Randomized Controlled Trial," Journal of the American Medical Association (Chicago, IL: American Medical Association, Oct. 10, 2001), Vol. 286, No. 14, p. 1725.
http://jama.jamanetwork.com/ar...

46. Effectiveness of OBOT

Researchers from Yale University "investigated the use of counseling and different frequencies of medication dispensing in primary care treatment with buprenorphine-naloxone. Neither the primary outcomes (the frequency of illicit opioid use, the percentage of opioid-negative urine specimens, and the maximum number of consecutive weeks of abstinence from illicit opioids) nor the proportion of patients who completed the study differed significantly among the three groups. Specifically, outcomes among patients receiving brief counseling combined with once-weekly medication dispensing did not differ significantly from outcomes among patients receiving either extended counseling or thrice-weekly medication dispensing did not differ significantly from outcomes among patients receiving either extended counseling or thrice-weekly medication dispensing. Patient satisfaction was significantly higher with once-weekly than with thrice-weekly medication dispensing, although because of the large number of statistical tests conducted, this may represent a chance finding."

Fiellin, David A., MD, Michael V. Pantalon, PhD, Marek C. Chawarski, PhD, Brent A. Moore, PhD, Lynn E. Sullivan, MD, Patrick G. O'Connor, MD, MPH, and Richard S. Schottenfeld, MD, "Counseling plus Buprenorphine-Naloxone Maintenance Therapy for Opioid Dependence," New England Journal of Medicine Vol. 355, No. 4, July 27, 2006, pp. 370-371.
http://content.nejm.org/cgi/re...

47. Effectiveness of Office-Based Buprenorphine Treatment

"Consistent with the findings of previous research with buprenorphine,1-4 the frequency of illicit opioid use decreased significantly from baseline to induction and was lowest during maintenance for all three groups. The mean percentages of patients who completed the 24-week study, which ranged between 39 and 48 percent, were similar to those found in previous studies, including one conducted in an office-based setting.1-4 Therefore, the majority of patients who entered this study either left treatment or were considered appropriate for transfer to a more structured treatment setting with methadone. Nonetheless, although we did not demonstrate the superiority of extended counseling or thrice-weekly medication dispensing over the relatively limited nurse-administered counseling and once-weekly dispensing, our findings support the feasibility of buprenorphine–naloxone maintenance in primary care.10,13,21"

Fiellin, David A., MD, Michael V. Pantalon, PhD, Marek C. Chawarski, PhD, Brent A. Moore, PhD, Lynn E. Sullivan, MD, Patrick G. O'Connor, MD, MPH, and Richard S. Schottenfeld, MD, "Counseling plus Buprenorphine-Naloxone Maintenance Therapy for Opioid Dependence," New England Journal of Medicine Vol. 355, No. 4, July 27, 2006, p. 371.
http://content.nejm.org/cgi/re...

48. Methadone vs. Buprenorphine Treatment

"Opioid dependence and addiction, whether to heroin or prescription pain relievers, is a serious, life-threatening medical condition. Methadone and buprenorphine are medications that permit addicted individuals to function normally within their families, jobs, and communities. While treatment with methadone is more established, it requires daily visits to an OTP. Not all individuals who could benefit from methadone treatment live within easy travelling distance of an OTP. Furthermore, the requirement for daily visits can interfere with jobs and other important activities. The introduction of buprenorphine for the treatment of opioid dependence has provided an alternative to methadone treatment for some opioid dependent persons; however, buprenorphine may not be appropriate for all opioid-addicted persons. The dramatic increase in the number of clients receiving buprenorphine through treatment facilities is an indication of the demand for safe and effective medications for the treatment of opioid addiction in the context of a broader treatment program."

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...

