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| A Model for Successful Medical Methadone Maintenance Programs |
| Feature Articles - Treatment Strategies or Protocols | ||||||||
| Written by Kenneth A. Harris, Jr., MD, PhD, Julia H. Arnsten, MD, MPH, | ||||||||
| Wednesday, 02 January 2008 | ||||||||
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Methadone maintenance is the most widely accepted and best studied
treatment for opioid dependence (National Consensus Development Panel
1998; Joseph et al. 2000; Ball & Ross 1991). Long-term methadone
treatment has been shown to be more effective than short-term treatment
(Sees et al. 2000) or non-agonist based treatment for opioid dependence
(Mattick et al. 2003), and there is a high rate of relapse to opioid
use when methadone is discontinued (Ball & Ross 1991; Dole &
Joseph 1978; Anglin et al. 1989).
Methadone maintenance treatment reduces morbidity and mortality from opioid addiction, societal costs from crime, and the spread of bloodborne diseases such as HIV infection (National Consensus Development Panel 1998; Barnett & Hui 2000; Novick et al. 1990). Conventional methadone maintenance programs Methadone maintenance has been successfully implemented worldwide in a variety of clinical settings (Simoens et al. 2005). In the United States, however, the benefits of this therapy are achieved within a framework of intense federal and state regulations. To prevent illicit sale of methadone and to ensure that substance abuse counseling is provided along with pharmacotherapy, its availability for the treatment of opioid dependence is restricted to specially licensed methadone maintenance treatment programs (MMTPs). Regulations require new clients to attend MMTPs daily for supervised methadone dosing; take-home doses are permitted only after clients have demonstrated treatment stability and safe methadone handling. Frequent contact with clinic staff facilitates engagement with counseling and vocational services, supporting recovery (Simpson et al. 1995). As patients stabilize in treatment, the intensity of their service needs typically diminishes. Even extremely stable patients, however, are required by federal and state regulations to visit their MMTP much more frequently than is considered necessary for patients receiving care for other chronic medical conditions. For some patients, mandated frequent MMTP attendance may challenge or undermine sustained recovery by jeopardizing employment or social relationships (Murphy & Irwin 1992; Joseph 1995). Contact with less stable MMTP patients or visits to the neighborhood where an MMTP is located can serve as unwelcome reminders of patients’ substance abuse histories. Office-based methadone maintenance: methadone medical maintenance (MMM) To better serve selected patients who have achieved long-term recovery while receiving methadone maintenance, physicians in several states have obtained federal approval to pilot a model of methadone treatment based in a private office setting rather than an MMTP. In the United Kingdom and Australia, this spectrum of opioid agonist treatment intensity across different settings is well established (Strang et al. 2005; Luger et al. 2000; Byrne & Wodak 1996). Initial reports from such office-based initiatives in the United States (known as methadone medical maintenance, MMM) demonstrated their feasibility and effectiveness (DesJarlais et al. 1985; Novick et al. 1988; Senay et al. 1993). Two randomized controlled trials have been published demonstrating comparable outcomes at six months, between the MMM approach and standard methadone maintenance (Fiellin et al. 2001; King et al. 2002). Four additional MMM programs in the U.S. have been evaluated in the literature, including a specialized clinic (Senay et al. 1994), private offices (Schwartz et al. 1999; Salsitz et al. 2000), and a primary care clinic (Merrill et al. 2005). Physicians in these MMM programs either had extensive prior experience with methadone maintenance or received training and had access to more experienced methadone providers. These programs typically served patients who have more social support and economic means than most patients receiving methadone treatment nationally. A fifth successful MMM program that serves a disadvantaged population in the Bronx, N.Y., was recently reviewed (Harris et al. 2006). The Bronx reports the highest poverty rate (27 percent) and the lowest median household income ($26,361) of all New York City boroughs (U. S. Census Bureau 2004). Einstein MMM program In 1998, the Division of Substance Abuse at Albert Einstein College of Medicine (AECOM) received authorization from the U.S. Food and Drug Administration and the New York State Office of Alcohol and Substance Abuse Services to treat opioid dependence in selected patients using the MMM model. The Division of Substance Abuse at AECOM and the affiliated Substance Abuse Treatment Program at Montefiore Medical Center together serve approximately 4,500 patients who receive traditional methadone maintenance treatment at 12 MMTP clinics at