22 May 2009

Drug decriminalisation in Portugal successful after 8 years.

Greenwald G. Drug Decriminalization in Portugal: Lessons for Creating Fair and Successful Drug Policies. Cato Institute. 2009

Dear Colleagues,

It has taken a long time, but finally we have convincing evidence, even proof, that decriminalising drugs helps drug users and society in practice. Like alcohol before it, the banning of drugs with criminal sanctions against users is a counter-productive and dangerous ‘experiment’ which should be abandoned in favour of more logical and effective ways to control drugs in society.

As a response to burgeoning drug use, the Portuguese government decriminalised all personal drug use, possession and cultivation from July 2001. The history of this goes back to at least 1996 and involved support from two successive Prime Ministers, a popular Portuguese media personality and some key legal figures at Lisbon University. There were also apparently New York and Californian connections in the lead-up to decriminalisation.

The approach taken by the Lisbon government removes legal sanctions for any adult detected with up to ‘ten days average use’ for any drug, psychoactive plant or ‘preparation’. Rather than a court, drug users who come to attention can still be dealt with by a ‘drug dissuasion commission’ (an imperfect translation I suspect). Set up in each health region, these are boards of three members including a health professional. They take into account whether the person is addicted or not and how much drug/drugs were involved. They can theoretically mandate treatment but in fact they have no power to enforce their advice, rather like medical advice for voluntary mental health cases.

Despite my best efforts to be informed, little solid evidence had emerged in the years following the removal of criminal sanctions for drug use and observers have speculated on the outcomes. Now Dr Greenwald and the Cato Institute have put together a comprehensive review which demonstrates from every aspect they examined, the exercise was beneficial. Dire predictions of mayhem from some quarters simply failed to occur. It appears that even in staunchly Catholic Portugal there is strong support for the policy and only a fringe group of activists opposes the current law.

Rather than a surge in drug use predicted by some, there were significant reductions in most types of drug use in Portugal each year following decriminalisation. While the UK topped most of the statistics for the periods covered by the report, by 2006 Portugal had some of the lowest drug use, HIV, overdose and other statistics in the entire EU. They reported no ‘drug tourism’ which some had predicted.

Holland and the state of South Australia both decriminalised cannabis use about 30 years ago and the results have been reportedly positive with few serious moves to reverse the decision. Two neighbouring jurisdictions, Belgium and Northern Territory have apparently done the same thing some years later.

Substantial resources have been redeployed from policing to treatment. I know from experience of patients who have visited that Portugal has an efficient system of well run opiate addiction clinics, for example, something which cannot be said of the UK a country which recently reclassified cannabis as being the equivalent of a dangerous narcotic and has some of the worst statistics in Europe regarding drug use and related viral infections.

Governments of all persuasions need to reduce the reliance on prohibitions or else drug related harms will continue to increase. Society generally is now sceptical of the effects of policing and is ready for change, either incrementally as done in Adelaide, but preferably ‘across the board’ as in Portugal. This very policy was proposed for Mexico but was cancelled at the last minute, probably after lobbying from an influential northern neighbour.

I would strongly recommend readers look over this 34 page report.

Comments by Andrew Byrne ..



20 May 2009

New York addiction conference April 2009

AATOD meeting, Hilton Hotel, New York City. 26-28 April 2009
American Association for the Treatment of Opioid Dependence.
Brief and selected commentary on this talk-fest, especially cardiac matters.

Dear Colleagues,

I was privileged to attend this conference which is the successor to the long-standing National Methadone Conferences which started in the 1970s. It is essentially the meeting for the American ‘methadone clinic’ sector held every 18 months but it now draws in patient advocates, scientific community, policy makers and even an international connection with ‘EUROPAD’ and occasional delegates from the wide world (I noted several other Australians attending). I had been asked to speak at the session on cardiac consequences of methadone - see below.

