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Journal of Addictive Diseases Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/wjad20
Methadone Medical Maintenance: An Early Twenty-First Century Perspective abc
David M. Novick MD
d
e
, Edwin A. Salsitz MD , Herman Joseph PhD & Mary Jeanne Kreek MD
a
a
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, New York, USA b
Department of Medicine, Kettering Medical Center, Kettering, Ohio, USA
c
Department of Internal Medicine, Wright State University Boonshoft School of Medicine, Dayton, Ohio, USA d
Department of Medicine, Mount Sinai Beth Israel Hospital, New York, New York, USA
e
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Institute for Treatment and Services Research, National Development and Research Institute, New York, NY, USA Accepted author version posted online: 25 Jun 2015.
To cite this article: David M. Novick MD, Edwin A. Salsitz MD, Herman Joseph PhD & Mary Jeanne Kreek MD (2015): Methadone Medical Maintenance: An Early Twenty-First Century Perspective, Journal of Addictive Diseases, DOI: 10.1080/10550887.2015.1059225 To link to this article: http://dx.doi.org/10.1080/10550887.2015.1059225
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ACCEPTED MANUSCRIPT Methadone Medical Maintenance: An Early Twenty-First Century Perspective David M. Novick, MD,1-3 Edwin A. Salsitz, MD,4 Herman Joseph, PhD,5 and Mary Jeanne Kreek, MD1 1
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, New
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York, USA 2
Department of Medicine, Kettering Medical Center, Kettering, Ohio, USA
3
Department of Internal Medicine, Wright State University Boonshoft School of Medicine,
Dayton, Ohio, USA 4
Department of Medicine, Mount Sinai Beth Israel Hospital, New York, New York, USA
5
Institute for Treatment and Services Research, National Development and Research Institute,
New York, NY, USA
Address correspondence to David M. Novick, MD, Digestive Specialists, Inc., 999 Brubaker Drive, Kettering, OH 45429. E-mail: [email protected] Short title: Methadone Medical Maintenance This article has not been published elsewhere and has not been submitted simultaneously elsewhere.
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ACCEPTED MANUSCRIPT ABSTRACT Methadone medical maintenance is the treatment of stable methadone-maintained patients in primary care physicians’ offices under an exemption from federal methadone regulations. Reports from seven such programs in six states show high retention and low frequencies of illicit drug use. Patients and physicians indicate high levels of satisfaction. Although methadone
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maintenance has a long history of safety and efficacy, most methadone medical maintenance programs are no longer operating or accepting new patients. Federal regulations for standard methadone clinics allow some features of methadone medical maintenance, and advocacy for state approval of these changes is strongly recommended.
KEYWORDS. Review, methadone, primary care, opioid, addiction, pharmacotherapy, buprenorphine, heroin.
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ACCEPTED MANUSCRIPT INTRODUCTION Methadone maintenance treatment has been validated as an effective treatment for opioid addiction by more than 50 years of research.1-5 A stable daily dose of methadone reduces or eliminates craving for opioids, prevents opioid withdrawal symptoms, and blocks the euphoric effects of additional opioids. These effects lead to reduced criminal activity, enhanced social
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rehabilitation, prevention of overdose deaths, and decreased likelihood of infectious diseases associated with drug injection. Long-term treatment is needed because of a high risk of relapse to opioid injection if the treatment is withdrawn. 6,7 Methadone is medically safe when given as maintenance treatment for 15 years or longer.8 Methadone is a long-acting opioid that can lead to normalization of physiologic functions which have become deranged during the use of the shortacting opioid, heroin.9-11 The ultimate goal of the treatment of opioid addiction is the participation of the patient in all aspects of society. This article reviews methadone medical maintenance, or medical maintenance, a program designed to meet the needs of people with an exemplary record of participation in methadone maintenance.
ESTABLISHMENT AND RATIONALE OF MEDICAL MAINTENANCE
In medical maintenance, rehabilitated methadone maintenance patients are transferred from a traditional clinic to a medical office for ongoing treatment. Table 1 shows the key
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ACCEPTED MANUSCRIPT features of medical maintenance as it was conceived as a pilot project at The Rockefeller University, New York, NY12 and then transitioned into the initial program based at Beth Israel Medical Center, New York, NY.13-16 This program was exempted from the existing methadone regulations by virtue of an Investigational New Drug (IND) permit from the Food and Drug Administration (FDA).13,14 Other programs and modifications will be described subsequently.
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Medical maintenance is appropriate for patients who have achieved a high level of social and personal adjustment and do not require ongoing counseling. Such patients are generally employed, married, and psychologically stable. They have severed their ties with the street drug culture and do not use alcohol or illicit drugs. The concept of medical maintenance closely mirrors the treatment of chronic diseases such as insulin-dependent diabetes. The methadone clinic, which at the onset of methadone maintenance offered essential services and structure to the patients, has for these patients become an obstacle for their further growth because of numerous regulations meant to monitor non-compliant patients. In the medical maintenance physician’s office, patients receiving methadone are integrated into a medical practice along with other patients being seen for various conditions. The physician may treat the patient’s other medical problems along with the opioid dependence. The patients may be seen up to every 28 days at the discretion of the physician and may receive a solid form of medication for take-home. These decisions are based on individual need and appropriateness rather than on regulations. At the visit, the patient takes the prescribed methadone dose for that day under observation in order to ensure tolerance to that dose. A urine sample is collected, and the patient pays a fee. There was no required counseling.
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ACCEPTED MANUSCRIPT Table 2 shows the main criteria for entry into medical maintenance as originally formulated and as presently permitted under a Federal Advisory of March 30, 200017 and updated Federal Regulations published on January 17, 2001. 18 In the New York program, a minimum of five years in methadone maintenance treatment was required. The five year requirement was set after carefully considering that a typical patient might need two years to resolve the personal and social problems brought about by heroin addiction and then should Downloaded by [University of Exeter] at 12:10 05 August 2015
show at least three years of adherence to the regulations of the methadone clinic. It was thought at the time of the creation of medical maintenance that a cautious approach, with the patients solidly ensconced in a lifestyle that was focused on work, family, or education, would yield better results. In retrospect, the five-year requirement was probably too restrictive; the present federal regulations permit eligibility for medical maintenance after two years of excellent performance in the methadone clinic. 19-21 State regulations may vary and can be more restrictive. Additional enrollment criteria include stable employment or other productive activity and a verifiable means of financial support. The New York program required that there has been no criminal activity, illegal drug use, or excessive alcohol use in the last 3 years. Prospective patients were interviewed and clinic records examined. The applicant was expected to have no ties to street activities and a positive record in methadone treatment: no lost medications, missed visits, behavioral problems, or positive urine tests for drugs of abuse. Participation in medical maintenance was voluntary. The benefits of medical maintenance are substantial (Table 3). 13,14,22 Patient confidentiality is protected, as the patient is not seen entering or leaving a methadone clinic. If
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ACCEPTED MANUSCRIPT the patient travels for business, they do not need to register with and attend a methadone clinic near their destination, a situation that also threatens confidentiality. Patients in medical maintenance are further removed from the drug culture. The 28-day reporting schedule and solid form of medication allow extended vacations or business trips and also the opportunity to accept a promotion or new job in a different location. Many patients found the liquid take-home medication, as required in standard methadone clinics at that time, to be confidentiality risk as it Downloaded by [University of Exeter] at 12:10 05 August 2015
could be found in the refrigerator by others. There was also the risk of accidental spills of liquid methadone. An additional benefit of medical maintenance is development of a trusting relationship with the physician. Other medical problems, whether or not related to the previous heroin addiction, can be treated at the same location. The addition of an advanced level of care with greater privileges makes methadone treatment more appealing to patients and rewards the patients who have made the most of this opportunity. 22 A benefit for society is the opening up of additional treatment slots in methadone clinics as patients are transferred to medical maintenance. This was an urgent need in the 1980s due to the new epidemic of human immunodeficiency virus (HIV) infection among people who inject drugs and is similarly urgent today with the heroin epidemic of the present decade23-26 and the high prevalence of hepatitis C.27,28 Another benefit to society is the increased access to treatment of addiction in primary care settings. RESULTS FROM THE INITIAL PROGRAMS New York
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ACCEPTED MANUSCRIPT Retention in treatment is an important and valid index of the effectiveness of an addiction treatment program. A 1994 report of the first 100 patients admitted to the New York program15 showed very high treatment retention: at one, two, and three years, retention was 98%, 95%, and 85%, respectively. The patients were followed for 3.5-9.25 years, or 42-111 months. The cumulative proportion of patients retained in treatment was 0.735 ± 0.048 at 5 years and 0.562 ±
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0.084 at 9 years. The median retention was 9 years. Only 15 patients were discharged for repeated adverse events.15 Regular or prolonged cocaine use was the factor in eleven.15 Three patients misused medication (took extra doses and ran short, lost medication, or urine negative for methadone), and one patient repeatedly missed appointments. Seven of the 72 patients who remained in good standing had an isolated or minor lost medication incident, and three had transient substance abuse which was successfully managed within the medical maintenance program. Seven patients voluntarily underwent gradual dose reductions of methadone, leading to discontinuation of this medication. Five patients died or were transferred to an extended care facility, and one voluntarily returned to his previous methadone clinic. All of the physicians had their primary training in internal medicine or family practice.13-15 Salsitz et al. published a longer-term follow-up of 158 patients who entered this medical maintenance program from 1983-98.16 Of this group, 132 (83.5%) remained in good standing. There was 58.8% retention at 10 years in treatment and 44.6% at 15 years. Other results were similar to the previous study except that 20 patients (13%) had died, and 15 (75%) of the deaths were related either to tobacco use (8 patients) or infectious complications of drug injection
