Literature Review - Methadone Maintenance Treatment

5. Program Policies

5.1 Admission Criteria

Specific admission criteria for entry into methadone maintenance treatment programs vary, depending on the country and the jurisdiction.¹¹

According to Gossop and Grant and Uchtenhagen (as cited in Ward, Mattick and Hall, 1998a, 178), internationally, the criteria for determining who enters methadone maintenance treatment have become more liberal in recent decades; the age requirement has been reduced, as has the length of dependence required for entering treatment. In addition, people who use other drugs in addition to illicit opioids may no longer be excluded. Gossop and Grant and van Ameijden (as cited in Ward et al., 1998a, 179) note that minimal entry criteria - in "low threshold" programs in the Netherlands, for example - also reflect an effort to provide methadone maintenance treatment as a public health measure to reduce the transmission of HIV among injection drug users.

Ward et al. (1998a, 198-199) argue that, because illicit drug use is such a costly problem - for individuals and for society - admission to treatment should be given to anyone for whom "the individual and social harms associated with illicit drug use are likely to be reduced by entry to treatment". Since there is a "growing body of evidence (see Chapters 2 & 3) that opioid replacement therapy can be an effective intervention in the lives of many drug users....then the harm associated with not taking [a] person into treatment has to be weighed against the benefits of reducing the severity of their drug-related problems" (Ward, et al., 1998a, 190).

In addition, according to their review of the evidence, Ward et al. (1998a, 192) suggest that "individuals should not be excluded from treatment because of the extent and severity of their problems" because there are no reliable criteria to determine which groups of individuals will not respond to treatment.

5.2 Assessment

According to the studies reviewed by Ward et al. (1998a, 195), "there is no evidence that a protracted assessment process for opioid replacement therapy results in the selection of a more motivated group of patients. On the contrary, the evidence indicates that an individual's suitability for opioid maintenance should be done briefly and medication administered as quickly as possible." Ward et al. (1998a, 193) point out that individuals who did not complete the assessment process may have been discouraged by the process itself. Maddux et al. (as cited in Ward et al., 1998a, 195) suggest that, following a brief initial assessment of suitability for treatment and the initial administration of methadone, a more thorough assessment could be completed as clients/patients come in to get their medication.

5.2.1 Overall Purpose of Assessment

Based on their review of the literature, Ward et al. (1998a, 199) conclude that assessment should be understood, not as a series of barriers to exclude certain individuals from treatment, but as an opportunity to "establish the beginnings of a working relationship." In other words, assessment is the start of the treatment itself, and the assessment interview is an important first opportunity to introduce a person to the program, and what to expect from it. According to research by Bell, et al., Kauffman and Woody, Langrod, Miller and Rollnick, and Woody et al. (as cited in Ward et al., 1998a, 196) a client's/patient's first contact with a treatment agency influences the nature of the therapeutic relationship that ensues.

Unfortunately, as Hunt et al. and Rosenblum et al. (as cited in Ward et al., 1998a, 196) found, methadone maintenance treatment has a poor image among injection drug users. Ward et al. (1998a, 196) suggest that, given their ambivalence about methadone, the assessment period should not be used to further discourage would-be participants, but rather should be seen as an opportunity to demonstrate the benefits of treatment. For example, the use of techniques such as motivational interviewing, developed by Miller and Rollnick, could be useful to help applicants consider the advantages and disadvantages of treatment (Ward et al., 1998a, 196). As Bell et al. (as cited in Ward et al., 1998a, 196) have pointed out, applicants need to make informed, rationale decisions as to whether or not to enter treatment, and the decision should be their responsibility. In addition to the purposes aforementioned, Miller and Rollnick (as cited in Ward et al., 1998a, 197) suggest that the assessment process is an opportunity to define a therapeutic relationship, and reconfigure the client's/patient's motivation to change their drug use and their attitudes to treatment.

