Physicians’ Guide: Opioid Agonist Medical Maintenance Treatment

D R A F T G U I D E L I N E S

All material appearing in this volume except that taken directly from copyrighted Physicians’ Guide: MedicaI Maintenance April 3, 2000 Page II sources is in the public domain and may be reproduced or copied without permission from the Substance Abuse and Mental Health Services Administration’s (SAMHSA) Center for Substance Abuse Treatment (CSAT) or the authors.

Citation of the source is appreciated.

This publication was written under contract number 282-98-0111 with Johnson, Bassin & Shaw, Inc. (JBS). Raymond D. Hylton Jr., M.S.N., served as the CSAT government project officer. Lynne McArthur, M.A., A.M.L.S., served as the JBS project director. JBS personnel included Patricia Kassebaum, M.A., editorial coordinator; Nancy Olins, M.A., senior writer /editor; and freelance writers Margaret K. Brooks, J.D., Paddy S. Cook, Deborah J. Shuman, and Sarah Davidson.

The opinions expressed herein are the views of the Consensus Panel members and do not reflect the official position of CSAT, SAMHSA, or the U.S. Department of Health and Human Services (DHHS). No official support or endorsement of CSAT, SAM HSA, or DHHS for these opinions or for particular instruments or software that may be described in this document is intended or should be inferred.

The guidelines proffered in this document should not be considered as substitutes for individualized patient care or treatment decisions.

The U.S. Government does not endorse or favor any specific commercial product or company. Trade or proprietary names (or company names) appearing in this publication are used only because they are considered essential in the context of the information reported herein.

Contents

Preface

The Medical Maintenance Consensus Panel is pleased to provide physicians and others with this Guide, which introduces and explains opiate agonist medical maintenance for stable, recovered, and socially rehabilitated patients.

This Guide represents the collective views and experience of members of the consensus panel, which was convened by the Center for Substance Abuse Treatment (CSAT) and includes non-Federal clinical researchers, physicians currently providing medical maintenance to patients, program administrators, and patient advocates. The clinical guidelines and recommendations contained in this document are now being made available for review and comment by practitioners in the field. An accompanying document, the Comprehensive Reference Book on Opioid Agonist Medical Maintenance, is also undergoing a wide-ranging field review.

These clinical guidelines are a critical step in supporting the major national policy shift now occurring on the treatment of opiate addiction. The Office of National Drug Control Policy (ONDCP), in its policy paper on opioid agonist treatment, stressed the urgent national need to expand methadone treatment capacity and to enhance the application of clinical standards (Federal Register July 22,1999, page 39851). ONDCP called for these two new directions in the future of methadone treatment:

A standardized accreditation system for opioid agonist treatment programs, with a transfer of regulatory oversight from the Food and Drug Administration (FDA) to the Substance Abuse and Mental Health Services Administration (SAMHSA)

A provision for individual physicians to administer methadone treatment to stabilized, methadone-maintained patients [medical maintenance]

Medical maintenance is a scientifically proven and recommended stage in the continuum of medical treatment for patients with opiate addiction. In this stage of treatment, stabilized and socially responsible methadone patients may elect to reduce the frequency of their clinic visits and to increase their quantities of take-home medication to last for a period of up to I month. This treatment, provided while the patient is under the care of a physician affiliated with an approved opioid treatment program, may occur in the physician’s office-based practice.

Office-based medical maintenance represents a shift from traditional opioid agonist therapy (OAT), which has been segregated from the rest of medical practice since its development in the 1960s by Drs. Vincent Dole and Marie Nyswander. Reforming the current methadone regulatory system has been encouraged for more than a decade, with recommendations for change coming from providers, researchers, blue-ribbon committees and field studies of methadone treatment programs. Reports by the General Accounting Office (1990), the Institute of Medicine (1995), and an NIH Consensus Development Panel (1997) have described and documented the clinical difficulties and public health problems resulting from the segregation of opioid agonist therapy from mainstream medical practice. All these reports have reflected similar conclusions, including; the Federal methadone regulations unnecessarily restrict the practice of medicine, discourage clinical judgment, and fail to focus on outcomes; and (2) clinical practice guidelines should supplement but not replace regulations, and should provide a vehicle by which patient care may be improved.

Following the lead of this impressive medical and scientific consensus, the medical maintenance consensus panel concurs that opioid agonist treatment in the United States should be as similar to the treatment of other biobehavioral disorders or chronic diseases as is possible. The panel has developed these clinical guidelines in a shifting and somewhat uncertain regulatory environment. It is our belief that Federal actions now underway will make it increasingly easy to establish medical maintenance practices. These promising developments include:

The recent availability of program exemptions under current regulations. The FDA has determined that medical maintenance treatment can be provided through program-wide exemptions under the current opioid treatment regulations. It is therefore possible under current regulations – and easier than in the past – to set up a medical maintenance practice.

An extensive CSAT accreditation Impact study. In this project to study the impact and costs of accreditation for the methadone/LAAM treatment system, specific standards have been developed by both the Joint Commission on Accreditation of Health care Organizations (JCAHO) and the Rehabilitation Accreditation Commission (CARF). This new system of accreditation for opioid agonist treatment programs, expected to be fully operational within 2 years, will position methadone maintenance treatment more closely within mainstream health care. Potentially, this new system will expand the availability of treatment within hospitals and health plans of all kinds – entities that are accustomed to meeting accreditation standards.

The Proposed Rule. The proposed Federal regulations would transfer Federal oversight of narcotic treatment programs to SAMHSA and to a monitoring system based on accreditation, with standards involving best practice guidelines and quality of care (Federal Register July 22, 1999). The Proposed Rule includes an option that would authorize the frequency of take-home doses and clinical visits recommended in this Guide for a medical maintenance practice. The consensus panel hopes that this Guide will encourage opioid treatment programs, independent Health care entities of all kinds, and private physicians to consider establishing a medical maintenance practice. These clinical guidelines, based on research findings and experience, will assist physicians to make informed clinical decisions and to treat their opioid-addicted patients with the respect and compassion they deserve.

Andrea G. Barthwell, M.D., Consensus Panel Executive Secretary

Joyce Lowinson, M.D., Consensus Panel Co-Chair

Mark Publicker, M.D., Consensus Panel Co-Chair

About This Consensus Panel Document

This Physicians’ Guide on Opioid Agonist Medical Maintenance Treatment was developed by an expert panel of clinical researchers and practitioners who currently provide medical maintenance to patients, program administrators, and patient advocates. The panel was made up of physicians and other probmionais representing psychiatry, primary care, seminal opioid agonist mmmli, and

current addiction medicine practice.

This Guide reflects the expertise and recommendations of the consensus panel, which developed and honed this document and the companion Reference Book during a series of committee weekday meetings. This Guide, based on the panel’s practical experience, sets forth standards and pincedurn for physicians to use in this new endeavor – the medical maintenance of well-stabilized methadone patients in office-based settings.

Members of the Medical Maintenance Consensus Panel

Executive Secretary: Andrea G. Barthell, M.D.

President

Encounter Medical Group, PC

Oak Park, Illinois

Cochair: Joyce H. Lowinson, M.D.

Adjunct Faculty

Rockefeller University

New York, New York

Cochair

Chairman Emultus:

Mark Pubileker, M.D.

Chief of Addiction Medicine

Kaiser Permanente

Kensington, Maryland

Vincent P. Dole, M.D

Rockefeller University

New York, New York

Steven Harding, M.D., Consultant

Members of the Medical Maintenance Consensus Panel

Office of General Counsel

Tennessee Department of Health

Goodlettsville, Tennessee

Diane Hare, R.N.

Catherine T. Baca, M.D. Nurse Manager

Clinical Supervisor Man Alive Research, Inc.

Center on Alcoholism, Substance Abuse and Addictions (CASAA)

Baltimore, Maryland

Albuquerque, New Mexico

Elizabeth F. Howell, M.D.

Substance Abuse Chief

Georgia Department of Human Resources Division of MHMRSA

Atlanta, Georgia

Elizabeth T. Khuri, M.D.

Director, Adolescent Development Program, Associate Professor.

Clinical Public Health and Pediatrics

New York Presbyterian Hospital

Cornell Weill Medical College

New York, New York

Walter Ling, M.D.

Friends Research Institute

Los Angeles, California

John J. McCarthy, M.D.

Medical Director/Executive Director

Bi-Valley Medical Clinic

Sacramento, California

Bruna Brands, Ph.D.

Clinical Trials Scientist

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Margaret Kent Brooks, J.D.

Consultant

New Perspectives

Montclair, New Jersey

Charles F. Cichon

Chief Compliance Analyst

Maryland Board of Physician Quality Assurance

Baltimore. Maryland

Alice Diorio, President

New England Regional Chapter of the National Alliance of Methadone Advocates

East Dummerston, Vermont

David A. Fiellin, M.D.

Yale University School of Medicine

New Haven, Connecticut

Members of the Medical Maintenance Consensus Panel

Audrey D. Sellers, M.D.

Medical Director

Bay Area Addiction Research and Treatment (BAART)

San Francisco, California

Edward Senay, M.D.

Chester, Indiana

Jose Luis Soria

Aliviane NO-AD, Inc

El Paso, Texas

Susan Storti. R.N.. M.A.

Center for Alcohol and Addiction Studies

Brown University

Providence, Rhode Island

Rick Talley

Director of Drug Treatment

City of Detroit Department of Human Services

Detroit, Michigan

Joseph Merrill, M.D., M.P.H.

Acting Instructor of Medicine

University of Washington

Harborview Medical Center

Seattle, Washington

Nick Vega Puente Chemical Dependency Program Division

Minnesota Department of Human Services

St. Paul, Minnesota

Deidra Roach, M.D.

Department of Health

Addiction Prevention and Recovery Administration

Washington, D.C.

Edwin A. Salsitz. M.D.

Attending Physician

Beth Israel Medical Center

New York, New York

Richard Schottenfeld, M.D.

Professor of Psychiatry

Community Mental Health Center

Yale University School of Medicine

New Haven, Connecticut

Additional Acknowledgments

The consensus panel also acknowledges with gratitude the assistance and advice provided by the attendees who represented various Federal agencies and the Center for Substance Abuse Treatment.

Anne L. Belk

Program Analyst

Drug Enforcement Administration

Arlington, Virginia

James Cooper, M.D.

Associate Director for Medical Affairs

National Institute on Drug Abuse

National Institutes of Health

Bethesda, Maryland

Denise Curry, M.A., J.D.

Chief, Liaison Unit

Office of Diversion Control

Drug Enforcement Administration

Arlington, Virginia

Gretchen Feussner

Drug Enforcement Administration

Arlington, Virginia

Janet M. Gardner

Staff Coordinator

Liaison and Policy Section

Drug Enforcement Administration

Arlington, Virginia

Patricia Good

Drug Enforcement Administration

Office of Diversion Control

Washington, D.C.

John S. Gustafson

Executive Director

National Association of State Alcohol and Drug Abuse Directors

Washington, D.C.

Michael R. Mapes

Deputy Chief

Liaison and Policy Section

Drug Enforcement Administration

Arlington, Virginia

Cynthia McCormick, M.D.

Food and Drug Administration Division of Anesthetic Critical Care and Addiction Drug Products

Rockville, Maryland

Barbara Roberts, Ph.D.

Executive Office of the President

Office of National Drug Control Policy

Washington, D.C.

Center for Substance Abuse Treatment (CSAT)

Office of Pharmacologic and Alternative Therapies

Mike Bacon, II, M.S. Public Health Advisor

Raymond D. Hylton, Jr., M.S.N. Public Health Advisor

Robert Lubran, M.S., M.P.A. Acting Director

Nicholas Reuter, M.P.H. Supervisory Public Health Advisor

Alan Trachtenberg, M.D., M.P.H. Medical Advisor

Introduction

Across the country, a significant number of patients are ready to graduate from the “methadone program’ (now referred to as the opioid treatment program, or OTP) to a less restrictive level of care. This group of patients is stable and requires few, if any, of the comprehensive services provided by OTPs to less stable patients. Moving into medical maintenance – a less intense and restrictive level of care – represents a major step in the rehabilitative process. These medical maintenance patients will also be making treatment slots available for some of the hundreds of thousands of people addicted to opiates who cannot currently enter our overcrowded public treatment system.

Although conventional methadone maintenance has enabled hundreds of thousands of former heroin addicts to re-join mainstream society, medical maintenance is relatively new. Generally, Federal regulations prohibit physicians from ordering or dispensing methadone to treat heroin addiction, unless the physician is affiliated with a methadone program, becomes a “program sponsor” (21 C.F.R., Part 291 .505(a)(7)), or obtains an Investigational New Drug (I ND) permit from the Food and Drug Administration (FDA). Becoming a program sponsor under 21 C.F.R. 291 requires simultaneous applications to the FDA and to the State Methadone Authority (SMA), with FDA’s approval dependent on the State’s approval of the sponsor. A determination is then made by the Drug Enforcement Administration (DEA) that the physician (or program) is in compliance with Federal controlled substances laws and that security measures are adequate to safeguard and prevent theft of the medication.

Overview of Medical Maintenance

Medical maintenance is an approach to office-based opioid therapy (OBOT) that can be implemented under current Federal regulations. It is a stage within the continuum of care for methadone-maintained patients who are stabilized, responsible, and socially rehabilitated. Medical maintenance is the first well-developed office-based model ready for implementation outside the research environment. Other forms of office-based opioid therapy, including other medications, are now being developed in research settings.