49. Frequency of Dosing with Buprenorphine

The New England Journal of Medicine published a study comparing methadone with LAAM [levomethadyl acetate] and buprenorphine. According to the report, "Most of the development and evaluation research on buprenorphine has been based on daily doses. Our study used thrice-weekly doses and found that outcomes were approximately equivalent to those with either daily methadone or thrice-weekly levomethadyl acetate. Thus, thrice-weekly buprenorphine may also offer greater convenience to patients and clinic staff."

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...

50. Efficacy of Naltrexone Treatment

"Studies conducted in St. Petersburg, Russia, for more than a decade have demonstrated the efficacy and safety of different naltrexone formulations (oral, implantable, injectable) for relapse prevention and maintenance of abstinence in detoxified opioid addicts. The positive results from different formulations seem related to two cultural factors. One is that relatives can be recruited to supervise daily dosing of the oral formulation. However, this advantage is decreasing as the addicted population ages. The second is that substitution therapy is not available; thus, naltrexone is the only effective medication available, which makes it easier to motivate patients to use it. Preliminary findings from studies of long-acting, slow-release formulations of naltrexone (implantable and injectable) suggest that they are more effective than the oral formulations and are likely to be important additions to current treatments. How they compare with maintenance treatment using methadone or buprenorphine in settings in which these three treatment options are available is a topic for future studies."

Krupitsky, Evgeny, Zvartau, Edwin, and Woody, George, "Use of Naltrexone to Treat Opioid Addiction in a Country in Which Methadone and Buprenorphine Are Not Available," Curr Psychiatry Rep. 2010 October; 12(5): 448–453. doi:10.1007/s11920-010-0135-5.
http://www.ncbi.nlm.nih.gov/pm...
http://www.ncbi.nlm.nih.gov/pm...

51. Methadone Mortality and Pain Medicine

"Taken together, the data confirm a correlation between increased methadone distribution through pharmacy channels and the rise in methadone-associated mortality. The data, thus, support the hypothesis that the growing use of oral methadone, prescribed and dispensed for the outpatient management of pain, explains the dramatic increases in methadone consumption and the growing availability of the drug for diversion to illicit use. Although the data remain incomplete, National Assessment meeting participants concurred that methadone tablets and/or diskettes distributed through channels other than OTPs most likely are the central factor in methadone-associated mortality."

Center for Substance Abuse Treatment, "Methadone-Associated Mortality: Report of a National Assessment," May 8-9, 2003, CSAT Publication No. 28-03 (Rockville, MD: Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration, 2004), p. 25.
http://proxychi.baremetal.com/...

52. Methadone - 3-11-10

"The current narcotic treatment system is able to provide the most effective medical treatment for opioid dependence, opioid agonist maintenance, to only 170,000 of the estimated 810,000 opioid-dependent individuals in the United States."

Fiellin, David A., MD, Patrick G. O'Connor, MD, MPH, Marek Chawarski, PhD, Juliana P. Pakes, MEd, Michael V. Pantalon, PhD, and Richard S. Schottenfeld, MD, "Methadone Maintenance in Primary Care: A Randomized Controlled Trial," Journal of the American Medical Association (Chicago, IL: American Medical Association, Oct. 10, 2001), Vol. 286, No. 14, p. 1724.
http://jama.jamanetwork.com/ar...

53. Cost of Untreated Opioid Dependence

"The financial costs of untreated opiate dependence to the individual, the family, and society are estimated to be approximately $20 billion per year."

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. 11.
http://consensus.nih.gov/1997/...

54. Buprenorphine Approval by FDA

"Federal statute, the Drug Addiction Treatment Act of 2000 (DATA 2000), has established a new paradigm for the medication-assisted treatment of opioid addiction in the United States (Drug Addiction Treatment Act of 2000). Prior to the enactment of DATA 2000, the use of opioid medications to treat opioid addiction was permissible only in federally approved Opioid Treatment Programs (OTPs) (i.e., methadone clinics), and only with the Schedule II opioid medications methadone and levo-alpha-acetyl-methadol (LAAM), which could only be dispensed, not prescribed.* Now, under the provisions of DATA 2000, qualifying physicians in the medical office and other appropriate settings outside the OTP system may prescribe and/or dispense Schedule III, IV, and V opioid medications for the treatment of opioid addiction if such medications have been specifically approved by the Food and Drug Administration (FDA) for that indication. (The text of DATA 2000 can be viewed at http://www.buprenorphine.samhs....) [NOTE: as of January 2019 that link was no longer valid. The new URL is https://www.ncbi.nlm.nih.gov/b...