5.2.2 Comprehensive Approach to Assessment

In addition to a medical assessment for the DSM-IV diagnosis of opioid dependence (Brands & Brands, 1998, 29), a comprehensive approach to assessment should include a "detailed exploration of the individual's history and current status" in terms of potential opioid-related medical/health complications; social complications, and psychological difficulties (Ward et al., 1998a, 190). The assessment process should include:

• physical examination, taking vital signs (Glezen & Lowery, 1999, 236), and ordering laboratory tests such as HCV and liver-function tests
• medical assessment by a physician or nurse-practitioner (Glezen & Lowery, 1999, 236), including taking a history of infections (e.g. HIV, HCV, tuberculosis) and other drug-related medical problems to determine extent of physical harm resulting from drug use
• assessment of the history/pattern of opioid and other substance use (Stitzer & Chutuape, 1999)
• determining the extent of social life disruption (through questions about involvement in crime, prostitution, loss of employment, broken relationships and loss of housing)
• questions about past and current involvement in high-risk behaviours, i.e. for the transmission of STDs, and for the transmission of HIV, HCV and other blood-borne pathogens
• assessment of the extent to which drug use and related problems have led to anxiety and depression (Ward et al., 1998a, 191)
• urine testing (Glezen & Lowery, 1999, 236)
• breath screening test for recent alcohol use (Glezen & Lowery, 1999, 236), and
• a meeting with counsellors to prepare the client/patient for methadone treatment (Glezen & Lowery, 1999, 236)

The use of assessment instruments such as the Addiction Severity Index (McLellan et al. as cited by Ward et al., 1998a, 191) and the Opiate Treatment Index (Darke et al., as cited by Ward et al., 1998a, 191) could help to "systematise and standardise" the assessment process, and also provide consistent data for program evaluation purposes.

A comprehensive approach includes ongoing assessment to identify emergent problems and needs during treatment.

5.3 Dosage¹²

5.3.1 Pharmacology of Methadone

The pharmacology of methadone makes it a very useful drug for treating opioid dependence. The advantageous features include the fact that methadone:

• is taken orally, which avoids risks associated with injection drug use
• has a long half-life, which means only a single daily dose is needed
• accumulates in the body, which means a steady blood level is achieved easily
• effectively suppresses opioid withdrawal symptoms, which increases comfort/compliance among clients/patients
• develops cross-tolerance (or blockades) to the effects of illicit opioid use, which decreases use of illicit opioids during maintenance
• has no serious long-term side effects when used on a long-term basis (Novick et al. as cited by Ward et al., 1998h, 207; Walsh & Strain, 1999, 50-51).

As with any drug, many factors affect the rate at which methadone is metabolized; according to Blum (as cited in Ward et al., 1998h, 207) these include individual differences in metabolic rate, excretion rate, physiological status [e.g., pregnancy], pathological status, and consumption of other drugs.

According to Leshner (1999), "The commonly held belief that methadone....[is] simply [a] substitute for heroin is wrong. Although this medication is a µ-opioid agonist, it's pharmacological and pharmacodynamic properties are quite different from heroin. Instead of destabilizing the individual, as heroin does, methadone....stabilize[s] the patient and facilitate[s] a return to productive functioning."

5.3.2 Use of Adequate, Individualized Dosages

Given that there is wide variation among individuals, in terms of their response to different doses of methadone (Strain, 1999b, 81), the evidence indicates that dosage of methadone should be individualized according to the needs of the person receiving the medication (Ward et al.,1998h, 206; Lowinson et al., 1997, 408)¹³.

5.3.3 Phases of Dosing

The purpose and amount of the dosage will also vary, depending on the dosing phase.

Initial Dose

The initial dose of methadone is given to relieve the symptoms of opioid withdrawal and establish a baseline reference point for subsequent dosing (Lowinson et al., 1997, 408). According to their review of the evidence, Ward et al.(1998h, 213) conclude that there is "considerable agreement" that initial doses should range from 10 - 40 mg. Other sources, however, have suggested an initial dose ranging from 15-30 mg (Brands et al., 2000, 236) or 20-40 mg (Lowinson et al., 1997, 408). Brands et al. (2000, 236) cite Caplehorn's study in which initial doses higher than 40 mg have led to deaths after three days of treatment.

