Abstract: This article presents strategies to improve the results of methadone treatment which currently are very variable. Dose levels and take-away provisions can have profound effects on the effectiveness of methadone treatment. Here we have some practical approaches to the patient who is not doing well in treatment.
Patients need sufficient doses and adequate psychosocial support.
A large and consistent body of research evidence gives us clear indications how to optimise the use of methadone in treating heroin addiction. Doses need to be sufficient in order to retain patients in treatment, reduce needle sharing and keep illicit drug use to a minimum. In addition, the regimen of dosing, supervision, urine testing and psychosocial supports need to be appropriate and acceptable to the patient population.
Some may be surprised at the statement that "95% of opioid dependent patients can achieve abstinence from injected drugs while in treatment". This is a quote from Dr Vincent P. Dole who originated methadone maintenance treatment. He said that to maximise outcomes in this way, methadone needs to be given in sufficient doses, in the right clinical circumstances and with adequate psychosocial supports [ref 1].
Clinical recommendations in several countries recommend doses in the range 60mg to 120mg daily for the majority of patients [ref 2] However, for a variety of reasons, many patients are still taking lower doses with correspondingly unsatisfactory results [ref 3.].
The initial methadone study in 1964 employed doses up to 180mg daily with a mean of 103mg (range 10-180mg) [ref 4.].
Cross tolerance between heroin and methadone.
Since there is cross tolerance with other opioids, patients who continue to use heroin regularly should be candidates for additional methadone. If heroin use has been sporadic and small in quantity, patients may well be advised to persist with the current dose. However, when heroin use has become regular such as several times weekly, a dose increase should be considered, usually of 5 to 10mg daily. This assumes that there is not excessive sedation from the dose and if there is any doubt an examination 3 hours after a supervised dose is often instructive and reassuring for both clinician and patients.
Inadequate doses of methadone can also be associated with increased cocaine use [ref 5]. Patients on inadequate methadone doses may also find it more difficult to stop drinking or to detoxify from benzodiazepines. Most importantly, they drop out of treatment and return to illicit drug use.
The patient's dose should be sufficient to abolish cravings for 24 hours. Sometimes the patient may not describe cravings, but will have other symptoms indicative of an inadequate dose. These can include a general malaise or frank depression. Patients will have one or two responses to such a situation, either suffer in silence or resort to illicit opioid use. Either way the patient is likely to be less than fully functional.
Patients needing more than 120mg may be rapid metabolisers and/or they may have had higher than average tolerance. Only a small proportion, perhaps a fifth of the total, need high dose (>120mg daily) and some only for short periods. Metabolism is a function of the patient's cytochrome enzyme characteristics and has little to do with how much drug they used or to their 'degree of addiction', etc. There is also a substantial minority, perhaps another 20%, who fare perfectly well on doses of less than 60mg daily.
There have been isolated reports of doses up to 300mg daily but these should only be used in specialist centres in clinical research settings. This may be due to altered opioid tolerance and/or metabolism and can be due to drug interactions or pregnancy. (see blood levels, below).
There may be a resistance to high doses from both patients and staff. This may be due to a natural conservatism or misunderstanding of the treatment. On occasions, genuine side effects can limit the usefulness of methadone. Some patients will tolerate such side effects, while others will reduce their dose or drop out. Doctors are used to this 'balancing act' with side effects caused by many other drugs. The patient is the final judge and will decide based on benefits versus adverse effects. Where outcomes are unsatisfactory despite dose adjustment then alternatives should be looked at such as adding an antidepressant or even changing the patient to buprenorphine.
Apart from some sedation in the first days of treatment, there are few side effects reported with methadone. Sweating and constipation are the only common side effects and these are rarely dose limiting. Impotence and menstrual irregularities are common with heroin and usual improve on methadone. The improvements following appropriate dose adjustments are usually very gratifying. Any side effect can be addressed by graduated dose reductions.
Strategies to encourage appropriate dosing.
It is often helpful for the prescriber to engage an unstable patient more intensively. While there is continued use of illicit opioids and/or stimulants there should probably be regular weekly consultations with the treating doctor. Such visits need be no more than 20 minutes in most cases. It is helpful to discuss a range of related issues such as general health, dose levels, side effects, supplementary drug or alcohol use, 'track' marks, vein care, finances, employment and family matters. Not all of these matters need to be broached at each visit.
It may then be helpful to focus on the person's major particular presenting problem or nominated goal. For example: 'I've just got to save some money for rent'; 'I really need to get away from the needle'; 'My liver pain is getting worse and worse'; 'I should take less time off work or else I might lose my job'; 'I need to spend more time with the family'. Any one of these would be a useful starting point as there is often intercurrent drug use contributing to the problem and making the goal less achievable. A notation should always be made in the medical records for future reference.
After these practical problems have been identified, it is then useful to assess the patient's responses to treatment, including current dose level and past history of MMT. It may be helpful to place the patient's treatment into perspective by pointing out the wide range of methadone doses used, even up to 300mg or more. Such "high-pointing" may have a reassuring effect in itself by taking the emphasis away from 'minor' dose adjustments.
It is then useful to discuss the benefits and drawbacks of a higher dose in the individual case. Side effects are usually minor when compared with the consequences of continued illicit drug use.
The patient may have been on higher doses previously with good results. Experience has shown that the majority of patients who have a relapse tend to have to return to their own maximum "plateau" dose before regaining control.
