6 December 2008

APSAD Annual Scientific Conference 2008 [part I]

APSAD Annual Scientific Conference 2008

Australasian Professional Society on Alcohol and other Drugs.

November 23 - 26, 2008 Part I (Sunday 23 Nov).

Dear Colleagues,

This year's APSAD conference was a fine affair. I must have been to 15 or more of these in most State capitals, Cairns and Canberra. I missed last year’s Fest in Auckland but those who attended said it was excellent. Like national leaders’ meetings with their funny hats, shirts and coats, each APSAD conference is characterised by its own conference attaché bag. This natural-inspired over-the-shoulder model was one of the few I could imagine using in the future.

The venue was splendid, Darling Harbour being just an 8 minutes (downhill) walk from Town Hall station which made me into a commuter again. With medical practice responsibilities I was a part-time conference goer. Thus these notes are incomplete and (as usual) opinionated.

The Sunday afternoon pre-conference session had been booked by the only drug company with a major stake in our field. Reckitt-Benckiser is manufacturer of buprenorphine which is the only registered alternative to methadone, the latter being a generic drug with small bread-and-butter profit lines in comparison. The sponsors began with the topics of pharmaceutical abuse and innovations in addiction management, then ending with two presentations on the potential cardiac complications of methadone before a panel discussion to which I had been invited (and generously funded).

Adrian Dunlop spoke eloquently about the past, present and future of addiction treatments.

Dr Eric Strain covered some historical details of non-medical use of pharmaceuticals in the US, giving some results on prevalence and consequences from household surveys over 25 years. Apparently most users obtained their supplies from one doctor; many from friends or relatives with less only ~1% or less from the internet. Australian figures may be quite different as people are entitled to attend more than one doctor on Medicare. Another speaker quipped that if Australia had a Bill of Rights, it would include being able to attend “as many doctors as you like”. Dr Strain touched on the gap between occasional use and dependent use, something some of us may still forget because of the selected referrals we receive. The other major differences between American street heroin users and those abusing pain killers is that the latter are more likely to be employed, white race and non-injectors. Dr Strain was too modest to mention his own research on buprenorphine abuse and perhaps too polite to mention the reported non-medical use of buprenorphine, including a naloxone combination product which became the drug of choice (mostly injected) by more than half those presenting for treatment in Wellington, New Zealand (see Robinson 1993).

Dr Nick Lintzeris gave some pointers about pharmaceutical abuse in Australia. His talk ending with a plea to put methadone treatment, including side effects, into context both globally, as well as for individual patients. In his rather frequent exposure during the conference, he reminded us that there are much more relevant issues for opioid therapy as patients get older such as testosterone levels, calcium leaching, osteoporosis, dental, viral and bowel problems.

Jason White detailed the rather sparse literature on cardiac complications in methadone recipients. He seemed persuaded that the connection between methadone and torsade is significant and that methadone treatment could be restricted or further regulated as a result. As a demonstration of patients on ‘normal’ methadone treatment coming to torsade, he cited Pearson and Woosley’s report of 59 FDA notifications from 1969 to 2002. While not fully documented, from the limited data 12 could have been on ‘standard’ MMT, 8 of whom were over 40 years of age. This leaves just 4 reported ‘standard’ MMT cases in the USA over a 33 year period in the age group we normally start on MMT. Justo’s more recent literature review found only 6 of 40 cases reported could have been on ‘standard’ MMT cases without other triggering factors (85% had one or more of these known causes of QT prolongation aside from high methadone doses).

QT prolongation on the cardiograph has long been know to occur in about a quarter of methadone patients yet its only serious consequence, ‘torsade de pointes’ tachycardia, hardly ever seems to occur in young patients (<40>40 years of age, electrolyte disturbance, etc.

As our patient population on maintenance treatment gets older so we must be more vigilant about this and other eventualities. As with other related medical issues, close attention should be paid to cardiac status. This may include an ECG in those taking over 150mg, those prescribed other ‘at risk’ medications or those with HIV or personal/family history of unexplained syncope or fainting.

At this session I was delighted to finally learn the origin of the term ‘ether-a-go-go’ which is from the rhythmic dancing induced in the legs of doomed drosophila drones (flies) under the influence of ether in genetic experiments on channel blockers.

We were then shown a 15 minute video ‘interview’ with Colorado cardiologist Dr Mori Krantz detailing blow by blow the now supposedly conclusive case for methadone’s guilt beyond reasonable doubt in causing fatal arrhythmias. The final proof of any medical argument, we are told, involves randomisation of subjects and so the RCT by Wedam is proffered. This trial, a secondary analysis of ECG tracings obtained incidentally in a 1990s RCT, showed very high rates of QT prolongation in the first 4 months of MMT but no cases of torsade. One of the panellists said to me privately that this appears to be rather persuasive of the safety of methadone rather than the opposite.