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ACCEPTED MANUSCRIPT (hepatitis C in four and HIV in three). Overall, 85 of 92 patients (92%) who were tested for hepatitis C antibody were positive, and 77 of 84 (92%) tested for HCV-RNA were positive. Four patients received liver transplants while remaining on methadone,27 and twenty patients had received antiviral therapy for hepatitis C.27, 28 Treatment retention was significantly associated with being married, a longer duration of methadone maintenance, and at least one
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discontinuation of methadone treatment.16 The patients in this program were exceptionally satisfied with their treatment.16 They cited high-quality medical care, enhanced confidentiality, reduced feelings of stigmatization,29,30 freedom to move to a more desirable location, greater employment opportunities, and ability to take vacations, among other benefits. Baltimore The Baltimore program started in October 1985. It was also initiated under an IND from the FDA but was initially limited to 21 patients.31 The study protocol was otherwise similar to the New York program but included a call-back procedure in which patients were told to return to the office in order to be sure that they had the correct number of unused methadone tablets.31 They reported a twelve-year follow-up in which only six (28.6%) of the 21 patients left the program for adverse events. Three of these 6 patients had positive drug tests. One other patient reported spilled methadone, missed an appointment, and abused alcohol, and two others had drug-related arrests. Only 12 (0.5%) of 2290 urine specimens collected over the twelve-year study period were positive for illicit drugs. There was no significant increase in the patients’ methadone doses and no evidence that methadone was being diverted to the community. 31
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ACCEPTED MANUSCRIPT This group has published two additional studies,32,33 in which they randomized patients to medical maintenance in a physician’s office, medical maintenance situated in the clinic, and routine methadone maintenance in the clinic. These studies included random monthly call-backs for medication checks in which patients had to call a dedicated phone line every Monday through Friday to see if they needed to bring their medication in for counting that day. Code numbers rather than patient names were used. Urine screening was done twice per month: at the call-back Downloaded by [University of Exeter] at 12:10 05 August 2015
visit and at the regular 28-day visit. Another innovation was a short-term use of intensified counseling and urine screening for those with positive urines. After four weeks of perfect attendance and negative urines, the patients returned to the group to which they were previously randomized. Patient satisfaction was measured systematically. Counseling was once per month. The investigators studied 92 patients for a twelve month follow-up period.33 The treatment retention rates were high in all groups: 92% for office-based medical maintenance, 79% for clinic-based medical maintenance, and 82% for routine care. Most of the patients who left the study did so because of dislike of the frequency of the call-backs and difficulty managing a 27-day supply of medication. Only 1.3% of the urines collected in the study were positive, whereas 4% of the medication recalls were not successful. Patients in either of the medical maintenance groups were significantly more satisfied with their treatment and significantly more likely to have initiated new vocational or social activities than those in routine care. This group later published favorable results of an effort to disseminate accurate data on medical maintenance to community-based programs.34 Chicago
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ACCEPTED MANUSCRIPT Senay et al. initiated a study in 1988 using significantly different entry criteria.35 Patients needed one or more years of methadone maintenance treatment and no positive urines, arrest, or non-adherence to treatment in the preceding 6 months. All were employed or with other productive use of time in the last 6 months. Patients were randomized to remaining in the clinic or to medical maintenance with medication dispensed every 14 days along with observed methadone ingestion. Urine testing was monthly with three random collections per year. There Downloaded by [University of Exeter] at 12:10 05 August 2015
were also random calls from the clinic nurse to bring in all bottles. One or more counseling sessions per month was required. There were 130 patients who participated in the study. 35 Treatment retention at one year was 73% in both groups. The majority of the discharges from the program were for two consecutive positive urines for illicit drugs rather than for misuse of medication. Urine screening results did not differ significantly between the two groups. The satisfaction of the medical maintenance patients was so high that the Institutional Review Board considered it a hardship for them to return to their previous treatment setting and allowed the patients to remain in medical maintenance.35 Later it became possible to expand the study, and similar results were seen in a preliminary analysis.36
REGULATORY CHANGES From its inception, standard methadone treatment was more highly regulated than any other medical treatment.19-21 The detailed regulations were more focused on adherence to rules and prevention of diversion than on the clinical outcome of the patient. The orientation was
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ACCEPTED MANUSCRIPT toward inspection and enforcement, although there was no regular schedule of oversight visits. Methadone maintenance programs had to be licensed and monitored by the FDA, the Drug Enforcement Administration (DEA), and state agencies. There were regulations concerning methadone dose, the amount of counseling provided, take-home medication, urine testing, and many other details. These regulations, particularly the required clinic visits one or more times weekly, were an obstacle to the progress and well-being of socially rehabilitated methadone Downloaded by [University of Exeter] at 12:10 05 August 2015
maintenance patients. The regulations also had the effect of isolating methadone maintenance treatment from mainstream medicine and limiting the expansion of maintenance treatment to all who needed it. In 2002, it was estimated that two-thirds of opioid-dependent people in the United States were not in any form of addiction treatment. 20 In 2000-2001, significant policy changes in the treatment of opioid addiction were enacted. The changes were partly a result of expert panels convened by the Institute of Medicine37 and the National Institutes of Health,38 both of which validated the efficacy of methadone maintenance treatment and promoted treatment expansion. There was ongoing concern about the spread of HIV and hepatitis C virus infection among people who inject drugs and their contacts. The aforementioned studies and emerging initiatives in New Haven, CT and Seattle, WA, in which medical maintenance was initiated on the basis of a program-wide exemption from the FDA rather than as a research protocol under an IND number, were considered. The new policies were developed to encourage expansion of addiction treatment and to increase the involvement of the medical profession in addiction treatment.19
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ACCEPTED MANUSCRIPT On March 30, 2000, top officials from the FDA and the Center for Substance Abuse Treatment released a joint advisory on medical maintenance. 17 They noted that medical maintenance has been provided ―in physicians’ offices that are affiliated with an opioid treatment program,‖ and they determined that ―medical maintenance treatment should be provided in accordance with the program-wide exemption provisions in the current opioid treatment regulations.‖17 The advisory states that a treatment program may apply to the FDA for an Downloaded by [University of Exeter] at 12:10 05 August 2015
exemption to regulatory requirements in order to provide medical maintenance.17 Subsequently, on January 17, 2001, new federal regulations on opioid agonist medications were published.18-21 Oversight of opioid treatment programs was transferred from the FDA to the Substance Abuse and Mental Health Service Administration (SAMHSA), a division of the Department of Health and Human Services. An accreditation-based system, similar to that for hospitals and other medical facilities, was established, with the focus on treatment outcomes rather than enforcement of regulations. Quality improvement and diversion control programs were required.18 The regulations also allowed some features of medical maintenance to be incorporated into standard methadone clinics: after two years in the program, one monthly visit and a one-month supply of take-home medication was allowed, and a solid form of medication was permitted.18 Yet another policy change was the Drug Addiction Treatment Act of 2000 (PL106310).19-21 This law allows qualified physicians to prescribe approved schedule III-V narcotic medications for maintenance and detoxification outside of established opioid treatment programs. Such prescribing privileges can be obtained through an approved 8 hour course or
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ACCEPTED MANUSCRIPT certification in addiction medicine or psychiatry. The intent was to make opioid addiction treatment available in physicians’ offices. The only drugs approved for use under this law are buprenorphine or buprenorphine-naloxone, in certain formulations (sublingual, but not transdermal or parenteral). Methadone is a schedule II drug and is not covered by this act. STUDIES DONE UNDER THE EXEMPTION PROCESS
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The studies that have been published under exemptions from the methadone regulations are reviewed here. New Haven Fiellin et al. published a randomized, controlled trial of patients in methadone maintenance who had no evidence of use cocaine or of opioids other than methadone for one year or longer.39 Patients were randomized to medical maintenance in the offices of primary care internists (22 patients) or ongoing routine care (24 patients) in their clinic. The medical maintenance patients took a daily dose of methadone in the presence of program staff and received 6 take-home doses of liquid methadone. The physician visits were monthly and consisted of 30-minute counseling and educational sessions. The two groups of patients were similar in most respects. The investigators found no difference in the two groups in illicit drug use or drug use meeting criteria for clinical instability (two consecutive positive urines or urines negative for methadone).39 They did note, however, a high frequency of either self-reported illicit drug use or positive urine tests in both groups, with an overall frequency of 48% (22 of 46). Only 9 of 46
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ACCEPTED MANUSCRIPT (20%) met the criteria for instability. Patients in the medical maintenance group were significantly more satisfied with their treatment than those in the usual care group. The physicians also reported satisfaction with their experience. Seattle These investigators initiated a medical maintenance program as an exemption to Federal
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and State regulations; the exemption process took 14 months.40 They studied 30 patients who had reliable clinic attendance, picked up methadone no more than three times per week, and had no positive urines for the preceding 12 months. A major difference in this model was the role of the pharmacist. A group of pharmacists was responsible for assessing patient stability, observing the ingestion of a dose of methadone, dispensing methadone tablets, and supervising urine collection, including temperature testing. Physician visits were monthly and adjusted as necessary. Random call-backs for medication checks and urine tests were also done. The one-year retention was 93% (28 of 30).40 The other two patients transferred to other programs. Only two patients (7%) had positive urine tests. All random urines were negative, and all medication call-backs showed accurate counts. The rate of patients reporting being very satisfied with their care was high, 26 of 30 (87%). Physician satisfaction was high, and physician attitudes toward treatment of addiction showed significant improvement after 6 months of participation. Bronx, NY
