Could additional methadone increase cravings? 'Addiction' thinks so!

Curran HV, Bolton J, Wanigaratne S, Smyth C. 'Additional methadone increases craving for heroin: a double blind, placebo controlled study of chronic opiate users receiving methadone substitution treatment. Addiction 1999 94(5), 665-674


Rather than a useful contribution to the literature this small study confirms much of what is known about methadone behavioural pharmacology. It has one surprising finding of increased cravings in those given a one third extra methadone dose on one day, blind, with a week 'wash-out' period. This finding, being based on surveys of 18 patients and which, although statistically significant (p=0.03), was based on questions of a like nature concerning heroin craving on a small number of cases in a purely subjective area. This finding has been used in the title as though a highly important new finding despite a lack of further statitsical analysis possible and perhaps desirable on such series. The finding is out of keeping with much of what we know of methadone and the methods require closer scrutiny before being accepted. The reviewers had a difficult task as the findings would be considered controversial and rather outlandish by some.

While this is a little pedantic, I would also dispute the part of the title which states these are patients 'receiving methadone substitution treatment'. The text reveals that the patients were indeed on a treatment with a policy of 'reductions' and eventual abstinence rather than 'methadone substitution' which I use synonymously with 'maintenance'. According to the latest UK dependency guidelines, 'methadone substitution treatment' requires an effective dose of 60mg to 120mg with only exceptional cases needing less or more. These patients were not doing particularly well, judging by the frequent reported use of illicit drugs by the group. The authors state that the patients were chosen on the basis that they were on stable doses, but that the clinic had a policy of reductions to abstinence. In this cohort the average dose was 43mg, about half the level found in good quality methadone treatment services generally (and these include some patients on reductions). Hence these patients were either on inappropriate, ineffective 'methadone substitution' as defined by the UK
Guidelines or they were on reduction treatment with evidence of instability. For these reasons any conclusions as delicate as whether additional methadone could affect cravings over a few hours are based on the most shaky grounds and should be received by the academic community only with great caution.

The authors chose not to develop discussion about the most glaring finding of the study which is that a proportion of English addicts seem to be receiving sub-standard and ineffective treatment in publicly funded clinics. Some would see this as scandalous.

Comment by Andrew Byrne ..

Where is your local GP?

Have you noticed? Your GP has gone. Yes, just not there any more! A community icon for generations, this Australian institution is now in its death throes.

To find the reason, we need go no further than the dentist who charges $50 for you to walk in the door and, more often than not, another $50 to do whatever needs doing in the 15 or 30 minutes you might be there.

A plumber, vet, electrician or builder will charge about the same. The appliance repair person charges even more.

So where do doctors fit into all this? Australians were told over 20 years ago that 'Medicare' would finance doctor's fees and it would be funded out of taxation. Doctors were told that bad debts would be a thing of the past and that they would be paid promptly for their services at 85% of an agreed or 'common' fee. Successive governments of both persuasions have supported Medicare and actively encouraged bulk-billing. To this day the 'phone information line will only give information if you state that you are bulk-billing the patient. There was no arbitrated mechanism for annual fee adjustments and only on government largesse were rebates increased, at ever decreasing increments. Anyone who expected otherwise was foolish indeed.

Differential fees were introduced for doctors who jumped onto the Vocational Register. It offered a temporary relief from financial ruin by paying an extra $2.50 per consultation for bulk billed customers and refunded the extra money to those privately billed.

Doctors' practices were examined more closely than any other worker in the land. How long we spent with individuals of certain ages and sexes ... what tests we ordered ... what drugs we prescribed. All this without our consent ... even those who never bulk billed were drawn in. Now we have ludicrous committees trying to assess our 'work values'. Practice incentives have been thought up by bureaucrats with no detailed knowledge of the supposed deficiencies of general practice. As an example, it was felt that all doctors should do house calls and, along with after hours care, this is written into the agreement to be on the Vocational Register. Are patients not the best arbiters of who is a good doctor? We do it for vets and dentists, knowing little about those fields, but knowing what we want as consumers.

GPs used to work on the same street corner for 40 years and more for two reasons: There was demand for their services ... and they earned a decent income in the process.

Now traditional general practice has become unviable. This has not happened because of the supermarket revolution elsewhere. People are not demanding big medical clinics ... but they are there and they can survive better in a cut-price atmosphere. Alternative pursuits, some very valid additions to practice, can help pay the bills. These are many and varied ... acupuncture, hypnotherapy, laser treatments, drug group counselling sessions and other pursuits.

Who do we have to blame for all this? Ourselves, or our immediate predecessors to be more accurate. Any group which accepts government money must be prepared to die. Like soldiers. That is what happened to nursing homes. A perfectly viable, profitable and expanding industry for an aging population has been stifled to death thanks to government interference. Restricted subsidies and uniform regulations for nursing homes have turned a varied and free environment for our old folk into a uniform, regimented and unfriendly set of small, safe bunkers. Only the seriously rich can expect adequate retirement care.