After pre-conference sessions on the weekend, the official opening was an address by Karen Carpenter-Palumbo, the Commissioner for the Office of Alcoholism and Substance Abuse Services of New York State. She spoke ‘loud, brash and somewhat arrogant’, as she put it, to emphasise the scope of the problem in her state but also the contribution New York has made to policy, research and funding of drug issues over the years. She answers directly to Governor Patterson who, we were told, had just signed away some of the worst elements of the Rockefeller laws … or ‘dropped the Rock’ as she put it. Further, the Governor had stated publicly that drug users should be ‘treated and not incarcerated’ in New York State. She used many catch-phrases, sounding rather like a campaigning politician, receiving a standing ovation at the end based on her stirring the crowd. “Ladies and gentlemen, methadone IS recovery!!” She spoke so close to her microphone that it was almost painful to the ears.

The Commissioner reminded us that 44% of those entering opiate maintenance treatment now were using prescription drugs and that 33% of entrants had self-injected. To emphasise the shortage of treatment availability, we were told that 15% of Americans in methadone treatment crossed state lines to do so. There are car pools of people travelling long distances, sometimes daily, to access treatment. Some even crossed two state lines to receive medication (and probably a few taking treatment in Canada). A Detroit addiction doctor told me that many of his addicted patients had outstanding legal matters and risked immediate arrest at the border. Hence despite good treatments in Canada, this was not an option for many addicted individuals in America, even those few who might reside close to the border.

There were too many break-out sessions for me to document here but all presentations were put onto a CD which was given to every delegate. I tried to keep abreast of several of the sessions but recommend looking at the program for your own area of interest. Conference abstracts and power point presentations were contained on a CD ROM given to every delegate on registration.

Maternal and neonatal outcomes were discussed in detail by Jack McCarthy, Hendree Jones and Karol Kaltenbach in a well-attended break-out session on the Monday morning. It was pointed out repeatedly that heroin, cocaine and alcohol are all very dangerous for both mother and unborn baby. Methadone treatment can reverse many of the worst consequences of such drug use. Detoxification is still requested by some women and a number of studies were quoted, each showing high rates of relapse (40 - 96%). It was agreed by most that reductions in methadone doses could be affected safely in the middle trimester of pregnancy but that this should be gradual and ONLY if the woman was not using other drugs and/or alcohol at the time. We were reminded that there was a stronger motivation to cease tobacco, alcohol and drugs as in this important period during which so much can be accomplished with adequate support rather than coercion. Of course on the other hand, great damage can also occur when a pregnant woman with drug/alcohol problems has no access to treatment which is still the case in much of America where there are still some areas which might be mistaken for a third world country, so scarce and/or expensive are these services.

Prison systems in Philadelphia have had an experimental pharmacotherapy intervention involving over 500 inmates over a number of years and results are positive, according to John Carroll and Roland Lamb. Similarly, reports from Rhode Island at a previous AATOD meeting had also been positive. However, such reports need to be contrasted with the country’s oldest custodial methadone delivery system at Riker’s Island in New York City which has recently been threatened with de-funding of the ‘KEEP’ program by New York State. Methadone has been available for pre-existing patients prior to sentencing but not in up-state regular jails where most sentences are served. As might be expected, the experience of methadone treatment in the custodial system report positive results. The main benefit to the community we were told were the dramatically lower recidivism rates in those receiving treatment when compared to addicted folk in jail who did not receive treatment (see power point presentations for exact figures). The lack of treatment in jails is yet another American tragedy where careful research has been ignored to the detriment of the entire society.

Many of these prisoners were victims of unfair and discriminatory laws and should not have been in jail at all. The severity of sentences was discussed at another forum later that week on the Upper West Side. The Voluntary Committee of Lawyers (VCL) honoured Federal District Judge Robert W Sweet for his stance in refusing to hear drug cases in his New York District court 20 years ago. In his acceptance speech he said that he had found that 80% of the work in his jurisdiction was related to minor or personal drug use/possession which he found completely unproductive. We were reminded of the cruel sentences still handed out in some states. In Alabama, for example, it was mandatory for the third cannabis offence to receive a virtual life sentence. Fortunately many states are now coming to terms with the enormous cost of all of this futile ‘war on drugs’ due to the economic crisis forcing every aspect of state expenditure to be reviewed. There are now many instances of early release of low-security prisoners to save money. Some optimistic commentators at the AATOD conference were now saying that “the stars are lining up” for change to the punitive American approach to drug/alcohol use.