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ACCEPTED MANUSCRIPT A study of medical maintenance from Bronx, NY has been published.41 This program has a much higher percentage of non-white patients (50%) than the other programs described above and is connected with a network of methadone clinics serving a population with a very low income. Eligibility criteria included no illicit drug use for the previous three years, employment or not employed secondary to disability or retirement, and psychiatric stability. Similar to the Seattle program, the pharmacist dispenses a monthly supply and performs clinical and Downloaded by [University of Exeter] at 12:10 05 August 2015
psychosocial assessments. The physician sees the patient monthly, does a medical and mental health assessment, and provides counseling. During the five-year follow-up, two of the 127 patients returned to a standard clinic because of opioid or cocaine abuse, one moved to another state, and nine died41. Only 0.8% of all the urine samples collected revealed opioids other than methadone, and 0.4% of the samples were positive for cocaine; all of these positive urines were from 7 patients41. This program is one of several in New York State which were set up under the guidance of one of the authors (H.J.). Table 4 summarizes the key features of these. New Mexico A 12-month study of 14 women in two cities in New Mexico was reported by Tuchman. 42 The patients had a stable dose of methadone and no evidence of heroin use for the preceding 6 months. Office-based evaluation and treatment was done in primary care offices or in a women’s medical clinic. Methadone was dispensed, and one dose administered under observation, by five community pharmacists using private consultation areas.42 A part-time (20 hours per week) social worker coordinated all aspects of the patients’ care and served as liaison between the
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ACCEPTED MANUSCRIPT patients, physicians, and pharmacists; this position was increased to full-time during the study based on ongoing needs assessment.42 Eleven of the 14 patients (78.6%) remained in the study for 12 months and were exceptionally pleased with their treatment. THE PRESENT SITUATION Taken together, the published studies of medical maintenance from 7 groups in 6 states
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show a high retention rate and low rates of use of illicit drugs. There are excellent results on random call-backs for urine testing and medication counts. There is high patient and physician satisfaction with this form of treatment. Three randomized studies support the use of medical maintenance.32,33,35,39 Medical maintenance can be an important means of expanding the overall addiction treatment capacity to respond to unmet needs. At this time there are major unmet needs. During the last 20 years, there has been an enormous increase in the abuse of prescription opioids, including hydrocodone and oxycodone, in the United States.23-25,43 The number of opioid abusers is estimated to have increased by 225% from 1992-2000.43 Physician prescribing of opioids has dramatically increased in part because of greater emphasis on treating pain maximally and reduced concern about the risks of addiction.43 This epidemic of prescription opioid abuse commonly begins from misuse of a person’s own prescription, introduction to opioids from friends, or easy access to prescriptions of family members.23 Recent efforts at reigning in excessive prescribing practices have led to reduced availability of opioids, and heroin has become an available and less expensive opioid for many.24,25 Several recent studies have shown a sharp increase in heroin use among those who previously abused prescription opioids. SAMHSA has estimated that from 2002-2011, the
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ACCEPTED MANUSCRIPT incidence of heroin use was 19 times higher in previous prescription opioid users, and in 2011, 79.5% of people who initiated heroin use had previously abused prescription opioids.26 The demographics of this new heroin epidemic differ from previous ones, in that the affected individuals are more likely to have used prescription opioids and to be white, female, older, and living in suburban or rural areas.25
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To the best of our knowledge, there have been only two specific publications on medical maintenance since 2006.34,42 Several of the medical maintenance programs have closed because of loss of funding or ascertaining that compliance with the methadone regulations, even under a program-wide exemption, was too time-consuming and impractical in a private practice model. For the latter reason, the New York program13-16 remains under an IND but cannot accept new patients. The Baltimore,31-34 Bronx, New York,41 and the other New York State programs (Table 4) continue to function under a program-wide exemption approved by SAMSHA. Interest has shifted markedly toward office-based treatment with buprenorphinenaloxone.4,44-46 Buprenorphine is a partial opioid agonist with adequate bioavailability when given sublingually. With sublingual administration, it has a long elimination half-life (37 hr),4,45 making it useful as a maintenance medication. Buprenorphine has a ―ceiling‖ or ―plateau‖ effect, meaning that above a certain dose, often 16-24 mg, there will be no additional opioid effects.4,45 Because buprenorphine is a partial agonist at the µ opioid receptor and has a long period of residency at receptor sites, it will displace other opioids already bound to the receptor. Displacement of a stronger opioid by a weaker one will lead to withdrawal symptoms (precipitated withdrawal).45 Maintenance treatment with buprenorphine must therefore be
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ACCEPTED MANUSCRIPT initiated when the patient is in at least mild withdrawal. 44,45 The addition of naloxone has no effect when buprenorphine is given sublingually, but the naloxone temporarily blocks the opioid effects if the drug is injected.4,45 The weaker efficacy of buprenorphine compared with other opioids suggest a reduced risk of overdose, though overdoses can occur. Numerous studies have confirmed the efficacy of buprenorphine-naloxone as a maintenance medication4,46 for both
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prescription opioid47 and heroin addiction.48 Buprenorphine-naloxone is a schedule III drug and is authorized for office-based treatment outside of licensed clinics under the Drug Abuse Treatment Act of 2000.19-21 This law permits physicians to prescribe buprenorphine after taking an 8-hour course on its use. From the physician’s point of view, prescribing buprenorphine-naloxone is relatively easy. In contrast, it took a group of dedicated investigators 14 months to obtain the exemption to use methadone (schedule II) for medical maintenance.40 Perceived advantages of buprenorphine-naloxone over methadone include reduced overdose risk, a more rapid progression to monthly take-home, less regulation generally, and less stigma.49 Overdoses are possible with buprenorphine, however, and diversion has been increasing.50 Similar to methadone, diverted buprenorphine is used as a substitute drug for heroin, for withdrawal symptom prevention, or for self-initiated withdrawal from opioids on the street, rather than a primary drug of abuse. 50 Some stable patients in medical maintenance have successfully transitioned to buprenorphine maintenance.51 In contrast, methadone has been studied for more years1,2 and has more long-term data on medical and physiological effects and long-term safety than does buprenorphine.8,9 Metaanalyses have shown that methadone maintenance has greater treatment retention52,53 than that
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ACCEPTED MANUSCRIPT with buprenorphine, especially when methadone is given in recommended higher doses (80-150 mg/day) which take advantage of methadone’s full agonist effect.54 Methadone maintenance has greater efficacy than buprenorphine-naloxone maintenance for patients with high-dose or longterm opioid use.49 Overdoses with methadone have increased in recent years, associated with a marked increase in prescription of methadone through pharmacies for the treatment of pain. Methadone overdose is often associated with the use of other psychoactive drugs and is Downloaded by [University of Exeter] at 12:10 05 August 2015
particularly likely if methadone is prescribed to opioid-naïve or weakly opioid-tolerant patients in high doses or with too-rapid induction.55-56 Overdoses of heroin or prescription opioids often follow release from abstinence-oriented residential programs when there is no option or availability of opioid maintenance treatment.57 The medical maintenance programs described in this article were the first to provide office-based opioid treatment since the 1920s14 and have set the stage for the dissemination of buprenorphine-naloxone treatment in physicians’ offices rather than licensed clinics. While buprenorphine-naloxone treatment continues to become more widely available as a response to the present epidemic of opioid addiction, medical maintenance has been largely forgotten. Yet, it still can have an important role in expanding overall treatment capacity. This is especially true now because the Affordable Care Act identifies addiction treatment as an essential benefit. 28 In view of the requirement that medical maintenance be formally linked to a licensed methadone treatment program and the need for a program-wide exemption with federal and state approval, it is likely that expansion and further research on medical maintenance will come about only by efforts of physicians associated with a methadone program affiliated with an academic medical center. Since two of the key features of medical maintenance – up to monthly take-home and
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ACCEPTED MANUSCRIPT solid form of methadone – are now permitted in standard clinics by federal regulations, 18-21 a more fruitful approach to improve opioid addiction treatment may be to advocate for more flexibility at the state level in implementing these two reforms. Acknowledgements: We thank Gregory James and Belinda Greenfield of the New York State Office of Alcohol and Substance Abuse Services for help in compiling information on the New
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York State Programs, and Margaret Chappell for the literature searches for this article.
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ACCEPTED MANUSCRIPT REFERENCES 1. Dole VP, Nyswander ME, Kreek MJ. Narcotic blockade. Arch Intern Med 1966; 118: 304-9. 2. Kreek MJ, LaForge KS, Butelman E. Pharmacotherapy of addictions. Nat Rev Drug Discov 2002; 1: 710-26.
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3. Sees KL, Delucchi KL, Masson C, et al. Methadone maintenance vs 180-day psychosocially enriched detoxification for treatment of opioid dependence: a randomized controlled trial. JAMA 2000; 283:1303-10. 4. Bart G. Maintenance medication for opiate addiction: the foundation of recovery. J Addict Dis 2012; 31:207-25. 5. Fullerton CA, Kim M, Thomas CP, et al. Medication-assisted treatment with methadone: assessing the evidence. Psychiatr Serv 2014; 65:146-57. 6. Anglin MD, Speckart GR, Booth MW, Ryan TW. Consequences and costs of shutting off methadone. Addict Behav 1989; 14:307-26. 7. Ball JC, Ross A. The effectiveness of methadone maintenance treatment. New York: Springer-Verlag, 1991. 8. Novick DM, Richman BL, Friedman JM, et al. The medical status of methadone maintenance patients in treatment for 11-18 years. Drug Alcohol Depend 1993; 33: 23545. 9. Novick DM, Ochshorn M, Ghali V, et al. Natural killer cell activity and lymphocyte subsets in parenteral heroin users and methadone maintenance patients. J Pharmacol Exp Ther 1989; 250:606-10.
