This article was downloaded by: [Australian National University] On: 07 January 2015, At: 09:46 Publisher: Routledge Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK

Journal of Psychoactive Drugs Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/ujpd20

Methadone Maintenance Treatment: A Primer for Physicians a

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Judith Martin , J. Thomas Payte & Joan Ellen Zweben a

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14th Street Clinic and Medical Group, Oakland , California

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Drug Dependence Associates , San Antonio , Texas Published online: 20 Jan 2012.

To cite this article: Judith Martin , J. Thomas Payte & Joan Ellen Zweben (1991) Methadone Maintenance Treatment: A Primer for Physicians, Journal of Psychoactive Drugs, 23:2, 165-176, DOI: 10.1080/02791072.1991.10472234 To link to this article: http://dx.doi.org/10.1080/02791072.1991.10472234

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Judith Martin, M.D.*; J. Thomas Payte, M.D.** & Joan Ellen Zweben, Ph.D.*** Abstract- The doctor-patient interaction in the methadone maintenance treatment clinic is qualitatively different from general medical settings. The patient presents with a specific request for treatment of opioid dependence, most often having already selected the methadone treatment modality, and the initial contact is centered around obtaining methadone. Addiction and needle use increase susceptibility to life-threatening illnesses, such as syphilis, endocarditis, tuberculosis, and AIDS. The physician is working with counselors, nurses, therapists and 12-Step programs, incorporating the best of the medical, psychodynamic, behavioral, and recovery models into treatment. Federal and state governments also control and regulate methadone treatment Given this complex picture, the basic techniques of methadone maintenance treatment are reviewed, including the intake examination, the annual examination, dose adjustment, withdrawal from methadone maintenance, management of pregnant patients, dual diagnosis patients, and severely ill or medically disabled patients. Keywords- dual diagnosis, methadone maintenance treatment, side effects, opioids, pregnancy, withdrawal

In the broadest sense, the responsibility of a physician is to comfort always, relieve often, and cure sometimes. Keeping this in mind may be helpful to the physician facing the devastating and as yet incurable, chronic, and progressive disease of opioid addiction. The usual doctorpatient interaction in family practice or internal medicine is that of the patient presenting with symptoms or concerns, and asking the physician to diagnose, treat, educate or reassure. The interaction is centered around getting or keeping the patient healthy, and both parties hold that as a priority. Both are concerned about abnormal laboratory test results or abnormal physical findings, both are intent on solving problems. Ideally, the patient chooses a practitioner who is empathetic and inspires confidence and trust. This type of medical practice is structured around such interactions. However, methadone maintenance treatment (MMT)

programs are set up to address one problem: chronic, severe, intractable opioid addiction. Patients who present usually request MMT, which gives the doctor-patient interaction a different complexion. Even though MMT programs incorporate the better aspects of a variety of other modalities and disciplines into the MMT model- such as 12-Step programs, behavior modification, and psychotherapy- and even though the physician is aware of the various manifestations and presentations of opioid addiction based on duration, dose, route of administration, abuse of or dependence on other drugs, psychiatric comorbidity (dual diagnosis), and human immunodeficiency virus (HIV) problems, the core of the initial doctor-patient contact would appear to revolve around methadone alone. Hopefully, most MMT program physicians will look beyond the immediate task of prescribing methadone to see the initiation of a long process to restore physical and psychological functioning and to facilitate an improved quality of life, which can be accomplished only if the opioid addiction is effectively treated. Most practitioners concur that addictive disorders are complex phenomena involving the interaction of biological, psychosocial, and cultural variables, all of which need to be addressed. To be maximally effective, this treaunent must incorporate a multidimensional team approach and be individualized based

*Medical Director, 14th Street Qinic and Medical Group, Oakland, California. **Chairperson, Committee on Methadone Treatment, American Society of Addiction Medicine; Founder and Medical Director, Drug Dependence Associates, San Antonio, Texas. ***14th Street Clinic and Medical Group, Oakland, California. Please address reprint requests to: Judith Martin, M.D., 14th Street Oinic and Medical Group, 1124 E. 14th Street, Oakland, California 94606.

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on the assessment of the patient. By becoming involved in all aspects of treatment and in patient education about methadone, its long-term safety, side effects, factors related to adequate blood levels, and prognosis, for example, the MMT physician can avoid feeling incidental and powerless, and being transformed into a gateway to treatment by way of a license to prescribe. The extent of physician involvement in the overall therapeutic process depends on knowledge and training in addiction medicine in general and a thorough knowledge of opioid dependence and MMT in particular. Areview of the MMT literature can be invaluable. The degree to which MMT is controlled and regulated by federal and state governments is unique and not found in any other form of medical practice. While regulations vary considerably among states, the entire process represents an unprecedented intrusion into the practice of medicine. With the first regulations promulgated by the Food and Drug Administration in 1973, the very nature ofMMT was altered from the original concepts of Vincent Dole and Marie Nyswander to make abstinence rather than rehabilitation the goal of treatment, which persists to this day to some degree. With total disregard for scientific and clinical findings, policymakers have often succeeded in limiting dose and duration of treatment, thus seriously reducing the effectiveness of this treatment modality. As a result, the MMT physician may feel that instead of relying on medical knowledge, clinical experience and professional judgment, decisions are made in accordance with federal and state regulations pertaining to MMT. Although this situation is changing for the better, many states continue to impose constraints that are unsupported by either clinical observation or systematically collected data. Hence, the effectiveness of the treatment modality can be undermined by the nature of the service delivery system. Within this context, the MMT physician must attempt to meet the needs of the patient.