A lunch meeting was held for about 200 clinic managers, researchers and policy makers on the Monday. This was addressed by ex-marine and now Washington DC Senior Public Health Advisor - Substance Abuse, Office of Public Health, Gregory Goldstein MPH. He spoke about the competing areas and priorities for his office in Washington, starting with a briefing on the latest issue, the influenza H1N1 outbreak.

In questions from the audience Dr Mary Jeanne Kreek made a brief tribute and commentary in response to the address reminding us of her 44½ years in the field and her work on opiate receptors. She stated that we now had two ‘marvellous’ drugs for opiate addiction but that current work may well turn up other medications for amphetamine, cocaine and other addictions. She sounded more hopeful than others in the room. One wonders whether stimulant users would care to take a pill which made their stimulants inactive. Equally would those who enjoy coffee, tobacco or alcohol take an experimental vaccine to negate the effects of their drug of choice?

The final question/comment was from the conference chair Ira Marion which was to ask if President Obama might be persuaded to make a visit to a ‘methadone clinic’ [sic] to show his administration supports such services. This was taken on notice by Mr Goldstein. In response, AATOD president Mark Parrino mentioned an anecdote about such a request under a previous administration in which the person making the request was simply told that they would only ask such a question if they did not value their present job!

I was one of four speakers in a workshop and panel discussion on cardiological status of methadone patients. Dr Mori Krantz gave his case for methadone being the causative agent for QT interval prolongation and torsade tachycardia which is potentially fatal. He has stated that methadone safety is a ‘national priority’. One by one he re-quoted the numerous studies which he believes conclude that, despite no actual cases, methadone may be a cause of torsade tachycardia. Chugh, Fanoe, Martell, Peles, Lipsky and Wedam were all studies without, as far as I can gather, any documented cases of torsade de pointes tachycardia. Krantz makes it clear that the Wedam randomised trial takes away doubts about subject selection and thus increases the significance of the findings. Yet this reports relatively high rates of substantial QT prolongation in a group of relatively young, otherwise healthy ‘street heroin addicts’ (some with chronic or mental illnesses were excluded). Yet this is the very group which appears to be almost immune from ‘torsade de pointes’ judging by their absence from the detailed reported cases. Krantz was careful to point out that without actual cases of torsade de pointes, some of these studies had limitations regarding causation.

I pointed out that with so few documented torsade cases in so many cited studies, one interpretation might be that in methadone treated patients, QT prolongation does not seem to induce torsade at all (cardiologists often cite amiodarone as being in this same category). It is surprising that Dr Krantz did not cite the only literature review of torsade in addiction cases. Justo, in the Addiction journal, reported several risk factors affecting virtually all 40 documented cases he identified in the literature up to 2006. These included high dose, co-medication, HIV, electrolyte disturbance, cirrhosis and structural heart disease.

Dr Krantz and Dr Barry Stimmel described the processes of their expert panel and its decision to publish recommendations, including cardiograph tracings before treatment, at three months and annually thereafter … with additional ECGs in those taking 100mg or more daily or with positive medical histories. Neither speaker explained why their advice was contrary to that given by Krantz consistently since 2002 that routine ECG was not necessary in MMT patients. The first three speakers, Stimmel, Martin and Krantz, were all co-authors on the Annals article proposing mandatory ECGs.

Dr Krantz contends that torsade will prove to be a major contributor to the death toll of those taking methadone, despite only one report in the literature in over 40 years. He stated that deaths were increasing significantly in both addiction treatment programs and the pain management field. This is not consistent with the reference he has quoted (Ballesteros) which shows 96% of such deaths in one state were treated for pain rather than addiction. Despite Krantz’s contention, I have read no evidence suggesting increased sudden deaths in the clinic treated population.