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ACCEPTED MANUSCRIPT 10. Bart G, Borg L, Schluger JH, Green M, Ho A, Kreek MJ. Suppressed prolactin response to dynorphin A1-13 in methadone-maintained versus control subjects. J Pharmacol Exp Ther 2003; 306: 581-7. 11. Schluger JH, Bart G, Green M, Ho A, Kreek MJ. Corticotropin-releasing factor testing reveals a dose-dependent difference in methadone maintained vs control subjects. Neuropsychopharmacology 2003; 28:985-94. Downloaded by [University of Exeter] at 12:10 05 August 2015
12. Des Jarlais DC, Joseph H, Dole VP, Nyswander ME. Medical maintenance feasibility study. Nat Inst Drug Abuse Res Monogr Ser 1985; 58:101-110. 13. Novick DM, Pascarelli EF, Joseph H, et al. Methadone maintenance patients in general medical practice: a preliminary report. JAMA 1988: 259: 3299-302. 14. Novick DM, Joseph H. Medical maintenance: the treatment of chronic opiate dependence in general medical practice. J Subst Abuse Treat 1991; 8:233-9. 15. Novick DM, Joseph H, Salsitz EA, et al. Outcomes of treatment of socially rehabilitated methadone maintenance patients in physicians’ offices (medical maintenance): follow-up at three and a half to nine and a fourth years. J Gen Intern Med 1994; 9:127-30. 16. Salsitz EA, Joseph H, Frank B, et al. Methadone medical maintenance (MMM): treating chronic opiate dependence in private medical practice – a summary report (1983-1998). Mt Sinai J Med 2000; 67:388-397. 17. Lepay D, Clark HW. Federal Advisory on Methadone Medical Maintenance Exemptions. Rockville MD, U.S. Department of Health and Human Services, 2000.
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ACCEPTED MANUSCRIPT 18. Substance Abuse and Mental Health Service Administration. Opioid drugs in maintenance and detoxification treatment of opiate addiction. Fed Regist 2001; 66:4076102. 19. Fiellin DA, O’Connor PG. New federal initiatives to enhance the medical treatment of opioid dependence. Ann Intern Med 2002; 137:688-92. 20. Kreek MJ, Vocci FJ. History and current status of opioid maintenance treatments: Downloaded by [University of Exeter] at 12:10 05 August 2015
blending conference session. J Subst Abuse Treat 2002; 23:93-105. 21. Merrill JO. Policy progress for physician treatment of opiate addiction. J Gen Intern Med 2002; 17:361-8. 22. Fiellin DA, Barthwell AG. Guideline development for office-based pharmacotherapies for opioid dependence. J Addict Dis 2003; 22:109-20. 23. Lankenau SE, Teti M, Silva K, Bloom JJ, Harocopos A, Treese M. Initiation into prescription opioid misuse among young injection drug users. Int J Drug Policy 2012; 23:37-44. 24. Unick GJ, Rosenblum D, Mars S, Ciccarone D. Intertwined epidemics: national demographic trends in hospitalizations for heroin- and opioid-related overdoses, 19932009. PLoS One 2013: 8:e54496. 25. Cicero TJ, Ellis MS, Surratt HL, Kurtz SP. The changing face of heroin use in the United States: a retrospective analysis of the past 50 years. JAMA Psychiatry 2014; 71:821-6. 26. Kuehn BM. SAMHSA: pain medication abuse a common path to heroin: experts say this pattern likely driving heroin resurgence. JAMA 2013: 310:1433-4.
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ACCEPTED MANUSCRIPT 27. Novick DM, Kreek MJ. Critical issues in the treatment of hepatitis C virus infection in methadone maintenance patients. Addiction 2008; 103:905-18. 28. Paley SJ, Kreek MJ. A window of opportunity: maximizing the effectiveness of new hepatitis C regimens in the United States with the expansion of the Affordable Care Act. Am J Public Health 2015; 105: 457-63.. 29. Olsen Y, Sharfstein JM. Confronting the stigma of opioid use disorder—and its Downloaded by [University of Exeter] at 12:10 05 August 2015
treatment. JAMA 2014; 311:1393-4. 30. Barry CL, McGinty EE, Pescosolido BA, Goldman HH. Stigma, discrimination, treatment effectiveness, and policy: public views about drug addiction and mental illness. Psychiatr Serv 2014; 64: 1269-72. 31. Schwartz RP, Brooner RK, Montoya ID, Currens M, Hayes M. A 12-year follow-up of a methadone medical maintenance program. Am J Addict 1999; 8:293-9. 32. King VL, Stoller KB, Hayes M, et al. A multicenter randomized evaluation of methadone medical maintenance. Drug Alcohol Depend 2002; 65:137-48. 33. King VL, Kidorf MS, Stoller KB, Schwartz R, Kolodner K, Brooner RK. A 12-month controlled trial of methadone medical maintenance integrated into an adaptive treatment model. J Subst Abuse Treat 2006; 31:385-93. 34. King VL, Burke C, Stoller KB, et al. Implementing methadone medical maintenance in community-based clinics: disseminating evidence-based treatment. J Subst Abuse Treat 2008; 35:312-21. 35. Senay EC, Barthwell AG, Marks R, Bokos P, Gillman D, White R. Medical maintenance: a pilot study. J Addict Dis 1993; 12:59-76.
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ACCEPTED MANUSCRIPT 36. Senay EC, Barthwell A, Marks R, Bokos PJ. Medical maintenance: an interim report. J Addict Dis 1994; 13:65-9. 37. Rettig RA, Yarmolinsky A, eds. Federal Regulation of Methadone Treatment. Washington, D.C.: National Academy Press, 1995. 38. NIH Consensus Conference. Effective medical treatment of opiate addiction. JAMA 1998; 280:1936-43. Downloaded by [University of Exeter] at 12:10 05 August 2015
39. Fiellin DA, O’Connor PG, Chawarski M, Pakes JP, Pantalon MV, Schottenfeld RS. Methadone maintenance in primary care: a randomized controlled trial. JAMA 2001; 286: 1724-31. 40. Merrill JO, Jackson TR, Schulman BA, et al. Methadone medical maintenance in primary care: an implementation evaluation. J Gen Intern Med 2005; 20:344-9. 41. Harris KA, Arnsten JH, Joseph H, et al. A 5-year evaluation of a methadone medical maintenance program. J Subst Abuse Treat 2006; 31:433-8. 42. Tuchman E. A model-guided process evaluation: office-based prescribing and pharmacy dispensing of methadone. Eval Program Plann 2008; 31:376-81. 43. Lembke A. Why doctors prescribe opioids to known opioid abusers. N Eng J Med 2012; 367: 1580-1. 44. Kraus ML, Alford DP, Kotz MM, et al. Statement of the American Society of Addiction Medicine Consensus Panel on the use of buprenorphine in office-based treatment of opioid addiction. J Addict Med 2011; 5:254-63. 45. Mauger S, Fraser R, Gill K. Utilizing buprenorphine-naloxone to treat illicit and prescription-opioid dependence. Neuropsychiatr Dis Treat 2014; 10: 587-98.
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ACCEPTED MANUSCRIPT 46. Thomas CP, Fullerton CA, Kim M, et al. Medication-assisted treatment with buprenorphine: assessing the evidence. Psychiatr Serv 2014; 65: 158-170. 47. Weiss RD, Potter JS, Fiellin DA, et al. Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: a 2-phase randomized controlled trial. Arch Gen Psychiatry 2011; 68:1238-46. 48. Kakko J, Svanborg KD, Kreek MJ, Hellig M. 1-year retention and social function after Downloaded by [University of Exeter] at 12:10 05 August 2015
buprenorphine-assisted relapse prevention for heroin dependence in Sweden: a randomised, placebo-controlled trial. Lancet 2003; 361:662-8. 49. Bonhomme J, Shim RS, Gooden R, Tyrus D, Rust G. Opioid addiction and abuse in primary care practice: a comparison of methadone and buprenorphine as treatment options. J Natl Med Assoc 2012; 104:342-50. 50. Cicero TJ, Ellis MS, Surratt HL, Kurtz SP. Factors contributing to the rise in buprenorphine misuse: 2008-2013. Drug Alcohol Depend 2014; 142: 98-104. 51. Salsitz EA, Holden CC, Tross S, Nugent A. Transitioning stable methadone maintenance patients to buprenorphine maintenance. J Addict Med 2010; 4:88-92. 52. Amato L, Davoli M, Perucci CA, Ferri M, Faggiano F, Mattick RP. An overview of systematic reviews of the effectiveness of opiate maintenance therapies: available evidence to inform clinical practice and research. J Subst Abuse Treat 2005; 28:321-9. 53. Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2014; 2:CD002207.
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ACCEPTED MANUSCRIPT 54. Peles E, Schreiber S, Adelson M. Factors predicting retention in treatment: 10-year experience of a methadone maintenance treatment (MMT) in Israel. Drug Alcohol Depend 2006; 82:211-7. 55. Substance Abuse and Mental Health Services Administration. SAMHSA and FDA join to educate the public on the safe use of methadone. April 28, 2009. http://www.samhsa.gov/newsroom/press-announcements/200904280215 Accessed Downloaded by [University of Exeter] at 12:10 05 August 2015
October 22, 2014. 56. Substance Abuse and Mental Health Services Administration. Substance abuse treatment advisory: emerging issues in the use of methadone. Spring 2009. http://store.samhsa.gov/shin/content/SMA09-4368/SMA09-4368.pdf Accessed October 22, 2014. 57. Cherkis J. Dying to be free: There’s a treatment for heroin addiction that actually works. Why aren’t we using it? Huffington Post, January 28, 2015. http://projects.huffingtonpost.com/dying-to-be-free-heroin-treatment. Accessed May 4, 2015.