be based on objective findings, such as dilated pupils and piloerection. While extensive needle marks and scarring (tracks) are supportive evidence, they are not exclusive to opioid abuse nor do they confirm current dependence. There are many good references to opioid dependence and its abstinence syndrome in the literature (e.g., Platt 1986). From the patient's point of view, the intake examination is just another hurdle, but hopefully the last, on the way to obtaining relief by way of treatment with methadone. In some clinics there are interviews, forms to be filled out, and sometimes hours, days, and even weeks of waiting to be seen. During this time, patients will continue to be at risk and may be in withdrawal and physical] y uncomfortable; their uppermost thought may be, "When do I get my dose of methadone?" Under some circumstances, such as very clear and severe withdrawal, it may be possible to expedite the essential elements of the workup to be able to give the patient the initial or emergency dose of methadone. The remainder of the intake process will go more smoothly. To avoid being at crosspurposes and developing a counterproductive adversarial relationship, one must bear in mind the acute discomfort of patients at the time of the intake interview, as well as an addict's need to feel that he or she has negotiated the system and obtained what was needed or desired. The following situations commonly occur: 1. The patient is intoxicated (e.g., slurred speech, pinpoint pupils, nodding off in the waiting room). The best way to prevent this situation is to give a clear message at first contact with the patient at the clinic that he or she will need to show signs of withdrawal in order to be given the first dose of methadone. The receptionist, intake worker, and brochures need to emphasize this point, as repetition is the key to conveying this message. The clinician can make the decision to fmish the physical exam, blood work and intake, and then have the patient return to receive the initial dose when withdrawal can be documented, or to start the process over another day. One should not spend a lot of time talking to or explaining things to an intoxicated person or one in withdrawal; the approach that rules are rules or it is unsafe are straightforward. The ability to set limits without being punitive is a key to maintaining a good treatment climate as well as fostering staff safety in tense situations. Patients should be told clearly and firmly what they need to do to be admitted into the treatment program. 2. The patient has a serious medical problem that does not require urgent treatment. Some examples are diabetics out of control, alcoholics with liver enlargement but no jaundice, or asthmatics who are wheezing. If the clinic is equipped to handle

THE INTAKE EXAM

During the intake examination, from the MMT physician's point of view, one is interviewing and examining patients who may be prone to life-threatening illnessessuch as syphilis, endocarditis, abscesses, hepatitis, tuberculosis, and AIDS - due to their addiction as well as unsterile needle use. Physicians must be thorough in evaluating and ruling out those diseases. In addition, because of the legal restraints on the practice of medicine in this context, the physician must document the signs of drug use and withdrawal in the patient, establishing the presence of current physiological dependence as well as other criteria for admission before placing a patient on opioid replacement therapy; that is, methadone maintenance. The diagnosis of current physiologic opioid dependence should Jowii/JI of Psychoactive Drugs

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about their physical health. One of the paradoxes of medical practice in an MMT program is that one finds many significant medical problems but very few of them are treated because of the patient's addiction. Denial is a common but unconscious barrier to seeking treatment 1be addict's reluctance to engage the health care delivery system is often based on some very real problems and some very bad experiences with health care delivery (Zweben & Payte 1990). Breast lumps may not be biopsied, decayed teeth may go unrepaired, or vaginal or rectal bleeding or discharge may go undiagnosed because patients do not want to keep appointments, experience the cruel discrimination, or spend the money; or they cannot sit for hours in a county facility. But they do care and ask questions, and they follow up when surfacing from addiction long enough to do so. The clinician must keep in mind that someone who may care a great deal about his or her health may abuse their body in these ways because of the very nature of the addictive disorder, which can be characterized as continued use despite known adverse consequences. The denial system may prevent any realization of the consequences of drug abuse. Once abstinent. clear information and recommendations are sometimes heard. The MMT program physician can help by providing referrals to physicians who do not discriminate against substance abusers or contact the physician and do a bit of diplomatic educating. The counselor can provide support and follow up the patient to see that he or she eventually complies and, if appropriate, to restate recommendations when the patient may be more able to take action.

primary outpatient care, treatment can be offered. If the patient has a regular doctor, a letter from the outside physician attesting to treatment or stabilization of a particular condition can be made a condition for admission or readmission. Once the patient has been stabilized on an adequate dose of methadone, he or she is better able to handle other health care issues. 3. The patient has an obvious, life-threatening problem that requires urgent care. This situation is usually fairly clear, such as a gangrenous hand or other extremity, frank pulmonary edema, or vomiting blood. Without being alarmist, the message to be conveyed is, "This condition could ldll you, we're calling an ambulance." The patient is often afraid of not being treated for withdrawal in the hospital. A letter stating that treatment for the addiction will be available on discharge may help, or a call to the emergency room physician may be warranted. When the situation alllows, some physicians prefer to complete the admission prior to referral to the hospital. Clinical experience indicates that patients who are already in an MMT program may receive beuer treatment for the condition. 4 . The patient has a potentially severe but undiagnosed medical problem, such as tuberculosis or pneumocystis pneumonia. With a new patient. this is the most difficult type of case. Aside from withholding methadone, there is no leverage to encourage an emergency room visit or a chest X ray. The withdrawal discomfort has priority in the patient's mind over spending money to diagnose a potential problem. Once the patient is admitted, despite concern over the health problem, the question must be addressed of the physician's (or clinic's) right to withhold treatment for condition A because the patient refuses to take care of condition B. There are few, if any, strictly medical contraindications to MMT in opioid addicts. However, this does not prevent the use of methadone or certain privileges for leverage to accomplish something that is clearly in the best interest of the patient This practice is referred to as contingency contracting and is common among MMT programs. The decision to withhold methadone or to refuse admission to the addict is used as a way of underscoring theserious nature of the potential problem. One should bear in mind that this is a purely pragmatic way of getting the patient to comply with what the clinician believes needs to be done. It is a question of treatment priorities, not what the patient perceives to be the priorities. A common misconception is that patients do not care JourMI of Psychoactive Drwgs

THE PHYSICIAN'S ROLE IN ONGOING TREATMENT Once the intake exam is completed, the patient on methadone maintenance is responsible for participating in the maintenance program according to federal and state guidelines and regulations as well as clinic-specific policies and rules. Basic compliance requirements vary among states but typically include daily dosing, periodic counseling sessions, urine testing, and yearly physical examinations. With the sole exception of the dispensing nurse, the counselor has the most contact with the patient, and it may be reasonable for the counselor to use therapy sessions and urine test results to evaluate progress. Any drug found on the urine screen counts as a positive (or dirty) urine, unless there is a current documented prescription for its use. In some programs, the outside physician's prescription is evaluated by the MMT program physician, and must be deemed appropriately prescribed and not merely legal to not count as a positive. A positive urine has therapeutic counseling value as well as behavioral consequences, such as loss of take-home privileges. By the same token, a negative urine provides an oppor167

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choactive substance, with a commitment to sobriety." MMT programs might stress issues of function and quality of life, while other modalities stress total abstinence from drugs as a prerequisite to improved function and quality of life. Markers of life-style changes include a reduction or elimination of the use of opioids and other drugs, steady employment, breaking connections with users, the ability to handle family and home responsibilities, and other patient goals established in the therapeutic treatment plan. Certain behaviors, such as blaming others for one's misfortunes, manipulating staff against each other, lying, missing counseling sessions or methadone doses, are seen as signs that the recovery process is not very advanced, regardless of whether or not the patient is using illicit drugs. MMT physicians and other staff must learn to accept that progress toward rehabilitation often comes slowly. Ball and colleagues (1988) showed the continued improvement from admission into the fifth year of treatment, as reflected in percentages of patients involved in injecting heroin.