San Francisco doctor Judy Martin said that she has been performing ECGs in all her patients for over a year. Despite this precaution, she still reported two of her patients developed torsade in the twelve month period, both apparently complex medical cases. It was hard to understand her continued staunch support for routine cardiographs for all new and continuing patients on methadone (I had a long talk with her afterwards). She stated that in her own clinic it was simple and cheap to get these tests organised. It is fortunate that her employers in California are so accommodating. In many American clinics it is still difficult to obtain even simple hepatitis C, HIV and other testing.

In the formal Q&A afterwards some simpler alternatives were raised such as ‘two finger’ tracings and automated versus manual calculations. One audience member pointed out the difficulties obtaining an accurate QTc measurement and asked whether the timing of cardiographs mattered in relation to methadone dose, meals, diurnal variation, lead placement, posture and other factors. It would seem that Dr Stimmel’s contention of “why not just do a cardiograph to define the risk?” could create a mine field for the unwary (and we now know that a cardiograph does not ‘define’ the risk of torsade to any useful degree. See Viskin et al 2005 below. Dr Martin’s final slide summarised her own clinic’s experience although did not bode well: “Doing the ECG is the least of it: evaluating and addressing contributing factors took the most time.”

In my own presentation I was at pains to point out that there were now over 70 cases of torsade in the literature and we can learn from them who is at risk (and perhaps even what to do to prevent such cases). There is no evidence that wholesale ECG tracings will prevent this complication since QTc is often normal before and after the precipitating event(s). There are many similarities in the reported cases, including very high doses (Krantz reported a mean dose of 400mg daily; Pearson 410mg), concomitant drug/alcohol use, older age groups (Krantz’s series had mean age of 49; Pearson 46) and co-existing viral infections (Justo found 16 of 40 (40%) cases were HIV positive). I could not find any cases reported from standard methadone treatment programs and there was only one single death, despite Dr Krantz’s slide stating that 8% died in Pearson’s series of 43 cases of torsade related to MMT. By my reading it was 1 of 43 (2%), not 5 of 59 (8%). Many of the latter had QT prolongation but no torsade and thus cannot be deemed ‘torsade’ deaths as Krantz has apparently done here.

I pointed out that in different ways, each of the case reports lent support to the contention, first proposed by Ellen Pearson after her FDA report, that there is a ‘threshold effect’ of methadone blood levels in which age, sex, electrolyte aberrations, structural heart disease, viral infections and alcohol can, when combined, can together cause torsade de pointes to occur.

Dr Stimmel indicated that one of the patients from 1973 with long QT had died. However, he failed to mention or include on his slide that his original report stated that the patient in question had an ‘impressive barbiturate habit as well as a sporadic history of parenteral cocaine use’ and further, that the coroner had found a fresh injection site (Lipsky). While discussing torsade and QT prolongation, Dr Krantz also put up another slide which may have been misinterpreted. It stated that Peles et al. reported 3 patients with long QT and that two of them died. Fortunately the author was actually present in the room, so Dr Peles herself was able to clarify to the audience (and the speaker) that neither of these two patients died from cardiac causes (both had confirmed non-cardiac causes of death) and hence should not be considered in the discussion on torsade de pointes.

None of the speakers alluded to the possibility that lengthened QT, high dose methadone and medical illnesses may just be ‘fellow travellers’ rather than a direct causative effect. It is clear that even significantly prolonged QTc in some groups appears to yield little or no risk of torsade in the absence of other factors, as with amiodarone, a drug which is apparently still used by cardiologists despite its propensity to cause significant QT prolongation.

Dr Gourevitch, who wrote the Annals editorial dealing with Krantz et al (2009) also addressed the workshop in question time with some clarifications. He had stated that the ‘expert panel’ had gone well beyond the research evidence in their recommendations. He emphasises that the issue is not as clear cut as the proponents had been saying in the session.

The remainder of the conference had many interesting sessions, workshops, plenaries and discussion groups on every aspect of addictions except the elephant in the room, decriminalisation of drugs for personal use which seems off limits. Medical cannabis (called “medicinal marijuana” by Americans) was mentioned frequently, as were drug courts and other moves away from law enforcement towards treatment.

