22 April 2003

American Association for the Treatment of Opioid Dependence (AATOD) National Conference

Integrating Evidence-Based Practices Within Opioid Treatment

Sun 13th to Wed 16th April 2003

I was privileged to attend the AATOD conference in the Renaissance Washington DC Hotel along with many of our field's eclipsing luminaries. Over 1000 health workers came from all over the US and overseas. Much was said in the formal lectures and workshops, but face-to-face meetings with long-time, long-distance colleagues, in some cases for the first time, was a unique pleasure.

On the Saturday there were pre-conference courses on buprenorphine prescribing in office based practice and another for 'methadone advocates' (NAMA). On the Sunday afternoon, two further parallel 'strands' took place, one for local policy folk, the other involving overseas researchers and clinicians. The latter described experiences in a variety of settings in Switzerland, Italy, Israel, Bulgaria, Ukraine, Slovakia and Slovenia. Two additional American collaborations included talks of neonatal abstinence syndrome (Dr Loretta Finnegan) and high dose methadone prescribing (Dr M. Shinderman). The Canadians and Europeans at the meeting added a much needed bredth of experience. This conference which was pervaded by reaction to the uniquely American antagonism to logical drug policies. This includes regulations preventing doctors from treating their dependent patients in accordance with long-standing concordant research, mostly performed in this country.

On Monday morning we were addressed by Association President Mark Parrino, Washington D.C. Mayor Williams, D.C. Health Director James Buford, DEA Diversion Administrator Laura Nagel and SAMSA Officer Charles Curie. Surveys showed that 7% of Americans interviewed had used an illicit drug in the previous month and it was estimated that 16,000,000 were regular drug users. Surprisingly, this was not used as evidence that current policies fail to protect US families against drug problems. We were, however, reminded that 'treatment works', despite common mythology to the contrary. The virtues and proven benefits of intensive psychosocial supports for maintenance patients were extolled. The speakers quoted from the few good studies which confirm scientifically what Hippocrates described over 2000 years ago (additional services improve medical outcomes).

Parrino and his knowledgeable presenters dwelt on the 'crucial' role of these psychosocial supports. Indeed, as with diabetes and other conditions, such services can significantly improve numerous treatment outcome measures. But we know that even with minimal services, dependent folk can attain positive results in many or even most cases. Nobody would suggest denying such services if they were available, but equally, to deny methadone or other medication in adequate supervised doses, because of a lack of counselors, funding, real estate, etc, would be unacceptable in other fields. The latest moves on buprenorphine prescribing may redress some of the calcification in US policies which continue to deny simple and effective treatments to most American addicts who cannot realistically advocate on their own behalves.

The morning workshops included 'ethnic considerations', smoking cessation, 'harm reduction' integration, office based prescribing and benzo abuse. It was disappointing to me that the conference organisers did not have more practising clinicians among the 14 plenary speakers, most of whom were administrators.

I attended a workshop on a needle exchange information initiative in New York City's Bronx, given by Dr Jennifer McNeely of the Albert Einstein Medical School. She pointed out just how difficult it was to get simple practical information to patients. She had to deal with various levels of administration just to be able to pass on the contact details of 3 Bronx pharmacies selling clean needles and syringes under the new Sate legislation. It would seem that a graffito on the washroom door with the phone contacts would have had the same effect. However, by going through the correct channels, McNeely has wisely ensured that in other states with similar waivers clinics will now be able to do the same thing, thus reducing viral transmission and ultimately saving lives. This in turn may reduce the hysteria in this country over issues such as needle availability. 'Harm reduction' and needle services were under the conference heading of "hot topics". This is intriguing since each is just so uncontroversial as to be official government policy in numerous other countries.

In the Q&A session, I mentioned some details of the Sydney medically supervised injecting center where 69,000 injecting episodes occurred over 2 years with no deaths or other significant problems. One clinic manager from Pennsylvania said that she cannot even get minor changes to her clinic approved and was very pessimistic about a syringe program opening in her state. And a legal injecting room seemed light years away.

Other workshops covered cardiac rhythms in opioid users, Federal Regulation, counselors eduction, 'recovery', addiction nursing, residential care and community transfers. Another was "Administrative Withdrawal: Ethics, Implementation, and Alternatives". Apparently in various places across the country currently there are hundreds or even thousands of patients experiencing this callous indignity for reasons I could not comprehend, considering the this country's abundance of resources.

