'Addiction' journal, April 2003.
# Randomized, controlled comparison of methadone vs. 'bup'.
# Methadone syrup injection in 1996/7 in Adelaide.
# Does methadone kill more people than heroin?
# Poor quality of agonist treatments in England/Wales.
# Does clonidine work for withdrawal symptoms?
# 'Reductions' of bup popular but 90% need repeat treatment.
Dear Colleagues,
This edition reveals an extraordinary wealth of clinically relevant research material ... but also shows an intriguing reversal of health priorities by the editors. Some truly 'landmark' research is 'buried', while the first two reports and their related editorials are on subjects of modest, local and/or historical moment. The injecting of methadone syrup in Adelaide from 1996/7 and opiate deaths in England 1993-98 are both subjects deserving of clarification. But as is so often the case with Addiction, the tenor seems to be to question whether methadone treatment is a valid intervention rather than how to use it more effectively. After 35 years of positive research, Addiction should abandon its persistently negative focus on methadone treatment. Agonist treatments are not perfect, but they are now used by most western health authorities as one helpful approach to opioid addiction.
As a lead research journal, Addiction's main focus should be how to maximise the benefits of this proven treatment, not to question its very existence. The first page of the April edition in entitled: "Methadone syrup injection in Australia: a sentinel finding?" The writers state that there is a lack of reports of methadone injecting outside of Australasia. They relate some alarming consequences of methadone injecting, each being potentially paralleled for street heroin injecting, yet neither the nature nor extent of the problem is backed up by references. In fact, one of their suggested solutions is to examine introducing a type of methadone which is suitable for injection. In fact, since this study was completed, a safer water solution of methadone has begun replacing the older 'syrup' mixture. It is disappointing that the Adelaide researchers only had 2 questions: had subjects 'ever injected' and 'was there any injecting in the previous 6 months?' Thus the story lacked quantitation. Hardly fodder for the lead research paper in the world's most venerable dependency journal!
'Addiction' might care to ask a guest writer to look at why agonist treatments are still so restricted and why so much is of such poor quality, especially in England, where Addiction is published. Established guidelines are almost completely ignored by doctors to the cost of their patients and the UK community. Professor Dole, who originated the use of agonist treatments in New York, states that injecting behaviour (and therefore its complications) can be almost completely eliminated in up to 95% of subjects by using adequate doses of methadone with appropriate supervision and sufficient support services. All treatment should be judged according to whether it is in accordance with established treatment guidelines (eg. Strang's UK guidelines). Maintenance treatments save the health care system more per dollar invested than most other interventions. They reduce crime, prevent HIV infection and probably also hepatitis C yet they are still maligned in a way which is not based on logic.
Amongst the plethora of clinical material, the April edition has two important items on subjects after my own heart. Mattick et al. have published their three-city study of double blind methadone versus buprenorphine maintenance (see my detailed review elsewhere). At 3 months they found only minor differences in retention, drug use and side effects between these two drugs. This trial is very important scientifically and of substantial clinical relevance. It probably should have been the first item in Addiction and certainly deserves an editorial, considering buprenorphine was released in the USA recently. This may seem a small criticism, but not so the fact that Hickman's study of opiate deaths in England gives text references as numbers, while the actual list is alphabetical, making the article incomprehensible to the reader. The author was kind enough to send me an earlier draft with his own numbered references. I am bemused by the lack of editorial control at Addiction which led to this error. One wonders that the proper peer review process did not prevent such an error. The management at Addiction owe Hickman and colleagues an apology for this humiliating error.
The content of Hickman's article relates to an issue into which I had a personal input back in 1997: that 'methadone kills more people than heroin'. It is a sad fact that the issue is still being debated rather than being acted upon. In fact the last time Addiction published my name unrelated to some gossip or ridicule from house writers, was on the issue raised by Newcombe. The item by Hickman shows that there are still many (possibly unnecessary) deaths from methadone in England and Wales, but not as many as caused by heroin, and the number is still increasing. Both Hickman and the editorialist touch on clinical practice in England, but neither seems able to state that there is strong anecdotal evidence pointing to abysmal compliance with clinical guidelines in England and Wales. The drug is usually prescribed by doctors with no training in addiction medicine, without supervision of the medication and at dose levels which are often inadequate to quell cravings for 24 hours. Such deficiencies are inconsistent with Strang's detailed official UK Dependency Treatment Guidelines (1999). There appears to be no coherent plan either by professional groups, the NHS nor the National Addiction Centre to address these failings, despite them probably leading to the deaths of many people annually. This edition would have been an ideal place to address the issue. I offered to write such a piece but editor Edwards, while conceding the need, has not followed up on the matter it would appear.
Another item, from the group at Johns Hopkins, gave trial subjects on 30mg daily doses of methadone injections of naloxone and medicated them with clonidine or lofexidine without placebo control. Approval was granted by The Johns Hopkins Bayview Medical Center Institutional Review Board and individual consent given. We are not told if this is a properly constituted ethics committee, but it is gratifying that subjects were offered either a 90 day reduction course of methadone and/or assistance with referral to a long term maintenance facility in Baltimore after their services in this somewhat brutal trial (for which they were paid volunteers). It is a moot point as to whether currently addicted individuals can consent to a single option, especially one which is not an appropriate treatment for addiction (fixed 30mg of methadone daily). Unsurprisingly, 6 subjects who agreed to participate dropped out at the prospect of naloxone injections. However, 8 of 14 who completed the twice weekly experimental in-patient protocol effectively showed that neither lofexidine nor clonidine did anything significant in reducing withdrawal symptoms. My patients have told me for years that clonidine does little for withdrawal symptoms. Now here at last is proof!
In yet another item from Baltimore 120 subjects were offered a three day course of buprenorphine using 'high' (4mg) or 'low' (2mg) dose. This can hardly rate as 'reduction treatment' since the drug takes at least 5 days just to stabilize. It is not stated which professional protocol this 'treatment' is taken from. One wonders at the wisdom of giving a "treatment" which has little if any scientifically proven benefit and then reporting near 90% failure rates in an international journal. There was apparently no safety net reported by these researchers who noted frequent relapses in their patients. At 1, 3 and 6 months there were progressively fewer patients were contacted (80%, 55%, 47%). The authors' first statistics do not take lost subjects into account and their 6 month abstinence figure of 62% (self report) and 25% (clear urine test) are then translated for clarity to 35 and 14 subjects out of the original 119 (29%, 12%). A proportion of those lost to follow up may have been dead but this is not addressed by the Gandhi and co-authors. Their conclusion that there was 'reduced frequency and intensity of drug use' following their "intervention" is based on respondents only and is thus of limited validity, like their 'treatment'. All patients deserve appropriate treatment and this means regular assessments and if agonist prescription is appropriate on one day, like insulin, lithium or Prozac, it is nearly always appropriate on the next. Discharge from treatment should never be arbitrary as it was for all of these patients.
comments by Andrew Byrne ..