Starting in 1983, a series of research studies began to demonstrate the long-term effectiveness of medical maintenance for the treatment of stabilized methadone patients (Novick et al. 1994; Senay et al. 1994a; Schwartz et a!. 1999). The findings from these follow-up studies are remarkably consistent: at least 70 percent of patients admitted to medical maintenance remain for years in this long-term care as heroin-abstinent, productively functioning people without any adverse consequences, such as methadone overdose or diversion. These medical maintenance research programs have operated under an Investigational New Drug (I ND) permit from the (FDA). Because the IND studies have demonstrated such positive findings on the efficacy of medical maintenance, the IND research mechanism is being phased out.

Other options have recently become available for those interested in setting up a medical maintenance practice. The Department of Health and Human Services (DHHS) and the DEA have made it possible for OTP sponsors to apply for exemptions that permit the practice of medical maintenance. (The State agency must also approve these exemptions.) As an example, the FDA recently approved a medical maintenance exemption for a treatment program in Seattle, Washington, in which 20 to 30 clinically stable methadone patients will receive methadone treatment and general medical services from primary care physicians in a medical center. A current DEA exemption in Connecticut is allowing methadone to be stored and dispensed from the offices of private physicians who are treating medical maintenance patients in their offices; these physicians work under contracts with a methadone clinic.

The Medical Maintenance Practice

This document provides guidelines recommended by the expert consensus panel for physicians to use in treating medical maintenance patients In these medical maintenance practices, the patient will be expected to cooperate with the physician in demonstrating compliance with all applicable laws and regulations, as well as in maintaining his or her own mental and physical health. Medical maintenance patients will also be expected to abstain from all illicit drugs and to refrain from

alcohol abuse. Physicians will offer treatment and encouragement for medical maintenance patients to stop smoking, just as they would for any patient who smokes. Medical maintenance physicians will monitor the routine and, in some cases, specific health care needs of their patients, ensuring that these needs are met.

Routine patient visits

The routine medical maintenance visit will be much like a visit for any other chronic disorder. The physician will briefly review the patient’s continued stability, as well as any new issues, with the patient. The physician will conduct urine or blood and other appropriate laboratory tests and evaluate the patient’s medication needs. The medication will be dispensed at the physician’s office, at a nearby pharmacy (the physician may create a partnership in which the pharmacy acts as a dispensing station for the physician), or at a “hub” clinic or medication unit, to comply with

Federal requirements. Concerning prevention of diversion, the medical maintenance physician may require the patient to respond within 24 or 48 hours to a request to present with his or her medication for a count and a laboratory test.

The panel expects about 15 percent of current patients in opioid agonist treatment will be eligible for and desire medical maintenance, as described in this document. This means that, even if clinics leave some slots open for patients who may need to return to the traditional clinic setting, there will be an increase in the number of available clinic slots.

Medical maintenance eligibility standards

Medical maintenance patients are a select group who have made a satisfactory adjustment to methadone maintenance and have been stabilized on methadone for a minimum of I year. “Stabilized” means their dependence on opioids is managed by a steady dose of methadone; regular urinalyses have established that these patients no longer use any illicit drugs; and they have demonstrated the ability and willingness to handle a supply of the medication safely, at home.

In addition, eligible patients must be engaged in socially acceptable and constructive activities, such as working, schooling, full-time volunteer work, or being a stay-at- home parent. Eligible patients may also be disabled. Having qualified for medical maintenance, these patients are indistinguishable from other patients in the physician’s practice.

Experience With Medical Maintenance

Medical maintenance has been or is being currently practiced – and evaluated – in New York City, Chicago, Baltimore, Seattle, and Waterbury, Connecticut. Studies to date on these programs have demonstrated that the large majority of patients in medical maintenance remain stable and that participation in medical maintenance often encourages further healthy development and even

more complete recovery. Medical maintenance patients are expected to disclose any “slip” to their physicians, and experience shows that these stable patients do make such voluntary disclosures to their physicians. With increased monitoring and treatment over a brief period of time, these

patients can often be helped back into full recovery.

The consensus panel’s recommendation of 1 year of stability is consistent with option 2 in the DHHS notice of proposed rule making on narcotic drugs in maintenance and detoxification treatment of narcotic (FederaI Register July 22 1999, page 39809-39857).

Research in medical maintenance originated in 1983 at The Rockefeller University in New York with 25 patients being treated for heroin addiction. Patients in this study had been in methadone maintenance treatment for a minimum of 5 years, were employed, and had no criminal involvement or drug or alcohol abuse for 3 years. Patients were given a month’s supply of methadone at a time. At the end of 6 years, 72 percent of the first 100 patients admitted to the study remained in medical maintenance treatment. Seven percent of patients in good standing elected to taper off methadone. One patient was voluntarily discharged (Novick et al. 1994). Four patients died from causes unrelated to opiate abuse and one patient was transferred to a chronic care facility for treatment of complications of AIDS.

Only 15 percent of the initial 100 patients had unfavorable discharges – 11 for repeatedly using cocaine, 3 for misusing their medication (repeatedly losing it, taking extra doses, or having urines negative for methadone), and one for repeatedly failing to keep scheduled appointments (an administrative violation). Unpublished data through 1998, from the same study still in operation, show that after 16 years experience with 158 patients, the 15 percent unfavorable discharge rate

has remained Constant (personal communication from Dr. Edwin Salsitz).

A similar study was conducted in Chicago of medical maintenance patients who met less restrictive criteria for acceptance than those in the New York study (at least I year in methadone treatment with 6 months or more of good performance). The Chicago patients picked up medication every other week. The Chicago study found that 73 percent of the pilot group (n 87) completed the first year in good standing. Eighty percent of this group (n 75) finished another 3 to 5 years in medical maintenance without major problems (Senay et al. 1994a, 1994b), an outcome similar to that of the New York study.

In a Baltimore study, 21 medical maintenance patients were followed up for 12 years (Schwartz et al. 1999). These patients were evaluated once a month by a primary care physician affiliated with a methadone clinic who collected urine toxicology samples and dispensed the monthly methadone dose. Patients reported on the benefits of the increased freedom for their travel and work, on the enhanced feeling of being trusted by their physician, and on the significant improvement in their quality of life. Of 2,290 urine specimens collected, fewer than 1 percent (0.5 percent) were positive for illicit drugs. Only six patients (28.6 percent) dropped out during the 12 years of the study.

It is these longitudinal studies which have led an array of experts to call for broader adoption of medical maintenance and further consideration of other types of office-based opioid treatment (National Consensus Development Panel on Effective Medical Treatment of Opiate Addiction [NIH 1997]; Institute of Medicine [Rettig and Yarmolinsky 1995]).

Advantages to Patients

Medical maintenance allows stabilized patients to be treated in a physician’s office practice almost exactly as are other patients with chronic illness. Relieved from weekly (or more frequent) visits to the conventional methadone clinic, patients find it easier to meet the demands of their lives – including their work, family, and/or educational pursuits – and to keep their identity as former addicts confidential. They are encouraged to take additional responsibility for their health care and report feeling better about themselves because they are treated as medical patients rather than as drug abusers or criminals. They know that participation in medical maintenance demonstrates respect for their years of excellent performance in treatment and appreciate being rewarded with a

greater degree of trust (Des Jarlais et al. 1985; Novick et al. 1988,1994).

Key Elements of a Medical Maintenance Practice

A physician interested in practicing medical maintenance should find a training course, establish a mentoring relationship with a more experienced practitioner, and implement the required practice protocols.

Training

A short initial educational program about the principles of medical maintenance is an important starting point for the physician. Training programs are about a day in length, with some sites offering weekend, half-day, and/or evening instruction. See Chapter 8 of the Comprehensive Reference Book on Opioid Agonist Medical Maintenance Treatment for a description of training programs.

Mentoring relationships

Once the medical maintenance physician has completed the training program, this physician should form a mentoring relationship with an addiction medicine specialist who has experience providing medical maintenance. An experienced colleague can offer advice and suggestions. For example, a mentor can help a physician who is just setting up a medical maintenance practice to: (1) develop protocols that satisfy regulatory requirements and (2) implement appropriate charting or record-keeping systems that combine accuracy with a sensitivity about confidentiality. A mentoring relationship will also provide a sounding board for the medical maintenance physician, should any problems arise in the practice. Mentors can provide invaluable support by meeting with medical maintenance physicians on a regular basis – either individually or in a group – to review and discuss routine issues and questions.

A strong mentoring relationship is particularly important for the generalist physician, as the mentor can provide guidance from the perspective of many years experience. This can help a generalist trying to determine for example, the appropriate level of care for a potentially relapsing patient. Even physicians who are experienced in treating addiction problems consult their colleagues to discuss problems and to gain other perspectives. If the new medical maintenance

physician cannot find a mentor, such large national organizations as the American Society of Addiction Medicine (ASAM) or the American Academy of Addiction Psychiatry (AAAP) may be helpful in locating one.

Practical requirement.

A practice in medical maintenance requires the physician to find a source of the medication. Because methadone is a Schedule II drug, physicians must make the necessary security arrangements to dispense it in the office or must find a pharmacy or methadone program to order and/or dispense the medication. Medication in solid form offers great advantages and should be

used whenever possible. A urine testing protocol must be established and a reliable laboratory engaged.

Physicians will also need covering physicians or arrangements with a clinic to dispense medication and otherwise cover the practice when they are unavailable. A relationship with a methadone program or another entity that can assume responsibility for a patient’s care provides an essential safety net should the patient develop a problem that cannot be resolved within the context of medical maintenance.

Finally, because patients in medical maintenance have employment and/or other responsibilities, it is important for the physician to maintain an efficient office schedule. Because of the stigma attached to opioid addiction, patients often do not inform their employers about their methadone treatment. Medical maintenance patients therefore need to be seen promptly as scheduled, so they can rely on fitting the required routine visits into their planned working hours.

Chapter 1. Opioid Addiction and Agonist Treatment

The Etiology of Opioid Addiction

For any given individual, it is impossible to determine whether repeated use of opioid drugs begins as a medical disorder (e.g., a genetic predisposition) or whether socioeconomic and psychological factors lead an individual first to try and later to compulsively use opiates. Opioid users often begin by snorting or smoking and then, depending on the local purity, may advance to drug injection. Whatever the mode of administration, ingesting heroin results in a quick rise in receptor occupation in the brain and a rapid onset of effects, often called a “rush.” The drug’s effects last 3 to 5 hours, when the user must seek more drug to prevent withdrawal syndrome and regain the

“rush.” Generally, ever-increasing doses are required to achieve these desired effects. This is pharmacologic tolerance.

An individual is considered addicted to heroin when, despite adverse effects, that person can no longer control his or her use of the drug. This definition holds even if physical dependence is not present. “The essential feature of Substance Dependence is a cluster of cognitive, behavioral, and physiological symptoms indicating that the individual continues use of the substance despite significant substance-related problems” (DSM IV 1994, p.176).

Opioid addiction is characterized by compulsive and repeated self-administration that usually results in tolerance, withdrawal symptoms, and compulsive drug-taking. Use continues and intensifies despite adverse consequences, such as health problems, job loss, ruptured social relationships, and legal troubles. Drug craving continues long after withdrawal is over and is the most powerful factor preventing addicted individuals from ending their heroin dependence permanently. (It should be noted that pain patients treated with opioids may also show tolerance

and withdrawal, but after resolution of the pain, find it relatively easy to withdraw from opioids. Unless such patients already have a history suggestive of drug abuse, they will seldom crave opioids post-withdrawal and will hardly ever go on to seek and use illicit drugs.)

The Development of Methadone Maintenance Treatment

Methadone maintenance treatment grew out of the concern of the medical community (particularly in New York City) about the toll heroin addiction was taking – on addicts and on society as a whole. During the mid- and late-1960s, heroin-related mortality was the leading cause of death in New York City for people between ages 15 and 25; the number of ‘+serum” hepatitis cases was increasing; and drug-related crime was reaching record levels. Dr. Marie E. Nyswander, a psychiatrist who had extensive experience in treating addicted patients at the Public Health Service Hospital in Lexington, KY, in her private practice, and at a storefront clinic in East Harlem, NY, became convinced that addicted patients could be treated within a general medical practice. However, she predicted that many would have to be maintained on opioids indefinitely, as the majority relapsed after detoxification. In 1964, Dr. Vincent Dole, a specialist in metabolism at The Rockefeller University, recruited Dr. Nyswander to join him in his research on addiction.

Drs. Nyswander and Dole hypothesized that heroin addiction is a metabolic disease and that chronic opioid administration brings about changes in the brain. Clinical and laboratory studies have suggested that narcotic hunger, which so often leads to relapse, is symptomatic of a metabolic dysfunction within the endogenous opiate receptor-ligand system that results from repeated rapid administration of opiates. This team foresaw the eventual discovery of opioid receptors; they accurately believed that addicted individuals could be helped by a medication that

would compensate for the long-term neurobiological changes involved in opiate addiction.

The Nyswander-Dole team first experimented with low doses of morphine, but found it unsatisfactory: Patients maintained on morphine were sedated and apathetic from the drug’s narcotizing effects. These patients required ever-increasing doses at more frequent intervals to remain comfortable. And patients remained preoccupied with drugs. Clearly, morphine was not a satisfactory alternative to heroin.

We now more fully understand why this is so. During the past two decades, evidence has accumulated that when a psychoactive drug has a rapid rate of action (i.e., when it quickly occupies, or binds to, the brain sites called receptors for that drug), the user experiences euphoria, finds the drug very attractive, and is more likely to abuse it again. Opiates, which are smoked or taken intravenously, reach the brain and bind to the receptor sites within seconds. Rapid onset is

followed by rapid offset. The intense heroin ‘high” is short-lived; the euphoria dissipates relatively quickly. The amount of the substance decreases over time, and as it is cleared, the individual experiences physical withdrawal and a negative affective state.