"In October 2002, FDA approved two sublingual formulations of the Schedule III opioid partial agonist medication buprenorphine for the treatment of opioid addiction. These medications, Subutex® (buprenorphine) and Suboxone® (buprenorphine/naloxone), are the first and, as of this writing, the only Schedule III, IV, or V medications to have received such FDA approval and, thus, to be eligible for use under DATA 2000."

Center for Substance Abuse Treatment. "Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction." Treatment Improvement Protocol (TIP) Series 40. DHHS Publication No. (SMA) 04-3939. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2004, p. xv.
https://www.ncbi.nlm.nih.gov/b...

55. Buprenorphine Formulation

"Buprenorphine is a long-acting partial opioid agonist91,92 that is classified as a Schedule III narcotic, in contrast to methadone and levomethadyl, which are Schedule II. Its potential advantages include a higher degree of safety than with methadone, coupled with an ameliorated withdrawal syndrome. This is due to its partial agonist property at the ?-receptor along with its being a weak antagonist at the k-receptor.93-95 It is available in a tablet form for sublingual administration and in parenteral form. Buprenorphine is metabolized through the cytochrome P450 pathway.96-97 The brand name for the buprenorphine monotablet is Subutex, and the combination buprenorphine hydrochloride–naloxone hydrochloride tablet is Suboxone (both Reckitt Benckiser Pharmaceuticals, Richmond, Va). Both formulations come in strengths of 2 and 8 mg. The combination product contains 0.5mg of the opioid antagonist naloxone hydrochloride and is designed to decrease the potential for abuse."

Mori J. Krantz, MD; Philip S. Mehler, MD, "Treating Opioid Dependence: Growing Implications for Primary Care," Archives of Internal Medicine, (Chicago, IL: American Medical Association, February 2004), Vol. 164, p. 281.
http://archinte.jamanetwork.co...

56. Buprenorphine for Maintenance or Detox

"Buprenorphine can be used for either longterm maintenance or for medically supervised withdrawal (detoxification) from opioids. The preponderance of research evidence and clinical experience, however, indicates that opioid maintenance treatments have a much higher likelihood of long-term success than do any forms of withdrawal treatment. In any event, the immediate goals in starting buprenorphine should be stabilization of the patient and abstinence from illicit opioids, rather than any arbitrary or predetermined schedule of withdrawal from the prescribed medication."

Center for Substance Abuse Treatment, Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction, Treatment Improvement Protocol (TIP) Series 40, DHHS Publication No. (SMA) 04-3939 (Rockville, MD: Substance Abuse and Mental Health Services Administration, 2004), p. 20.
https://www.ncbi.nlm.nih.gov/p...
https://www.ncbi.nlm.nih.gov/b...

57. Effectiveness of Buprenorphine Treatment

"A number of clinical trials have established the effectiveness of buprenorphine for the maintenance treatment of opioid addiction. These have included studies that compared buprenorphine to placebo (Johnson et al. 1995; Ling et al. 1998; Fudala et al. 2003), as well as comparisons to methadone (e.g., Johnson et al. 1992; Ling et al. 1996; Pani et al. 2000; Petitjean et al. 2001; Schottenfeld et al. 1997; Strain et al. 1994a, 1994b) and to methadone and levo-alpha-acetyl-methadol (LAAM) (Johnson et al. 2000). Results from these studies suggest that buprenorphine in a dose range of 8–16 mg a day sublingually is as clinically effective as approximately 60 mg a day of oral methadone, although it is unlikely to be as effective as full therapeutic doses of methadone (e.g., 120 mg per day) in patients requiring higher levels of full agonist activity for effective treatment.