Some patients will volunteer that they have taken large doses of 'street' methadone and can report the results. "Have you ever taken extra methadone?" "What happened when you did?" "How much did you take?" "Did you get 'stoned'?" "Did you use other drugs or alcohol afterwards?" This is all taken in the strictest medical confidence, and it is worthwhile saying so, even to the point of not writing actual details in the regular medical records if the patient prefers.
Fear of eventual reductions.
There is often a resistance to higher doses because of a fear of 'coming down again' and 'how hard it will be'. We need to reassure patients that reductions from 100mg to 50mg are the easy part and can often be done within a month or two. However, the major effort is needed for the lower steps of reductions such as from 50 to 25, or 25 to zero, according to most patients. Such drops usually take months and sometimes even years.
Fear of methadone in pregnancy.
Some women state that pregnancy is a good reason for not increasing doses. But in a setting of continued heroin use it is more important than ever. It is much safer to take a little more methadone and eliminate extraneous street drug or alcohol use wherever possible. While abstinence is doubtless preferable, there is also a high risk of foetal complication from relapse during the stressful episodes which inevitably occur, even in normal pregnancies.
Fear of incarceration.
Another common piece of 'home logic' from the patient may be: "I might be arrested and then I will hang out in the cells". Patients who give false names for minor infringements or 'warrants' cannot very well request methadone in their own name. We can reassure such anxious patients on two accounts. Those fearing arrest should also be reminded that when taking adequate doses of methadone they are far less likely to be apprehended. And if arrested, a stable patient on higher doses is more likely to be able to provide a good record of attendance and progress, thus making bail or acquittal more likely.
But patients who are taken into custodial care should receive every endeavour by their doctor to have their medication continued by some means or other. All prisons have medical services with access to appropriate medications. Methadone and even buprenorphine are becoming more routine in jails around the world. It works as well and may be even more important than in the community due to the higher risks in prison.
Fear of termination of treatment.
We should also reassure patients that their treatment will not be terminated arbitrarily. It is no longer acceptable to cease treatment abruptly, especially as a 'punishment' for continued illicit drug use. If there are serious behavioural problems, patients may sometimes be transferred to another service, but they should always have some realistic medicated option, even though it may not be as convenient.
Intolerance of methadone additives.
Another barrier to correct dosing may be the various constituents of prescribed methadone. Sorbitol, alcohol, preservatives, flavouring, colouring and other ingredients appear to affect some people adversely. Sugar-free solution is now available in Australia and its release has revealed a substantial proportion of patients are much better off without the additives in the older preparation. Considering the poor dental health of many methadone patients it may be that the pure solution should be use first-line.
In summary, unstable and unhappy patients should carefully consider the matter of dose for a reasonable period before deciding on an increase. The dose can always be reduced again if desired. It is very important that the patient does not feel forced into higher doses without consent. It is the patient who must bear the consequences of higher or lower doses. And there is often excess sweating and constipation. Research shows added benefits when patients have a direct input into their dose level. This happens with other forms of therapeutics such as analgesic, antidepressant, antipsychotic and anxiolytic treatment.
Blood 'trough' levels for guidance and reassurance.
Another strategy in some cases is to order a 'trough' blood methadone level, 24 hours after a supervised dose. This is advisable for patients taking doses above 120mg daily, at least once, to demonstrate their rapid metabolism. It is a safeguard for both patient and doctor. In those who are still using other drugs, the level is very often in the low range, indicating the scope for substantial dose increases. This information always helps patients and their doctors to know that they are not having the drug 'build up' in the body, nor that it is 'getting into the bones' or cause other residual side effects. It is very rare to find levels in the 'toxic' range (>1.0mg/l) but a small number may have very high tolerance and require such levels under specialist treatment. It is clear that those in the range 0.2 to 0.6mg/l do better than those with levels below that range. Most patients are quite happy and stable in the lower end of that range. Dose increases should only be implemented with patient consent and for clinical reasons such as illicit drug use, cravings, insomnia, depression, etc, and only when these symptoms do not resolve with simple measures and the passage of some time.
Ref 1. Dole VP. In Ball J, Ross A: The Effectiveness of Methadone Maintenance Treatment. Springer-Verlag, New York 1986. Foreword p viii.
Ref 2. Drug Misuse and Dependence - Guidelines on Clinical Management. 1999 The Stationary Office. Working Group Chair: Strang J.
Ref 3. D'Aunno T, Folz-Murphy N, Lin X. Changes in Methadone Treatment Practices: Results from a Panel Study, 1988 - 1995. American Journal of Drug and Alcohol Abuse 1999 25;4:681-700
Ref 4. Dole VP, Nyswander ME. A medical treatment for diacetylmorphine (heroin) addiction. J Amer Med Assoc 1965;193:646-50 '193(8) 80-84'
Ref 5. Hartel DM, Schoenbaum EE, Selwyn PA, Kline J, Davenny K, Klein RS, Friedland GH. Heroin use during Methadone Maintenance Treatment: The Importance of Methadone Dose and Cocaine Use. Am J Public Health. 1995;85:83-88.
written by Dr Andrew Byrne and Dr Richard Hallinan
Sincere thanks are due to Dr Stefan Goldfeder who suggested the exercise originally and gave useful comments on the manuscripts at several points during its gestation.