So to the solution ... if it is not too late. I suggest that GPs do not do anything relating to a new matter for less than about $50. This is comparable with the minimum fee for many other professionals such as plumbers, vets, dentists, decorators, etcetera.

Even if an old patient just wants 'a certificate', they need to be told that they are also expecting the service which backs up that certificate, such as a history, physical and record in the medical notes. They may need their blood pressure measured. It is now widely recognised that visits to the GP for unrelated causes are important points of intervention, including blood pressure, smoking, drinking and diet just to name the most obvious. With the history known there could be Pap tests, thyroid, work related illnesses, chest X rays and a myriad of other areas which may need attention.

If the patient only gets $21 back from Medicare that is not the doctor's business. Most patients assume that doctors make lots of money and that they pay dearly in their taxes to ensure this is the case. They may not know that GPs mostly earn very modest incomes. Most specialists and employed doctors have kept their income parity, having had strong lobbies to look after their interests. GPs lobby groups have consistently acted against the interests of their constituency and continue to do so to this day. The AMA and GPs College have both failed dismally while the latter has facilitated much of the erosion to doctors' independence.

Most workers in the position doctors find themselves today would use strong-arm industrial tactics with no holes barred. Do Australian GPs have the will to take on this fight? If not, it means that the Australian public can bid farewell to the old family doctor forever. What is your strategy?

Written by Andrew Byrne ..

What can you do to reduce the alarming drug overdose death toll?

by Andrew Byrne ..

The press has been full of the disastrous toll from heroin overdoses in recent weeks, especially from Victoria. As doctors, we must face our responsibility to the community to address these matters in any way possible.

The overdose death rate in Australia rose gradually from 30 to 40 per million over a number of years in the mid 1990's. Although official figures are not available, this rate appears to have gone up from 4 deaths per week to almost 14 as reported from Victoria this year. One newspaper described it as "the overdose epidemic Australia had to have". Mostly in metropolitan Melbourne, 2 deaths per day are causing great tragedy to the families who are both ill-prepared and perplexed.

It is clear that every one of these heroin overdoses is preventable.

The means of prevention are a number of well known proven strategies as well as some proposed innovations which have shown promise in trials here and overseas. It is accepted that preventive education of addicts, availability of needles and syringes as well as methadone treatment are all effective in stemming some of the potentially lethal complications of drug use. 'Safe injecting rooms', heroin prescription, rapid detoxification, oral morphine, long acting methadone and buprenorphine are among other strategies which deserve further examination.

Improvements to our emergency services are unlikely to reduce the toll much since, in most areas, they are prompt and effective at saving lives when they are called in time.

Educating drug users about the means to save lives is important. 'Do not inject while alone'. 'Use small quantities initially'. 'Call emergency services immediately if overdose is suspected'. 'Use clean syringes'. 'Do not mix drugs and alcohol'. These are all simple but life-saving messages.

Increasing the accessibility of good quality methadone treatment will certainly reduce the death rates. It is well established that once in treatment, the mortality diminishes significantly. Methadone treatment should be available to all who require it, like any other effective pharmacotherapy. The indications are simple: chronic compulsive opiate use with proven inability to withdraw. For historical reasons this is still restricted in some states and has been banned altogether in the Northern Territory. A recent review in the Journal of the American Medical Association stated that "All persons dependent on opiates should have access to methadone hydrochloride maintenance therapy under legal supervision" [ref 1].

It is likely that bringing addicts out of secluded locations and into 'safe houses' will also spare some lives. Supervision is available and help can be summoned if overdose occurs. Most importantly, these marginalised folk can come into contact with treatment services.

Switzerland and Holland both have official death rates of less than 5 per million compared to our rates of over 40. If we could copy their examples, over 500 young Australian lives could be saved each year. These countries must be 'doing something right'. Injecting is far less common among the young in Holland where the average age of heroin injectors is around 40 years of age. The Swiss introduced 'safe injecting rooms' over 6 years ago. Switzerland has had heroin prescribed for certain groups of resistant addicts for over 5 years. Cannabis is decriminalised in Holland.

Whatever the reasons for our high overdose death rates, we desperately need to investigate all these means for reducing it. The prime reason for NOT having a heroin trial, 'sending the wrong message,' is now out of date. The second reason sometime proffered is that it 'has not worked' overseas. This is intriguing as the reported outcomes of the London, Zurich and Geneva based trials all showed benefits to addicts and society generally and a referendum in Switzerland endorsed the practice of heroin prescription to seriously addicted patients under strict supervision.

Politics, personal prejudice and international pressure must be put aside since Australian lives are too important. We need to approach this epidemic from a scientific standpoint as we did with HIV. If we can match our successes there is very much to gain.