It was when the Nyswander-Dole team turned to methadone hydrochloride, a synthetic opioid agonist, that it found success. Taken by mouth, methadone is slowly, but almost completely, absorbed from the gastrointestinal tract. After extensive initial hepatic uptake, the drug is gradually released from hepatic storage in an unchanged form into the effluent blood. The result is a relatively flat curve of methadone blood plasma levels over a 24-hour period, with peak levels (2

to 6 hours) normally less than twice the trough level (Payte and Khuri 1993). Methadone is thus constantly available at the appropriate opiate receptor sites, a critical effect for the normalization of endocrine and neuroendocrine functions that occurs during its long-term administration (Kreek 1991; Zweben and Payte 1990). When methadone is administered daily at a full “blocking” dose, it creates an opioid tolerance that is difficult to overcome with an injection of heroin (i.e., the rate of new receptor occupation is minimal, even if the patient injects a rapidly acting agonist such as heroin). This tolerance also tends to protect the patients from heroin overdose, should they lapse to injection while in treatment. Methadone has six major advantages over heroin and morphine:

Methadone’s track record

Methadone has been used to treat heroin addicts safely for over 30 years. During the early years, there was concern that some uninformed or unscrupulous practitioners might be using methadone to treat patients in inappropriate ways. Both the Federal and State governments stepped in and developed regulations to protect the public health from such ill-advised practices. At the Federal level, the Special Action Office for Drug Abuse Prevention (SAODAP) was created in the early 1970s under the directorship of Dr. Jerome Jaffe. One of SAODAP’s early priorities was to promulgate FDA regulations that would govern the use of methadone for opioid addiction. This office also published monographs that set forth the recommended treatment regimen for methadone maintenance. These efforts were intended to place a greater emphasis on counseling and rehabilitation services, rather than simply dispensing methadone to patients. Currently, there are more than 140,000 patients in opioid agonist treatment programs around the country.

Nevertheless, the controversy that greeted the advent of maintenance treatment has continued to this day. That controversy has spawned literally hundreds of studies of methadone maintenance, Including clinical trials, that have demonstrated its safety and effectiveness (Rettig and Yarmolinsky 1995, p.21). For example, a number of clinical experiments randomly assigned heroin-addicted people who were involved in criminal activity to either methadone maintenance or to non-methadone outpatient treatment. These studies have repeatedly shown that those assigned to methadone maintenance treatment achieve significantly greater and more permanent reduction in drug use and criminal activity and an increase in socially productive activities (such as employment, education, or responsible child rearing). Long-term outcome data show that persons in methadone maintenance treatment earn more than twice as much money annually as those not in treatment (National Consensus Development Panel on Effective Medical Treatment of Opiate Addiction [NIH 1997]). Patients enrolled in long-term methadone treatment are far healthier, their death rate is less than a quarter of the rate among those not enrolled in methadone treatment.

Opioid Agonist Treatment (OAT) Today in the 1990s

LAAM (levo-alpha acetylmethadol) became a very useful addition to the therapeutic armamentarium. While methadone and LAAM represent important breakthroughs in addiction treatment, opioid treatment programs (OTPs) offer patients a great deal more than a steady supply of a legal drug. Giving up heroin addiction requires addressing personality traits, family lifestyles, job skills, friendship patterns, and recreational activities. Opioid treatment programs combine the administration of medication with behavioral therapies, counseling, and other supportive services that address problems like joblessness (Zweben and Payte 1990). It is the opioid agonist medication (methadone or LAAM) that enables patients to stop using heroin (and other opioids). It is counseling and other services that enable patients to repair the damage that their drug use has caused to their health, their families, and their potential for leading productive, stable lives. The risk of relapse continues to diminish over time so long as adequate pharmacologic support is maintained for the opioidergic components of the brain.

Procedures for methadone or LAAM maintenance in clinics

Patients first entering opioid agonist treatment must appear at the clinic daily, or every other day if taking LAMM, to ingest their medication. As patients become stabilized and begin to make positive changes in their lives, they become eligible for medication take-home privileges and a reduced pick-up schedule of up to once a week. Counseling services may also be gradually reduced in accordance with patients’ needs. Adherence to the treatment regimen – including responsible handling of take-home doses and continued abstinence from illegal drug use or alcohol abuse – is carefully monitored by the treating physicians or counselors. Any significant misstep results in the patient’s placement back into an earlier phase of treatment, including more trips to the program for medication and counseling. The medical maintenance physician need not be tied to the take-home privileges and pick-up schedule used by the clinic, once exemptions from the Federal regulations have been obtained.

Therapeutic Considerations

Chapter 2. The Medical Maintenance Practice: General Therapeutic Considerations

Medical care for patients with a history of opioid addiction who are in remission on pharmacotherapy is considered comparable to routine and ongoing care for patients with diabetes, hypertension, or medically treated depression. It involves arranging for dispensing of medication and regular monitoring to ensure that the disease continues to be adequately controlled. Such patients are defined under DSM IV as being in remission on agonist maintenance from their opioid dependence.

Management of Chronic Disease

Like many other chronic diseases, opioid addiction has both physiological and behavioral components that can best be monitored with standardized tools. Specifications for dosing and monitoring medical maintenance patients are elaborated in Chapter 4 of this Guide (see Routine Monitoring and Intervention). As for any chronic disease, all symptoms the patient reports require evaluation. The most important component of medical care for any patient with a chronic disease is a trusting relationship with a physician. The patient must feel comfortable confiding in the physician about anxieties and other problems or symptoms as soon as they develop. The physician must recognize that the patient is doing his or her best to handle a sometimes trying disease and give the person the same consideration and treatment as any other patient who has a chronic disease and special needs related to that condition.

General care of the Patient

In addition to routine care for opioid dependence in remission, patients in medical maintenance therapy need the usual physical examinations and laboratory tests for prevention, early detection, and appropriate treatment of any medical and psychiatric conditions they may develop. The type and frequency of these tests are dictated by the patient’s age, gender, and risk status (e.g., lifestyle history). Prevention, detection, and management of other age- or gender-related medical conditions should follow established standards for the medical profession (e.g., cancer or infectious disease screening). Other sections of this Guide detail the most frequent medical complications of patients with a history of injection drug use (see Managing the Patient’s Medical and Psychiatric Needs in Chapter 4).

The medical maintenance physician will manage some, but probably not all, of the patient’s identified medical or mental health problems. Which problems can be managed by the medical maintenance physician – and which will require referral to a specialist – will depend on the physician’s skills and qualifications. For example, a psychiatrist may treat both diagnosed depression and opioid addiction in a female patient but may refer her elsewhere for routine physical examinations and obstetric care; a family practice physician may provide prenatal care and delivery; and an internist may refer pregnant patients for these aspects of care.

Regulatory Process and Medical Maintenance Models

Opioid agonist treatment (OAT) with methadone or LAAM is subject to State and Federal laws and regulations. The Federal and State regulatory processes have been in place for 30 years. Drug Enforcement Administration (DEA) regulations prohibit any individual physician from prescribing “narcotic drugs for the treatment of narcotic addiction.” Instead, these medications must be dispensed from an approved opioid agonist treatment provider. In practice, this has resulted in few or no individual physicians being approved to order methadone unless they are part of an approved narcotic addiction treatment clinic. Therefore, before treating medical maintenance patients, a physician will need to become a Federal – and State-approved medical maintenance doctor. The Federal and State system now in place is described in other documents, listed below. Assistance is available from both Federal and State agencies to help physicians who seek to meet the regulatory requirements.

The Current Regulatory Process

The Federal rules prescribe a number of patient services and certain record-keeping practices (for a copy of the current FDA and DEA regulations and an explanation of the proposed SAMHSA IFDA rule, see the Appendix of the Comprehensive Reference Book on Opioid Agonist Medical Maintenance Treatment). CSAT has developed a technical assistance publication that describes the current regulatory requirements for obtaining Federal approval to provide opioid agonist treatment. This document is available from the National Clearinghouse for Alcohol and Drug Information (NCADI; phone 1-800-729-6686). The CSAT home page will provide updated information about regulatory requirements. (For CSAT’s website, go to www.samhsa.gov/csat/csat.htm.)

A Federal statute and regulations also protect information about patients in substance abuse treatment, severely restricting communications about patients (42 U.S.C. -1 290dd-2; 42 C.F.R. Part 2). Unlike the usual practice in which doctor- patient privilege applies, providers of opioid agonist treatment are generally prohibited not only from disclosing the names of persons in addiction treatment, but even their presence in such treatment, unless very specific procedures have been followed. The Federal statute and regulations are examined in depth in Chapter 7 of the companion volume in this series, Comprehensive Reference Book on Opioid Agonist Medical Maintenance Treatment, which is available from NCADI.

State requirements vary widely. Some States, such as New Mexico, have chosen to rely entirely on Federal regulations and enforcement. Others, such as California, have chosen to promulgate regulations to supplement the Federal rules. When State and Federal regulations appear to be in conflict, the stricter standard prevails. (Opioid agonist treatment is not available in eight States.) TAP 12 also provides guidance about State regulatory requirements.

Three Program Models

Physicians and institutions seeking approval under current Federal regulations to practice medical maintenance can currently choose among three different models:

1. The Opioid Treatment Program (OTP) hub model
2. The independent agency coordinating hub model
3. The physician as program sponsor model

(See Appendix A for diagrams of these models). In all three models, a federally approved practitioner must apply for an exemption to the FDA regulations to permit the time between patients’ visits to be increased and to permit medication to be dispensed in the more manageable solid form. In all three models, the flow of information between partners must comply with the Federal confidentiality statute and regulations. Finally, approval by the State Methadone Authority is required for all the exemptions needed to practice medical maintenance under these models.

Model 1: The Opioid Treatment Program (OTP) hub

In this model, a physician or a medical group practice adds medical maintenance patients to his or her practice from an OTP that is already operating with Federal approval. In effect, the physician becomes an extension of the existing program – part of a “program without walls” – and an offsite member of the OTP’s medical staff. The OTP would request approval from the FDA for the medical maintenance physician(s) and/or pharmacy to become a satellite or medication unit. Medication would be dispensed by the physician from his or her office, by the OTP itself, or by a medication unit. If the physician is dispensing the medication, the OTP would package, label, and deliver it to the physician, who would store it in a DEA-approved safe. If an independent pharmacy is part of the arrangement, the physician would send medication orders to the pharmacy directly, without using a prescription. In most cases, the ‘hub” in the model will be a conventional methadone clinic.

The clinic hub model will be the simplest to establish under current regulations. In a variation of this model, a larger institution, such as a local public health agency or hospital, would apply to become an OTP. The institutional hub would coordinate a medical maintenance practice consisting of office-based health professionals and pharmacies, networked together, to provide comprehensive health care services for patients. The institutional OTP hub model may offer the advantage of serving greater numbers of patients and providing patients with more comprehensive services than a clinic hub could. A large institutional OTP may also have more latitude in matching patients and physicians and in locating methadone programs able to accept any patient who needs to return to a more intensive level of care.

Model 2: The independent agency coordinating hub

In this second model, the physician would contract with an independent agency that serves as a liaison between one or more conventional methadone clinics and one or more physicians who have agreed to take stabilized patients into their office practices. The independent agency could be any one of a variety of organizations such as a State Methadone Authority, a regional mental health coordinating council, an HMO, or a local public health service. The independent agency would take responsibility for assessing patients’ eligibility for medical maintenance and matching them with interested physicians. It would make arrangements for patients’ medication with a pharmacy or a conventional clinic. The agency would be the intermediary between physicians and the clinics, helping them to resolve any problems or disagreements. The independent agency could also help patients find any other services or care they need.

Model 3: The physician as program sponsor

This third model requires the physician to seek approval to become an OTP directly from the State Methadone Authority and the FDA (as well as to register with the DEA). In this model, the physician could be independent from any clinic. The physician would either dispense medication directly from the office, make an arrangement with an approved OTP for patients to obtain take-home doses from its pharmacy, or file a request for approval of an offsite dispensing station at a participating pharmacy.

The physician hub model has the advantage of facilitating development of close patient-physician relationships. It might be particularly suitable in rural areas far from conventional methadone clinics, where patients currently commute long distances for treatment.

In actual practice, most medical maintenance practices will take elements from one or more of these models or create elements of their own. All are likely to be hybrids, because those who apply to FDA and the State Authority for exemptions and waivers – whether difl ice, independent entities or physlcians – will submit individualized applications for approval. These applications will be tailored to suit the particular mix of existing clinics and practitioners in their area who are interested in serving this group of stable patients and can comply with State regulations.

Proper Regulatory Change

With publication of the proposed rules that would transfer the overnight and monitoring of opioid agonist treatment (OAT) from the FDA to SAMHSA, the current Federal regulatory process may change. The CSAT homepage will be continuously updated to ensure that physicians have the information they need. Information about the State Methadone Authorities and State agency directors will be maintained in the CSAT homepage.

Since medical, pharmacy, and nursing practice are entirely regulated by the States, physicians setting out to practice medical maintenance must ensure that their treatment protocols comply with State statutes and regulations as well. State statutes governing the specific responsibilities of physicians, nurses, mid-level providers, pharmacists, and other categories of health professionals

vary in what they mandate, permit, and prohibit.

Confidentiality

The Federal confidentiality rules and regulations, as well as the specific relationship between the physician and the “hub,” will affect how the medical maintenance physician communicates with the referring methadone maintenance program and others, as well as how records are kept.

Communications with consent

When the medical maintenance physician receives the patient’s record from the methadone program, it may contain a detailed consent form that the patient has signed and a notice that re-disclosure is prohibited. This consent form (see Exhibit 28 A) is almost always required when a methadone clinic communicates with anyone about a specific patient. Medical maintenance physicians should familiarize themselves with the form (which is discussed at length in Chapter 7 of the Comprehensive Reference Book on Opioid Agonist Medical Maintenance Treatment) and – into the habit of using it whenever communicating information that reveals the fact that the patient is in medical maintenance treatment. Any time information is released pursuant to the patient’s written consent, it should be accompanied by a “Notion or Prohibition on Re-disclosure of Information” (see – N Exhibit B).