tunity for positive reinforcement and recognition of progress in treatment, leading to appropriate rewards. It is very important for the physician to be oriented to what the structured incentives (rules) and various policies are in the clinic. For example, what does it take to earn a weekly take-home privilege? What privileges are lost by a confrrmed positive urine? What is the minimum number of counseling sessions required each month? What is the procedure if a patient does not come in to dose for three days in a row? In a recovery-oriented MMT program, abstinence is redefined as not using any psychoactive substances other than methadone; nicotine and caffeine are usually also excepted. It is very important to make a distinction between dependence and addiction. A person can regularly take a dependence-producing substance without manifesting the distinguishing characteristics of addiction: compulsion, loss of control, and continued use despite adverse consequences. For example, a 55-year-old woman taking diazepam (Valium) prescribed by her physician for an anxiety disorder is physically dependent on the drug. If she does not escalate her dose or engage in drug-seeking behavior and her functioning is improved rather than impaired, she may be considered physically dependent but not manifesting signs and symptoms of an addictive disorder. This concept can be powerful to the MMT patient who is often unable to enjoy major rehabilitative accomplishments because of the stigma attached to being on methadone. From this philosophical viewpoint, the patient who is not using illicit drugs but is taking licit drugs as prescribed is in recovery. Methadone is thus viewed as just another medication, no different in principle from antidepressants or antipsychotics. Payte (1989) has proposed an alternative definition of abstinence: to be free from any use of illicit psychoactive drugs, the inappropriate use of licit psychoactive drugs, and the continued use of any substance despite known adverse consequences. The MMT physician also needs to be familiar with the Twelve Steps and what is involved with each step, and how a 12-Step program works. If one creatively redefines abstinence, then patients can participate in a full program of recovery using the 12-S tep process without feeling that they are not in recovery because they are taking methadone. Counselors and physicians should also be familiar with the recovery process, and use this model to judge progress in treatment. Recovery has been variously defined based on treatment philosophy. The present authors have adopted the following definition of recovery within the context of MMT: learning to live a comfortable and responsible life free from any use of illicit psychoactive drugs and from the inappropriate use of licit drugs. This differs from the current American Society of Addiction Medicine ( 1990) definition of "a process of overcoming both physical and psychological dependence on a psyJo&Una/ of Psychoactive Drugs

THE FOLLOW-UP VISIT In some clinics, particularly when the program physician is an addiction treatment specialist, the physician assumes responsibility for overall treatment planning and execution in the context of a multidisciplinary treatment team. Follow-up visits may be monthly with the interval between visits being extended as progress in treatment is realized. The stable patient may be seen once or twice a year. In cases where the physician is not an integral part of the total care process but the state requires it, and where the patient is complying with the clinic's rules, the physician's only direct contact may be the yearly physical examination. The annual examination is set up to be an interim history of the entire year, reviewing any new health problems, new medications or surgery, and sometimes resolution of old health problems, such as healing of tracks and abscesses. It should also be an evaluation of progress within the program. For example, what kind of employment or education was undertaken, and when was the last use of illegal or addictive drugs? What addictions (such as cigarette smoking) remain to be confronted? Have any dose changes been necessary and what effect did they have? The underlying questions focus on whether the MMT program is working for the patient. Elsewhere in this issue of the Journal of Psychoactive Drugs, Avram Goldstein stresses that "the sole criterion of success [of MMT) is substantial reduction (ideally, cessation) of heroin use." That reduction then makes therealization of broader program goals, such as improved social function and vocational training possible. Methadone does not (and was never intended or claimed to) make any of these things happen (Newman 1987). The determination of what constitutes benefiting from treat168

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ment covers a wide spectrum. The physician must avoid the trap of considering less than ideal treaunent outcome as a failure; damage control is a worthy accomplishment. The program may be considered to be working for the patient who fixes once a week instead of several times daily and was only arrested once in the previous 12 months. The patient is still engaged in treatment, and the longer he or she remains in treatment the more likely a favorable outcome (Simpson 1981). Are there any danger signs (symptoms or life-style changes) that might indicate an imminent relapse? For example, the patient may no longer use heroin, but may have increased beer drinking from one to six bottles a night over the first year of treatment, and been arrested twice for drunk driving. Or the patient may be abstinent and compliant with the program, but states that there is a hearing about child custody next weclc and he or she has had increased craving. In the first case, random alcohol tests may need to added prior to methadone dosing, or disulfrram (Antabuse) treatment may be needed. In the second case, the patient may need an increase in counseling support and/or a temporary dosage increase during the current crisis.

that blind dose the patient according to reported symptoms; others have a preset maximum dose for everyone. In most cases, however, dose can be adequately determined by a skilled physician based on objective and subjective findings. In some cases, use of24-hour blood plasma levels of methadone can be quite useful. Urinary pH can play a role in renal reabsorption of methadone having a considerable influence on the half-life. One of the present authors (Payte) has found that a three- to four-hour and a 24-hour blood plasma level are helpful. While the absolute level is important, the rate of change or the difference from the peak and trough levels may be of considerable clinical importance. It is important to be aware that methadone dose is a highly charged issue for patients, and supervisory medical and counseling staff must remain vigilant that frustrations over patient behavior do not translate into inappropriate power struggles over dose. For example, it is not uncommon for clinics to lower dose as a penalty for using heroin or other drugs, despite growing evidence that inadequate dose is often the basis for using. Many clinicians explicitly foster patient collaboration in dose regulation as a means of strengthening the therapeutic alliance and developing willingness to work on other issues. One empirical study (Havassy, Hargreaves & DeBarros 1979), which explored self-regulation of dose, documented that patients on a selfregulation regimen (versus standard practice of having staff determine the dose) did not greatly increase their doses, and some decreased their doses substantially. These researchers concluded that patients did not use self-regulation to ingest massive doses of methadone, nor did they create medical, behavioral and/or administrative problems; consequently, some of the problematic restrictions of MMT are not needed. Determining an adequate and appropriate dose of methadone is based on clinical evidence that the following three effects of methadone will be achieved. These are based on what K.reek (1987) identified as "important, separate effects" of methadone. The realization of these effects constitutes a reasonable clinical assurance that a steadystate has been achieved by providing the drug at the appropriate receptor sites at all times. The fourth consideration in the following list is not clearly associated with methadone in the context of chronic, stable dose administration, but it is known to virtually all clinicians who work in the MMT field. 1. Prevention of onset of withdrawal symptoms for 24 hours or more. Symptoms of withdrawal include the autonomic-type symptoms, such as palpitations, sweating, nausea, diarrhea and rhinorrhea. with the corresponding physical fmdings, such as increased pupil size and tachycardia. Symptoms may also include various types of pain and achiness. Severity of early withdrawal is entirely subjective, so adjustments are often made