As above, hardly anyone has ever seen a case except in patients who are already stressed and in highly complex medical circumstances. I note that since his classic description of 17 non-fatal cases in 2002 (8 were pain management cases), Krantz has only reported two other individual cases of torsade, one of which was attributed to cocaine.

In the video, we are told that because one cannot diagnose an electrical disturbance after death, coroners are unable to detect whether the death was due to cardiac arrhythmia or respiratory depression from the drug. In fact many cases are very clear at autopsy as having the classic findings of post mortem sub-acute lung changes and high blood levels as to leave little doubt about the cause of death. So while Krantz’s proposition may be true for a certain minority, with a 20% mortality, there ought to be 4 times as many (80%) torsade survivors. Yet few if any of these ever seem to get to an emergency room (or ambulance) and have their potentially fatal problem diagnosed with a simple cardiograph tracing. Such reports are exceedingly rare or non-existent. I called one of Australia’s busiest casualty departments to be told that their long-time medical director had never seen a case of methadone associated torsade. He also pointed out that for the past several years modern cardiograph machines have given an automated print-out of QTc, making this information much more available than previously. This just might be the single most important cause of the ‘epidemic’ of electrical changes in the absence of actual symptomatic disease.

Further on in the presentation Krantz states the obvious “it’s not to say that there is an epidemic of cardiac events in America”. Yet elsewhere he has written that a large number of patients are at risk of developing torsade. Fanoe’s Copenhagen syncope study was put up as a written question in the video ‘interview’ (there was no interviewer as such) but Krantz failed to comment on it for some reason. Fanoe showed that out of 800 cases (with no torsade reported) that high rates of syncope (over 20% in most dose groups) in methadone patients was at least in part explained by cardiac conduction problems such as torsade. This is hard to understand for a complication known to occur in less than 1% of patients. Krantz then alluded to Chugh’s Portland study suggesting that it lent support to his torsade theory, yet like so many of the other quoted references, this is another report which does not document any torsade cases at all.

Do I belabour the point? If this is a serial killing, Miss Marple, where are the bodies?
[more about lives saved in another conference posting shortly]

Comments by Andrew Byrne ..

Dr Andrew Byrne MB BS (Syd) FAChAM (RACP)
Dependency Medicine,
75 Redfern Street, Redfern,
New South Wales, 2016, Australia
Email - ajbyrne@ozemail.com.au
Tel (61 - 2) 9319 5524 Fax 9318 0631
Surgery web page: http://www.redfernclinic.com/#news

Robinson GM, Dukes PD, Robinson BJ, Cooke RR, Mahoney GN. The misuse of buprenorphine and a buprenorphine-naloxone combination in Wellington, New Zealand. Drug Alcohol Dependence 1993 33;1:81-6

Strain EC, Stoller K, Walsh SL, Bigelow GE. Effects of buprenorphine versus buprenorphine/naloxone tablets in non-dependent opioid abusers. Psychopharmacology (Berl) 2000 Mar;148(4):374-83

Justo D. Methadone-Induced Long QT Syndrome vs Methadone-Induced Torsades de Pointes. Arch Intern Med 2006 166:2288

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

Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, D. Robertson AD, Mehler PS. Torsade de Pointes Associated with Very-High-Dose Methadone. Ann Intern Med. 2002 137:501-504

Krantz MJ, Rowan SB, Mehler PS. Cocaine-related torsade de pointes in a methadone maintenance patient. J Addict Dis. 2005;24(1):53-60

Krantz MJ, Garcia JA, Mehler PS. Effects of buprenorphine on cardiac repolarization in a patient with methadone-related torsade de pointes. Pharmacotherapy 2005 25:611-614

Fanoe S, Hvidt C, Ege P, Jensen GB. Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen. Heart 2007;93;1051-1055

Chugh SS, Socoteanu C, Reinier K, Waltz J, Jui J, Gunson K. A Community-Based Evaluation of Sudden Death Associated with Therapeutic Levels of Methadone. American Journal of Medicine 2008 121: 66-71

5 December 2008

APSAD Annual Scientific Conference 2008 [part II]

APSAD Annual Scientific Conference 2008 [part II]
November 23 - 26, 2008

The plenary sessions on Tuesday were excellent, starting out with an American statistician, Rosalie Liccardo Pacula talking about the new generation RAND drug use modelling. This appears to be an enormously detailed, almost 4-dimensional system of looking longitudinally at multiple individual markers as well as societal/drug changes. Already they are able to predict drug trends with far fewer people than household surveys but there is still more work to be done to hone this new tool. Like all statistical models, it is only as good as the information fed into it. [http://www.apsad2008.com/abstract/300.asp]

Next we heard Prof Ross Homel giving a talk about complex family interventions, often involving three generations, with the emphasis on child safety, development and education. He gave numerous examples of what they are doing in a non-Government organisation associated with Mission Australia. There were vastly diverse interventions from group therapies, vocational referrals to literacy programs. Their main aim was to embed such programs into schools where there was a high proportion of disadvantaged children.