Exhibit A. Consent for the Release of Confidential Information

(Name of patient)

(Generic Form)

authorize (Name of medico maintenance physician) to disclose to (Name of person or organization to which disclosure is to be made) the following information:

(Nature of the information, as limited as possible)

The purpose of the disclosure authorized herein is to: (Purpose of disclosure, as specific as possible)

I understand that my records are protected under the Federal regulations and cannot be disclosed without my written consent unless otherwise provided for in the regulations. I also understand that I may revoke this consent at any time except to the extent that action has been taken in reliance on it and that in any event this consent expires automatically when Dr [name of medical maintenance physician no longer is providing me with medical maintenance

Dated:

(Signature of participant)

Exhibit B. Confidentiality Notice Prohibiting Redisclosure

The following notice prohibiting redisclosure of patient information (reprinted from the confidentiality regulations) must be provided to recipients of confidential information.

This information has been disclosed to you from the records protected by Federal confidentiality rules (42 C.F.R. Part 2). The Federal rules prohibit you from making any further disclosure of this information unless further disclosure is expressly permitted by the written consent of the person to whom it pertains or as otherwise permitted by 42 C.F.R. Part 2. A general authorization for the release of medical or other information is NOT sufficient for this purpose. The Federal rules restrict any use of this information to criminally investigate or prosecute any alcohol or drug abuse patient. Relationships with a clinic and any mentors can be structured so that consent is not

routinely required (see Chapter 7 in the Comprehensive Reference Book on Opioid Agonist Medical Maintenance Treatment). Communications to other individuals and entities that are made without the patient’s consent and disclose that the patient is in treatment for an addiction must fit within one of the narrow circumstances permitted by the regulations (see Chapter 7 of the Comprehensive Reference Book on Opioid Agonist Medical Maintenance Treatment),

Record-keeping

A central challenge for physicians providing medical maintenance will be to develop a charting or record-keeping system that combines accuracy and clinical utility with adequate sensitivity about confidentiality. Records must be accurate so that physicians can consult them at later visits to refresh their memories about patients’ histories and the results of physical examinations and tests. Physicians also must rely on colleagues to assume care for patients when they are unavailable; accurate and complete information in those circumstances is critical. Finally, physicians have an interest in documenting the services they provide to protect themselves should their care be challenged – by the patient, a third-party payer, or the State.

Accuracy is not, however, the only value to be weighed. Physicians must also consider the special protection that any patient’s drug treatment records have under the Federal regulations, protection that other medical records do not enjoy. For example, the Federal rules require that providers keep written records about substance use disorder treatment, including methadone treatment, in a secure room, a locked file cabinet, a safe, or other similar container (42 C.F.R. 1 (2.16). A detailed discussion of this issue can be found in Chapter 7 of the Comprehensive Reference Book on Opioid Agonist Medical Maintenance Treatment. Briefly, there are two ways a physician can ensure the safety of medical records:

The physician can separate from patients’ records all data regarding addiction treatment and keep it in a locked cabinet or other similarly secure area.

The physician can put the complete records of patients in addiction treatment in a locked cabinet or other similarly secure area.

In either case, the physician should appoint a “gatekeeper familiar with the record-keeping system and the reasons for the extra security to be responsible for deciding when others – within or outside of the office – will have access to medical maintenance-related information. Whether or not stored separately from the rest of the medical chart, information about a patient’s addiction or treatment may not be sent with the rest of the person’s medical information in response to a routine consent for release, unless accompanied by a request meeting all of the Federal requirements. Medical maintenance physicians should keep this in mind when responding to such requests from life insurance companies or others who may mistakenly think that a routine consent form entitles them to all of the medical information in the possession of the physician.

Opioid Agonist Medical Maintenance Practice: The First Visit

Preparation

Before the first appointment, the physician can gather a good deal of information about the patient from the referring clinic as well as directly from the patient.

Clinic records

Before the initial visit, the physician should obtain and review the patient’s records from the transferring methadone clinic. Those records should include the following information:

Information from the patient

Much of the information the physician will need to gather from a medical maintenance patient is identical to information gathered from any new patient (e.g. contact information, medical history, recent surgeries). In addition, the physician will want to know:

Some medical maintenance physicians believe it Is more efficient and effective to have patients fill out a medical and biographical form before the Initial visit. These physicians believe that this way of gathering Information enables them to focus on key Issues during the initial appointment. Physicians wishing to follow this practice will find a sample patient information form as Exhibit C. Other medical maintenance physicians believe it is batter to ask the patient questions about his or her medical history and life experiences during the initial visit. They believe that engaging the patient face-to-face offers a better way to begin a good doctor/patient relationship and has the added benefit of allowing patients to ask follow-up questions when appropriate. Exhibit D contains a list of sample questions which experienced medical maintenance physicians ask during their first appointment with patients.

Information for the -patient

Physicians may find it useful to send information about their practice to new patients prior to an initial appointment. The physician’s OSYIW. The patient should receive a card with:

Exhibit C. Sample Patient Information Form

Biographical Information

Vocational information

Medical Information

Addiction and Treatment History

Exhibit D. Sample Questions for Initial Patient Visit

Information About the Patient

The physician’s expectations. The physician will provide the patient with an explanation of his or her rules and expectations, including the following:

The patient’s expectations. In any pre-visit mailing to the patient, the physician should also include a list of what the patient can expect, including the following:

The Initial Appointment

Since a good physician-patient relationship is critical to the success of medical maintenance, the physician should use the first visit to begin establishing a foundation of trust with the patient. For the most part, this calls for doing what a physician normally does during the first visit of any patient: gather information from the patient, examine the patient, and answer the patient’s questions.

Establishing a relationship

In monitoring the medical maintenance patient, a good relationship requires that the physician balance trust in the patient with an alert concern for potential problems. Experienced practitioners believe that stable methadone patients should not be scrutinized for potential relapse so closely that a trusting physician-patient relationship becomes impossible. This is especially true for medical maintenance patients, who have met stringent acceptance criteria and are likely to continue to do well. The medical maintenance patient is no more likely than any other patient with a chronic disease to minimize – or exaggerate – symptoms. Responding with distrust to a patient’s report of difficulty will undermine the patient’s confidence in the physician-patient relationship. To retain patients’ trust and respect, the physician must be open, understanding, and willing to listen to and help patients, especially when they are struggling.

If the physician has the patient’s clinical records and the patient’s self-reported medical/biographical information, during the first visit the doctor and the patient can focus on:

Areas that appear to need attention

A discussion of office procedures, rules, and expectations

Any questions the patient has

The physician should insist on complete candor about other therapies and medications that the patient is taking. Full disclosure is necessary so that the physician will be able to anticipate any medication interactions and pain management issues, as well as coordinate care with physicians treating co-occurring disorders. In addition, the physician should review medication storage arrangements with the patient and document that review in the patient’s record.

Experienced practitioners recommend asking the patient whether his or her spouse or significant other knows about the treatment and, if so, what that person’s views are about medical maintenance. Because of the stigma that attaches to addiction, patients often do not share information about their treatment with others in their lives, including significant others, physicians, and employers.

If the patient and the significant other are willing, a subsequent meeting with the physician is advisable. The patient’s partner can provide useful and corroborating information about the patient’s background and current status, be briefed about the physician’s expectations and routine requirements, and discuss his or her attitudes about ongoing methadone maintenance. If significant people in the patient’s life, such as the employer, do not know about the patient’s methadone treatment, the physician must take care not to violate the patient’s confidentiality. For example, any telephone messages left at the patient’s workplace should not -led the fact that they come from a doctor’s office.

Examining the patient

As with other new patients, the physician’s initial physical examination should be targeted or comprehensive, based on the patient’s medical history and the medical records forwarded by, in this case, the methadone clinic. The medical maintenance physician may also order laboratory tests. Close examination of liver enzymes is often indicated. if the patient has not been tested previously for HIV and Hepatitis C, then such counseling end testing should be offered.

Orienting Patient to Treatment

During the Initial visit, the medical maintenance physician should counsel the patient on the risks and benefits of opioid agonist maintenance therapy and obtain a consent to treatment.

Obtaining Consent to Disclosure of Information

As noted above, Federal rules prohibit the disclosure of information about a patient in methadone treatment unless the patient has signed a special consent form (see Exhibit A), or the situation fits within another of the narrow exceptions to the rules.

Early In treatment – preferably during the first visit, the physician should obtain permission (a signed consent that complies with 42 C.F.R. Part 2) from the patient to communicate with:

The referring methadone clinic

The patient’s other treating doctors and dentists, as needed includng physician(s)

Any mentors the medical maintenance physician may consult

Sample consent forms for a variety of situations are shown In the Comprehensive Reference Book on Opioid Agonist Medical Maintenance Treatment (see Appendix 34 H). – Although some of these relationships can be structured in a way that obviates the consent requirement, the physician should use the initial appointment to review the persons or organizations with whom the physician will be communicating. The physician should obtain written consent from the patient for those that require consent.

Creating a medical maintenance patient record. Unless the patient has already been seeing the physician for other health problems, admission procedures should also include opening a new medical record. The record will document the results of the initial interview, physical examination, urine toxicology studies, and any ordered laboratory tests. At a minimum, the new medical maintenance record should contain the following:

Post-visit Review

After the initial appointment, the physician should decide what immunizations, laboratory tests, other evaluations, or dosage changes the patient needs in the immediate future. If the originating clinic has conducted thorough annual reviews and documented the treatment plans and progress, the patient may need only routine monitoring and care in the near future. Many new medical maintenance patients, however, will need some immediate laboratory tests, as dictated by the findings of their admission examinations.

Chapter 4. Routine Monitoring and Intervention

In all likelihood, care of the medical maintenance patient will be limited to routine evaluation and monitoring of the patient’s continuing stability. Routine monitoring also calls for supporting and encouraging the patient’s continued stability, identifying potential problems, and intervening to resolve them.

Monitoring the Patient. Routine monitoring will include observing the patient’s affect, inquiring about the patient’s satisfaction with the current regimen, and asking the patient about any new medical, psychological, or stress-related symptoms.

Observing. During routine office visits, the physician should observe the medical maintenance patient for signs of continuing stability in those areas outlined in Exhibit E.

Inquiring and communicating. The physician should regularly ask whether the patient is experiencing problems related (or attributed) to the current medication dose, and how many doses, if any, the patient has in reserve. The patient’s reported count of medication doses should match the physician’s record. The physician should explore any deviation from expectations or established norms reported by the patient and ascertain the reasons for the variances. When needed, the physician will collect a urine specimen for testing. (For more information on urine testing. see ‘Drug Testing” later in this chapter – and also Appendix B.) At each visit, the physician should also ask whether the patient is experiencing any worrisome physical or emotional symptoms, whether the patient has any new medical complaints or has begun treatment for any new problems, and whether the patient feels under greater stress than usual. There should be specific as well as open-ended questions to encourage the patient to discuss anything he or she finds troubling. If the previous urine toxicology results are negative for methadone or positive for unapproved substances, this too should be discussed, if it has not already been resolved. (See Chapter 6, Managing Threats to Stability, for a discussion of this issue.)

Exhibit E. Check-oft List for Routine Visits

Routine Monitoring for Continued Stability

Behaviors

Observations

On time for appointments

Complied with previous random callback

Payment prompt

Number of doses in reserve

Inquiries

Employment

Family/friends

Social activities

Special issues

Well-Being

Affect normal?

dose holding?

Complaints about side effects?

Any new physical complaints, problems, or treatment?

Any new medication (s) begun-prescription or OTC?

Urine specimen collected

Physical welI-being

Affect unchanged?

Self-report

Emotional

Notes:

Adjusting the Patient’s Dose

The optimum dose for methadone stabilization varies widely among patients. The traditional recommended methadone doses are 50 to 100 mg per day. However, some patients can be stabilized at 15 mg, while others will be stable at 200 mg. As with methadone, the optimum maintenance dose for stabilized patients on LAAM also varies significantly among patients. Most stable patients will maintain the desired effect on equal doses of LAMM (ranging from 60 to 140 mg per dose) taken once every 48 hours (CSAT 1995a, pages 19-22). Some patients can be stabilized at less than 60 mg. Doses exceeding 140 mg must be justified in the medical record (CSAT 1995a, page 19).

For any medication to be effective, a patient must be getting an adequate dose. For patients on opioid agonist treatment, a medication dose should accomplish the following five objectives (CSAT 1998; Kauffman and Woody [CSAT 1995b]; Rettig and Yarmclinsky 1995):

Adjustments up or down

Although the referring clinic should have carefully adjusted the patient’s dose for optimal stability of the receptor sites, the dose may not be — or remain — optimal. Some experienced medical maintenance physicians find that it is not unusual for his new patients to need a higher therapeutic dose than was provided by the referring clinic. There are a number of reasons for this;

The optimal methadone dose for an individual may change over time; variations in dosage are a normal part of treatment and are not necessarily a sign of treatment failure or an indication of patient instability.

While LAAM is not currently available for “take home” doses, the SAMHSA-CSAT proposed regulations would remove this restriction and make LAAM an appropriate medication for medical maintenance.

Temporary or permanent changes in the patient’s physical or emotional status may have an impact on the necessary dosage.

Some clinics have a bias in favor of a particularly low dose and put most of their patients on that dose, even if it is not optimal for them.

Patients, family, and even other health professionals may place a false value on a particular dose number or range.

Patients who need an increased dose are often reluctant to request an increase because some clinics require more frequent appointments when a dose is raised.