THE DOSE ADJUSTMENT Dose adjustments for each patient are part of the MMT program, and may require additional appointments with the physician in the course of treatment. At many clinics, for example, the initial dose is no greater than 30 mg. An initial dose of 30 mg may or may not be adequate. Federal guidelines do provide for the physician to exercise clinical judgment in determining dosage during induction, provided that such actions are justified in the clinical record. As the induction phase continues, daily doses are adjusted by dispensing nurses under an induction order by the physician or by protocol guidelines, with patient and counselor input and with physician supervision. Methadone dosage should be individually determined by a well-trained clinician based on subjective and objective data, and it must be adequate at all times (American Society of Addiction Medicine 1990). If the dose is adequate, then the numbers are irrelevant; but in most cases the maintenance doses will be adjusted to the 60 to 100 mg range. The March 1990 report by the U.S. General Accounting Office (GAO/HRD-90-104) on methadone maintenance noted low-dose policies in many programs. The report referred to the National Institute of Drug Abuse position that 60 mg is the lowest effective maintenance dose and that doses in the range of 20 mg to 40 mg are inappropriate. In some states or clinics, dose raises above 80 mg requires special procedures. The rationale for such requirements is not known, as there is nothing in the literature to support such a limit. Medical appointments may also be requested by the counselor or nurse if they have questions about the patient's dose. There are some clinics Journal of Psychoactive Drugs

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craving is severe, and whether the patient still can get high when using. In addition, some evaluation of the level of activity or somnolence may help. Some patients may prefer to feel sedated, and decide they need a dose high enough to make them drowsy. After some level of trust has been established there can be education on this point, and what constitutes a normal degree of alertness and physical activity. Medical reasons that shorten the half-life of methadone should be ruled out in any dose raise request. This is especially true if the patient has been fine at a steady dose and suddenly starts having withdrawal symptoms. Increased metabolic rate in hyperthyroidism or pregnancy, or induction of liver enzymes by alcohol or a newly prescribed drug- such as phenytoin or other anticonvulsants, with the exception ofvalproic acid (Saxon, Whittaker & Hawker 1989)- are some examples of this. A sudden increase in strenuous, daily physical activity may fall under this heading. Documentation by serum methadone levels may become a useful tool as laboratory fees for this test are reduced. Liver damage from alcohol at first induces enzymes, thus speeding up methadone metabolism, but in severe hepatitis or cirrhosis the requirement for methadone may actually drop as the liver becomes less able to break it down. On the other hand, research (Novick et al. 1985) has not only established the absolute safety of methadone in severe alcoholic liver disease, but it has also demonstrated that with maintenance of normal methadone doses there was no buildup; in fact, peak levels of methadone were reduced. Careful monitoring is advised in such cases. Physical examination and laboratory tests at the follow-up physician visit depend on the history obtained. At the very least, it should include vital signs, signs of use (e.g., fresh tracks), withdrawal signs, and an examination of the liver. Of considerable concern to the MMT practitioner is the possibility that in spite of raising the methadone dose the patient will continue to use opioids, increasing opioid tolerance in a never-ending cycle. Prior to ordering the dose increase, the clinician should make an effort to determine if the patient really wants to stop using the illicit opioid If this appears to be the case, then the patient must be made aware that the discontinuation of fixing must ccr incide with the dose increase. Ideally, the dose increase should meet the combined tolerance resulting from methadone plus the illicit opioid. The transaction may include a therapeutic agreement with the counselor, physician, and patient at the time of dose raise. For example, if a patient is taking 80 mg and is still waking at 3:00a.m. with withdrawal symptoms relieved by use of heroin, the agreement might be to raise the dose to 90 or 100 mg at once, with the patient promising not to use for at least two weeks (the time it takes to become tolerant to the increased

based on subjective reporting by the patient. 2. Reduction or elimination of drug craving. The desire to use drugs may be quite intense for patients and may be based on physical, psychodynamic and/or social factors. A patient cannot be considered to be stabilized on methadone if he or she is still wanting desperately to use. If this is the case, a dose raise is indicated. Whether this is a physical effect on receptors or a reassurance effect that the treatment system is responsive to this very uncomfortable symptom may be irrelevant No physician or other staff member has the skill or tools to verify the authenticity of accounts of drug hunger or subjective withdrawal. 3. Blockade of the euphoric effects of any illicitly self-administered narcotics (Kreek 1987). This falls under the category of reducing incentives to use. Many patients report an inability to feel high when using other drugs at a particular methadone dose. This is referred to as a blockade dose of methadone. It may not translate into a biochemical blockade of receptors, but it does represent an increase in tolerance to preclude the usual effects associated with street drugs. There are times when a raise in dose can be a very practical way of discouraging illicit narcotic use. 4. Control of emotional pain. If one uses a psychodynamic model, which views addiction as a way to numb emotional pain from various psychological traumas, it makes sense to try to achieve emotional comfort for the patient Some patients have been self-treating with their narcotic abuse, and while in MMT an underlying related psychiatric diagnosis may emerge (Mirin et al. 1988; Mirin 1984; O'Brien, Woody & McLellan 1984). Many appear to have low stress tolerance or a poorly developed ability to soothe themselves when upset (Khantzian & Schneider 1986; Khantzian 1985, 1982, 1981 ). The counselor is in the best position to detect developing anxiety or depressive symptoms, which the patient often feels as a need to use drugs. For example, a visit from relatives or an impending trial may present as a dose increase request. This can be an ideal time to introduce nonchemical coping skills. However, if a significant risk is perceived, an increase in the dose of methadone may be ordered. It may be that this benefit will persist only until tolerance to the increased dose is established. One might consider reducing the dose after the stressful event passes. The above considerations should be held in mind at the time of a physician appointment to consider a dose adjustment. The medical history should include questions about withdrawal symptoms, frequency of use, whether JowrNJI of Psyclwaclive Drugs

