Physicians’ Guide: Opioid Agonist Medical Maintenance Treatment

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

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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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).

(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),

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

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.

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:

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.

Date: _______________

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

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

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

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.

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.

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.

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.

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

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.

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.

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;

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.

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?

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.

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.

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.

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.

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.

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.

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.

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:

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.

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.

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

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].

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)

Individual contracts or agreements with primary care physicians

Code: —— Optional arrangements

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.

Code: Optional arrangements

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.   

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

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