six locations throughout the Bronx. Patients in this large MMTP network were the source of referrals to the MMM program. Initial criteria for entry to MMM included: employment; no evidence of opioid, cocaine or illicit benzodiazepine abuse for the preceding three years; and psychiatric stability, as determined by the evaluating physician. Subsequently, patients who were unemployed by virtue of disability or retirement have been allowed to participate in MMM. Eligible patients are identified by system-wide review of urine toxicology data and clinical evaluation by MMTP staff. Substance abuse counselors identify clients who are stable in treatment and who they believe will benefit from the less structured MMM setting. In most cases, the patients referred are working people who have been on methadone maintenance for years and require very little substance abuse counseling or other services. Most view methadone simply as a medication, and the ongoing treatment of their opiate dependence is not a major focus of their lives. The counselor makes referrals by submitting relevant information from a patient’s record to the MMM pharmacist, and the client is then interviewed by a physician, to explain the program and confirm that entrance criteria are met. Client interest and social and psychiatric stability are taken into account when enrolling patients in MMM. AECOM’s network of MMTPs has a central pharmacy. For patients enrolled in our MMM program, the pharmacy distributes monthly supplies of methadone in tablet form to participating patients. The methadone is prescribed by a physician who meets monthly with patients in an office setting adjacent to the central pharmacy. MMM physicians provide substance abuse counseling and review patients’ medical and mental health issues. A clinical note documenting the visit, including any changes in treatment or adverse events, is entered into the chart by the physician at every visit. The MMM clinical pharmacist, integral to the care provided by the program, also assesses patients for clinical and psychosocial stability. The pharmacist is available to program participants on a daily basis, and is able to contact physicians as necessary. The physicians and pharmacist have extensive experience with methadone maintenance therapy, and provide informal counseling and support to help patients maintain recovery and to identify triggers for relapse. Most ongoing treatment for medical and psychiatric comorbidities is provided outside the AECOM system through patients’ traditional health insurance plans. Relapses to substance abuse are addressed with the patient by the MMM physician and pharmacist, who may recommend more intensive treatment, including return to traditional MMTP. Patients pay a monthly rate for MMM, adjusted for their income. Safe handling and storage of methadone are emphasized in the intake interview. Scheduled monthly urine samples are obtained to monitor for illicit substance use and confirm use of methadone, in accordance with federal guidelines. Random urine samples may be taken more frequently, as clinically appropriate. Urine samples are tested for opiates, cocaine, benzodiazepines and methadone. Steps taken to avert diversion include unannounced recalls of methadone to determine that patients are self-dosing properly, and observed administration of a prescribed dose at the office visit to establish continued opioid tolerance. Evaluation of the Einstein MMM In 2004, a retrospective chart review of the Einstein MMM was conducted to gather demographic, drug use and clinical parameters of all patients admitted to the MMM program since its inception in 1998 (Harris et al. 2006). A single reviewer used a standardized chart abstraction instrument to gather data. The MMM medical record of each patient, which included preadmission material from the MMTP from which the patient was referred, was reviewed. We compared demographic characteristics of methadone medical maintenance patients with those of AECOM’s traditional MMTP population, using 2002 data. Patient characteristics From January 1999 to July 2004, 127 patients were enrolled in MMM. Mean duration of MMM enrollment was 2.7 years, for a total of 341 patient years of treatment in MMM. Compared with patients in the traditional MMTPs, MMM patients were older (52 vs. 44 years), and a significantly larger proportion were male (72 vs. 59 percent, p = .004) and Caucasian (50 vs. 17 percent, p < .001). Ninety-two percent were employed on enrollment to MMM, and the remainder were either retired or permanently disabled. Seventy-one percent had at least the equivalent of a high school education. Mean monthly income was $2,700 at enrollment, derived from a wide variety of occupations. Categories of employment roughly corresponded to educational level achieved. Sixty-two percent of MMM participants reported a history of arrest on initial enrollment into methadone treatment, and 75 percent were currently married or partnered. The mean age of first heroin use was 19, and patients had received methadone treatment for an average of 18 