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dose) because it will defeat any benefit of the dose increase. If at the end of the two-week period there are still withdrawal symptoms, the dose can be raised to 100 mg or more, if not done earlier. At this point, blood plasma levels of methadone can be considered. During the twoweek period, random urine tests are performed to document abstinence. The advantages of this kind of agreement are twofold First, the patient feels that he or she has been heard because the system has been responsive and acted rapidly to relieve symptoms. In the event the dose is not adequate, the two weeks of abstinence bring tolerance threshold down to maintain the patient in his or her comfort zone. It is important that the patient knows this is not the last resort and that a contingency plan exists in case the new dose is not enough. Second, a precedent has been set: the counselor and the physician have acted as helpers, within a structure that sets clear limits and has defined expectations of the patient This therapeutic model will be used over and over in the recovery process. For many years, one of the present authors (Payte) has used a temporary increase followed by a gradual taper to the previous maintenance dose. This is usually done from 80 to 100 mg, with an abrupt increase of 20 mg or more. Then after 7-10 days, if stable, the dose can be reduced at a rate of 4 to 5 mg every 7-14 days to the original maintenance dose. At times, a dose well in excess of 100 mg may be needed to regain control.

withdrawal several times a day, constipation is usually not a complaint on admission, but it often develops after steady-state methadone is achieved. Tolerance does develop to the constipating effect, but may take several months to a year or more. Consequently, treatment of this side effect is sometimes necessary. A reduction in dose may be helpful in some cases. Harsh laxatives are to be avoided as dependence is easily established It is important that the patient's diet is varied and contains some grains and fiber. The following four measures are a standard treatment for constipation; no one or two steps will be effective by themselves and best results are achieved by applying all four measures: (1) a stool softener, such as docusate sodium (250 mg)- take two capsules in the morning and evening until relieved, then two capsules daily in the morning; (2) a lubricant, such as Kondremul or plain mineral oil- take four tablespoons daily at bedtime until relieved, then two tablespoons daily at bedtime; (3) a natural laxative, such as six to 10 stewed prunes daily; and (4) fluids -drink at least two quarts of water daily. Another common problem in MMf is weight gain. In some cases, food would seem to function as a replacement drug, as overeating assumes patterns of addictive behavior; but more often weight gain is thought to be a result of changes in life-style and is probably not a hypothalamic or metabolic effect of methadone. In the early stages of treatment the patient may move from being very active physically in drug seeking and various illegal street activities to a more sedentary or even isolated life. For example, patients in early treatment may become isolated at home watching TV all day in an attempt to avoid the temptation to be with their usual friends. Even walking down the street may be a hazardous activity because of street contacts. An exercise program may be suggested in the early stages of treatment, but it may be beyond theresources of patients to carry out. Inasmuch as many patients are heavy smokers, the usual respiratory and cardiovascular problems associated with heavy smoking are encountered. Concern is often expressed over the respiratory depression attributed to methadone. In chronic administration of methadone, tolerance to respiratory depression is developed to the extent that even in cases of chronic obstructive pulmonary disease, methadone can be continued under careful supervision.

SIDE EFFECTS In general, side effects of (as well as toxicity to) methadone are similar to those for morphine, which are well described in standard pharmacology texts, such as Jaffe and Martin's chapter (1985) in The Pharmacological Basis of Therapeutics. While the steady-state property of methadone allows a degree of adaptation and normalization of endocrine and neuroendocrine effects that cannot take place with short-acting opioid agonists (Kreek 1986), it may make other side effects, such as constipation, more problematic. Excessive sweating, lymphocytosis, and increased plasma concentrations of prolactin, albumin, and globulins have been noted during chronic administration of methadone (Jaffe & Martin 1985). One is in the position of choosing a steady blood level of a long-acting,legally prescribed opioid over the repeated euphoria-to-withdrawal cycle experienced several times a day with injected heroin. In other words, almost any problem that can occur with methadone can also occur with heroin, but may be perceived in an altered manner due to differences in pharmacokinetics. Tolerance to the constipating side effect of methadone develops slowly, in some cases taking up to three years (Kreek 1991). Perhaps because the active user goes into JourNJI of Psychoactive Drugs

WITHDRAWAL FROM METHADONE MAINTENANCE For the majority of opioid-dependent patients, MMf is most effective as a long-term modality. Withdrawal from methadone maintenance carries substantial risk associated with relapse to injection drug use. Ideally, withdrawal should be attempted only when strongly desired by therehabilitated patient Reported relapse rates vary from 80% 171

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is likely to achieve and maintain a comfortable opioid-free state for more than just a few months? In reality, the likely candidates cannot be selected; consequently, the patient who wants to try and who is prepared and well informed should be supported in the effort Should the MMT physician ever recommend this risky procedure? Perhaps not; the decision must be a team effort that includes the patient. Some patients are going to be successful, but all patients should know that they have as good a chance as anyone else. Most of the life changes that are assumed to be helpful, such as avoiding the company of other drug users, reducing known sources of stress, and the ability to maintain employment, can best be monitored by the counselor or recovery-oriented therapist. The physician's role is to support and add credibility to the counselor's message. But there are some speciflc medical triggers, such as acute pain and chronic pain syndromes, that will make relapse more likely. For example, a patient who has always used narcotics to self-medicate migraines or lower back pain may need basic education about alternative, localized treatment measures, such as heat, ice, massage, and exercise. Biofeedback, chiropractic or acupuncture may also be available in some communities.

to 90% and more by the end of the first year. Ball and colleagues ( 1988) reported that 82.1% of MMT patients return to injection heroin use by a 10- to 12-month period. Despite the grim prognosis, the MMT physician will be involved in withdrawal efforts from maintenance. In the event of relapse or impending relapse, additional therapeutic measures should be used, including rapid resumption of MMT when appropriate (American Society of Addiction Medicine 1990). There are basically three types of managed withdrawals that occur in most clinics. The frrst is an administrative withdrawal, which is done in response to some persistent or serious form of program noncompliance. The most common ones are related to clinic rules and implemented by preset protocol. For example, if a patient does not present for the annual examination, a daily drop in dose begins until the patient complies with this requirement or is discharged for noncompliance. The amount of the daily lowering of dose depends on the original dose, and the withdrawal is spread over a time span (e.g., two to four weeks) to allow the patient to establish compliance. In cases of this nature, the goal is to move the patient into compliance rather than terminate treatment by withdrawal. More serious behavioral problems, which might involve violence or the threat of violence, may require more immediate action. A second type of withdrawal is withdrawal on request, which is a patient right ensured by federal regulation. It is seen frequently with patients in early recovery. There is denial about the extent of life-style changes that are assumed to be needed to support abstinence, and patients are "ready to go off methadone now." The motivation is largely external and the decision made on impulse. It may be in response to a desire to escape the disruptive effects of program participation. The patient may be responding to pressure from family, friends or employers. At this stage the patient does not want to hear about dismal relapse rates, but he or she may be able to hear other advice about going very slowly and monitoring withdrawal and craving symptoms. When a patient-instigated withdrawal results in relapse, he or she may see it as a major failure and be very confused about why they could not get off methadone. It is important for patients to know that it is not a worsening of their initial addiction but a manifestation of how severe it was, and that relapses are a part of the disease and recovery process. Patients may be able to identify environmental or physical triggers and begin work on healthier living patterns. The third and least common type of methadone withdrawal occurs when the patient, physician, and counselor agree to attempt withdrawal as part of the recovery process having achieved psychosocial rehabilitation. This is what many treatment professionals wish for, but it is usually unsuccessful. How can the patient be identified who Journal of Psychoactive Drugs