It was most appropriate that Prof Ann Roche gave the Rankin Oration this year. She did a broad overview of our field and her involvement in it looking back and then giving some views about the future using many clever and apposite quotes from Woody Allen, Elenor Roosevelt, the Dalai Lama and others. One memorable quote from the conference was a post-modern concept for the single woman to ask of any man she dates: �Is this really the man I want to look after my children on weekends?�

Greg Dore then revealed just what we all needed to know about hepatitis C. He dealt with the progress of the epidemic since it was first formally recognised in our communities around 1990. With no initial symptomatology in most patients, it is hard to determine the true incidence. However, by looking at the prevalence in young age groups one can determine changes from time to time. This would seem to indicate that although there are still many reported new cases each year, fewer of these appear to be true new infections as the prevalence in younger people is dropping more rapidly than in the overall population. [http://www.apsad2008.com/abstract/294.asp]

The range of treatments was detailed, pointing out the major improvements in recent years. We can now expect up to 80% �cure� rates (absent viral PCR at 6 months) in genotypes 2 and 3 with around 50% for genotypes 1 and 4. With several innovations such as closer viral load monitoring, liver "fibro-scans" and treatments for anti-viral side-effects, better results can be expected in the next few years. It is only by combining all of our resources, including GPs, addiction clinics, pharmacies and liver specialists that we will be able to address this epidemic which has a high proportion of patients on opioid therapies.

A talk was then given by Marina Davoli from Rome about the Cochrane Collaboration and internet library. Australia has had a special contribution to several areas and we have the only free access for internet users. Australian and New Zealand have also contributed much more serious research than other comparable western countries by population. This underlines all the evidence based interventions we use today.

I missed the session chaired by Dr Deborah Zador on opioid overdose but happily the conference abstracts are all available on the internet (see below). Dr Zador wrote some of the most important seminal studies on the subject in the 1990s. Two papers were given about naloxone, both its distribution amongst the drug using population and intriguingly by the intranasal route by paramedics in the overdose situation. The �Good Samaritan� provisions and international developments were detailed by Paul Dietze and Simon Lenton. [http://www.apsad2008.com/session/353.asp]

Bethany Butler reported some more results in an on-going study of several thousand NSW cases starting for the first time on methadone (~2500) or buprenorphine (~3500). There was no significant difference in the overall mortality in the groups (~65 subjects in each) but an excess mortality (~5-fold) in the methadone group in the first 2 weeks of treatment (7 versus 2). As well as direct toxicity, this might also be explained by methadone patients being in a higher risk group to start with. Even so, only a randomised trial can scientifically compare the two treatments and this is probably no longer ethical as most patients know which drug they want (see Pinto). It is certainly gratifying that when used in the normal course of practice that patients on each of these drugs have a marked drop in mortality. This study found those who remained in treatment were about three times less likely to die.

Next Louisa Degenhardt gave a paper on her group�s investigations of all deaths in NSW opioid maintenance cases since 1985, showing some differences over time. Overall 0.9% of subjects died each year of follow-up: 0.6% for those in treatment compared with 1.2% for those who had left. There was with a much higher chance of dying in the first two weeks of treatment when rate was 4.2%. This latter has dropped significantly since the early 1990s and does not apply at all to buprenorphine cases. The authors state that the treatments have the same mortality rates since those on buprenorphine have a lower retention rate, consistent with the comparative literature.

Finally, the session was given information about significant reductions in local ambulance attendances during the opening hours of the Sydney injecting centre (MSIC) as well as comparisons with the 2 years prior to its opening.

On the Wednesday morning we heard a plenary talk by Nicholas Lintzeris on the directions of treatment in the 21st century. He alluded to the shortage of doctors working in the field, the use of new medications requiring less supervision and models of treatment from elsewhere such as France. His subtext seemed to be individualising treatments rather than having rules and one-size-fits-all. He quoted the average age of methadone prescribers approaching the average daily dose! [Which is now about 75mg!] The speaker also did a study with Adam Winstock regarding attitudes towards withdrawal from treatment.