According to Lowinson et al. (1997, 408), the severity of withdrawal symptoms is not necessarily an indication of higher tolerance or higher initial or maintenance dose. According to Drummer et al. (as cited in Ward et al., 1998h, 211) for non-tolerant individuals, a dose above 40 - 60 mg may be lethal. Ward et al. (1998h, 213) conclude that the initial dose should be based on a "careful assessment" by a physician experienced with opioid dependency.

Some authors cite evidence that suggests that split, e.g., twice daily (Institute of Medicine (IOM), as cited in Strain, 1999a, 54) or serial dosing (Ward et al., 1998h, 213) may be useful when clinicians have doubts about the level of tolerance. Extra care should be taken in dosing people with severe liver dysfunction (Ward et al.,1998h, 213).

Induction

During the induction phase (Lowinson et al., 1997, 408), the initial dose is gradually increased over a period of weeks to achieve a level that is adequate and safe (Ward et al., 1998h, 211). According to Brands et al. (2000, 236), most clients/patients can be stabilized on methadone within two to six weeks of starting treatment.

Methadone has a long elimination half-life of 24 to 36 hours, which means that, 24 hours after the initial dose, half of the original dose remains in the body (Lowinson et al., 1997, 408). Methadone can accumulate in the tissues during successive doses (Ward et al., 1998h, 213). This means the level of methadone can increase, even without an increase in the dose level (Lowinson et al., 1997, 408). Accumulation continues until a steady-state is achieved after 4-5 half lives (Lowinson et al., 1997, 408). As it can take five days to achieve a steady state plasma level of methadone - and given that Caplehorn has shown that methadone's long half-life can result in an accumulation of methadone and a resulting overdose one or two weeks after treatment begins¹⁴ - Brands et al. (2000, 236-237) suggest that dose adjustments in the range of 5-15 mg of methadone should be made only every three or four days, "depending on the severity and daily duration of the patient's withdrawal symptoms or drug cravings."

Lowinson et al. (1997, 408) divides the induction phase into "early" induction and "late" induction. In early induction, the focus is on relieving withdrawal symptoms and reducing craving by reaching a dosage that is equivalent to the established opioid tolerance level. Late induction involves increasing or decreasing the dosage to a level that is adequate to achieve the desired effects (i.e., prevent/reduce withdrawal symptoms; prevent/reduce drug craving; prevent relapse; restore disrupted physiological functions to or toward normalcy). For example, dosage may need to be increased to create cross-tolerance or a "blockade" effect and discourage the use of illicit opioids, or a lower - but still effective -dosage may be sought. Brands et al. (2000, 237) suggest that: "once a daily dose of 60-80 mg has been reached, the rate and amount of dosage adjustments should be decreased to no more than 5-10 mg every one to two weeks."

Maintenance

During the maintenance phase, an adequate, stable dosage of methadone is continued indefinitely. A steady-state of methadone is achieved and maintained, sometimes for long periods of time (Lowinson et al., 1997, 408). Brands et al. (2000, 237) note that ongoing monitoring of the adequacy of the dose is based on client/patients' self-reports of withdrawal symptoms. They suggest that clients/patients should be asked how long the methadone is lasting in terms of relieving withdrawal symptoms. The optimal dose is one that is effective "throughout the night". They suggest that dose adjustments should not be used as a means of either rewarding or punishing clients/patients. They point out that dosage increases do not necessarily encourage clients/patients to seek higher-than-needed doses, citing research by Resnick, Butler and Washton that indicates instead that clients/patients who were allowed to self-adjust their doses made "only moderate adjustments, well below the maximum attainable dose"(Brands et al., 2000, 237).

The issue of dose adequacy is also framed by the longstanding debate about the merits of "high" versus "low" dose methadone. This debate is largely about what dose level is deemed "adequate" (Ward et al., 1998h, 214). Questioning of the original high-dose protocol established by Dole and Nyswander, however, has led to the development of low-dose methadone programs in the United States. Research findings, however, tend to support the original high-dose protocol. For example, in a recent study by Strain, Bigelow, Liebson and Stitzer (1999, Abstract) both moderate- and high-dose methadone treatment resulted in reductions in illicit opioid use, but the group of people who received high doses had significantly greater decreases in illicit opioid use. Brands et al. (2000, 236) note that research by Strain, Stitzer et al. and Caplehorn and Bell has suggested that higher methadone doses (greater than 60 mg/day) are more effective than lower doses in terms of retaining clients/patients in treatment, and decreasing heroin use.