Ref 1: Effective Medical Treatment of Opiate Addiction. National Consensus Development Panel on Effective Medical Treatment of Opiate Addiction. JAMA 1998 280:1936-1943

Gradual detoxification to 0.5mg buprenorphine 'effective' over 10 days

Diamant K, Fischer G, Schneider C, Lenzinger E, Pezawas L, Shindler S, Eder H. Outpatient Opiate Detoxification Treatment with Buprenorphine. European Addiction Research 1998 4:198-202

There are impressive outcomes reported in this Vienna study of well-motivated heroin addicts doing a structured 10 day out-patient graduated detoxification using buprenorphine sub-lingual tablets.

The authors of the study chose 50 motivated heroin or opium addicts and administered up to 10 days out-patient treatment with reducing doses of buprenorphine. Doses were titrated daily depending on the degree of withdrawal symptoms. The maximum dose was on day 2 at 2.6mg. Doses averaged 2mg daily for the first 5 days, then reducing to 1.5mg for 2 days, 1.0mg for 2 days and 0.5mg on the tenth day. For only 20% of cases was it the first formal attempt at withdrawal. Withdrawal symptoms were measured on the WANG scale and were most severe initially but waned substantially despite buprenorphine dose decreases.

Patients were also routinely given an antacid preparation (famotidine or 'Pepcidine') and night time sedation if required (prothipendyl - an antihistaminic sedative).

With 15 patients dropping out, this treatment was acceptable to 35 of the 50 patients (31 male, mean age 27) yielding an overall 70% 'success' rate. Even if only a half of these remained abstinent for the medium term, it could still be considered better outcome than traditional drug free treatment.

Buprenorphine is a semi-synthetic narcotic derived from thebaine. It is long acting (>36 hours) and has opioid agonist as well as antagonist effects, rather like pentazocine (Fortral). It has been available in Australia since 1992 as an injected or sublingual analgesic but it is not yet licensed for maintenance addiction treatment. Such maintenance treatment may require much higher doses, up to 32mg daily, so 0.2mg SL tablets are not suitable. In addition, this drug, as a Schedule 8 can only be used in addicts with prior permission from the health authorities in most Australian states.

A large multi-centre trial of the sub-lingual version has reported preliminary results which apparently confirm overseas experience showing safety and efficacy when compared with methadone maintenance. Buprenorphine also has a number of important advantages over methadone such as a longer duration of action, allowing second daily attendance, a lower potential for acute toxicity as well as a possible antidepressant effect. The researchers pointed out that this drug will not be a replacement for methadone, but may be a useful alternative for those in whom methadone is not suitable.

This drug's wider availability in Australia will greatly enhance our repertoire in dealing with drug addiction. In France it has been available on normal doctors prescription for over 3 years with apparently good results in up to 50,000 patients. In the meantime, less satisfactory drugs such as codeine compounds, propoxyphene, quinine, clonidine and metoclopramide may be used to mitigate some of the symptoms of withdrawal. It is to be hoped that this drug can be marketed in a suitable preparation for addiction as soon as possible.

comments by Andrew Byrne ..

A decade of caring for drug users

[Letter in Br J Gen Pract. 1999 Feb;49(439):146.]
Sir,

Martin et al�s report on treating drug dependent patients in general practice is heartening (October Journal).1 It is a shame that the authorities do not reward such innovative and successful interventions with appropriate payment, encouragement, and replication elsewhere. Oral supervised methadone is well established as an effective management for heroin addiction.

Although it was obviously successful in numerous cases, the research evidence for injected methadone is still rudimentary. Like heroin prescription, it should probably be reserved for patients who have failed at standard treatments such as oral methadone or supported detoxification.

After 14 years of prescribing and dispensing methadone in our general practice in Sydney, we have found that oral methadone suits up to 90% of heroin injectors who present for treatment. There should be no arbitrary limits on daily doses (we use up to 350 mg daily; mean = 85 mg). It is normal practice in most jurisdictions for at least two doses per week (up to 7 in new or unstable patients) to be consumed under supervision. The use of non-supervised methadone may be effective in certain cases but this has not been demonstrated generally in the research literature. It omits a fundamental safeguard for compulsive drug users and also increases the possibility of drug diversion.

Oral methadone �failures� should be candidates for studies of alternatives such as injected methadone, prescribed heroin, rapid detoxification, oral long-acting morphine, or other approaches. There is no reason for this to happen only in specialist units. A general practice with sufficient experience in dependency, as in this case, is perfectly capable of doing the same as, or even better than, existing dependency units.

Andrew Byrne

Reference

1. Martin E, Canavan A, Butler R. A decade of caring for drug users entirely within general practice. Br J Gen Pract 1998; 48: 1679-1682.