PREGNANT PATIENTS Methadone is probably less toxic to the fetus than heroin mixed with contaminants from dirty needles. The treatment staff needs to have a clear focus on whatever works to keep the woman from using alcohol or other drugs. This is especially true during the AIDS epidemic. Ideally, one wishes babies to be born drug free, and usually the pregnant woman shares this wish for her child; thus many will express a strong desire to taper off methadone, despite the hazards of getting off and the absence of favorable conditions for staying drug free. The denial of the pregnant addict on methadone may take the form of "I can get off this stuff for my baby's sake." At the same time, the half-life of methadone may be shortened by pregnancy, and life, family, and legal custody issues raise the stress level. Consequently, the pregnancy of a patient in MMT is taken very seriously, and there is usually an increase in support and services offered to her in the clinic. There may be arequirement for periodic physician evaluation, even aside from specialized prenatal care, which is often done off-site. Whether or not withdrawal can harm the fetus is a question that arises if detoxification is contemplated. Can the physical withdrawal constellation, which includes autonomic discharge, hypertension, vomiting, and abdominal cramps lead to miscarriage or premature labor? The traditional approach has been to limit dose lowering to the second trimester to minimize these dangers, and to lower very slowly, such as 2 to 5 mg a week during that time. 172

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Withdrawal from methadone during pregnancy can be accomplished in expert hands with careful fetal monitoring. The patient in withdrawal is at considerable risk and should be monitored closely, so that at the first sign of relapse or impending relapse other therapeutic measures can be taken, including the resumption ofMMT when appropriate. Careful selection of candidates for this procedure is essential in view of the likely return to injection heroin use and/or alcohol and other drugs. In summary, MMT in conjunction with intensive prenatal care for pregnant opioid-dependent women can reduce the incidence of intrauterine death, neonatal death, and prematurity and its concomitant problems. When managed properly, NAS is fairly straightforward and manageable (Finnegan 1986). There are significant problems, but in general, after NAS has abated, infants develop and function within normal limits (Kaltenbach & Finnegan 1989).

There are no systematic studies to support this, and perhaps technology for monitoring pregnancy can be used to allow safe detoxification at any point Perhaps the most concerted efforts should be to get the patient off cigarettes, which are known to be associated with premature labor and low birth weight problems (U.S. Department of Health and Human Services 1988). A review of the literature does little to settle some of the persistent questions surrounding the use of methadone during pregnancy. Intrauterine opioid withdrawal is clearly a stressful event. Zuspan and colleagues (1975) showed that even a controlled methadone withdrawal during pregnancy resulted in fetal stress, as evidenced by increased levels of epinephrine and norepinephrine in amniotic fluid. Stauber, Schwerdt and Hollenbach (1982) described fetal effects of uncontrolled opioid withdrawal, including extremely marked fetal movements, with increased oxygen consumption and a danger of intrauterine asphyxia sometimes resulting in intrauterine death. Methadone dose has been associated with the presence of neonatal abstinence syndrome (NAS) (Suffet & Brotman 1984). Dose has been associated with the status ofNAS (Green et al. 1979). Dose has been associated with the frequency ofNAS (Madden et al. 1977). Dose has also been associated with the severity ofNAS (Ostrea, Chavez & Strauss 1975). Moreover, dose was found to have TW consistent relationship with severity of NAS (Rosen & Pippenger 1975). Decreasing steady-state predose and peak postdose levels of methadone in the third trimester may explain why dose increases are needed late in pregnancy (Kreek 1979). Current thinking about dose recognizes that adequacy of dose is just as important during pregnancy as at any other time. The MMT physician should remain focused on therapeutic objectives and use the lowest effective dose rather than getting caught in the politics of the lowest possible dose, which is an invitation to disaster. It remains unclear as to what the advantages are of prenatal intrauterine withdrawal over neonatal withdrawal. The former might be preferred because it is not as visible. A variety of articles from the 1960s and 1970s supports methadone doses of no more than 20 mg during pregnancy (e.g., Strauss et al. 1976). Many are based on retrospective studies with inadequate controls, and different or contradictory conclusions were reached (Ostrea, Chavez & Strauss 1975). MMT clinicians working with populations of hard-core, chronic, intractable heroin addicts being maintained on methadone may find that suggested dose extremely difficult to achieve without supplemental drug use on the part of the pregnant addict Finnegan (1991) has repeatedly stressed the large number of confounding variables inherent in studies, which makes a clear demonstration of a single variable, such as methadone, difficult at best. JourMI of Psychoactive Drwgs

DUAL DIAGNOSIS A major psychiatric disorder may be masked by drug use and uncovered during abstinence, or drug use may induce psychiatric or mental symptoms. In either case, the MMT physician will see patients with severe emotional and psychiatric disorders. This is often noticed first by the clinic personnel who see the patient most frequently, such as the dispensing nurse, counselor or receptionist, because there are clinic policies and rules about disruptive or bizarre behavior, or threats of suicide. One cannot wait until abstinence has been maintained for weeks or months to deal with the problem. Intervention often is called for before it can be established if the diagnosis represents a temporary drug-related condition or a primary second diagnosis. Referral to a psychiatrist who is familiar with addiction, recovery, and MMT is very helpful; however, in some communities they are not available. If this is the case, the MMT physician may be in the role of teaching another physician about MMT and about special considerations when working with addicted populations (Zweben & Smith 1989). Dual diagnosis issues have been covered more extensively in the literature (see Zweben 1991).