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ACCEPTED MANUSCRIPT Table 1. Key Features of the Initial Medical Maintenance Program in New York Treatment of stable methadone maintenance patients in physicians’ offices Patients were transferred from standard methadone clinics Urine testing and observed dosing
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Flexible visit and medication take-home, up to 28 days* Solid form of methadone* No required counseling *Changes in Federal Regulations concerning methadone in 2001 permit provision within standard methadone clinics of a up to a one-month take-home medication and a solid form of methadone for patients who are ―responsible in handling opioid drugs.‖18
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ACCEPTED MANUSCRIPT Table 2. Criteria for Entry to Medical Maintenance in the Initial Medical Maintenance Program Five or more years in methadone maintenance treatment* Stable employment or other productive activity Financial support
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No drug or alcohol abuse for 3 years* No criminal activity for 3 years* Adherence to clinic rules and standards Emotionally stable Voluntary *Much shorter intervals have been recommended in subsequent programs.
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ACCEPTED MANUSCRIPT Table 3. Benefits of Medical Maintenance Confidentiality Patients are further removed from the drug subculture Trusting physician-patient relationship
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Ease of travel General medical problems treated at same location Expanded employment activities Stable patients leave the methadone clinic, opening up spaces for new patients Makes methadone treatment more attractive by rewarding progress and allowing the opportunity to earn privileges
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ACCEPTED MANUSCRIPT Table 4. New York State Medical Maintenance Programs Not Included in Other Publications*§ Location
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Albany
Buffalo
East Meadow
Rochester
No. of Patients
29
29
13
12
Site of
Site of
Counseling
Physician’s
Methadone
Office
Dispensing
Primary care
Commercial
center within
pharmacy on
hospital
hospital grounds
Separate area of
Physician’s
Counselor is
methadone clinic
office
assigned
Separate area of
Physician’s
No
methadone clinic
office
Hospital
Physician’s
No
No
office
*All programs followed inclusion criteria per New York State guidelines including a minimum of four years of methadone maintenance treatment and three years with no alcohol or drug abuse or criminal involvement. §One other program had functioned for ten years but closed in 2011. It had used a commercial pharmacy for 10 years uneventfully; but after the pharmacy was sold, the pharmacy lost its authorization to dispense methadone due to concerns about record keeping.
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Journal of Addictive Diseases Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/wjad20
Methadone Medical Maintenance: An Early Twenty-First Century Perspective abc
David M. Novick MD
d
e
, Edwin A. Salsitz MD , Herman Joseph PhD & Mary Jeanne Kreek MD
a
a
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, New York, USA b
Department of Medicine, Kettering Medical Center, Kettering, Ohio, USA
c
Department of Internal Medicine, Wright State University Boonshoft School of Medicine, Dayton, Ohio, USA d
Department of Medicine, Mount Sinai Beth Israel Hospital, New York, New York, USA
e
Click for updates
Institute for Treatment and Services Research, National Development and Research Institute, New York, NY, USA Accepted author version posted online: 25 Jun 2015.
To cite this article: David M. Novick MD, Edwin A. Salsitz MD, Herman Joseph PhD & Mary Jeanne Kreek MD (2015): Methadone Medical Maintenance: An Early Twenty-First Century Perspective, Journal of Addictive Diseases, DOI: 10.1080/10550887.2015.1059225 To link to this article: http://dx.doi.org/10.1080/10550887.2015.1059225
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ACCEPTED MANUSCRIPT Methadone Medical Maintenance: An Early Twenty-First Century Perspective David M. Novick, MD,1-3 Edwin A. Salsitz, MD,4 Herman Joseph, PhD,5 and Mary Jeanne Kreek, MD1 1
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, New
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York, USA 2
Department of Medicine, Kettering Medical Center, Kettering, Ohio, USA
3
Department of Internal Medicine, Wright State University Boonshoft School of Medicine,
Dayton, Ohio, USA 4
Department of Medicine, Mount Sinai Beth Israel Hospital, New York, New York, USA
5
Institute for Treatment and Services Research, National Development and Research Institute,
New York, NY, USA
Address correspondence to David M. Novick, MD, Digestive Specialists, Inc., 999 Brubaker Drive, Kettering, OH 45429. E-mail: [email protected] Short title: Methadone Medical Maintenance This article has not been published elsewhere and has not been submitted simultaneously elsewhere.
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ACCEPTED MANUSCRIPT ABSTRACT Methadone medical maintenance is the treatment of stable methadone-maintained patients in primary care physicians’ offices under an exemption from federal methadone regulations. Reports from seven such programs in six states show high retention and low frequencies of illicit drug use. Patients and physicians indicate high levels of satisfaction. Although methadone
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maintenance has a long history of safety and efficacy, most methadone medical maintenance programs are no longer operating or accepting new patients. Federal regulations for standard methadone clinics allow some features of methadone medical maintenance, and advocacy for state approval of these changes is strongly recommended.
KEYWORDS. Review, methadone, primary care, opioid, addiction, pharmacotherapy, buprenorphine, heroin.
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ACCEPTED MANUSCRIPT INTRODUCTION Methadone maintenance treatment has been validated as an effective treatment for opioid addiction by more than 50 years of research.1-5 A stable daily dose of methadone reduces or eliminates craving for opioids, prevents opioid withdrawal symptoms, and blocks the euphoric effects of additional opioids. These effects lead to reduced criminal activity, enhanced social
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rehabilitation, prevention of overdose deaths, and decreased likelihood of infectious diseases associated with drug injection. Long-term treatment is needed because of a high risk of relapse to opioid injection if the treatment is withdrawn. 6,7 Methadone is medically safe when given as maintenance treatment for 15 years or longer.8 Methadone is a long-acting opioid that can lead to normalization of physiologic functions which have become deranged during the use of the shortacting opioid, heroin.9-11 The ultimate goal of the treatment of opioid addiction is the participation of the patient in all aspects of society. This article reviews methadone medical maintenance, or medical maintenance, a program designed to meet the needs of people with an exemplary record of participation in methadone maintenance.
ESTABLISHMENT AND RATIONALE OF MEDICAL MAINTENANCE
In medical maintenance, rehabilitated methadone maintenance patients are transferred from a traditional clinic to a medical office for ongoing treatment. Table 1 shows the key
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ACCEPTED MANUSCRIPT features of medical maintenance as it was conceived as a pilot project at The Rockefeller University, New York, NY12 and then transitioned into the initial program based at Beth Israel Medical Center, New York, NY.13-16 This program was exempted from the existing methadone regulations by virtue of an Investigational New Drug (IND) permit from the Food and Drug Administration (FDA).13,14 Other programs and modifications will be described subsequently.
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Medical maintenance is appropriate for patients who have achieved a high level of social and personal adjustment and do not require ongoing counseling. Such patients are generally employed, married, and psychologically stable. They have severed their ties with the street drug culture and do not use alcohol or illicit drugs. The concept of medical maintenance closely mirrors the treatment of chronic diseases such as insulin-dependent diabetes. The methadone clinic, which at the onset of methadone maintenance offered essential services and structure to the patients, has for these patients become an obstacle for their further growth because of numerous regulations meant to monitor non-compliant patients. In the medical maintenance physician’s office, patients receiving methadone are integrated into a medical practice along with other patients being seen for various conditions. The physician may treat the patient’s other medical problems along with the opioid dependence. The patients may be seen up to every 28 days at the discretion of the physician and may receive a solid form of medication for take-home. These decisions are based on individual need and appropriateness rather than on regulations. At the visit, the patient takes the prescribed methadone dose for that day under observation in order to ensure tolerance to that dose. A urine sample is collected, and the patient pays a fee. There was no required counseling.