Next we had an interesting session on the introduction of buprenorphine into practice in the US. Dr Laura McNicholas gave a brief overview of the pharmacology and therapeutics, then Dr David Feillin related a number of trials of the sub-lingual combination drug including naloxone. Most of these trials involved supervised administration of the drug as distinct from the current waiver arrangements to dispense up to a month's supply at a time without supervision. Also, most of the extensive buprenorphine literature has been performed with pure buprenorphine, yet the recommendation is for American physicians to use mainly the combination product with naloxone. The claims that this is safe and effective in both treatment and avoiding diversion are not based on much scientific evidence. This shows that the drug can be abused by novice or occasional users and further, that the naloxone is absorbed up to 10% and has some clinical effects such as pupil changes. In the Q&A session mention was made of a twelve month Swedish/American study which compared buprenorphine maintenance with detox. The detox group had near zero retention rates at 2 months and, worryingly, 20% of the subjects had died. One must question the ethics of giving a virtual placebo treatment to half of such trial cases without some formal safety net.

On the Tuesday morning there were 4 papers delivered at the first plenary session. Before introducing Marc Gourevitch of the Bronx in New York City, Andrea Barthwell alluded to a concept I have always avoided: "conquering addiction". The term "brain disease" was also used in the plenaries, reflecting official policy edicts from the 1990s. The problem is that if drug addiction is a brain disease, then about 90% of us have it! I feel on safer ground calling drug dependency a 'condition'. Then, like dandruff, pregnancy, obesity or baldness, it is the sufferers who can decide if and when it becomes a 'disease' (and there were numerous user representatives present at the meeting). Dr Gourevitch spoke modestly and authoritatively about co-existing disorders in dependent patients.

Dr Leonard Seeff was ill and at short notice Dr Larry Brown spoke well on the difficult subject of HIV in dependent patients. Dr George Woody then dealt with non drug related symptoms in dependent patients. He quoted DSM IV and even later definitions of the various presentations (mentioning that the DSM V was due out in 2010!). Symptoms from a number of pre-treatment surveys found high rates of anxiety, phobic disorders, ASPD, auditory hallucinations, etc. We were also told that just as drug users suffer from a wide variety of psychiatric disorders, equally, up to 50% of mental patients can present with co-existing substance abuse problems. When the primary condition is treated the other symptoms will resolve spontaneously in a proportion of cases. We were told that two weeks was a good interval in new methadone patients to reassess such problems which may need specific interventions such as antidepressants. It would appear that MMT can improve depression, anxiety and in some cases paranoid symptoms. It has long been believed that opioids have some anti-psychotic properties.

Regarding hepatitis and HIV infections, "prevention is better than cure" is an old maxim which was apparently NOT emphasised. Needle availability was an unpardonable omission in these plenaries. It is disappointing when respected scientific experts fail to say what needs to be said. Needle availability prevents viral disease transmission and does NOT encourage drug use. Several US states have introduced 'waivers' against the bans on pharmacies selling injecting equipment (see workshop above).

After the morning plenaries there were workshops on a variety of issues: dual diagnosis, homelessness, pregnant patients. In a well attended session, Dr Peter DeMaria spoke about 'Optimizing methadone doses'. He used a number of case histories to show that dose manipulation, splitting, increases, etc can turn around a 'failure' in treatment. One case history was a MMT patient who had used heroin continuously for 12 months in treatment while on 120mg daily. While it was helpful to examine the methadone level and a dose increase, it might also be questioned why the patient was treated for twelve months in this clearly unstable state, and all the attendant risks (but better late than never!).

DeMaria also took us back to the basic pharmacology of methadone to explain withdrawal symptoms with a helpful graph of methadone levels over 48 hours and thus two doses. He reminded us of the words of Sir William Osler: "Listen to the patient, he's telling you what's wrong with him". [I seem to recall that Osler continued: "... and if you listen hard enough he may also tell you the treatment"].

DeMaria stated that daily doses of 80 to 120mg are adequate for about three quarters of patients, but that others, some with aberrant metabolism need extra, split doses or alternative drug or non-drug treatments. Drug interactions were covered in detail, including phenytoin, fluvoxamine, antiretrovirals (three of them only), anti-fit meds etc. It was gratifying that the hall was packed with attentive clinicians from all over the US since one major consistent finding of surveys of clinics is inadequate dose levels across the board (this also occurs in Australia, Great Britain and elsewhere). Then we had mention of the stereoisomers of methadone and cytochrome metabolism ... rather too complex and speculative for us front-line workers perhaps, unlike the rest of this practical presentation.