TEAMWORK WITHIN THE CLINIC Collaboration between medical and counseling staff is essential to create a healthy treatment climate for patients. Much of the stress experienced by patients can be reduced by creating appropriate staff expectations and by strengthening teamwork. Dispensing and counseling staff are on the front line and in a good position to observe early warning signs of patient deterioration. A mechanism is needed for the dispensing staff to alert the counselor when signs of trouble are observed. It is important that management works to foster good relationships between medical 173

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staff and counseling staff, as one or the other may feel that a given problem area is its exclusive territory. For example, the client may go to the nurse or physician seeking a dose increase to deal with what the counselor views as an emotional issue. The physician should also bear in mind that counselors vary a great deal in their training, and some have had little experience with medicine or medical systems. It is usual! y helpful for the physician to offer periodic training to the counseling staff on such issues as theories of the origin of opioid addiction and the rationale for using methadone, common or esoteric side effects and their possible remedies, and how rapidly will a dose increase take effect. Informing the counselor of new developments, such as the ability to evaluate plasma levels at a lower cost, may strengthen the counselor's ability to do problem-solving in puzzling situations. In addition, such training helps bridge the gap between the two disciplines, by increasing familiarity with how each approaches problems and by promoting the development of a shared language. Some counselors may come from a drug-free treatment background (either via 12-Step programs or therapeutic communities) and have negative attitudes toward the use of methadone. Familiarity with the recovery process in addictive disease is invaluable, provided there is no overt or subtle message critical of the patient who requires MMT.

selor, patient, and physician input. An exception may be filed to allow take-home privileges, curbside dosing in the patient's car, or telephone contact with the counselor instead of regular visits. Patients may need the assistance of a social worker to obtain Supplemental Security Income or Medicare. Special payment plans might be set up with clinic administrators in fee-for-service settings. Flexible strategies, always within legal guidelines, should be instituted to maintain the patient in treatment and prevent relapse at this stressful time. It is important to be as clear as possible about what can and cannot be done to accommodate the patient's disability. For example, physicians may not be able to write triplicate prescriptions to treat pain within a drug abuse treatment seuing, but can attempt to work with the patient's outside physician to encourage appropriate pain management Transportation to the clinic may be too difficult if the patient lives many miles away, but courtesy dosing at a closer facility might work tem porarily. In order to arrange for these exceptions, it is important to know the extent of a patient's disability and the prognosis for recovery. For example, when will the patient be able to walk, sit, ride in a car, or stand in line? Will the patient be incontinent and unable to give urine samples? Is this a temporary weakening from chemotherapy or is the patient terminally ill? Answers to questions like this are sometimes blurred or manipulated by the patient in an attempt to bypass clinic rules . Compassionate flexibility in setting individualized limits for this newly disabled patient conveys the message that one is willing to work together to continue recovery and prevent relapse.

SEVERELY ILL PATIENTS Some patients may have severe medical illnesses that are directly or indirectly related to their addictive disorder; or the illness may be an unrelated coexisting problem. Whenever renal or liver function is severely impaired, extra care should be exercised in monitoring for proper dose. Neither situation constitutes a contraindication for methadone. Careful dose adjustments may be needed, and whenever long-term treatment with a new drug is instituted, status should be reviewed. Most common medical problems are compatible with program compliance, including required counseling, urine testing, and routine earning of take-home privileges. Hospitalization of patients is handled differently in different communities. In general, the daily methadone dose is continued throughout the hospital stay, and may be administered like any other medication on the chart orders, or in some cases it is brought to the hospital by the methadone clinic's dispensing nurse. On discharge, a call to the clinic documents the amowll and time of last dosing, and dosing is taken up again according to clinic routines. The patient is interviewed and examined by the clinic physician on return to the clinic to ascertain that the dose is still appropriate. Disabled patients may require some adjustments in clinic routines. Treatment should to be tailored, with counJournal of Psychoactive Drugs

THE PATIENT WITH LIMITED COMMITMENT TO RECOVERY Sometimes it is difficult to believe that patients really want to get off drugs. Even though patients have presented for treatment, paid the fees, and filled out the forms, they may also be abusive to staff, continue to use illicit drugs, and not show up for regular doses or appointments. This usually occurs early in the course of treatment, and the unwelcome behaviors often subside as the patient begins to know the counselor and clinic staff personally. The structured part of the treatment plan is key here . One of the messages to be conveyed to patients is that the rules are real, and these are the limits set by the clinic staff (and the government in some cases). Experienced clinic staff know not to assume that patients will always be this way, that it might be the addiction talking, and that next week things may be totally different and to welcome appropriate behavior as it appears on the horizon. Staff teamwork is especially important here, particularly a sensitivity on the part of the staff to the behavior of patients, which could 174

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are usually started on methadone; the alcohol abuse is addressed in counseling. When appropriate, disulfiram can be administered at the dispensing window. Deciding who to test and under what circumstances affects the entire clinic and treatment staff. Policy should be carefully determined so that alcoholic patients are not refused MMT and life-threatening illnesses are not ignored.

polarize them in a conflict over whether to terminate treatment. Inasmuch as the literature suggests a strong correlation between retention and outcome (Gerstein & Harwood 1990; Hubbard et al. 1989), it is important to make every effort to reach the difficult patient and cultivate staff tolerance for slow progress.

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OTHER DRUG ABUSE IN METHADONE MAINTENANCE

HIV DISEASE AND METHADONE Numerous studies have demonstrated that MMT is effective in reducing the incidence and spread of HIV disease among injection opioid users (Barthwell & Senay 1989; Brown et al. 1989; Cooper 1989). Novick and colleagues (1989) have shown that the significant abnormalities of cellular immunity associated with injection heroin abusers can be normalized with long-term methadone maintenance.

Abuse of alcohol, cocaine, benzodiazepines, nicotine, and other drugs is common in methadone-maintained patients. In general, they should be treated as separate but related problems against a background of continued methadone maintenance. Before launching an intervention into this drug abuse, one must be certain that it does not represent self-medication in response to an inadequate methadone dose. Even if a patient is taking 100 mg daily, the numbers alone do not assure that the drug is available at the receptors on a continual basis. One of the present authors (Payte) has seen very low (less than 100 ng/ml) and "none detected" methadone blood levels 24 hours after an observed dose of 100 mg. It is also important to remember that just because a patient is abusing diazepam, for example, it does not mean that MMT is not working. Continued or resurgent alcohol abuse is a heartbreakingly common problem in MMT, often leading to severe complications and death. Some clinics have standardized on-site alcohol testing protocols using breath or saliva. Giving a dose of a psychoactive substance to a patient known to have a positive test for alcohol (however tolerant they may be) is not advisable. To tell a severe alcoholic that he or she cannot be medicated if they test positive for alcohol is sometimes the same as saying that he or she can never be medicated with methadone, because it is impossible for them to remain alcohol free for even a day or two. Alcoholism is not a contraindication to MMT, and patients

CONCLUSION A current perspective on sound medical practices for the admission and management of methadone maintenance patients has been presented. It is important for physicians to appreciate that in many parts of the country, medical decision-making is unduly influenced by policies established by personal preferences rather than informed data. The recommendations in the present article are consistent with the voluminous literature on methadone maintenance, which has been more thoroughly researched than any other drug abuse treatment modality. It is expected that understanding will continue to grow, and some oftoday's practices will be refined in the light of future developments, with the aim of improving the ability of MMT programs to respond to the complex needs of the opioid-dependent population.