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ACCEPTED MANUSCRIPT Table 2 shows the main criteria for entry into medical maintenance as originally formulated and as presently permitted under a Federal Advisory of March 30, 200017 and updated Federal Regulations published on January 17, 2001. 18 In the New York program, a minimum of five years in methadone maintenance treatment was required. The five year requirement was set after carefully considering that a typical patient might need two years to resolve the personal and social problems brought about by heroin addiction and then should Downloaded by [University of Exeter] at 12:10 05 August 2015
show at least three years of adherence to the regulations of the methadone clinic. It was thought at the time of the creation of medical maintenance that a cautious approach, with the patients solidly ensconced in a lifestyle that was focused on work, family, or education, would yield better results. In retrospect, the five-year requirement was probably too restrictive; the present federal regulations permit eligibility for medical maintenance after two years of excellent performance in the methadone clinic. 19-21 State regulations may vary and can be more restrictive. Additional enrollment criteria include stable employment or other productive activity and a verifiable means of financial support. The New York program required that there has been no criminal activity, illegal drug use, or excessive alcohol use in the last 3 years. Prospective patients were interviewed and clinic records examined. The applicant was expected to have no ties to street activities and a positive record in methadone treatment: no lost medications, missed visits, behavioral problems, or positive urine tests for drugs of abuse. Participation in medical maintenance was voluntary. The benefits of medical maintenance are substantial (Table 3). 13,14,22 Patient confidentiality is protected, as the patient is not seen entering or leaving a methadone clinic. If
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ACCEPTED MANUSCRIPT the patient travels for business, they do not need to register with and attend a methadone clinic near their destination, a situation that also threatens confidentiality. Patients in medical maintenance are further removed from the drug culture. The 28-day reporting schedule and solid form of medication allow extended vacations or business trips and also the opportunity to accept a promotion or new job in a different location. Many patients found the liquid take-home medication, as required in standard methadone clinics at that time, to be confidentiality risk as it Downloaded by [University of Exeter] at 12:10 05 August 2015
could be found in the refrigerator by others. There was also the risk of accidental spills of liquid methadone. An additional benefit of medical maintenance is development of a trusting relationship with the physician. Other medical problems, whether or not related to the previous heroin addiction, can be treated at the same location. The addition of an advanced level of care with greater privileges makes methadone treatment more appealing to patients and rewards the patients who have made the most of this opportunity. 22 A benefit for society is the opening up of additional treatment slots in methadone clinics as patients are transferred to medical maintenance. This was an urgent need in the 1980s due to the new epidemic of human immunodeficiency virus (HIV) infection among people who inject drugs and is similarly urgent today with the heroin epidemic of the present decade23-26 and the high prevalence of hepatitis C.27,28 Another benefit to society is the increased access to treatment of addiction in primary care settings. RESULTS FROM THE INITIAL PROGRAMS New York
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ACCEPTED MANUSCRIPT Retention in treatment is an important and valid index of the effectiveness of an addiction treatment program. A 1994 report of the first 100 patients admitted to the New York program15 showed very high treatment retention: at one, two, and three years, retention was 98%, 95%, and 85%, respectively. The patients were followed for 3.5-9.25 years, or 42-111 months. The cumulative proportion of patients retained in treatment was 0.735 ± 0.048 at 5 years and 0.562 ±
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0.084 at 9 years. The median retention was 9 years. Only 15 patients were discharged for repeated adverse events.15 Regular or prolonged cocaine use was the factor in eleven.15 Three patients misused medication (took extra doses and ran short, lost medication, or urine negative for methadone), and one patient repeatedly missed appointments. Seven of the 72 patients who remained in good standing had an isolated or minor lost medication incident, and three had transient substance abuse which was successfully managed within the medical maintenance program. Seven patients voluntarily underwent gradual dose reductions of methadone, leading to discontinuation of this medication. Five patients died or were transferred to an extended care facility, and one voluntarily returned to his previous methadone clinic. All of the physicians had their primary training in internal medicine or family practice.13-15 Salsitz et al. published a longer-term follow-up of 158 patients who entered this medical maintenance program from 1983-98.16 Of this group, 132 (83.5%) remained in good standing. There was 58.8% retention at 10 years in treatment and 44.6% at 15 years. Other results were similar to the previous study except that 20 patients (13%) had died, and 15 (75%) of the deaths were related either to tobacco use (8 patients) or infectious complications of drug injection
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ACCEPTED MANUSCRIPT (hepatitis C in four and HIV in three). Overall, 85 of 92 patients (92%) who were tested for hepatitis C antibody were positive, and 77 of 84 (92%) tested for HCV-RNA were positive. Four patients received liver transplants while remaining on methadone,27 and twenty patients had received antiviral therapy for hepatitis C.27, 28 Treatment retention was significantly associated with being married, a longer duration of methadone maintenance, and at least one
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discontinuation of methadone treatment.16 The patients in this program were exceptionally satisfied with their treatment.16 They cited high-quality medical care, enhanced confidentiality, reduced feelings of stigmatization,29,30 freedom to move to a more desirable location, greater employment opportunities, and ability to take vacations, among other benefits. Baltimore The Baltimore program started in October 1985. It was also initiated under an IND from the FDA but was initially limited to 21 patients.31 The study protocol was otherwise similar to the New York program but included a call-back procedure in which patients were told to return to the office in order to be sure that they had the correct number of unused methadone tablets.31 They reported a twelve-year follow-up in which only six (28.6%) of the 21 patients left the program for adverse events. Three of these 6 patients had positive drug tests. One other patient reported spilled methadone, missed an appointment, and abused alcohol, and two others had drug-related arrests. Only 12 (0.5%) of 2290 urine specimens collected over the twelve-year study period were positive for illicit drugs. There was no significant increase in the patients’ methadone doses and no evidence that methadone was being diverted to the community. 31
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ACCEPTED MANUSCRIPT This group has published two additional studies,32,33 in which they randomized patients to medical maintenance in a physician’s office, medical maintenance situated in the clinic, and routine methadone maintenance in the clinic. These studies included random monthly call-backs for medication checks in which patients had to call a dedicated phone line every Monday through Friday to see if they needed to bring their medication in for counting that day. Code numbers rather than patient names were used. Urine screening was done twice per month: at the call-back Downloaded by [University of Exeter] at 12:10 05 August 2015
visit and at the regular 28-day visit. Another innovation was a short-term use of intensified counseling and urine screening for those with positive urines. After four weeks of perfect attendance and negative urines, the patients returned to the group to which they were previously randomized. Patient satisfaction was measured systematically. Counseling was once per month. The investigators studied 92 patients for a twelve month follow-up period.33 The treatment retention rates were high in all groups: 92% for office-based medical maintenance, 79% for clinic-based medical maintenance, and 82% for routine care. Most of the patients who left the study did so because of dislike of the frequency of the call-backs and difficulty managing a 27-day supply of medication. Only 1.3% of the urines collected in the study were positive, whereas 4% of the medication recalls were not successful. Patients in either of the medical maintenance groups were significantly more satisfied with their treatment and significantly more likely to have initiated new vocational or social activities than those in routine care. This group later published favorable results of an effort to disseminate accurate data on medical maintenance to community-based programs.34 Chicago
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ACCEPTED MANUSCRIPT Senay et al. initiated a study in 1988 using significantly different entry criteria.35 Patients needed one or more years of methadone maintenance treatment and no positive urines, arrest, or non-adherence to treatment in the preceding 6 months. All were employed or with other productive use of time in the last 6 months. Patients were randomized to remaining in the clinic or to medical maintenance with medication dispensed every 14 days along with observed methadone ingestion. Urine testing was monthly with three random collections per year. There Downloaded by [University of Exeter] at 12:10 05 August 2015
were also random calls from the clinic nurse to bring in all bottles. One or more counseling sessions per month was required. There were 130 patients who participated in the study. 35 Treatment retention at one year was 73% in both groups. The majority of the discharges from the program were for two consecutive positive urines for illicit drugs rather than for misuse of medication. Urine screening results did not differ significantly between the two groups. The satisfaction of the medical maintenance patients was so high that the Institutional Review Board considered it a hardship for them to return to their previous treatment setting and allowed the patients to remain in medical maintenance.35 Later it became possible to expand the study, and similar results were seen in a preliminary analysis.36
REGULATORY CHANGES From its inception, standard methadone treatment was more highly regulated than any other medical treatment.19-21 The detailed regulations were more focused on adherence to rules and prevention of diversion than on the clinical outcome of the patient. The orientation was
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ACCEPTED MANUSCRIPT toward inspection and enforcement, although there was no regular schedule of oversight visits. Methadone maintenance programs had to be licensed and monitored by the FDA, the Drug Enforcement Administration (DEA), and state agencies. There were regulations concerning methadone dose, the amount of counseling provided, take-home medication, urine testing, and many other details. These regulations, particularly the required clinic visits one or more times weekly, were an obstacle to the progress and well-being of socially rehabilitated methadone Downloaded by [University of Exeter] at 12:10 05 August 2015
maintenance patients. The regulations also had the effect of isolating methadone maintenance treatment from mainstream medicine and limiting the expansion of maintenance treatment to all who needed it. In 2002, it was estimated that two-thirds of opioid-dependent people in the United States were not in any form of addiction treatment. 20 In 2000-2001, significant policy changes in the treatment of opioid addiction were enacted. The changes were partly a result of expert panels convened by the Institute of Medicine37 and the National Institutes of Health,38 both of which validated the efficacy of methadone maintenance treatment and promoted treatment expansion. There was ongoing concern about the spread of HIV and hepatitis C virus infection among people who inject drugs and their contacts. The aforementioned studies and emerging initiatives in New Haven, CT and Seattle, WA, in which medical maintenance was initiated on the basis of a program-wide exemption from the FDA rather than as a research protocol under an IND number, were considered. The new policies were developed to encourage expansion of addiction treatment and to increase the involvement of the medical profession in addiction treatment.19
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ACCEPTED MANUSCRIPT On March 30, 2000, top officials from the FDA and the Center for Substance Abuse Treatment released a joint advisory on medical maintenance. 17 They noted that medical maintenance has been provided ―in physicians’ offices that are affiliated with an opioid treatment program,‖ and they determined that ―medical maintenance treatment should be provided in accordance with the program-wide exemption provisions in the current opioid treatment regulations.‖17 The advisory states that a treatment program may apply to the FDA for an Downloaded by [University of Exeter] at 12:10 05 August 2015