In terms of determining what the limits of methadone dose should be, the sources consulted for this review either do not set specific limits (Lowinson et al., 1997, 408), or suggest a variety of daily dose ranges: 50 - 100 mg/day (Ward et al, 1998h, 214); 20 -100 mg/day, depending on their needs (Strain, 1999b, 81); or from 50-120 mg/day (Brands et al., 2000, 236). Some people receiving methadone may require more than 100 mg/day (Strain et al., as cited in Leavitt, Shinderman, Maxwell, Chin and Paris, 2000, 408). The key aspect in determining dose, according to Brands et al. (2000, 236) is to provide an "optimal dose", i.e., one that "relieves withdrawal symptoms and drug cravings without sedation or other side-effects." [Tapering the Methadone Dose (See Section 5.6)]

5.4 Duration of Treatment

Ward et al. (1998b, 330) examine the viability of long and short-term approaches to treatment - including studies of treatment duration and post-treatment outcome; reasons for leaving treatment and post-treatment outcome; outcomes of removing treatment; and predictors of treatment tenure. They (Ward et al.,1998b, 329) conclude that a short-term approach to methadone maintenance will only be suitable for a minority of people who are opioid dependent. These individuals tend to be those with a short history of opioid dependence and access to significant social and psychological resources.

The majority of clients/patients will resume heroin use if they stop taking methadone (Ward, Mattick & Hall, as cited in Ward, Mattick and Hall, 1998c, 337). According to Lowinson et al. (1997, 412) Ball and Ross "found that 82% of the patients had relapsed to intravenous drug use after having been out of treatment for 10 months, or more, with almost half (45.5%) relapsing after having been out of treatment for one to three months." Ward et al. (1998b, 329) conclude that the goal of treatment for most people who are opioid dependent should be maintenance on methadone. This is because a maintenance orientation increases the likelihood that people will remain in treatment - and will thereby achieve the individual (and societal) benefits of treatment. Lowinson et al. (1997, 412) also point out that Ball and Ross found that length of time in treatment was the "major factor in outcome."

In their summary, Ward et al. (1998b, 330-31) suggest that "the evidence does not allow the specification of an optimum duration for methadone maintenance which would be applicable to all individuals." They also note that some evidence suggests that the majority of people are more likely to benefit from two to three years of maintenance on methadone, compared to shorter periods. In general, however, longer periods of treatment are better than shorter periods of treatment because longer stays in treatment are associated with better outcomes, specifically reduced illicit opioid use and reduced criminal activity. Individuals who leave methadone maintenance treatment before they have made significant changes, are much more likely to relapse to opioid use and criminal activity. For most people who are opioid-dependent, limiting the duration of treatment - either for financial reasons or because of program philosophy - results in serious negative consequences.

Ward et al. (1998b, 331) conclude that "the optimum duration for methadone maintenance is, therefore, for as long as the patient benefits from taking a daily dose of methadone, and given the chronic, relapsing nature of opioid dependence, there is no reason to believe that this would be for a short period of time while heroin remains relatively freely available in our society."

Involuntary discharge from treatment should be approached very cautiously given the potential consequences of discharging people from treatment. Lowinson et al. (1997, 412) note that Dole and Joseph "found that death rates for discharged persons were more than twice those of patients still in treatment." The major difference in the cause of deaths was the increase in drug-related deaths after discharge. Although that study found a sharp increase in narcotics-related deaths after leaving treatment, since that time, the AIDS epidemic has arrived, and "by 1986, AIDS had become the major cause of death among methadone patients in New York City programs." Recent research by Salsitz, Joseph, Frank, Perez, Richman, Salomon, Kalin and Novick (2000, 392) found that complications resulting from HCV infection were the second most common cause of death among clients/patients in a methadone maintenance treatment program, after smoking related conditions (Lowinson et al, 1997, 412).