Another session, by researcher and editorialist Stewart Leavitt, was entitled "Can Addiction Research be Trusted?" He helped us with just how to assess the clinical significance of particular studies from the anecdotal ('n=1') to RCT to the hallowed 'metanalysis'. But he warned that some such studies may be "gigo" (garbage in, garbage out) since overall conclusions are only as reliable as the data they are based on. Leavitt also gave us a timely lesson on the two common ways of interpreting studies over time (1) ITT or 'intention to treat' and (2) PP 'per protocol' (analysis of only those who finish the intervention). Both have pros and cons depending on the proportion of drop outs. He introduced the terms "PLUS-cebo" (for positive effects) and "NOCI-bo" (harm causing) for the more usual term for 'dummy' treatments which do often have apparent effects in trial subjects.

Leavitt then shattered the illusion of the "Farmington consensus" (which may not be a 'consensus' at all) that all research associated with 'inappropriate' sponsorship should be rejected for publication. This ban, largely aimed at tobacco and alcohol sponsorship, could also be levelled at drug companies, health authorities, policing interest, drug cartels, etc. Dr Leavitt pointed out that all research is biased by the nature of the authors, their background, ethnicity, funding, etc. Thus it is the reader who should look at what is disclosed regarding possibly conflicts of interest, who is writing/funding the research and then decide for themselves its 'rigour' and/or relevance for their practices. 'Publication bias' was also covered in which studies which have positive outcomes are more likely to be completed and published. Laura McNicholas MD from Philadelphia VA questioned some details from the floor concerning research samples - which were clarified. Extensive references and comprehensive handouts were given on a number of clinical and ethical matters of interest and the declaration that Leavitt's service is sponsored by a manufacturer of methadone and naltrexone.

The Tuesday evening dinner included 13 awards in honour of Vincent P. Dole and Marie Nyswander who together pioneered methadone treatment. While I have no objection to credit being recognised when it is due, Washington DC is hardly the place for accolades over drug treatment or policy in the centre of these continuing epidemics (addition, HIV, hepatitis C). Hence to avoid any ill feeling, I avoided this part of the proceedings and retired back to my lodgings early to gather my thoughts. It had been a marvellous three days meeting up with dozens of colleagues from all over the US as well as further afield.

I have great admiration for all these dedicated and hard working front-line professionals, some of whom operate in situations of poor funding, dangerous work environments and limited scope for professional advancement. Even simple advocacy can be hazardous in America. But one remains in hope of improvements, and that conferences like this might seed some such positive moves.

The above is not intended to be a comprehensive summary of the conference which also had 22 diverse poster displays and many other workshops, plenaries and 'round table' discussions I could not get to.

comments by Andrew Byrne ..

4 April 2003

Addiction summaries: methadone versus buprenorphine. Does clonidine work?

'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 ..

How does buprenorphine compare with methadone? A rigorous multi-centre study from Australia.

Buprenorphine versus methadone maintenance therapy: a randomized double-blind trial with 405 opioid-dependent patients. Mattick RP, Ali R, White JM, O'Brien S, Wolk S, Danz C. Addiction 2003 98:441-452

Dear Colleagues,

This vital multicentre trial comparing 3 months maintenance treatment gives us invaluable information on the use of buprenorphine for heroin addicts. Unlike some other fixed dose studies, the patients in both groups here were treated in a clinical, 'naturalistic' manner with flexible doses supervised with true 'blinding' of medications (each started with active/dummy). Inductions and dosing practices were in broad accordance with established guidelines, such as those from the UK (Strang, 1999) and the various Australian clinical guidelines. In the second month of treatment daily doses of up to 150mg of methadone and 32mg of buprenorphine were used (means 57mg and 11mg respectively). Dose increases were in response to patient reports of cravings, illicit drug use and doses just 'not holding' them.