years before MMM enrollment. There had been no adjustment in methadone dose since MMM enrollment for 91 patients (72 percent). Average methadone dose across the MMM population, therefore, increased slightly over the course of medical maintenance (from 66 to 72 mg), but remained significantly lower than the average dose of patients in the traditional MMTP system (100mg). Eighty-four percent of MMM patients reported a history of injecting drugs. Injecting was strongly associated with hepatitis C virus (HCV) infection, which was highly prevalent (84 percent). Only 6 percent of MMM participants with known HIV status were HIV positive, compared with a 20 percent HIV prevalence among AECOM’s traditional MMTP population. Fifty-eight percent of MMM participants were regular smokers. Nine patients died while enrolled in MMM. Four deaths were related to HCV; two were due to pulmonary disease; and one patient committed suicide. Exact causes of death of the other two could not be determined, but the patients were known to have multiple medical problems, and to have died from natural causes. Though psychiatrically unstable patients were excluded from MMM participation, 25 percent of MMM patients reported some psychiatric morbidity. In the year preceding chart review, nearly half of these patients were either not receiving mental health treatment, or their source of mental health care was not recorded. Toxicology data and retention in treatment To confirm proper handling and self-dosing of methadone, a single unannounced medication recall was conducted for 28 percent of MMM patients. There were no discrepancies at any of these recalls. Urine toxicology results were analyzed for the three years following MMM enrollment. The results indicate an extremely low level of illicit substance use: 0.8 percent of the aggregate urine samples were positive for non-prescribed opiates, and 0.4 percent were positive for cocaine. Seven patients accounted for all urine samples, suggestive of illicit substance use. Approximately two-thirds of the positive urine samples were derived from a single patient, who relapsed first with cocaine, then with opiates. Another patient developed worsening depression, employment problems and relapse to heroin use. Both of these patients eventually returned to traditional MMTP clinics for more intensive treatment. The other five patients with positive urine toxicology results were counseled by the MMM physician and pharmacist and remained in MMM without further evidence of substance abuse. One patient left the program because of relocation to another state. Only three patients left MMM for any reason other than death, resulting in an overall program retention rate of 98 percent. Einstein MMM compared to other MMM programs We compared the AECOM MMM program with the four other methadone medical maintenance programs that have been evaluated in the peer-reviewed literature (Senay et al. 1994; Salsitz et al. 2000; Schwartz et al. 1999; Merrill et al. 2005) and with two six-month randomized controlled trials of MMM (Fiellin et al. 2001; King et al. 2002). Two programs (in Manhattan (Salsitz et al. 2000) and Chicago (Senay et al. 1994)) enrolled comparable numbers of patients; and two (Manhattan (Salsitz et al. 2000) and Baltimore (Schwartz et al. 1999) were evaluated for periods of greater than one year. A substantially greater proportion of AECOM MMM patients are of minority background, and treatment retention (98 percent) compares favorably with that of other programs. Discussion and conclusions The experience with MMM at Einstein demonstrates that selected patients from a socioeconomically disadvantaged population of persons receiving long-term methadone treatment remained clinically stable, and engaged in treatment in a far less intensive setting than traditional methadone maintenance. Our MMM participants represent a distinct sample with respect to the general MMTP patient population from which they were drawn. MMM participants’ older age likely reflects their greater number of years receiving methadone maintenance treatment. Higher proportions of men and of whites in our MMM sample may be due to the original admission requirement of employment, reflecting socioeconomic forces at play in the Bronx as in all U.S. cities. Alternatively, selection bias by MMTP staff may have contributed to observed demographic differences. Methadone is most effective at relieving craving for opioids when properly dosed, often in the range of 80 to 120 mg daily (Dole & Nyswander 1965; Strain et al. 1999; Faggiano et al. 2003; Donny et al. 2005). It is interesting to note that the mean dose among all patients enrolled for more than six months in the traditional MMTPs was within this range, while the mean dose among MMM patients was significantly lower. Furthermore, methadone dose increased over the course of MMM treatment for 26 percent of participants, suggesting that some patients may not have been optimally dosed prior to MMM entry. It is possible that some patients enrolled in MMM might have been reluctant to report symptoms