Comments by Andrew Byrne ..


Viskin S, Rosovski U, Sands AJ, Chen E, ... Zeltser D. Inaccurate electrocardiographic interpretation of long QT: The majority of physicians cannot recognize a long QT when they see one. Heart Rhythm 2005;2: 569-574 [Byrne commentary: http://www.redfernclinic.com/c/2009/03/inaccurate-electrocardiographic.php4

Peles E, BodnerG, Kreek M, RadosV, AdelsonM. Corrected-QT intervals as related to methadone dose and serum level in methadone maintenance treatment (MMT) patients: a cross-sectional study. Addiction. February 1 2007;102(2):289-300

Wedam EF, Bigelow GE, Johnson RE, Nuzzo PA, Haigney MCP. QT-Interval Effects of Methadone, Levomethadyl, and Buprenorphine in a Randomized Trial. Arch Intern Med 2007 167;22:2469-2473

Ballesteros MF, Budnitz DS, Sanford CP, Gilchrist J, Agyekum GA, Butts J. Increase in Deaths Due to Methadone in North Carolina. JAMA 2003 290:40

Krantz MJ, Martin J, Stimmel B, Mehta D, Haigney MCP. QTc Interval Screening in Methadone Treatment. Ann Intern Med 2009 150;6:387-395

Gourevitch MN. First Do No Harm ... Reduction? Annals of Internal Medicine 2009 150;417-8

Editor’s response on Krantz et al: http://www.annals.org/cgi/eletters/0000605-200903170-00103v1#112632

Andrew Byrne response to Krantz et al: http://www.annals.org/cgi/eletters/0000605-200903170-00103v1#112623

AATOD conference link: http://www.aatod.org/pdfs/2009/Conference_Glance.pdf

Clinic web page: http://www.redfernclinic.com/c/

Opera blog: http://www.redfernclinic.com/opera/critique/blog/

New York in spring: http://ajbtravels.blogspot.com/

11 May 2009

Measuring QT interval: more complex than you may think!

Inaccurate electrocardiographic interpretation of long QT: The majority of physicians cannot recognize a long QT when they see one. Viskin S, Rosovski U, Sands AJ, Chen E, ... Zeltser D. Heart Rhythm 2005 2;6:569-574

Dear Colleagues,

In this well conducted study from Israel 4 cardiograph tracings (2 with long QT syndrome vs. 2 normal controls) were sent to about 1000 doctors in several countries, including Australia for their assessments. Clinicians included QT interval specialists, electro-physiology experts, cardiologists and ‘other physicians’.

Correct classification of all four ECGs was gratifyingly 96% in QT specialists and their results were used as the expected ranges. Only 62% of arrhythmia experts and less than 25% of other physicians (including cardiologists) were correct in all four cases.

More than 80% of arrhythmia experts but less than 50% of regular cardiologists and less than 40% of non-cardiologist physicians calculated the QTc interval correctly in all four trial subject ECGs. Much of the inaccuracy occurred in the correction for rate - clearly many doctors did not know how to do this important step. The most common errors were underestimating the QTc of patients with long QT syndrome and overestimating the QTc of healthy patients.

While there is talk about alleged dangers of heart rhythm disturbances in association with methadone treatment, the QTc interval is often discussed as if it were a constant. Automated calculations are not dealt with in this article but their use is becoming widespread in advanced centres but is apparently rare in the developing world where most dependent individuals live. Even so, abnormal automated results are also subject to certain difficulties, needing the human touch … which from this study would still appear to be far from perfect, even in specialist hands.

This interesting report should remind us that the QT interval issue in methadone treatment needs to be looked at from a practical standpoint related to patient safety and treatment effectiveness. To date few if any young, new or uncomplicated patients treated with standard induction protocols have been reported to develop torsade. And this is despite many such patients being reported to have substantial QT interval prolongation (Wedam found >10% had over 500ms at some stage in the first three months of standard treatment).