REFERENCES Counwright, D.; Joseph, H. & Des Jarlaia, D. 1989. Addicts Who Survived: All Oral Hi.rtoryofNarcotic Use inA!Mrica,J923-1965. Knoxville: Univenity of Tennessee Preu. Finnegan, L.P. 1991. Senior Advisor on Women's Issues, National Instiwte on Drug Abuse; Associate Director for Medical and Clinical Affairs, Office for Substance Abuse Prevention. Personal communication. Finnegan, L.P. 1986. Neonatal abstinence syndrome: Asseument and pharmacotherapy. In: Rubaltelli, F.F. &. Granati, B. (Eds.)NeoMtal Therapy : An Update . New York: Elsevier. Gerstein, D.R. &. Harwood, HJ. (Eds.) 1990. Treating Drwg Problems: Volwme 1. Washington D.C. : National Academy Preas. Green, M; Silverman, I.; Suffet F.; Taleporos E.&. Turkel, W.V. 1979. Outcomes of pregnancy for addicts receiving comprehensive care. American JourMI ofDrwg and A/coital Abwse Vol. 6(4): 413-429. Havauy, B.; Hargreaves, W.A. &. DeBarros, L. 1979. Self-regulation of dose in methadone maintenance with contingent privileges.

American Society of Addiction Medicine. 1990. American Society of Addiction Medicine policy statement on methadone treatment. Washington, D.C.: American Society of Addiction Medicine. Ball, J.C.; Lange, W.R; Myen, C.P & Friedman, S.R. 1988. Reducing lhe risk o( AIDS lhrough methadone maintenance trealmcnL JourNJJ of Health and Social Behavior Vol. 29: 214-226. Barth well, A.&. Senay, E. 1989. Patients successfully maintained with methadone escaped immunodeficiency virus infection [letter]. Archives ofGuural Psychiatry Vol. 46(10): 957-958. Brown, L.S., Jr.; Otu, A.; Nemoco, T.; Ajuluchukwu, D. & Primm, B.J. 1989. Human immunodeficiency virus infection in a cohon of intravenous drug users in New York City: Demographic, behavioral, and clinical features. New York Swte JourNJI ofMedicine Vol. 89(9): 506-510. Cooper, J .R, 1989. Melhadooe treaunent and acquired immiDlOdeficicncy syndrome. JourtWI of the American Medical Association Vol. 262(12): 1664-1668.

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Novick, D.M.; Kreek, MJ.; Arns, P.A.; Lau, L.L.; Yancovitz, S.R. & Gelb, A.M. 1985. Effect of severe alcoholic liver disease on the dis position of methadone in maintenance patients. Alcoholism: Clinical and Experimental Research Vol. 9(4): 349-354. Novick, D.M.; Ochshorn, M.; Ghali, V.; Croxson, T.S.; Mercer, W.D .; Chiorazzi, N. & Kreek, M.J. 1989. Natural killer cell activity and lymphocyte subsets in parenteral heroin abusers and long -term methadone maintenance patients. Journal of Pharmacology and Experimenlal Therapeutics Vol. 250(2): 606-610. O'Brien, C.P.; Woody, G.E. & McLellan, A.T. 1984. Psychiatric disorden in opioid dependent patients. Journal of Clinical Psychiatry Vol. 45(12): 9-13 . Ostrea, E.M., Jr.; Otavez, CJ. & Strauss, M .E. 1975. A study of the factors that influence the severity of neonatal narcotic withdrawal. Addictive Disease Vol. 2(1 -2): 187- 199. Payte, J.T. 1989. Combined treatment modalities: The need for innovative approaches. Journal of Psychoactive Drugs Vol. 21 (4): 431 -434. Platt, J.J. 1986. Heroin Addiction : Theory, Research, and Treatment . Malabar, Florida : Krieger. Rosen, T.S. & Pippenger, C.E. 1975. Disposition of methadone and its relationship to severity of withdrawal in the newborn . Addictive Disease Vol. 2(1-2): 160-178. Saxon, AJ.; Whittaker, S. & Hawker, C .S. 1989. Valproic acid, unlik e other anticonvulsants, has no effect on methadone metabolism : Two cases. Journal of Clinical Psychology Vol. 50: 228-229. Simpson, D.D. 1981. Treatment for drug abuse : Follow-up outcomes and length of time spent. Archives of General Psychiatry Vol. 38 : 875-880. Stauber, M.; Schwerdt, M . & Hollenbach, B. 1982. Pregnancy, labor, and puerperium in heroin addicted women with reference to the present state of knowledge. [authors' trans .] Geburtshilfe und Frauenheilkunde Vo1.42(5): 345-352. Strauss , M.E.; Andreseko, M .; Stryker, J .C. & Wardell , J .N. 1976. Relationship of neonatal withdrawal to maternal methadone dose. American Journal of Drug and Alcohol Abuse Vol. 3(2): 339 -345. Suffet, F. & Brotman, R. 1984. A comprehensive care program for pregnant addicu: Obstetrical, neonatal, and child development outcomes. International Journal of the Addictions Vol. 19(2): 199-219. U.S . Department of Health and Human Services . 1988. The Health Consequences of Smoking : Nicotine Addiction . A Report of the Surgeon General. Washington, D.C.: U.S. GPO. Zuspan, F.P.; Gumpel, J.A .; Mejia-Zelaya, S.; Madden, J. & Davis, R. 1975. Fetal stress from methadone withdrawal. American Journal of Obslelrics and Gynecology Vol. 122(1 ): 43-46. Zweben, J.E. 1991 . Counseling issues in methadone maintenance treatment. Journal of Psychoactive Drugs Vol. 23(2). Zweben, J.E. & Payte, J.T. 1990. Methadone maintenance in the treatment of opioid dependence: A current perspective. Western Journal of Medicine Vol. 152(5): 588-599. Zweben, J.E. & Smith, D.E. 1989. Considerations in using psychotropic medication with dual diagnosis patients in recovery. Journal of Psychoactive Drugs Vol. 21 (2): 221 -229.

201. Mirin, S. 1984. Substance Abuse and Psychopathology. Washington D.C.: American Psychiatric Press. Mirin, S.M.; Weiss , R.; Michael, J. & Griffin, M. 1988. Psychopathology in substance abusers: Diagnosis and treatment. American Journal of Drug and Alcohol Abuse Vol. 14(2): 139-157. Newman, R.G. 1987. Methadone treatment: Defining and evaluating success . New England Journal ofMedicine Vol. 317(7): 447-450.

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