of craving or withdrawal while enrolled in the traditional MMTP, perhaps wishing to avoid appearing clinically “unstable.” In the MMM setting, patients may have felt more free to acknowledge and discuss such symptoms, resulting in dose increases. Enhanced patient understanding of the relative benefits of proper methadone dosing may have reflected the integral role the clinical pharmacist plays in our MMM program. The relatively low rate of HIV infection among MMM participants may reflect the demonstrated protective effect of methadone maintenance against acquiring HIV infection by needle use (Novick et al. 1990). It is also possible that HIV-infected patients were less likely to meet the original MMM eligibility requirement of employment. The high rate of HCV among MMM participants is consistent with ready transmission of this virus early in the course of injection drug use (Garfein et al. 1996), resulting in injectors being infected with HCV before first entering methadone treatment. MMM programs described in the literature vary considerably with respect to treatment setting, populations served, and duration of observation. All demonstrate alternative models for providing methadone maintenance to opioid dependent persons. The robust treatment retention rate we report after five years of operation suggests that the program we describe successfully meets its patients’ needs. The MMM participants in our program are socioeconomically more diverse than those in reports from other MMM programs. Patients’ income levels and categories of employment suggest that the group is comprised principally of middle and working class persons; only 14 percent had a college or postgraduate education. The stability of this group is perhaps, not surprising given their mean duration of methadone treatment of 18 years. Our program demonstrates that methadone treatment in a low intensity setting can achieve positive outcomes in diverse patient populations. The high degree of success demonstrated here suggests that eligibility and referrals to this MMM program may have been more restrictive than necessary; however, logistical constraints have limited the number of patients that can be accommodated. Our study has several limitations. The retrospective design limits data collection to variables recorded in patients’ clinical records. Inaccuracies and omissions in medical charts are possible. While the low attrition rate suggests a high level of patient satisfaction, we do not have data directly addressing patients’ perceptions of the program. Enrollment criteria were relatively strict, so we could not address whether MMM would be equally effective if offered to a broader sample of patients enrolled in traditional MMTPs. New modes of treatment for opioid dependence In the United States, only a fraction (approximately 20 percent) of opioid dependent individuals receive pharmacotherapy for this chronic condition (Fiellin & O’Connor 2002). Access to methadone maintenance therapy varies greatly by location, with limited availability of treatment slots, resulting in waiting lists in many areas. Providing methadone to selected patients in physicians’ offices and other less regulated settings may be an effective means of expanding access to treatment (Fiellin and O’Connor 2002). Scarce addiction treatment resources could be allocated more effectively were it possible for more stable patients to migrate into less intensive opioid pharmacotherapy treatment settings. Buprenorphine, recently approved for outpatient treatment of opioid dependence, will enhance availability of such treatment options (O’Connor et al. 1996; O’Connor et al. 1998). Some stable patients may successfully transition from methadone to buprenorphine therapy (Whitley et al. 2004); for others, methadone will remain the preferred treatment for their opioid dependence. The two randomized controlled trials to examine MMM (Fiellin et al. 2001; King et al. 2002) drew patients from populations similar to that treated in our program. The favorable outcomes they report complement our findings from a non-research setting, lending additional support to careful expansion of this model to more diverse populations with varying levels of clinical stability. Further research is needed to define long-term outcomes associated with more inclusive eligibility criteria for MMM, and to assess the effectiveness of integrated and stand-alone MMM programs. More widespread adoption of the methadone medical maintenance model for eligible patients in traditional MMTPs is an important strategy for ensuring access to treatment and diminishing stigma for opioid dependent persons. Kenneth Harris, Jr., MD, PhD trained in internal medicine, and is currently the clinic medical director of a methadone maintenance treatment program at Albert Einstein in the Bronx. Julia H. Arnsten, MD, MPH is the chairman of the Division of General Internal Medicine at Montefiore Medical Center in the Bronx. She coordinates and carries out clinical research with a focus on substance abusing populations. Herman Joseph, PhD has over 