The physician should regularly review the patient’s satisfaction with the current dose regimen and discuss whether an adjustment is necessary. A patient’s request for dose adjustments, either increases or decreases, should be fully and thoroughly explored in an atmosphere of mutual trust to determine what critical events in the patient’s life may be contributing to the desire for a dose change. Decisions should be based on clinical observations; laboratory findings, when these are

available; and documented discussions with the patient that take into account subjective feelings as well as objective signs.

Factors that may contribute to a request for a higher dose include the following:

Factors that might contribute to requests for a decreased methadone dosage include:

If both the patient and the physician agree that a dose change is indicated, they must decide when to initiate it. If the patient’s medication comes in solid form, the change can begin immediately, yet another reason why solid medication is preferable in medical maintenance. Some patients who receive liquid medication will be willing to wait until the next appointment so that the physician can make necessary arrangements for the medication. Others will want the change to be effective immediately. To the extent possible, the physician should accommodate the patient’s wishes and if that is not possible, explain why any delay is necessary. A new appointment, sooner than the usual interval, should be scheduled for initiating the new dosage.

In general, daily doses should be increased or decreased by no more than 10 to 20 percent at a time. The patient may feel some sedation immediately after an increase in dosage, but tolerance occurs within a few days (Zweben and Payte 1990). Changes should not be made at intervals that are closer together than days, or 5.5 times the half-life of methadone. Both the patient’s report of the effects of the new dosage and any observed symptoms should be noted before the dosage is changed again. Medical maintenance physicians should always be aware that a dose reduction might precipitate withdrawal symptoms or craving and should discuss this possibility with the patient before initiating the decrease.

Tapering therapeutic withdrawal

Therapeutic withdrawal is not an objective of medical maintenance and patients whose initial goal is withdrawal from methadone should generally be handled in the clinic setting. However, over time, some medical maintenance patients may want to try to taper off methadone. The physician and patient should discuss the reasons underlying the desire to taper off. If the patient is determined, the physician should respect the decision. A patient who does not get medical support for an attempt to taper off may try uncontrolled withdrawal on his or her own, making problems even more likely. The physician should get the patient’s agreement to an open-ended timetable. A medical maintenance physician whose patient is about to undertake therapeutic withdrawal should discuss the situation with more experienced colleagues. Therapeutic withdrawal is a transition period, and may require additional therapeutic intervention and services. For a detailed discussion of this issue, see Chapter 4 of the Comprehensive Reference Book on Opioid Agonist Medical Maintenance Treatment.

Drug Testing

Since 1972, the FDA methadone regulations have required that urine specimens be periodically collected and tested for the presence of designated drugs; namely, for opiates, methadone, amphetamines, cocaine, and barbiturates. In addition, if a program has determined that any other rug or drugs are being abused in that particular locality, the FDA requires that each test should screen for these local drugs of abuse as well. The consensus panel recommends that patients also be screened for sedatives/hypnotics. The current Federal regulations require monthly testing. Testing is considered “random” if patients are tested without previous notice on any eight of their visits and know that they are also subject to callback at any time. The CSAT homepage (www.samhsa.gov/CSAT) will list updated drug testing guidelines for various medical situations. (Note that these differ from the rules for drug screening in the workplace.) The physician should also check with the State Methadone Authority about any State requirements regarding testing.

Frequency

Experienced practitioners agree that frequency of urine testing should be based on the physician’s knowledge of the patient. Random callbacks for urine testing (and medication checks) are necessary only when the physician has reason to suspect that the patient is diverting methadone or using illicit drugs.

Medical maintenance physicians should also be familiar with:

Test results that indicate a potential problem. In a medical maintenance practice, a problematic urine test result is never an occasion for punishing a patient who is experiencing problems. it is crucial for medical maintenance physicians to avoid relying solely on urine test results to determine whether a patient is using illicit or unapproved substances and is in danger of relapse. Understanding this principle is key to running a successful medical maintenance practice. All urine results that are positive for opioids (e.g., morphine, codeine, Dilaudid, oxycodone) or other illicit or non-prescribed substances, or are negative for methadone, should be discussed with the patient immediately. If, when presented with an abnormal test result, a patient asserts that he or she has missed no methadone doses and taken no illicit drugs, the physician should take the statement seriously. Listen to the patient in order to surface other explanations. For example, take a careful history of the patient’s recent use of any prescribed drugs or over-the-counter (OTC) preparations. The physician can discuss the results of this history with the laboratory pathologist or chemist, as well as with mentoring colleagues, to determine whether other substances that the patient reported taking might have caused a positive screen or confounded the results. The remaining portion of the initial specimen, if it has been properly saved, can be retested or the initial finding confirmed by collecting another specimen or series of specimens and ordering future screens with confirmatory testing (Manno 1986b; Marion 1993, p.62). Both the test results and any response by the patient should be documented in the clinical record. (For more detailed discussion of this issue, see “Dealing With Questionable Urine Toxicology Results” in Chapter 6.) CSAT will maintain updated guidelines for urine testing in addiction treatment on the OPAT section of its homepage.

Managing the Patient’s Medical and Psychiatric Needs. Medical maintenance patients will be no more vulnerable to acute disease than other patients but, because of their prior intravenous drug use, are more likely to suffer from certain chronic conditions.

Co-occurring physical disorders. New medical maintenance patients should be screened for hepatitis B and C, for tuberculosis, and for the Human lmmmunodeficiency Virus (H IV), if they have not recently been screened. The physician should consider not only what is mandated or 28 recommended, but also the patient’s social, family, and medical history. Smoking should be routinely considered a risk, as tobacco use is common in this population and death rates from tobacco-related causes are particularly high. Every effort should be made to help patients stop smoking, including advice and counsel from the physician, medically approved approaches, and referral to community resources.

Co-occurring psychiatric disorders. The most frequently encountered psychiatric diagnoses among persons with opioid dependence are mood disorders (depression and bipolar disorder), anxiety disorders, antisocial personality disorder, posttraumatic stress disorder, and schizophrenia. Any persistent and severe psychiatric problem is likely to have been identified and stabilized during earlier phases of opioid agonist treatment, and the medical maintenance selection process will have screened out patients whose psychiatric condition is unstable. Nonetheless, episodes of depression or anxiety may occur or recur while the patient is receiving medical maintenance, and these require identification and treatment as they would for any other patient.

Appropriate pharmacotherapy and psychotherapy for treatment of psychiatric disorders can be ongoing or initiated while the patient is receiving medical maintenance. More specific information regarding management of psychiatric disorders in this population can be found in the following documents produced by CSAT and available through the National Clearinghouse for Alcohol and Drug Information (NCADI) (1-800-729-6686):

These TIPs can be downloaded from http://www.treatment.org; click on CSAT TIPs under documents. They can also be searched online through the National Library of Medicine’s HSTA website; this site can be accessed from http://www.samhsa.gov/csat/csat.htm.

Annual Review

Once a year, the physician and patient should set aside time for a more thorough appointment to discuss the efficacy of the treatment, the patient’s satisfaction with medical maintenance, and the risks and benefits of continuing treatment.

Chapter 5. Common Clinical Management Strategies

In the course of the physician’s routine monitoring of a medical maintenance patient, situations may arise that require dose adjustments, rescheduled appointments, or intervention by the physician. These situations do not necessarily indicate instability. Rather, they involve situations that arise in the lives of almost everyone; these situations require the physician’s attention because methadone is a Schedule II drug.

Five such situations are discussed here:

This chapter outlines strategies for managing each of these situations through dose adjustments, rescheduled appointments, or advocacy for the patient.

When a Patient Is Unable to Come to the Office

Inclement weather and other unforeseen circumstances. Because the patient relies on an uninterrupted supply of medication, the physician should, as a common practice, order or dispense several extra days’ worth of medication to be held in reserve by the patient. In other words, if the patient is due back in the physician’s office in 2 weeks, the physician should order or dispense 15 to 18 days’ worth of medication. This practice provides a ‘safety net,” should the weather or an emergency preclude keeping a scheduled appointment or picking up medication on a given day. Usually, the “safety net” will prove unnecessary, and the patient will take the reserve doses before starting on the medication dispensed or ordered at the rescheduled visit. (Some medical maintenance physicians ask patients to bring reserved doses to the office at each visit.)

Travel. Patients’ freedom to travel is an important advantage of medical maintenance. With a larger supply of take-home medication (and less frequent visits to the office), the patient may be able to arrange his or her travel around the periodic appointments. On occasion, however, the patient may ask to change a regular appointment or add a visit, and the physician should arrange the appointments to accommodate the patient’s travel. If a patient’s travel is unplanned or arises from an emergency and the patient does not have sufficient take-home doses available, the physician should accommodate the patient by communicating with an opioid agonist treatment program at the patient’s destination(s) to arrange for medication pick-up. Physicians can find the names and contact information about methadone providers as follows:

Through the State Methadone Authority (SMA) in each State or at http://www.samhsa.gov/csat/opat/optreatment.htm; pull up Listing of State Methadone Authorities

At the time of this writing, methadone maintenance treatment is unavailable in Idaho, Mississippi, Montana, New Hampshire, North Dakota, South Dakota, Vermont, and West Virginia.

For methadone patients interested in foreign travel, a useful information source is the Worldwide Travel Guide for Methadone Patients (INDRO) on the SAMHSA website listed above; pull up Worldwide Travel Guide. This guide supplies information on the import regulations for methadone in foreign countries and on the possibilities of maintaining treatment abroad.

Pain Management. The pain management needs of a medical maintenance patient may differ from those of other patients. The routine methadone dose of a patient in medical maintenance does not offer any analgesia, and a patient’s opiate tolerance must be taken into account when managing acute or chronic pain. Opioid partial agonists are absolutely contraindicated in these patients.

Managing acute pain. Medical maintenance patients will be tolerant to the analgesic effects of methadone. Because of cross-tolerance between methadone and other opioids, these patients may sometimes require higher or more frequent doses of opioids than do other patients with similar pain (Payte and Khuri 1993, p.55). Patients in opioid agonist treatment who are experiencing acute pain, but who do not obtain adequate relief from non-opioid analgesics, need and deserve additional, short acting opioids – often in larger doses and/or at shorter intervals than patients who are not tolerant to opioids. The strategy would be to administer larger than usual short-term doses. These should be administered In addition to patients’ normal or regular dose of methadone (Kaufitnan and Woody [CSAT I 995b]).

Managing chronic pain. Untreated chronic pain can be a potent trigger for relapse. Splitting daily methadone doses into equal portions to be taken four times per day can be one way to treat some patients. However, other patients will need increased dosages of opioids to manage their chronic pain. Being a medical maintenance patient should not preclude the use of additional opioids for long-term pain management when these would be otherwise appropriate. Medical maintenance patients may require higher dosages given at shorter intervals than patients who are not in medical maintenance.

The medical maintenance physician should consider consulting with a pain management specialist or referring patients to a pain center. If a patient is seeing a pain management specialist, the medical maintenance physician should continue to stay involved to ensure proper care (Payte and Khuri 1993). Once an effective dose of analgesic medication is established, previously ineffective pain treatment modalities can be surprisingly helpful. At this point, the medical maintenance physician should resume full care for the patient. Support, reassurance, and companion are essential features in managing the patient with chronic pain.

Hospitalization. An important responsibility of medical maintenance physicians is to protect their patients from undue pain and suffering during periods of hospitalization. Patients on methadone deserve adequate anesthesia and analgesia. Accomplishing this may require that medical maintenance physicians advocate for their patients and educate the patients’ other physicians about their pain management. Education and advocacy about adequate pain medication may include:

Exhibit F. Letter to Hospital Physicians

Date: _______________

Dear Doctor:

The bearer of this letter is a patient in a medical maintenance treatment program for addictive illness. Methadone patients frequently need treatment for other medical, surgical, and dental conditions. Many health care professionals are unfamiliar with methadone maintenance, reacting to these patients with fear, prejudice, and other negative subjective responses. In turn, because of previous biased experiences, many patients are reluctant to disclose their methadone treatment to health care professionals.

Methadone had been used to treat opioid dependence for over 30 years and is both effective and safe in chronic administration. It is specifically used to normalize the endorphin dysregulation, which occurs after years of opiate abuse. Patients develop complete tolerance to the analgesic, sedative, and euphorigenic effects of the maintenance dose of methadone. Tolerance does not develop to methadone’s capacity to prevent the onset of abstinence syndrome. With a half-life of over 24 hours, methadone has a relatively flat blood plasma level curve that will prevent the onset of abstinence syndrome for over 24 hours without causing any sedation, euphoria, or impairment of function.

The most common problem we encounter in a methadone maintained patient is management of pain. Since the patient is fully tolerant to the maintenance dose of methadone, no analgesia is realized from the regular daily dose of methadone Relief of pain with methadone, and then providing additional analgesia thus depends upon maintaining the established tolerance threshold with methadone, and then providing additional analgesia. When pain is not severe, non-narcotic analgesics should be used. For more severe pain, the use of opioid agonist drugs is quite appropriate with the following provisions:

Possible need to Increase the dose of an opioid agonist drug due to the cross tolerance to methadone Duration of analgesia may be less than usual. The methadone tolerant patient should never be given Opioid agonist/antagonist drugs such as Alwin, Stadol, and Nubain. Severe opiate

abstinence syndrome can be precipitated by drugs of this type. Closely supervise the quantity and duration of opioid agonist drugs. Similar precautions are Indicated In prescribing sedative/hypnotic and central nervous system stimulant drugs. The abuse potential of all benzodiazepines is quite high.