"A meta-analysis comparing buprenorphine to methadone (Barnett et al. 2001) concluded that buprenorphine was more effective than 20–35 mg of methadone but did not have as robust an effect as 50–80 mg methadone -- much the same effects as the individual studies have concluded."

Center for Substance Abuse Treatment, Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction, Treatment Improvement Protocol (TIP) Series 40, DHHS Publication No. (SMA) 04-3939 (Rockville, MD: Substance Abuse and Mental Health Services Administration, 2004), pp. 20-21.
https://www.ncbi.nlm.nih.gov/p...
https://www.ncbi.nlm.nih.gov/b...

58. Effectiveness of Buprenorphine and Buprenorphine/Naloxone

"Buprenorphine and naloxone in combination and buprenorphine alone are safe and reduce the use of opiates and the craving for opiates among opiate-addicted persons who receive these medications in an office-based setting."

Fudala, Paul J., PhD, T. Peter Bridge, MD, Susan Herbert, MA, William O. Williford, PhD, C. Nora Chiang, PhD, Karen Jones, MS, Joseph Collins, ScD, Dennis Raisch, PhD, Paul Casadonte, MD, R. Jeffrey Goldsmith, MD, Walter Ling, MD, Usha Malkerneker, MD, Laura McNicholas, MD, PhD, John Renner, MD, Susan Stine, MD, PhD, & Donald Tusel, MD for the Buprenorphine/Naloxone Collaborative Study Group, "Office-Based Treatment of Opiate Addiction with a Sublingual-Tablet Formulation of Buprenorphine and Naloxone," New England Journal of Medicine, Sept. 4, 2003, Vol. 349, No. 10, p. 949.
http://content.nejm.org/cgi/re...

59. Effectiveness of Buprenorphine Treatment

The Danish National Board of Health reported in 2000 that "The Buprenorphine project was initiated in the City of Copenhagen during the autumn of 1998 and was evaluated this year. In conclusion the report points out that this type of substitution therapy is suitable for clients who have not previously been subjected to methadone treatment and which are resourceful. Furthermore, the report concluded that buprenorphine treatment may contribute by a significant percentage to the drug addict becoming drug-free and being able to revert to normal life through work, activation and education rather than any other kind of therapy.20"

Report to the European Monitoring Center on Drugs and Drug Addiction by the Reitox National Focal Point of Denmark, Sundhedsstyrelsen (National Board of Health), "Denmark Drug Situation 2000: National Report on the State of the Drugs Problem in Denmark" (Denmark: National Board of Health and EMCDDA, December 2000), p. 73, citing Leif Skauge, "Erfaringer med implementering af buprenorphinbehandling ved Kobenhavns Kommune," handout at the Drugs Council's research conference in March 2000.
http://www.emcdda.europa.eu/at...

60. Regulation and Certification of Opioid Treatment Programs (OTPs)

Laws and Policies

"Methadone, in use since 1964 for the treatment of opioid dependence, may be dispensed only in federally approved Opioid Treatment Programs (OTPs). Treatment protocols require that a client take the medication at the clinic where it is dispensed daily.4 Take-home dosages are allowed only for clients who have been on an established maintenance program for an extended period of time.
"In October 2002, buprenorphine was approved by the Food and Drug Administration (FDA) for the treatment of opioid dependence. Physicians who obtain specialized training may prescribe buprenorphine. Some of these physicians are in private, office-based practices; others are affiliated with substance abuse treatment facilities or programs and may prescribe buprenorphine to clients at those facilities. Additionally, OTPs may also prescribe and/or dispense buprenorphine."

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. 1.
http://www.samhsa.gov/data/2k1...

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