If the overall numbers randomized to each treatment are considered (205 and 200), the retention rates at 13 weeks can be calculated at 58.5% for methadone and 48% for buprenorphine. My amateur statistical estimation sees this as reaching significance. However, in their own calculations, these authors exclude the patients who did not receive an initial dose (significantly, 3 for methadone and 8 for buprenorphine, a drug with more clinical limitations on starting) making their retention rates 59.4% and 50.0% (p=0.06). While this may seem picky, the authors also spend some effort looking at this significance. Regarding (1) the mean length of stay, 59 vs. 67 days and (2) evidently by applying a survival analysis across the 13 weeks there was a significant difference between the groups (but not at 6 weeks). The authors speculate about a possible 'type I error' since there were some parallel questions with possible 'overlapping' factors.

The overall findings are that this study again confirms that in the normal clinical context buprenorphine is almost as good as methadone at retaining opioid-dependent patients in treatment. It also showed equal benefits regarding reduced illicit heroin use and equal side effect profile for those remaining in treatment. This profile is much more extensive that my own experience: up to two dozen significant side effects suffered by patients in both groups (eg. nausea 16-17%; vomiting 8%; 'flu symptoms 7-10%; headache 11-13%). In my own practice I have seen virtually no side effects with buprenorphine and only sweating, constipation and some sexual dysfunction as prominent problems in some methadone patients. I understand that these researchers spared no effort in regularly canvassing for reports of side effects, some of which just might have been from withdrawals or other causes, hence a possibility of over-reporting compared to other research.

The question seemingly posed originally by these researchers, "is buprenorphine better than methadone" is no longer a useful question to my mind. We now known from years of research that buprenorphine works well as an outpatient treatment for opioid addiction, in many ways comparable with methadone prescription. Now we need to implement the treatment in a logical fashion for those who may benefit from it. The drug is much more expensive than methadone. It has limited long term safety data, although that which exists is reassuring. Buprenorphine is not proven safe in pregnancy although there too, early studies indicate no problem in many pregnancies studied while the drug was continued.

Hence, like the second antibiotic introduced after penicillin, buprenorphine should be used initially for those unable or unwilling to take methadone. It may be that it will become a first line drug at some stage but in my book it is currently an excellent alternative in cases where there are problems with methadone. My own practice has 15% of our maintenance patients taking buprenorphine. The state of NSW has 1,600 out of 16,000 on the newer drug 2 years after its introduction under the same general conditions as for methadone maintenance (but fewer take-home provisions).

Comments by Andrew Byrne ..

Lancet article - strong science but serious ethical issues.

1-year retention and social function after buprenorphine-associated relapse prevention treatment for heroin dependence in Sweden: a randomised, placebo-controlled trial. Kakko J, Svanborg KD, Kreek MJ, Heilig M. (2003) Lancet 361:662-668

Dear Colleagues,

The Swedes have produced some of the most quoted data showing the life saving properties of methadone maintenance, partly because this treatment is so severely restricted in Sweden. Thus trial candidates who are randomized not to receive prescription treatment, or who are discharged from treatment, rarely receive agonist maintenance therapy which might be available in the normal course of medical practice in other ‘normal’ countries.

From work performed in the 1980s, Grönbladh and colleagues showed a very high mortality in those rejected from methadone treatment - almost 8% per year. In an even more rigorous and controlled study using sublingual buprenorphine, Kakko et al. have found what the accompanying Lancet editorial calls: "massive 20% mortality at one year in the placebo group versus 0% in the buprenorphine group [which] is immensely concerning". Indeed, a trial using placebo in heroin addiction treatment would be considered unethical in Australia.

This trial provides strong support for buprenorphine maintenance since at a fixed dose of 16mg daily it had a 12 month retention rate of 75% and no deaths, compared with placebo: 0% retention at 2 months and four out of twenty being dead from overdose by 12 months. All 'placebo' (actually '6 day reduction') cases had access to intensive levels of psychosocial supports, some of which were reported to have induced paradoxical cravings. I understand that one of the 5 buprenorphine drop-outs has also since died.

The mortality rate is even more worrying considering that these candidates were chosen from over 400 applicants based on less severe dependency and less poly drug/alcohol use. Thus none of the chosen candidates was suitable for the stringent Swedish criteria for methadone prescription (4 years hospital-documented multiple daily heroin use). All but one were injectors.
All of the placebo patients showed positive urine tests for opiates before dropping out of treatment. Thus none was an early abstinence success - despite this being the consented aim of the trial. About 75% of urine tests of the buprenorphine patients were negative for illicit substances tested for. Thus despite continued if less frequent drug use was still associated with good retention and reduced health problems measured in a variety of ways by these researchers.