In the hospital setting, the admitting physician may be tempted to treat the opioid dependence itself, usually by doing a methadone graded reduction of dose If successful, the graded reduction may result in a reduction or elimination of the physiological dependence, but has no effect on the disease itself. Even after discontinuing methadone, significant signs and symptoms of abstinence may persist for 4 or more weeks. The relapse rate associated with withdrawal alone approaches 100%. A relapse rate to street/illicit drugs Increases risk of overdose, hepatitis, HIV, and a host of biomedical, psycho social, and other complications.

If you have any questions or concerns about our mutual patient In relation to methadone or drug dependency, please call me. I would be delighted to hear from you.

Sincerely,

Name of OBOT Physician

(Letter adapted from one written by Thomas Payte, M.D.)

Exhibit G. Use of Narcotic Drugs in Hospitals

Food and Drug Administration (HHS), 21 C.F.R. Ch. 1 -1 291.505 (April 1,1998 edition)

(f) Conditions for use of narcotic drugs in hospitals for detoxification treatment –

(1) Form. The drug may be administered or dispensed in either oral or parenteral form (see paragraph (d)(6)(iii) of this section).

(2) Use of narcotic drugs in hospitals – (I) Approved uses. For hospitalized patients, the use of a narcotic drug for narcotic addict treatment may be administered or dispensed only for detoxification treatment. If a narcotic drug is administered for treatment of narcotic dependence for more than 180 days, the procedure is no longer considered detoxification but is, rather, considered maintenance treatment. Only approved narcotic treatment programs may undertake maintenance treatment. This does not preclude the maintenance treatment of a patient who is hospitalized for treatment of medical conditions other than addiction and who requires temporary maintenance treatment during the critical period of his or her stay or whose enrollment in a program which has approval for maintenance treatment using narcotic drugs has been verified. (See 21 C.F.R. 20 I 3O6.O7(c))

A physician practicing medical maintenance must be prepared to intervene and advocate for a hospitalized patient to ensure that the patient continues to receive appropriate medication and is protected from unnecessary pain and suffering.

Elective hospitalization

If the patient’s hospitalization is for an elective procedure the physician and patient should discuss how opioid agonist treatment might affect or be affected by that procedure and how continuation of maintenance treatment can be achieved. The best way to deal with these issues is for the patient to sign consent forms permitting communications between the medical maintenance physician and the attending physician and hospital pharmacy. If a patient is undergoing surgery or may experience pain, the attending physician and other members of the Health care team should know that the patient is being treated with methadone in an ongoing program of opioid agonist treatment. This knowledge enables the Health care team to make appropriate plans for anesthesia and pain relief.

Communication with the attending physician will also enable the medical maintenance physician to provide information about the timing and amount of the patient’s dosage and to request notification of the date, time, and amount of the patient’s last dose before discharge. This will give the medical maintenance physician the opportunity to inform and educate hospital staff about opioid agonist treatment and to remind them of their professional responsibilities to provide ongoing treatment for their patient’s chronic addiction problem, just as they would for diabetes or any other chronic illness.

Some patients may not want their other physicians to know about their participation in medical maintenance. These patients may hope to administer their own medication during hospitalization, using take-home doses in the hospital without telling the attending physician. Clearly, this is not an advisable plan. By offering to call the attending physician, discuss maintenance treatment, and answer questions about, for example, anesthesia and pain management, the medical maintenance physician can reassure the patient that he or she should receive appropriate care. The preferred option is for the hospitalized patient to remain on methadone as a chronic medication. Short-acting opioids are a second acceptable option. However, shorter acting opioids can present problems for methadone patients, since the patients will experience mood swings that do not occur with methadone.

With this option, either the medical maintenance physician or the recovering community may need to provide support for the patient. If the patient is unable to take anything by mouth (and the hospital does not have methadone in parenteral form) or the hospital has no methadone at all, the physician should consult the mentor for help in reaching a solution.

Emergency hospitalization

Preparation is not possible when the patient’s hospitalization is an emergency. The physician should discuss with the patient in advance which hospitals in the area tend to be more responsive to the requirements of patients maintained on opioid agonist therapy. Then, should the patient have a choice of hospital to use in an emergency, the patient can use the more appropriate one. The physician can also offer the patient a card or med-alert bracelet for the emergency room that lists the medical maintenance physician’s name, telephone number, and the patient’s current dose. This will give the emergency room physician accurate information about the patient’s dose and a way to confer with the medical maintenance physician when necessary.

To ensure ongoing treatment when the patient is admitted on an emergency basis, the physician should call the attending physician, the charge nurse, and the hospital pharmacy. If the pharmacist questions the legality of maintaining the patient on medication during the hospitalization, the doctor should send a letter regarding the DEA regulations via fax (see Exhibit H).

Administration of Narcotics by Programs and Hospitals

Compounder

A program engaging in maintenance or detoxification treatment which also changes the dosage form of a narcotic substance for use in maintenance or detoxification treatment at other locations.

There are six (6) registration categories (business activities) of Narcotic Treatment Programs:

A. Maintenance Program Only

B. Detoxification Program Only

c. Maintenance and Detoxification Program

D. Compounder With a Maintenance Program

E. Compounder With a Detoxification Program

F. Compounder With Both a Maintenance and Detoxification Program

A program must register under the category which applies to its business activity.

A program must register for detoxification and/or maintenance or compounder with detoxification and/or maintenance. The program must register as a compounder if they compound narcotics on the premises for use at a program on-site and off-site. If compounding or distribution for other programs occurs at a location where no program exists, the compounding location must register with DEA as a manufacturer and/or distributor.

Problems have arisen regarding narcotic prescription orders (primarily in methadone) A physician may prescribe methadone or any other narcotic for analgesic purposes only. A patient who is to be or is being maintained or detoxified cannot receive a narcotic prescription order for this purpose. The individual must receive the necessary narcotics at a registered narcotic treatment program. In this case, the narcotics can be dispensed or administered, but not prescribed.

Only 4 specific individuals employed by the narcotic treatment program can dispense or administer narcotics to a patient: (1) the licensed physician, (2) a registered nurse under the direction of the licensed physician, (3) a licensed practical nurse under the direction of the licensed physician, or (4) a pharmacist under the direction of the licensed physician. This regulation is to prohibit the receptionist or counselor or another untrained individual (in some cases even a patient) from administering narcotics to the patient.

A physician who is not part of a narcotic treatment program may administer narcotic substances to an addicted individual to relieve that individual’s acute withdrawal symptoms while the physician makes arrangements to refer the individual to a narcotic treatment program. Not more than 1 day’s medication may be administered at one time. This treatment cannot last more than 3 days and may not be renewed or extended.

Exhibit H. Drug Enforcement Administration Information:

Administration of Narcotics by Programs and Hospitals (cont.)

A hospital that has no program on the premises or a physician who is not part of a treatment program may administer narcotics to a drug dependent individual for either detoxification or maintenance purposes if the individual is being treated for a condition other than the addiction. It is assumed that the physician or hospital staff will not take advantage of this situation and detoxify or maintain a drug dependent person who has sustained a very minor injury or illness which will not prevent him from going to a registered program.

Questions regarding any part of the Narcotic Addict Treatment Act of 1974, or any part of the regulations pertaining to the Act, should be directed to the nearest office of the Drug Enforcement Administration or Food and Drug Administration.

Narcotics for Patients With Terminal Illnesses or Chronic Disorders

Controlled substances and, in particular, narcotic analgesics. may be used in the treatment of pain experienced by a patient with a terminal illness or chronic disorder. These drugs have a legitimate clinical use and the physician should not hesitate to prescribe, dispense, or administer them when they are indicated for a legitimate medical purpose. It is the position of the Drug Enforcement Administration that these controlled substances should be prescribed, dispensed, or administered when there is a legitimate medical need (From U.S. Department of Justice. Physician’s Manual: An Informational Outline of the Controlled Substances Act of 1970. Washington, D.C.: Drug Enforcement Administration, revised March 1990, p.21).

Pregnancy

Methadone maintenance is associated with healthy outcomes for both mother and infant. Methadone is not teratogenic to the fetus and there is no evidence that it causes developmental problems. Patients can breast feed their infants. Withdrawal from methadone or reduction of dosage during pregnancy is hazardous to the fetus and may destabilize the mother; consequently, these should never be done without the advice of an expert in the field. The patient should be reminded that the safest place for the baby to be withdrawn is outside the womb in the hospital nursery under direct medical care.

Medical maintenance patients who become pregnant need not be transferred back to the originating clinic or to a specialty clinic. Indeed, pregnant patients should be transferred to medical maintenance if otherwise eligible, especially if a transfer will improve convenience for patients in receiving comprehensive prenatal care.

The physician who is not an addiction specialist can care for a pregnant patient with the support of a colleague who has experience in managing opioid agonist treatment during pregnancy. The medical maintenance physician, if not managing the pregnancy directly, should be in communication with the patient’s obstetrician. That physician may need education about the compatibility of maintenance treatment with pregnancy to avert any ill-advised attempt to withdraw the patient from opioids. The obstetrician should also be warned that nalbuphine hydrochloride, commonly administered to patients in labor, should not be used as it will precipitate acute opioid withdrawal.

During the later stages of pregnancy, methadone doses may need to be adjusted. The greater plasma volume and other aspects of pregnancy can result in a reduced or more rapid fall of methadone level in the blood. As a result, the pregnant woman’s maintenance dosage may be insufficient to prevent cravings or withdrawal. These changes in plasma levels may require that the dose be increased and/or that the single daily dose of methadone be split and taken twice a day to achieve a more even blood level throughout the 24-hour period.

The medical maintenance physician, the obstetrician, and the pediatrician should consult the following protocols and guidelines for managing pregnancy and encouraging breast feeding in opioid-maintained women, as well as managing withdrawal syndrome in the neonatal nursery:

TIPs No.2 and No. 5 can be searched online through the National Library of Medicine’s HSTA website; this site can be accessed from www.samhsa.gov/csat/csat.htm.

Drug-Drug Interactions

Medical maintenance patients, like all patients, may have various chronic medical and psychiatric co-occurring conditions that may require multiple medications. Drug interactions involving methadone are generally not significant, but they can result in considerable discomfort to the patient. The following factors complicate the picture:

Careful review of possible drug-drug interactions is therefore required before a physician adds, combines, adjusts, or subtracts drugs (see Tables 1-A through 1-D). Because the literature provides limited guidance on the interactions of other drugs with methadone. medical maintenance physicians need to listen carefully to their patients for signs suggesting the need for a dose change. When the patient begins any new medication, the medical maintenance physician needs to be alert for possible interactions with methadone and to stay in closer touch with the patient.

Contraindicated Drugs

Some drugs should never be used in patients on stable opioid agonist treatment. These include narcotic antagonists, such as naltrexone, naloxone, and nalmefene, and such mixed opioid agonist-antagonists as pentazocine, butorphanol, nalbuphine hydrochloride, buprenorphine, and dezocine. These drugs can precipitate a severe abstinence syndrome in patients who are tolerant to methadone. Interferon, often used in the treatment of Hepatitis C, can mimic withdrawal. Benzodiazepines (e.g., diazepam) should be prescribed with caution. They are a common drug of abuse in opiate-addicted patients. When combined with methadone, they can produce a “high” not normally experienced when either drug is used alone.

Drugs inducing (or accelerating) methadone metabolism or excretion Barbiturates and hypnotics, including phenobarbital, butabarbital sodium, mephobarbital, pentobarbital, and secobarbital, accelerate methadone metabolism by inducing hepatic microsomal enzymes, which may precipitate withdrawal symptoms. An increase in the dose of methadone may be necessary when the patient starts or discontinues these medications.

Table 1-A. Drugs Which are Contraindicated (May Precipitate Withdrawal)

Reprinted from Addiction Treatment Forum, Spring 1997 -1998 Lanmark Group Inc.

Table 1-B. Drugs That May Lower Plasma Levels of Methadone or Decrease Methadone Effects

Reprinted from Addiction Treatment Forum, Spring 1997 -1998 Lanmark Group Inc.

Table 1-C. Drugs That May Increase Plasma Levels or the Effects of Methadone

Reprinted from Addiction Treatment Forum, Spring 1997 -1998 Lanmark Group Inc.

Table 1-D. Additional Factors Impacting Methadone Metabolism

Moderating Effects

The anti-ulcer medication cimetidine (Tagamet *), which may increase methadone’s effects, has been used clinically to offset the metabolism-stimulating effects of drugs such as the anticonvulsant carbamazepine (Tegretrol *). The addition of cimetidine helps to maintain therapeutic methadone blood levels.

Personal Differences

Drug metabolism differences have been noted among ethnic groups such as Asians, Caucasians, and African Americans. Age also plays a role, affecting changes in drug metabolism and interactions.

For unknown reasons, some persons are naturally “aberrant metabolizers” and seem to “burn away methadone up to four times faster than others.

Methadone works best when administered in optimal therapeutic doses However. many factors may influence its blood serum concentrations and ultimate effectiveness. Achieving optimal dose levels, or assessing the origins of adverse reactions or alterations In methadone effectiveness, should take into account multiple factors.

References

Jalvik, A.; Isaac, P,; Janecek, E. Help for heroin dependence. Pharmacy Practice (10): 43-54. October 1996.

Murray, T Protease inhibitors affect methadone metabolism. The Medical Post, The preceding tables are not proposed as being all-inclusive of drugs that may be contraindicated or possibly interact with methadone in some fashion. New pharmacotherapies are being constantly introduced and only further clinical experience will determine their compatibilities with methadone. December 2,1997 (Toronto, Ont).

Nilison, M.I., et al. Effect of urinary pH on the disposition of methadone in man EurJ Clin Pharm. 22:337-342, 1982.

.

Payte J T , St peter, J and Andersen, S., informal communications, Spring 1997.

Physicians’ Desk Reference, 50th ed., Montvale, NJ: Medical Economics Co., 1996.