In our own practice we have faced numerous challenges in obtaining a confirmed corrected QT (QTc) interval in those who may be at risk of torsade - largely those needing methadone doses in excess of 150mg daily. In New South Wales since 2002 there has been a requirement for a cardiograph with detailed QTc interval before patients are permitted to exceed 200mg daily dose of methadone. Our difficulties have included (1) specified QT request ignored by cardiologist, (2) a bland response: “normal tracing, including QTc”, (3) some approximate figures: eg. “QTc around 0.3ms” and (4) some results which were just wrong when checked by us. We have become reasonably adept at doing these measurements simply because of the variable results we have obtained from cardiology reports.

Of the growing number of torsade reports in the literature, nearly all are of patients with (1) multiple medical illness and/or (2) multiple drug/alcohol use and/or (3) taking very high doses of methadone (>150mg). Fortunately only one death was reported amongst about 80 such cases I found in the literature. See Justo’s review in Addiction for 40 such detailed cases up to 2006: he found virtually all had co-existing contributors over and above standard methadone treatment.

Thus we can define a sub-group of methadone patients in whom torsade may be a credible risk and act accordingly. These would include those prescribed the drug in very high dose, those over 40 years of age, female gender, co-prescribed medications, HIV infected, continued use of illicit drugs and/or those with structural heart disease. The most obvious is the co-prescription of drugs known to prolong the QT interval such as erythromycin, droperidol and cisapride.

Just doing an ECG in such cases on its own has limited if any likelihood of avoiding torsade. Most of the reported cases in the literature had a normal ECG before and/or after the torsade episode where one was available. Thus an ECG tracing in such cases is only a starting point or baseline. At best it would detect most cases of familial long QT syndrome (Smith) should this occur in a methadone patient (some may have died during exposure to illicit drugs such as cocaine or amphetamine).

Torsade has also been reported with normal and shortened QT intervals, so this is by no means a yes or no situation - like most other situations in medicine it is a continuum. This is why diagnosis should always be individual and why clinical guidelines should be reserved for particular public health priorities, and only when they are evidence based and known to do more good than harm.

Fortunately, the majority of methadone dependency patients are not in a risk category and do not need cardiography. On the other hand, most should probably be recommended hepatitis testing since this is a major public health issue and a communicable disease.

Thus, despite talk about supposed dangers of high doses, there are in fact far more dangers by using inadequate doses. This is especially so in high risk individuals such as during pregnancy, those with co-existing mental illness and/or continuing drug use. We should be confident to prescribe higher doses for those who need them, based on clinical factors with no arbitrary maximum cut-off. There are major benefits in using adequate doses as shown by many controlled comparative studies. The side effect profile is relatively low as long as patients are properly assessed. Many well run clinics have mean doses around 100mg daily which is about the same as the original report by Dole and Nyswander in 1965. Most well run clinics also have a small number of patients taking over 200mg daily due to rapid metabolism and/or high tolerance to the drug. Not all patients do well on methadone and in some countries there has been considerable experience with buprenorphine which suits a substantial minority of opioid dependent individuals.

Nonetheless, we need to remember that some patients on opioid maintenance treatments are now in the age groups which are subject to other illnesses. These include osteoporosis, hypertension, heart failure, cirrhosis, dementia, etc. These are best addressed by a well co-ordinated “shared care” model utilising family physicians and appropriate specialists.

Comments by Andrew Byrne ..


Wedam EF, Bigelow GE, Johnson RE, Nuzzo PA, Haigney MCP. QT-Interval Effects of Methadone, Levomethadyl, and Buprenorphine in a Randomized Trial. Arch Intern Med 2007 167;22:2469-2473

Smith WM. Cardiac repolarisation: the long and short of it. MJA 2008 188;12:688-689

Justo D, Gal-Oz A, Paran Y, Goldin Y, Zeltser D. Methadone-associated Torsades de Pointes (polymorphic ventricular tachycardia) in opioid-dependent patients. Addiction. 2006 101:1333-1338

Recommended audio critique of the subject by Dr Gavin Bart: https://umconnect.umn.edu/methadoneqtcscreening/