exemption to regulatory requirements in order to provide medical maintenance.17 Subsequently, on January 17, 2001, new federal regulations on opioid agonist medications were published.18-21 Oversight of opioid treatment programs was transferred from the FDA to the Substance Abuse and Mental Health Service Administration (SAMHSA), a division of the Department of Health and Human Services. An accreditation-based system, similar to that for hospitals and other medical facilities, was established, with the focus on treatment outcomes rather than enforcement of regulations. Quality improvement and diversion control programs were required.18 The regulations also allowed some features of medical maintenance to be incorporated into standard methadone clinics: after two years in the program, one monthly visit and a one-month supply of take-home medication was allowed, and a solid form of medication was permitted.18 Yet another policy change was the Drug Addiction Treatment Act of 2000 (PL106310).19-21 This law allows qualified physicians to prescribe approved schedule III-V narcotic medications for maintenance and detoxification outside of established opioid treatment programs. Such prescribing privileges can be obtained through an approved 8 hour course or
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ACCEPTED MANUSCRIPT certification in addiction medicine or psychiatry. The intent was to make opioid addiction treatment available in physicians’ offices. The only drugs approved for use under this law are buprenorphine or buprenorphine-naloxone, in certain formulations (sublingual, but not transdermal or parenteral). Methadone is a schedule II drug and is not covered by this act. STUDIES DONE UNDER THE EXEMPTION PROCESS
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The studies that have been published under exemptions from the methadone regulations are reviewed here. New Haven Fiellin et al. published a randomized, controlled trial of patients in methadone maintenance who had no evidence of use cocaine or of opioids other than methadone for one year or longer.39 Patients were randomized to medical maintenance in the offices of primary care internists (22 patients) or ongoing routine care (24 patients) in their clinic. The medical maintenance patients took a daily dose of methadone in the presence of program staff and received 6 take-home doses of liquid methadone. The physician visits were monthly and consisted of 30-minute counseling and educational sessions. The two groups of patients were similar in most respects. The investigators found no difference in the two groups in illicit drug use or drug use meeting criteria for clinical instability (two consecutive positive urines or urines negative for methadone).39 They did note, however, a high frequency of either self-reported illicit drug use or positive urine tests in both groups, with an overall frequency of 48% (22 of 46). Only 9 of 46
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ACCEPTED MANUSCRIPT (20%) met the criteria for instability. Patients in the medical maintenance group were significantly more satisfied with their treatment than those in the usual care group. The physicians also reported satisfaction with their experience. Seattle These investigators initiated a medical maintenance program as an exemption to Federal
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and State regulations; the exemption process took 14 months.40 They studied 30 patients who had reliable clinic attendance, picked up methadone no more than three times per week, and had no positive urines for the preceding 12 months. A major difference in this model was the role of the pharmacist. A group of pharmacists was responsible for assessing patient stability, observing the ingestion of a dose of methadone, dispensing methadone tablets, and supervising urine collection, including temperature testing. Physician visits were monthly and adjusted as necessary. Random call-backs for medication checks and urine tests were also done. The one-year retention was 93% (28 of 30).40 The other two patients transferred to other programs. Only two patients (7%) had positive urine tests. All random urines were negative, and all medication call-backs showed accurate counts. The rate of patients reporting being very satisfied with their care was high, 26 of 30 (87%). Physician satisfaction was high, and physician attitudes toward treatment of addiction showed significant improvement after 6 months of participation. Bronx, NY
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ACCEPTED MANUSCRIPT A study of medical maintenance from Bronx, NY has been published.41 This program has a much higher percentage of non-white patients (50%) than the other programs described above and is connected with a network of methadone clinics serving a population with a very low income. Eligibility criteria included no illicit drug use for the previous three years, employment or not employed secondary to disability or retirement, and psychiatric stability. Similar to the Seattle program, the pharmacist dispenses a monthly supply and performs clinical and Downloaded by [University of Exeter] at 12:10 05 August 2015
psychosocial assessments. The physician sees the patient monthly, does a medical and mental health assessment, and provides counseling. During the five-year follow-up, two of the 127 patients returned to a standard clinic because of opioid or cocaine abuse, one moved to another state, and nine died41. Only 0.8% of all the urine samples collected revealed opioids other than methadone, and 0.4% of the samples were positive for cocaine; all of these positive urines were from 7 patients41. This program is one of several in New York State which were set up under the guidance of one of the authors (H.J.). Table 4 summarizes the key features of these. New Mexico A 12-month study of 14 women in two cities in New Mexico was reported by Tuchman. 42 The patients had a stable dose of methadone and no evidence of heroin use for the preceding 6 months. Office-based evaluation and treatment was done in primary care offices or in a women’s medical clinic. Methadone was dispensed, and one dose administered under observation, by five community pharmacists using private consultation areas.42 A part-time (20 hours per week) social worker coordinated all aspects of the patients’ care and served as liaison between the
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ACCEPTED MANUSCRIPT patients, physicians, and pharmacists; this position was increased to full-time during the study based on ongoing needs assessment.42 Eleven of the 14 patients (78.6%) remained in the study for 12 months and were exceptionally pleased with their treatment. THE PRESENT SITUATION Taken together, the published studies of medical maintenance from 7 groups in 6 states
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show a high retention rate and low rates of use of illicit drugs. There are excellent results on random call-backs for urine testing and medication counts. There is high patient and physician satisfaction with this form of treatment. Three randomized studies support the use of medical maintenance.32,33,35,39 Medical maintenance can be an important means of expanding the overall addiction treatment capacity to respond to unmet needs. At this time there are major unmet needs. During the last 20 years, there has been an enormous increase in the abuse of prescription opioids, including hydrocodone and oxycodone, in the United States.23-25,43 The number of opioid abusers is estimated to have increased by 225% from 1992-2000.43 Physician prescribing of opioids has dramatically increased in part because of greater emphasis on treating pain maximally and reduced concern about the risks of addiction.43 This epidemic of prescription opioid abuse commonly begins from misuse of a person’s own prescription, introduction to opioids from friends, or easy access to prescriptions of family members.23 Recent efforts at reigning in excessive prescribing practices have led to reduced availability of opioids, and heroin has become an available and less expensive opioid for many.24,25 Several recent studies have shown a sharp increase in heroin use among those who previously abused prescription opioids. SAMHSA has estimated that from 2002-2011, the
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ACCEPTED MANUSCRIPT incidence of heroin use was 19 times higher in previous prescription opioid users, and in 2011, 79.5% of people who initiated heroin use had previously abused prescription opioids.26 The demographics of this new heroin epidemic differ from previous ones, in that the affected individuals are more likely to have used prescription opioids and to be white, female, older, and living in suburban or rural areas.25
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To the best of our knowledge, there have been only two specific publications on medical maintenance since 2006.34,42 Several of the medical maintenance programs have closed because of loss of funding or ascertaining that compliance with the methadone regulations, even under a program-wide exemption, was too time-consuming and impractical in a private practice model. For the latter reason, the New York program13-16 remains under an IND but cannot accept new patients. The Baltimore,31-34 Bronx, New York,41 and the other New York State programs (Table 4) continue to function under a program-wide exemption approved by SAMSHA. Interest has shifted markedly toward office-based treatment with buprenorphinenaloxone.4,44-46 Buprenorphine is a partial opioid agonist with adequate bioavailability when given sublingually. With sublingual administration, it has a long elimination half-life (37 hr),4,45 making it useful as a maintenance medication. Buprenorphine has a ―ceiling‖ or ―plateau‖ effect, meaning that above a certain dose, often 16-24 mg, there will be no additional opioid effects.4,45 Because buprenorphine is a partial agonist at the µ opioid receptor and has a long period of residency at receptor sites, it will displace other opioids already bound to the receptor. Displacement of a stronger opioid by a weaker one will lead to withdrawal symptoms (precipitated withdrawal).45 Maintenance treatment with buprenorphine must therefore be
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ACCEPTED MANUSCRIPT initiated when the patient is in at least mild withdrawal. 44,45 The addition of naloxone has no effect when buprenorphine is given sublingually, but the naloxone temporarily blocks the opioid effects if the drug is injected.4,45 The weaker efficacy of buprenorphine compared with other opioids suggest a reduced risk of overdose, though overdoses can occur. Numerous studies have confirmed the efficacy of buprenorphine-naloxone as a maintenance medication4,46 for both
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prescription opioid47 and heroin addiction.48 Buprenorphine-naloxone is a schedule III drug and is authorized for office-based treatment outside of licensed clinics under the Drug Abuse Treatment Act of 2000.19-21 This law permits physicians to prescribe buprenorphine after taking an 8-hour course on its use. From the physician’s point of view, prescribing buprenorphine-naloxone is relatively easy. In contrast, it took a group of dedicated investigators 14 months to obtain the exemption to use methadone (schedule II) for medical maintenance.40 Perceived advantages of buprenorphine-naloxone over methadone include reduced overdose risk, a more rapid progression to monthly take-home, less regulation generally, and less stigma.49 Overdoses are possible with buprenorphine, however, and diversion has been increasing.50 Similar to methadone, diverted buprenorphine is used as a substitute drug for heroin, for withdrawal symptom prevention, or for self-initiated withdrawal from opioids on the street, rather than a primary drug of abuse. 50 Some stable patients in medical maintenance have successfully transitioned to buprenorphine maintenance.51 In contrast, methadone has been studied for more years1,2 and has more long-term data on medical and physiological effects and long-term safety than does buprenorphine.8,9 Metaanalyses have shown that methadone maintenance has greater treatment retention52,53 than that
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ACCEPTED MANUSCRIPT with buprenorphine, especially when methadone is given in recommended higher doses (80-150 mg/day) which take advantage of methadone’s full agonist effect.54 Methadone maintenance has greater efficacy than buprenorphine-naloxone maintenance for patients with high-dose or longterm opioid use.49 Overdoses with methadone have increased in recent years, associated with a marked increase in prescription of methadone through pharmacies for the treatment of pain. Methadone overdose is often associated with the use of other psychoactive drugs and is Downloaded by [University of Exeter] at 12:10 05 August 2015
particularly likely if methadone is prescribed to opioid-naïve or weakly opioid-tolerant patients in high doses or with too-rapid induction.55-56 Overdoses of heroin or prescription opioids often follow release from abstinence-oriented residential programs when there is no option or availability of opioid maintenance treatment.57 The medical maintenance programs described in this article were the first to provide office-based opioid treatment since the 1920s14 and have set the stage for the dissemination of buprenorphine-naloxone treatment in physicians’ offices rather than licensed clinics. While buprenorphine-naloxone treatment continues to become more widely available as a response to the present epidemic of opioid addiction, medical maintenance has been largely forgotten. Yet, it still can have an important role in expanding overall treatment capacity. This is especially true now because the Affordable Care Act identifies addiction treatment as an essential benefit. 28 In view of the requirement that medical maintenance be formally linked to a licensed methadone treatment program and the need for a program-wide exemption with federal and state approval, it is likely that expansion and further research on medical maintenance will come about only by efforts of physicians associated with a methadone program affiliated with an academic medical center. Since two of the key features of medical maintenance – up to monthly take-home and
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ACCEPTED MANUSCRIPT solid form of methadone – are now permitted in standard clinics by federal regulations, 18-21 a more fruitful approach to improve opioid addiction treatment may be to advocate for more flexibility at the state level in implementing these two reforms. Acknowledgements: We thank Gregory James and Belinda Greenfield of the New York State Office of Alcohol and Substance Abuse Services for help in compiling information on the New
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York State Programs, and Margaret Chappell for the literature searches for this article.