5.5 Urinalysis and Monitoring of Drug Use during Treatment

5.5.1 Purpose of Urinalysis

In Canada - as in most other countries - people being treated with methadone maintenance must provide urine samples for toxicology screening. These samples are tested both to monitor compliance with methadone and to confirm self-reported use of any other drugs. Although urinalysis has traditionally been a component of most methadone treatment - and the results have been used primarily for patient management and program evaluation and research purposes (Ward et al., 1998i, 240) - it is, nevertheless, controversial. Ward, Mattick and Hall (1998i, 259) point out that urinalysis actually only measures drug use as an outcome, but there are many other important outcomes that should be taken into account such as improved health, social and psychological functioning and reduced criminal involvement.

5.5.2 Advantages and Disadvantages

Ward et al. (1998i, 242-243) summarize the suggested advantages and disadvantages of urinalysis as follows (see Table 5 ):

Table 5: (based on Ward et al., 1998i, 242-243)

• Advantages of urinalysis
• Objective measurement of drug use on which to base clinical decisions
• Monitoring of illicit drug use for program evaluation
• Monitoring of patient compliance in taking methadone
• Reduction in illicit drug use
• Suitability of results for legal purposes
• Increased patient contact with the treatment program
• Provision of a basis for staff-patient bond

• Disadvantages of urinalysis
• Implied distrust of patients
• Humiliation of patients and staff
• Inaccuracy as an indicator of drug use
• Expense

Ward et al. (1998i, 244-249) note that the most reliable method of detecting drug use is to collect and test urine samples on a daily basis, but it is not usually a practical option due to the costs, time and inconvenience for clients/patients. As a result, programs use a number of different approaches - fixed-day schedules and random schedules (including random selection of daily collected samples; fixed-interval, and random-interval schedules) - none of which ensure complete reliability in terms of detecting drug use, for various reasons.

The supervised collection of urine samples is a common practice, and is intended to ensure that samples are not tampered with. Without supervision, however, Ward et al. (1998i, 248) note that:"....it is probably impossible to devise a tamper-proof collection system." Meanwhile, there are important negative effects that result from supervision including the humiliation experienced by both clients/patients and staff. According to Ward et al.(1998i, 249): "The extent to which the negative effects of supervision on patients are worthwhile has to be weighed against the need for accurate urinalysis results."

Based on their review of the evidence, Ward et al. (1998i, 251), conclude that, if the main purpose of using urinalysis is to deter the use of illicit drugs, then research results suggest that urinalysis is not an effective method of deterrence. They argue that: "On the basis of the available evidence, it has to be concluded that there is no compelling evidence that the absence of urinalysis leads to an increase in illicit drug use."

5.5.3 Contingency Management

Despite the fact that there is little evidence to support the use of urinalysis as a means of decreasing illicit drug use, Ward et al. (1998i, 252) point out that there has been a great deal of emphasis on how best to use urinalysis results to affect drug-using behaviour. Much of this work has involved the use of behaviour modification (or contingency management) techniques -offering positive reinforcements such as increased doses and take-home privileges for negative screens, and applying negative reinforcements such as dose reductions or expulsion from treatment for positive screens.

There are distinct differences in how various authors view the effectiveness of contingency management techniques. According to a review by Robles, Silverman and Stitzer et al. (1999, 196), the use of contingency management techniques to impact on a range of behaviours - including "drug abstinence" - is effective. They (Robles et al., 1999, 218) conclude that: "Taken together, the results clearly show that drug use can be reduced when positive consequences (take-home privileges, dose increases, money) are offered for abstinence or when adverse consequences (dose decreases, treatment termination) are made contingent on continued drug use....".

The review by Ward et al. (1998i, 254) offers a somewhat different interpretation. They point out that "....although there is suggestive evidence that supports the use of dose increases and decreases in reducing illicit drug use among methadone patients, only the use of take-home methadone as a reward has been widely evaluated and found to be effective." In addition, programs that use negative consequences tend to achieve only small reductions in drug use, and drop-out rates from such programs are high. Given that people who do not receive treatment are at high risk for infection with HIV, HCV and other blood-borne pathogens, practices that increase the drop-out rate are being increasingly questioned.