30 years experience in methadone treatment, and is one of the earliest advocates for office-based opioid addiction treatment. Joe Hecht, RPh, a clinical pharmacist with vast experience in methadone treatment, coordinates the Methadone Medical Maintenance program. Ira Marion, MA, has been the director of the Albert Einstein Division of Substance Abuse for over 30 years. Marc N. Gourevitch, MD, MPh is the chairman of the Division of General Internal Medicine at New York University Medical Center, and former Medical Director at the Einstein Division of Substance Abuse, where he expanded the medical services offered at Einstein’s methadone maintenance clinics, where treatment for hepatitis C infection, as well as primary medical care, is now available. References Anglin, M. D., Speckart, G. R., Booth, M. W., & Ryan, T. M. (1989). Consequences and costs of shutting off methadone. Addictive Behaviors, 14, 307-326. Ball, J., & Ross, A. (1991). The effectiveness of methadone maintenance treatment: Patients, programs, services, and outcomes. New York: Springer-Verlag. Barnett, P. G., & Hui, S. S. (2000). The cost-effectiveness of methadone maintenance. Mount Sinai Journal of Medicine, 67, 365-374. Barnett, P. G., Rodgers, J. H., & Bloch, D. A. (2001). 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JAMA, 280, 1936-1943. Novick, D. M., Pascarelli, E. F., Joseph, H., Salsitz, E. A., Richman, B. L., Des, J., Anderson, M., Dole, V. P., & Nyswander, M. E. (1988). Methadone maintenance patients in general medical practice. A preliminary report. JAMA, 259, 3299-3302. Novick, D. M., Joseph, H., Croxson, T. S., Salsitz, E. A., Wang, G., Richman, B. L., Poretsky, L., Keefe, J. B., & Whimbey, E. (1990). Absence of antibody to human immunodeficiency virus in long-term, socially rehabilitated methadone maintenance patients. Archives of Internal Medicine, 150, 97-99. Novick, D. M., Joseph, H., Salsitz, E. A., Kalin, M. F., Keefe, J. B., Miller, E. L., & Richman, B. L. (1994). 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. Journal of General Internal Medicine, 9, 127-130. O’Connor, P. G., Oliveto, A. H., Shi, J. M., Triffleman, E., Carroll, K. M., Kosten, T. R., & Rounsaville, B. J. (1996). A pilot study of primary-care-based buprenorphine maintenance for heroin dependence. American Journal of Drug and Alcohol Abuse, 22, 523-531. O’Connor, P. G., Oliveto, A. H., Shi, J. M., Triffleman, E. G., Carroll, K. M., Kosten, T. R., Rounsaville, B. J., Pakes, J. A., & Schottenfeld, R. S. (1998). A randomized trial of buprenorphine maintenance for heroin dependence in a primary care clinic for substance users versus a methadone clinic. American Journal of Medicine, 105, 100-105. Salsitz, E. A., Joseph, H., Frank, B., Perez, J., Richman, B. L., Salomon, N., Kalin, M. F., & Novick, D. M. (2000). Methadone medical maintenance (MMM): treating chronic opioid dependence in private medical practice—a summary report (1983-1998). Mount Sinai Journal of Medicine, 67, 388-397. Schwartz, R. P., Brooner, R. K., Montoya, I. D., Currens, M., & Hayes, M. (1999). A 12-year follow-up of a methadone medical maintenance program. American Journal of Addiction, 8, 293-299. Sees, K. L., Delucchi, K. L., Masson, C., Rosen, A., Clark, H. W., Robillard, H., Banys, P., & Hall, S. M. (2000). Methadone maintenance vs 180-day psychosocially enriched detoxification for treatment of opioid dependence: a randomized controlled trial. JAMA, 283, 1303-1310. Senay, E. C., Barthwell, A., Marks, R., Bokos, P., Gillman, D., & White, R. Medical maintenance: a pilot study. (1993). Journal of Addictive Diseases, 12, 59-76. Senay, E. C., Barthwell, A., Marks, R., & Bokos, P. J. (1994). Medical maintenance: an interim report. Journal of Addictive Diseases, 13, 65-69. Simoens, S., Matheson, C., Bond, C., Inkster, K., & Ludbrook, A. (2005). The effectiveness of community maintenance with methadone or buprenorphine for treating opiate dependence. British Journal of General Practice, 55, 139-146. Simpson, D. D., Joe, G. W., Rowan-Szal, G., & Greener, J. (1995). Client engagement and change during drug abuse treatment. Journal of Substance Abuse, 7, 117-134. Strain, E. C., Bigelow, G. E., Liebson, I. A., & Stitzer, M. L. (1999). Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial. JAMA, 281, 1000-1005. Strang, J., Sheridan, J., Hunt, C., Kerr, B., Gerada, C., & Pringle, M. (2005). The prescribing of methadone and other opioids to addicts: national survey of GPs in England and Wales. British Journal of General Practice, 55, 444-451. U. S. Census Bureau, Housing and Household Economics Division, Small Areas Estimates Branch. (2004). Small Area Income & Poverty Estimates. Available at: http://www.census.gov/hhes/www/saipe/county.html. Accessed November 8, 2005. Whitley, S. D., Arnsten, J. H., & Gourevitch, M. N. (2004). Co-locating buprenorphine and methadone maintenance treatment: challenges and opportunities. Abstract, American Association for the Treatment of Opioid Dependence Conference 2004, Orlando, FL, October, 2004.
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