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ACCEPTED MANUSCRIPT REFERENCES 1. Dole VP, Nyswander ME, Kreek MJ. Narcotic blockade. Arch Intern Med 1966; 118: 304-9. 2. Kreek MJ, LaForge KS, Butelman E. Pharmacotherapy of addictions. Nat Rev Drug Discov 2002; 1: 710-26.
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ACCEPTED MANUSCRIPT 18. Substance Abuse and Mental Health Service Administration. Opioid drugs in maintenance and detoxification treatment of opiate addiction. Fed Regist 2001; 66:4076102. 19. Fiellin DA, O’Connor PG. New federal initiatives to enhance the medical treatment of opioid dependence. Ann Intern Med 2002; 137:688-92. 20. Kreek MJ, Vocci FJ. History and current status of opioid maintenance treatments: Downloaded by [University of Exeter] at 12:10 05 August 2015
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ACCEPTED MANUSCRIPT 27. Novick DM, Kreek MJ. Critical issues in the treatment of hepatitis C virus infection in methadone maintenance patients. Addiction 2008; 103:905-18. 28. Paley SJ, Kreek MJ. A window of opportunity: maximizing the effectiveness of new hepatitis C regimens in the United States with the expansion of the Affordable Care Act. Am J Public Health 2015; 105: 457-63.. 29. Olsen Y, Sharfstein JM. Confronting the stigma of opioid use disorder—and its Downloaded by [University of Exeter] at 12:10 05 August 2015
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ACCEPTED MANUSCRIPT 36. Senay EC, Barthwell A, Marks R, Bokos PJ. Medical maintenance: an interim report. J Addict Dis 1994; 13:65-9. 37. Rettig RA, Yarmolinsky A, eds. Federal Regulation of Methadone Treatment. Washington, D.C.: National Academy Press, 1995. 38. NIH Consensus Conference. Effective medical treatment of opiate addiction. JAMA 1998; 280:1936-43. Downloaded by [University of Exeter] at 12:10 05 August 2015
39. Fiellin DA, O’Connor PG, Chawarski M, Pakes JP, Pantalon MV, Schottenfeld RS. Methadone maintenance in primary care: a randomized controlled trial. JAMA 2001; 286: 1724-31. 40. Merrill JO, Jackson TR, Schulman BA, et al. Methadone medical maintenance in primary care: an implementation evaluation. J Gen Intern Med 2005; 20:344-9. 41. Harris KA, Arnsten JH, Joseph H, et al. A 5-year evaluation of a methadone medical maintenance program. J Subst Abuse Treat 2006; 31:433-8. 42. Tuchman E. A model-guided process evaluation: office-based prescribing and pharmacy dispensing of methadone. Eval Program Plann 2008; 31:376-81. 43. Lembke A. Why doctors prescribe opioids to known opioid abusers. N Eng J Med 2012; 367: 1580-1. 44. Kraus ML, Alford DP, Kotz MM, et al. Statement of the American Society of Addiction Medicine Consensus Panel on the use of buprenorphine in office-based treatment of opioid addiction. J Addict Med 2011; 5:254-63. 45. Mauger S, Fraser R, Gill K. Utilizing buprenorphine-naloxone to treat illicit and prescription-opioid dependence. Neuropsychiatr Dis Treat 2014; 10: 587-98.
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ACCEPTED MANUSCRIPT 46. Thomas CP, Fullerton CA, Kim M, et al. Medication-assisted treatment with buprenorphine: assessing the evidence. Psychiatr Serv 2014; 65: 158-170. 47. Weiss RD, Potter JS, Fiellin DA, et al. Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: a 2-phase randomized controlled trial. Arch Gen Psychiatry 2011; 68:1238-46. 48. Kakko J, Svanborg KD, Kreek MJ, Hellig M. 1-year retention and social function after Downloaded by [University of Exeter] at 12:10 05 August 2015
buprenorphine-assisted relapse prevention for heroin dependence in Sweden: a randomised, placebo-controlled trial. Lancet 2003; 361:662-8. 49. Bonhomme J, Shim RS, Gooden R, Tyrus D, Rust G. Opioid addiction and abuse in primary care practice: a comparison of methadone and buprenorphine as treatment options. J Natl Med Assoc 2012; 104:342-50. 50. Cicero TJ, Ellis MS, Surratt HL, Kurtz SP. Factors contributing to the rise in buprenorphine misuse: 2008-2013. Drug Alcohol Depend 2014; 142: 98-104. 51. Salsitz EA, Holden CC, Tross S, Nugent A. Transitioning stable methadone maintenance patients to buprenorphine maintenance. J Addict Med 2010; 4:88-92. 52. Amato L, Davoli M, Perucci CA, Ferri M, Faggiano F, Mattick RP. An overview of systematic reviews of the effectiveness of opiate maintenance therapies: available evidence to inform clinical practice and research. J Subst Abuse Treat 2005; 28:321-9. 53. Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2014; 2:CD002207.
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ACCEPTED MANUSCRIPT 54. Peles E, Schreiber S, Adelson M. Factors predicting retention in treatment: 10-year experience of a methadone maintenance treatment (MMT) in Israel. Drug Alcohol Depend 2006; 82:211-7. 55. Substance Abuse and Mental Health Services Administration. SAMHSA and FDA join to educate the public on the safe use of methadone. April 28, 2009. http://www.samhsa.gov/newsroom/press-announcements/200904280215 Accessed Downloaded by [University of Exeter] at 12:10 05 August 2015
October 22, 2014. 56. Substance Abuse and Mental Health Services Administration. Substance abuse treatment advisory: emerging issues in the use of methadone. Spring 2009. http://store.samhsa.gov/shin/content/SMA09-4368/SMA09-4368.pdf Accessed October 22, 2014. 57. Cherkis J. Dying to be free: There’s a treatment for heroin addiction that actually works. Why aren’t we using it? Huffington Post, January 28, 2015. http://projects.huffingtonpost.com/dying-to-be-free-heroin-treatment. Accessed May 4, 2015.
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ACCEPTED MANUSCRIPT Table 1. Key Features of the Initial Medical Maintenance Program in New York Treatment of stable methadone maintenance patients in physicians’ offices Patients were transferred from standard methadone clinics Urine testing and observed dosing
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Flexible visit and medication take-home, up to 28 days* Solid form of methadone* No required counseling *Changes in Federal Regulations concerning methadone in 2001 permit provision within standard methadone clinics of a up to a one-month take-home medication and a solid form of methadone for patients who are ―responsible in handling opioid drugs.‖18
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ACCEPTED MANUSCRIPT Table 2. Criteria for Entry to Medical Maintenance in the Initial Medical Maintenance Program Five or more years in methadone maintenance treatment* Stable employment or other productive activity Financial support
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No drug or alcohol abuse for 3 years* No criminal activity for 3 years* Adherence to clinic rules and standards Emotionally stable Voluntary *Much shorter intervals have been recommended in subsequent programs.
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ACCEPTED MANUSCRIPT Table 3. Benefits of Medical Maintenance Confidentiality Patients are further removed from the drug subculture Trusting physician-patient relationship
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Ease of travel General medical problems treated at same location Expanded employment activities Stable patients leave the methadone clinic, opening up spaces for new patients Makes methadone treatment more attractive by rewarding progress and allowing the opportunity to earn privileges
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ACCEPTED MANUSCRIPT Table 4. New York State Medical Maintenance Programs Not Included in Other Publications*§ Location
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Albany
Buffalo
East Meadow
Rochester
No. of Patients
29
29
13
12
Site of
Site of
Counseling
Physician’s
Methadone
Office
Dispensing
Primary care
Commercial
center within
pharmacy on
hospital
hospital grounds
Separate area of
Physician’s
Counselor is
methadone clinic
office
assigned
Separate area of
Physician’s
No
methadone clinic
office
Hospital
Physician’s
No
No
office
*All programs followed inclusion criteria per New York State guidelines including a minimum of four years of methadone maintenance treatment and three years with no alcohol or drug abuse or criminal involvement. §One other program had functioned for ten years but closed in 2011. It had used a commercial pharmacy for 10 years uneventfully; but after the pharmacy was sold, the pharmacy lost its authorization to dispense methadone due to concerns about record keeping.
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