Although Robles et al. (1999, 218-219) note that "aversive procedures may cause treatment dropout and associated adverse outcomes," their overall support for the use of contingency management techniques in methadone treatment appears high. However, Ward et al. (1998i, 253) are much stronger in their critique of negative reinforcement techniques, concluding that: "Although popular in the past, the use of negative consequences and expulsion from treatment as a response to drug-positive urine samples has little experimental support and may have serious public and individual health consequences." They (Ward et al., 1998i, 254) argue that such a decision should only be considered as a last resort because of the consequences, i.e. inflicting on clients/patients the pain of withdrawal.

5.5.4 Self-reports of Drug Use

The use of urinalysis to monitor drug use is based on the assumption that people receiving treatment cannot be trusted to tell the truth about their drug use. Research reviewed by Ward et al. (Magura et al.; Magura & Lipton, as cited in Ward et al.,1998i, 254-255), however, suggests that, under certain circumstances, people will provide reasonably accurate reports about their use of drugs. Traditionally, however, these conditions have not been the status quo in methadone maintenance treatment programs. Magura et al. (as cited in Ward et al., 1998i, 255) found that self-report provides as much information about drug use as does urinalysis, but both methods used together reveal more than either one used alone. Ward et al. (1998i, 260) conclude that "research has consistently demonstrated that under conditions where methadone patients do not have to be concerned about being punished for doing so, they will be truthful about their drug use." A recent review by Darke (1998a, 262) explored the literature on the reliability and validity of self-reported drug use, criminality and HIV-risk taking among injection drug users. Darke concludes the "self reports of illicit behaviours are sufficiently reliable and valid to provide descriptions of drug use, [drug] related problems, and the natural history of drug use."

5.5.5 Hair Analysis

It is important to note that there are other options for monitoring drug use that may offer some advantages for practitioners and people receiving treatment. For example, according to McPhillips, Strang and Barnes (1998, 287), hair analysis is a "powerful new tool [that] should be more widely employed in clinical practice and psychiatric research." According to studies reviewed, DuPont and Baumgartner (1995, Abstract), hair analysis is more effective than urinalysis at identifying drug users.

5.6 Tapering from Methadone

In the context of methadone maintenance treatment, the term "tapering" is a term that encompasses measures that are sometimes referred to as either "withdrawal management" or "detoxification".

Based on their review, Ward et al. (1998c, 353) conclude that it is necessary to manage methadone withdrawal syndrome and to deal with people's fears of tapering from methadone. They suggest that the tapering process should involve:

• a slow tapering of the methadone dose¹⁵
• an individualized approach to rate of dose reduction
• involving clients/patients in decision making processes, such as whether or not to reduce doses "blindly" (i.e., without client/patient knowing about the reduction) (Ward et al., 1998c, 354)
• the provision of accurate information about the tapering experience as it is happening
• the provision of supportive counselling during the transition from maintenance to abstinence
• if possible, the continuation of counselling after methadone administration ceases to help address post-methadone syndrome (Ward et al., 1998c, 355), and
• if possible, involvement in after care services and programs (Ward et al., 1998c, 355).

According to Ward et al. (1998c, 354), tapering is a very difficult time for clients/patients so the process of disengagement should be considered part of the treatment process, rather than the end of treatment.

Since the likelihood of relapse is so high, Ward et al. note that people who want to leave methadone should be advised that tapering off methadone is an option, but that it is possible to continue on methadone maintenance and lead a fulfilling life (Ward et al., 1998c, 353). In some cases, people who no longer need a highly structured treatment program may be able to continue receiving "medical" maintenance (Novick & Joseph, as cited in Ward et al., 1998c, 338).

The decision to taper off methadone may be influenced by any or all of the following: clients'/patients' expectations about tapering off methadone quickly and without any difficulties; pressure from family and friends who may not recognize that recovery is a long-term process; clients/patients sense of the stigma associated with being on methadone; and/or staff's beliefs and attitudes about the abstinence and/or methadone (Ward et al., 1998c, 354)

The inconvenience of regular attendance at pharmacy/physician's or counsellor's office/clinic may also be a reason for stopping treatment.

As Ward et al., (1998c, 354) point out: "A patient-centred approach to these issues is one where staff orient their attitudes about treatment to the patient rather than to their own beliefs about the desirability of this or that practice."

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