Swedish drug policy is based on the belief that all drug addicts can and should stop using certain proscribed drugs immediately (abstinence orientated, or 'zero tolerance'). While this has been long abandoned in most other countries, Sweden continues despite their own research showing excess deaths, continued drug use and high rates of viral disease transmission when such policies are pursued. One fails to understand how in such a modern democracy such ill-founded policies are used.

Yet the world's two most persuasive studies are from their own country showing that if heroin addicts are left untreated (or "treated" in the compulsory manner used in Sweden) then the result is a high mortality of young Swedes from a totally preventable and treatable cause, drug overdose.

For related editorial commentary: Law FD, Nutt DJ. Maintenance buprenorphine for opioid users. Editorial. Lancet (2003) 361:634-5

comments by Andrew Byrne ..

2 April 2003

Methamphetamine addiction: review article.

Journal of Substance Abuse Treatment (2003) 24:267-277

Cretzmeyer M, Vaughan Sarrazin M, Huber DL, Block RI, Hall JA. Treatment of methamphetamine abuse: research findings and clinical directions.

Dear Colleagues,

This 'review article' looks at the modern stimulant epidemic from a clinical standpoint. On searching the literature, these authors found some treatment protocols, each of limited if any proven value in stimulant addiction, but each describing some 'promise' for methamphetamine dependency. Unlike the treatment of opioid and nicotine dependency, none involved prescribing of stimulants as either maintenance or reduction regimens as is used in the UK and in trials in Australia.

Amphetamine analogues are regularly prescribed by doctors and, unlike in the case of opioids for pain, there seems to be no 'grey area' between this and 'recreational' use despite some similarities in the expectations of both types of consumer. Like alcohol, opiates and other drugs, it is clear that stimulants have benefits and risks. Indeed, they are apparently dispensed to US Air Force pilots to increase attention and reduce fatigue. Yet current bans have never stopped many long-haul truck drivers claiming the same benefits from regular but completely unsupervised and unresearched stimulant use.

The first treatment protocol quoted by these authors, remarkably, involves the almost completely discredited 'aversion therapy'. It was used in the most clumsy and misguided manner using stand-in drugs for the stimulants and emetics or low voltage electrocution as the 'punishment'. Despite the absence of a control group and no valid scientific outcome data, these authors accept the treatment as 'promising'. And this was not in Abu Graid prison, but America in the 1990s.

The second was using first-generation antidepressants which the authors claim were successful or 'promising' based upon an improvement from 17 to 34 days retention with active imipramine over placebo, proving little except that these drug-users could detect placebos. 34 days in the life of a drug user is not exactly long-term.

The Californian 'Matrix' program is a psychosocial treatment model funded by the US drug agency, NIDA. It may be that the name 'matrix' is the most important component of its 'success' or 'promise'. The quoted trial here, with or without desipramine, only had 13 subjects who were amphetamine dependent. They were randomised three ways and ethnic differences confounded the already insignificant outcomes at 6 and 12 months. Why such a trial was quoted in a scientific paper I cannot tell.

'Case management' is examined next and it was found, unsurprisingly, that giving high quality vocational counselling improved employment outcomes and decreased depression levels. Case management did not reduce drug use compared with controls and thus it cannot be considered a 'treatment' for stimulant dependency on this evidence.

This review by a group of eminent experts seems to indicate an unwillingness on their part in the current US political climate to examine medical dependency problems from a purely scientific viewpoint. If patient outcome is paramount, it is essential to look beyond our own jurisdiction to see what is being done elsewhere. No promising modality should be 'off limits'. Substitute prescribing is not mentioned by these researchers for unstated reasons and when I wrote to them, I was asked to explain what I meant! As long as US researchers feel unable to write freely about harm reduction measures, and while needle services are not available in most areas, American citizens, including non-drug users, will continue to be exposed to high risks of HIV/AIDS, hepatitis C and the enormous social costs of unchecked non-medical drug use.

comments by Andrew Byrne ..


Cooper D, Souther L, et al. Public Health Consequences Among First Responders to Emergency Events Associated With Illicit Methamphetamine Laboratories - Selected States, 1996-1999. JAMA (2000) 284; 21

Volkow ND, Chang L et al. Association of Dopamine Transport Reduction With Psychomotor Impairment in Methamphetamine Abusers. Am J Psychiatry 2001;158:377-382