Rettig, R.A.; Yarmolinsky, A. (Eds ) Besides those precautions noted in the tables, several other factors may be important: Federal Regulation of Methadone Treatment. Washington, DC.

Institute of Medicine Report,’ National Academy Press, 1995.

Woods, J. How methadone works. Available online: https://www.methadone.org/how.html

Psychoactive Medications

All benzodlazepines, sedatives, and antidepressants may generally augment the effects of methadone to cause drowsiness.

Protease Inhibitors

Both methadone and protease inhibitors (used for the treatment of HIV) are metabolized by the liver.

Hepatitis

Hepatitis B and C, which are becoming more common among opioid users, may alter the pharmacokinetics of methadone metabolism by the liver and result in unexpected blood levels.

OTC Medications

Acetaminophen (e g. Excedrin *, Tylenol *) has inherent toxicities that can affect hepatic drug metabolism and impact methadone blood levels.

Fruit Juices

Grapefruit juice may intensify methadone’s effects if the two are regularly taken together. Some authorities attribute this to the inhibitory effect of grapefruit juice on certain liver enzymes, thus resulting in higher methadone blood plasma levels. Others have noted high concentrations of flavonoids in grapefruit as a possible causative agent.

Orange juice does not have the same methadone potentiating effect.

Vitamins

Large doses of vitamin C could create a more acidic urine that inhibits reabsorption of methadone by the kidneys. This would reduce the half life of methadone and result in decreased blood levels.

Reprinted from Addiction Treatment Forum, Soring 1997 1 1998 Lanmark Group, Inc.

Anti-convulsant medication for epilepsy and trigeminal neuralgia, such as carbamazepine or phenytoin, may lower plasma levels of methadone, precipitating acute withdrawal symptoms and craving. Methadone dose adjustments may be necessary when therapy with these drugs is initiated or discontinued.

Rifampin, used to treat pulmonary tuberculosis, may also accelerate methadone metabolism and require methadone dose adjustments.

Both methadone and protease inhibitors used in HIV therapy are metabolized by the liver. Research suggests that ritonavir and indinavir may result in reductions of up to 50 percent in methadone metabolism.

Urinary acidifiers, such as ammonium chloride, ascorbic acid, or potassium or sodium phosphate, may increase the excretion of an opioid agonist, resulting in decreased methadone plasma concentration and causing withdrawal symptoms.

Anticholinergic agents or other medications with anticholinergic activity may cause severe constipation when used concurrently with any opioid agonist.

Drugs inhibiting the metabolism (enhancing the effects) of methadone

Certain drugs inhibit the metabolism of methadone and may prolong its effect. These drugs include: Cimetidine, an H2 receptor antagonist used in treatment of gastric and duodenal ulcers and gastric reflux disease Ketoconazole, an antifungal agent Erythromycin, an antibiotic.

Drugs used to treat depression and anxiety may prolong or potentiate methadone’s effect, resulting in drowsiness. These include such drugs as: Amitriptyline Diazepam Fluvoxamine maleate

Urinary alkalizers, used to treat kidney stones and gout, may enhance the effects of methadone.

Ethyl alcohol, used to excess, will also enhance methadone’s effects.

Drugs whose effects may be altered by methadone

Methadone may alter the pharmacokinetics of drugs like desipramine (Norpramin), a tricyclic antidepressive, and zidovudine (Retrovir, AZT combinations) used in treatment of HIV.

Over-the-counter drugs and vitamins

Inherent toxicities in acetaminophen (Excedrin, Tylenol) may affect hepatic drug metabolism. Large doses of Vitamin C can reduce the half-life of methadone and result in decreased plasma levels. Ascorbic acid and such other acidifiers as ammonium chloride or potassium or sodium phosphate may increase excretion, resulting in decreased methadone plasma concentration and causing withdrawal symptoms. Certain foods, like grapefruit juice, can intensify methadone’s effects when taken simultaneously with methadone.

For a website with information on drug interactions, visit Clinical Pharmacology online at www.cponline.gsm.com.

Potential Side Effects of Methadone

Methadone is safe and well-tolerated with few significant side effects. The three most commonly encountered side effects are constipation, increased sweating, and sexual dysfunction. Other side effects, such as sedation and decreases in blood pressure and heart rate, disappear as tolerance to methadone develops.

Constipation: While many medical maintenance patients develop tolerance to this effect, others may need to adopt a regular regimen of fiber and stimulant laxative use.2

Increased sweating: Patients may interpret this as evidence of withdrawal. Clonidine, either oral or via skin transdermal patch, may help decrease it.

Sexual dysfunction: While this tends to normalize over time, some patients may benefit from treatment with sildenafil.

Other side effects may include:

Hyperprolactinemia: This may affect fertility in women and lower testosterone levels in men. Since other medications can also cause hyperprolactinemia, a review of all medications is indicated.

Weight Gain

A Preliminary Communication” recently published in the Journal of the American Medical Association presents early evidence that methlynaltrexone may be effective in ameliorating methadone-induced constipation (Yuan et al. 2000). In a double-blind, controlled trial of 22 methadone-maintained patients with constipation, low doses of intravenous methylnaltrexone induced laxation without opioid withdrawal in subjects on high methadone dosages. This trial suggests that the methadone constipating effect is predominantly mediated by receptors located in the peripheral gastrointestinal tract; methylnaltrexone apparently affects these receptors but does not penetrate into the brain. These findings suggest that clinical trials of oral methyl naltrexone would be warranted (Yuan et al. 2000).

Chapter 6. Managing Threats to Stability

Patients selected for medical maintenance are a highly stable group; most will remain stable, requiring only routine medical care, adjustments of dose level, and counseling. Yet, a small percentage do experience some threat to stability. This chapter outlines a process for managing such events.

Early signs of destabilization can manifest themselves in a variety of ways:

In observable behavioral changes, including missing or being late for appointments, losing medication, not following through on the current treatment plan, showing changes in affect, or appearing disheveled, drunk, or “high.”

In self-reports of difficulty, including reports of increased stress, drug cravings, drug use, family problems, a change of job or job loss, or renewed relationships with old drug-using buddies.

In concrete findings such as toxicology results; the patient’s urine sample may test positive for illegal drugs or test negative for methadone. While the appearance of any of these observations or reports may indicate there is a threat to the patient’s stability, these signs may also signify nothing more than a case of forgetfulness, a concern about an upcoming stressful event, or a false-positive test result. It is important that the physician not assume the worst and overreact by taking some quick actions such as returning the patient to the clinic. Instead, the physician should respond with rationality and judgment in dealing with the event. There can be a reasonable explanation for unreasonable behavior. An event that might signify destabilization does not necessarily signify a threat to stability or, worse yet, demonstrate that the patient has already relapsed. It falls to the physician to;

Process for Managing Potential Threats to Stability

It is the uncommon events among medical maintenance patients — the outliers that indicate the need for every medical maintenance physician to undergo some training in medical maintenance for opioid treatment patents. Training will enable a physician to respond with decisiveness and confidence when dealing with signs of patient destabiliztation.

Clarifying the situation

The first key step is for the physician to clarify whether there is a threat to stability. There are a variety of techniques available to the physician:

Discussion with the patient. It is important to discuss the issue with the patient directly. Does the patient have a reasonable explanation for the missed appointment, the lapse, or the positive drug test? Does that explanation make sense as presented? Is the event part of a pattern of events? Are there other signs of physical instability?

The physician’s response to a patient =s explanation of the reasons for a missed appointment, reported cravings, or an abnormal urine test result will also depend upon the patient’s history and the length (and strength) of the relationship the physician has with the patient.

Consultation with an experienced colleague and/or the laboratory. In some cases, the physician will continue to have doubts about the significance of an event, such as a missed appointment or a questionable urine test result. Discussion with a physician who has experience working with many OAT patients over the years can be particularly helpful in formulating next steps. If a laboratory test result is at issue, it can be fruitful to discuss other possible explanations for the test result with the laboratory director.

Employing a routine intervention to further clarify or resolve the Issue.

If the physician continues to question whether there is a Potential threat to stability, the physician can intervene in a routine way to resolve the problem or clarify Its extent For example, if the patient has missed an appointment because of misunderstanding the date or time, the physician can provide a card with the appointment time. If the patient tells the physician about an instance of drug craving, the physician may, alter discussion, adjust the methadone dose or refer the patient for counseling or other brief additional intervention. If a drug test is positive for cocaine and the patient denies use, the physician can have the sample retested or test another sample.

Small steps such as these can help the physician determine whether a threat to stability exists. If no threat exists, no more need be done. If the threat exists, the physician should intensify contact with the patient. A routine intervention (e.g., a referral for counseling or more frequent appointments) may resolve the problem. Help can also be requested from any specialist involved with the patient, such as the patient’s psychiatrist or employment counselor.

Responding when a significant (clear) threat to stability exists.

If the physician determines that a threat to stability exists and routine intervention fails to resolve it (or seems inappropriate), more intensive intervention is called for. As with any patient with chronic disease, the physician’s response will depend upon his or her ability and willingness to cope with the presenting problem. The physician’s response will also depend upon his or her relationship with the patient and their access to opioid treatment programs that could admit the patient if transfer is required. Whatever the medical maintenance physician’s response, the physician should guard against allowing personal feelings (such as anger, frustration, or disappointment) to interfere with arriving at and applying a clinical intervention that is in the patient’s best interests.

When a significant threat to stability exists, the physician should consult a more experienced practitioner to discuss the presenting problems and the patient’s response(s) to the clinical interventions to date.

The process just outlined can be applied in many different circumstances. What follows are examples of its application when the physician receives questionable urine toxicology results. The Comprehensive Reference Book on Opioid Agonist Medical Maintenance Treatment contains other applications.

Dealing With Questionable Urine Toxicology Results.

If a drug screen is negative for methadone or positive for an illegal drug, the physician should use the above process to explore whether a threat to stability exists and to determine a course of action.

When Toxicology Results Are Negative for Methadone

Clarifying the situation

The first step is to try to determine whether the test result indicates a threat to stability or an anomaly. If a drug screen fails to detect methadone, there are a number of possible causes:

Any urine test result that is negative for methadone should be discussed with the patient immediately. If the patient missed a dose, the physician should ask for an explanation and listen carefully. It is possible that the dose was missed because of illness or an emergency. The physician should note any abstinence symptoms, which should correspond with the patient’s report. The physician may also wish to consult an experienced colleague about the reasonableness of the patient’s explanation.

If the patient reports no missed doses, it is possible that the laboratory made an error or that the concentration of methadone in the patient’s urine fell below the cutoff for the test the laboratory was using (due to the specimen being too dilute for the parent compound or metabolite to be detected and/or because the patient’s dose is low). To clear up these questions, the physician can:

The physician should consult experienced practitioners, who may have other suggestions.

Employing a routine intervention to further clarify or resolve the issue

If discussions with the patient and consultation with the laboratory and colleague(s) fail to resolve whether there is a threat to stability, the physician can apply a routine intervention that will either eliminate the threat or illuminate its significance. At a minimum, the physician should increase monitoring of the patient, including requiring more frequent office visits (with counseling and urine testing) and fewer take-home doses. If the patient admits having missed a dose or two, the dose should be reestablished with caution. If there is doubt about decreased tolerance, the doses should be split or the patient should wait in the physician’s office after ingesting the medication for a period of observation. If the physician concludes that the negative toxicology result was due to a single missed dose or laboratory omission, there is no need to take further action.

Responding when a significant (clear) threat to stability exists

A more serious situation exists if the patient admits having stopped taking the medication or having presented someone else’s urine. The situation is also more serious when the physician finds that increased monitoring and counseling do not resolve the problem promptly. More than one missed dose in a short period of time may indicate that the patient is diverting (selling) the medication. Missing doses or substituting someone else’s urine specimen suggests that the patient is not appropriate for medical maintenance and should be transferred to a more intensive level of care.

When Toxicology Results Are Positive for Non-prescribed Drug(s)

Clarifying the Situation

If a drug screen is positive for non-prescribed drugs, the first step is to determine whether the test result is accurate. If the patient has not alerted the physician about having a lapse, the physician should immediately speak with the patient. A patient’s denial of drug use when confronted with a single positive urine screen can often be accepted, based on the physician’s assessment that the patient is telling the truth. In addition to a patient’s use of the drug of interest, a positive drug screen can also result from:

If the patient denies drug use, the physician should take a careful history of the patient’s recent use of prescribed and over-the-counter medications and discuss the test results with the laboratory, as well as with an experienced colleague.

Employing a routine intervention to further clarify or resolve the issue

If discussions with the patient and consultation with the laboratory and colleague(s) fail to resolve whether there is a threat to stability, the physician can intervene in a routine way to resolve the problem or clarify its significance:

Responding when a significant (clear) threat to stability exists

The physician must respond promptly when it is clear that the patient is using illicit drugs. As is the case with non-adherence to methadone dosages, if the patient admits drug use, the physician and patient should have an extended discussion about the reason(s) for the lapse and what steps need to be taken to ensure it does not recur. If increased monitoring and periodic counseling do not resolve the problem promptly, more intensive intervention should be developed through discussion with the patient and consultation with the mentor. More intensive intervention might include:

The mentor can help the physician to analyze the situation and the patient’s response(s) as they evolve.

If other measures fail, the patient can be referred back to the originating or the hub methadone clinic. The medical maintenance physician should be sensitive to the fact that a patient returning to the clinic may find this termination or interruption of the physician-patient relationship quite painful. The patient may view the transfer back to the clinic as a personal failure or as a rejection by the physician.

The physician should help the patient understand that transfer to the clinic is in the patient’s best interests. It ensures that the patient will receive the kind of help needed – more intensive care from a more comprehensive setting. The physician should try to bolster the patient’s confidence in his or her ability to regain stability. In order to provide the clinic with the information it will need about the patient’s care in medical maintenance and to consult with clinic staff as necessary, the physician should ask the patient to sign consent forms authorizing these disclosures.

When Toxicology Results Are Negative for Non-prescribed Drug(s).

‘Normal = test results should be interpreted cautiously, as false negative results are possible. Negative test results for drugs other than methadone can actually reflect a number of situations, including:

Because a negative test result can be misleading, a patient’s report of a lapse to illicit drug use should always be credited, even if the urine test does not confirm the lapse.

Table 2. Variations in Drug Detection Periods on Screening Tests

Drug

Source: B-Valley Medical Clinic, lnc., Sacramento, CA, 1998 (California Society of Addiction Medicine 1998).

A Final Word

Adding medical maintenance patients to a medical practice can be tremendously rewarding. It allows physicians to meet the needs and wishes of patients and enable them to lead more independent and productive lives. These are patients who respond well to the opportunity to manage their treatment medically and to lead lives that are not limited by their need to obtain daily medication.

References

California Society of Addiction Medicine (CSAM). Guideline for the Role and Responsibilities of Physicians in Narcotic Treatment Programs. Oakland, CA: California Society of Addiction Medicine, September 1998.

Center for Substance Abuse Treatment (CSAT). Improving Treatment for Drug-7 Exposed Infants: Treatment Improvement Protocol (TIP) Series No.5. Kandall, S.R. (chair). DHHS Pub. No. (SMA) 93-2011. Rockville, MD: Substance Abuse and Mental Health Services Administration, 1993a. Center for Substance Abuse Treatment (CSAT). Pregnant, Substance-Using Women: Treatment Improvement Protocol (TIP) Series No.2.

Mitchell, J. (chair). DHHS Pub. No. (SMA) 93-1998. Rockville, MD: Substance Abuse and Mental Health Services Administration, 1993b. Center for Substance Abuse Treatment (CSAT). State Methadone Treatment Guidelines: Treatment Improvement Protocol (TIP) Series, No.1.

Parrino, MW. (chair). DHHS Pub. No. (SMA) 93-1991. Rockville, MD: Substance Abuse and Mental Health Services Administration, 1993c. Center for Substance Abuse Treatment (CSAT). Assessment and Treatment of Patients with Coexisting Mental Illness and Alcohol and Other Drug Abuse: Treatment Improvement Protocol (TIP) Series, No.9.

Ries, R. (chair). DHHS Pub. No. (SMA) 94-2078. Rockville, MD: Substance Abuse and Mental Health Services Administration, 1994. Center for Substance Abuse Treatment (CSAT). LAAM in the Treatment of Opiate Addiction: Treatment Improvement Protocol (TIP) Series, No.22.

Marion, L.J. (chair). DHHS Publication No. (SMA) 95-3052. Rockville, MD: Substance

26 Abuse and Mental Health Services Administration, 1995a. Center for Substance Abuse Treatment (CSAT). Matching Treatment to Patient Needs in Opioid Substitution Therapy: Treatment Improvement Protocol (TIP) Series, No.20.

Kauffman, J.F. and Woody, G.E. (co-chairs). DHHS Publication No. (SMA) 95-3049. Rockville, MD: Substance Abuse and Mental Health Services Administration, 1995b. Center for Substance Abuse Treatment (CSAT). Approval and Monitoring of Narcotic Treatment Programs: A Guide on the Roles of Federal and State Agencies: Technical Assistance Publication Series No.12, by McArthur, L.C., and Y. Goldsberry. DHHS Publication No. (SMA) 96-3100. Rockville, MD: Substance Abuse and Mental Health Services Administration, 1996.

Chiang, C.N. and Hawks, R.L. Implications of drug levels in body fluids: Basic concepts. In: Hawks, R.L. and Chiang, C.N. (eds.) Urine Testing for Drugs of Abuse. DHHS Publication No. (ADM) 87-1481. Rockville, MD: National institute on Drug Abuse Research Monograph 73, 1986.

Des Jarlais, D.C.; Joseph, H.; Dole, V.P.; and Nyswander, M.E. Medical maintenance feasibility study. In: Ashery, R.S., ed. Progress in the Development of Cost Effective Treatment for Drug Abusers. National Institute on Drug Abuse Research Monograph Series 58; Rockville, MD, 1985, pp.101-110. Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM IV). Washington, DC: American Psychiatric Association, 1994.

Federal Register, Department of Health and Human Services, Food and Drug Administration, 21 C.F.R. Part 291, 42 C.F.R. Part 8 Nol. 64, No. 140/July 22,1999/Proposed Rules, pages 39810-39857.

Finkle, B.S.; Blanke, R.V.; and Walsh, J.M. (eds). Technical, Scientific and Procedural Issues of Employee Drug Testing: Consensus Report. DHHS Publication No. (ADM) 90-1684. Rockville, MD: Alcohol, Drug Abuse, and Mental Health Administration, 1990.

Kreek, M.J. Using methadone effectively: Achieving goals by application of laboratory, clinical, and evaluation research and by development of innovative programs. In: Pickens, R.W.; Leukefeld, C.G.; and Schuster, C.R. (eds.). Improving Drug Abuse Treatment.’ NIDA Research Monograph 106. DHHS Publication No. (ADM) 91-1754. Rockville, MD: National Institute on Drug Abuse, 1991.

Ling, W.; Charuvastra, C.; Kaim, S.C.; and Klett, J. Methadyl acetate and methadone as maintenance treatments for heroin addicts. Archives of General Psychiatry 33:709-20, 1976.

Manno, J.E. Interpretation of urinalysis results. In: Hawks, R.L. and Chiang, C.N. (eds.) Urine Testing for Drugs of Abuse: NIDA Research Monograph 73. DHHS Publication No. (ADM) 87-1481. Rockville, MD: National Institute on Drug Abuse, 1986a.

Manno, J.E. Specimen collection and handling. In: Hawks, R.L. and Chiang, C.N. (eds.) Urine Testing for Drugs of Abuse: NIDA Research Monograph 73. DHHS Publication No. (ADM) 87-1481. Rockville, MD: National Institute on Drug Abuse, 1986b.

Marion, L.J. Urinalysis as a clinical tool. In: Center for Substance Abuse Treatment. State Methadone Treatment Guidelines: Treatment Improvement Protocol 3 (TIP) Series No.1. Parrino, M.W. (ed.) DHHS Publication No. (SMA) 93-4 1991. Rockville, MD: Substance Abuse and Mental Health Services Administration, 1993.

National Institutes of Health (NIH). Effective Medical Treatment of Opiate Addiction. NIH Consensus Statement 15(6):1-38, November 17-19,1997. See also the Journal of the American Medical Association 280:1936-43,1998. NIH consensus statement no.108 is available in electronic form on the World Wide Web from: http://consensus.nih.gov; go to consensus statements [choose index by subject and then pharmacology].

Novick, D.M.; Joseph, H.; Salsitz, E.A.; Kahn, M.F.; Keefe, J.B.; Miller, E.L.; and Richman, B.L. Outcomes of treatment of socially rehabilitated methadone maintenance patients in physicians’ offices (medical maintenance): Follow up at 4 to 9 ╝ years. Journal of General Internal Medicine 9:127-130,1994.

Payte, J.T. and Khuri, E.T. Principles of methadone dose determination. In: Center for Substance Abuse Treatment. State Methadone Treatment Guidelines: Treatment Improvement Protocol (TIP) Series 1. Parrino, M.W. (ed). DHHS Publication No. (SMA) 93-1991. Rockville, MD: Substance Abuse and Mental Health Services Administration, 1993.

Rettig, R.A. and Yarmolinsky, A. (eds.). Federal Regulation of Methadone Treatment.’ Institute of Medicine. Washington, DC: National Academy Press, 23 1995.

Schwartz, R.P.; Brooner, R.K.; Montoya, l.D.; Currens, M.; and Hayes, M. A 12- 25 year follow-up of a methadone medical maintenance program. American Journal on Addictions 8:293-299,1999.

Senay, E.G.; Barthwell, A.G.; Marks, R.; and Bokos, P. Medical maintenance: A five year experience. In: Problems of Drug Dependence 1994, Proceedings of the 56th Annual Scientific Meeting, The College on Problems of Drug Dependence, Inc,: NIDA Research Monograph Series, Volume II. Rockville, MD: National Institute on Drug Abuse, 1994a, pp.153, 471

Senay, E.G.; Barthwell, A.G., Marks, R., and Bokos, P.J. Medical maintenance: An interim report. In: Magura, S., Rosenblum, A. (eds). Experimental Therapeutics in Addiction Medicine I 3(3):65-69, I 994b.

U.S. Department of Justice. Physician’s Manual: An Informational Outline of the Controlled Substances Act of 1970. Washington, D.C.: Drug Enforcement Administration, revised March 1990. p.21.

Yuan, C.-s.; Foss, J.F.; O’Connor, M.; Osinski, J.; Karrison, T.; Moss, J.; and Roizen, M.F. Methylnaltrexone for reversal of constipation due to chronic methadone use. Journal of the American Medical Association 283(3):367- 4 372, 2000.

Zweben, J.E. and Payte, J.T. Methadone maintenance in the treatment of opioid dependence: A current perspective. In: Addiction Medicine [Special Issue]. Western Journal of Medicine 152(5)588-599, 1990.

Appendix A

Diagrams of Medical Maintenance Models go here ( see bottom below text)

Appendix A-I. OTP Hub Model

Opioid Treatment Program Clinic Responsibilities

Individual contracts or agreements with primary care physicians

Appendix A-2. Independent Agency Coordinating Hub Model

The independent entity that is the coordinating hub could be a university-based research group, State Methadone Authority, regional coordinating center for mental health, health maintenance organization, hospital-based medical practice, or local government entity, such as a public health department

Code: —— Optional arrangements

Institutional Entity Responsibilities

Note: In the past, independent entities could apply under an Investigational New Drug (IND) mechanism to set up a research program with exemption from Federal regulations. This option is being phased out. Physicians who operate from an independent hub in a different neighboring State must obtain a license in their own State.

Appendix A-3. Physician as Program Sponsor Model

Code: Optional arrangements

Autonomous Physician Hub Responsibilities

Note: In the past, individual physicians could apply for a medical maintenance practice through the IND research mechanism. This option is being phased out.

Appendix B. Interpretation of Urine Toxicology Results

Although toxicology studies provide an objective measure of adherence to treatment, they are not infallible. Interpretation of results, whether they are “normal,” negative for methadone, or positive for non-prescribed drugs, can be complicated by a number of factors:

Drug class. Detection of drug metabolites in the urine depends upon the drug or drug class being tested and the way in which the drug is absorbed by and eliminated from the body. Drugs remain in the body for various lengths of time: some. such as cocaine, are eliminated relatively rapidly, whereas others, such as marijuana, are eliminated much more slowly (see Table 2).

Quantity, timing, and frequency of use. The higher the dose a patient takes and the more recently use occurred, the more likely it is that the drug will be detectable in the urine specimen. Most drugs accumulate in the body if they are taken regularly rather than intermittently.

Amount and concentration of urine specimen. The water content of urine varies throughout the day and varies among individuals, affecting test results. Water dilutes the amount of drug found, whereas dehydration yields an abnormally concentrated urine specimen. Laboratories can check for acceptable values of specific gravity, pH, and can perform a creatinine analysis of the urine, dividing the drug concentration (in nanograms per milliliter) by the creatinine concentration (in milligrams per milliliter)

to determine the nanograms of drug per milligrams of creatinine (Chiang and

Hawks 1986; Finkle et al. 1990; Manno 1986a,b).

Accuracy can also vary with the amount of urine collected. Most laboratories accept a urine volume of 30 mL for analysis. If possible, this amount should be collected at one time. However, the total volume can be accumulated. if necessary, by having the patient wait and provide additional urine, which is then combined with the initial specimen (Finkle et al. 1990).

Quality of the laboratory. The OBOT physician should, after consultation with the mentor, select a reliable laboratory for urine testing, avoiding any laboratory that insists on using inappropriate methods, such as those required for Federal workplace testing. In particular, the laboratory should agree to report any analytically meaningful signal from drug assays, rather than reporting such a signal as negative merely because it does not exceed the Federal workplace screening standard.

Analytic methodology used. Different laboratory tests have various degrees of sensitivity and specificity. In general, methadone programs use screening procedures that are highly sensitive in order to minimize the possibility of a false-negative result. Most laboratories that contract with methadone maintenance clinics to screen urine samples use some type of immunoassay or thin-layer chromatography (TLC). Programs generally do not employ confirmatory testing to substantiate positive results.   

The following resource can be recommended to a doctor interested in
the use of methadone in the treatment of addiction and chronic pain in
office based practice.


This free ‘on-line’ publication from Butler Hospital, Brown University,
Rhode Island, uses resources from a wide range of experts in North
America. The course comprises a series of work pages and linked
slides/overheads. It is attractive and ‘user-friendly’. There are no
log-ins, passwords or other ‘net hurdles. Just open each page and press
the ‘forward’ arrow after each (or open a few in advance and ‘save’).
There are also a number of challenging case studies. The whole course could
be completed in less than two hours by an experienced physician. There is no
exam! It is a good starting point for dependency management.

New England Addiction Technology Transfer Center (“ATTC”),
Funded by Center for Substance Abuse Treatment SAMHSA.

http://www.caas.brown.edu/ATTC-NE/pubs/OBOT/
http://www.caas.brown.edu/ATTC-NE/pubs/OBOT/CS1.html
(case histories)
http://www.caas.brown.edu/ATTC-NE/pubs/OBOT/OBOT.html
(this is for the entire course in text form – allow at least 3 minutes
for full document to open).

Return to OBOT Index Page