Next, those of us nursing a headache from the previous night�s dinner at L�Aqua Restaurant were given a fascinating talk by Sharon Walsh who is working in Kentucky on the effects of non-medical use of pharmaceuticals. She reminded us that in some areas there is now as much or more such abuse as for heroin. [This was also reported recently from inner Sydney in an ABC radio story which was nominated for a Walkley Award.] The emergence of prescription drug abuse may mean that we need to alter our approach and will increase the need for treatment services. Despite street and prescription drug use having essentially the same dependency diagnosis, these occur in quite different demographics (see Dr Strain�s talk from Sunday). The new RACP Policy on Prescription Opioids and Chronic Non-malignant Pain was introduced in another session, mapping out a plan for problematic use of prescription opioids in Australia and New Zealand [http://www.apsad2008.com/session/374.asp].

Dr Walsh reported on her results in human laboratory studies on oxycodone (Oxycontin; Prolodone), hydromorphone (Dilaudid) and hydrocodone. The latter is not available in Australia but is a constituent of Vicodin, a commonly abused drug in America. While hydromorphone is thought to be about 7 times stronger than morphine for its analgesic effects, in experiments on recreational users the differences between these three drugs were only marginal. [http://www.apsad2008.com/session/380.asp]

Despite running short of time, the next speaker Mark Tyndall spent some minute or two giving a hilarious description of the harm reduction aspects of pedestrians running red �WALK� signs. Next the hapless visiting Canadian described his shock at being taken to a surf beach where crashing waves buffeting swimmers who risked life and limb against the elements which were anything but �pacific� of late. His implication, I think, was that life savers are the equivalent of harm reduction services for drug users.

Returning to his subject, a square kilometre of western urban Canada, there were an estimated 6000 drug users, mostly injectors, of whom 25% had already contracted HIV and 90% hepatitis C. Services were and are grossly inadequate despite statistics which show disastrous rates of just aboot everything one would not want in one�s neighbourhood (crime, public injecting, overdose, deaths, hospital admissions, HIV cases, infections, etc). The Vancouver injecting centre is slightly larger in scale and opening hours, but shares all the essential characteristics of the Sydney injecting centre at Kings Cross (on which some say it was modelled). It has registered over 10,000 Canadian drug users (not all injectors as in Sydney). There are moves to close down this centre despite a wealth of public health research showing benefits to drug users and the community generally at modest cost (or even a net saving to the health system). Its closure would be a most pointed and poignant natural experiments in public health, comparable perhaps with the Broad Street pump exposure in London in the 1800s.

Next I attended a break-out session in which Carla Treloar spoke about the impressions people had about hepatitis C (http://www.apsad2008.com/session/388.asp). The myths were myriad. Defeatist misconceptions abounded. Some of her quotes were classics. Clearly our first job with hepatitis C is to inform people about the truth. Yes, the disease is still difficult and poorly understood. But we now have simple ways of determining the stage of the disease (�fibroscans�, risk criteria, etc) and we have reasonable and tolerable treatments with success rates up to 80%.

Nick Lintzeris reported some findings of an excellent intervention started some years ago in western Sydney in which OTP patients were offered a rapid vaccination program for hepatitis B. The results and a literature review showed that people at risk should probably be given a booster just about any time they are prepared to take one when it is available, even in quite short succession or as a booster down the line. Strict and appointment based regimens are perhaps not best suited to our patient group and so haphazard inoculations are probably more effective than no inoculations at all.

Some 9 cases of bacterial endocarditis in Newcastle area were reported next by Andrew Taylor. These formed a small minority of the total number of such cases in the region. Candida and staphylococcus aureus were common pathogens. The costs of such treatment to the health care system were high and the savings in prevention substantial.

The final segment of the conference for me at least was our own pet topic, hepatitis C outcomes. Carolyn Day, Paul Haber and colleagues reported on the barriers to addressing this public health priority (http://www.apsad2008.com/abstract/263.asp). From the low rates of assessment and treatment, even some prominent and well run clinics seem not to have effective strategies for testing and referring their patients. Some have no idea what proportion of their patients have been tested. Where resources allow, this can be pro-active, �on-site� and direct to hepatology services. Alternatively, referral to the individual patient�s GPs may be the best way to handle such matters in some situations. It is no longer acceptable to do nothing as advocated by some, claiming that �the treatment is worse than the disease�(!!). Some clinic practices seem so calcified that they have not even managed the change from methadone syrup (containing alcohol, caramel, sorbitol, gum, etc) to the safer �pink� methadone, despite majority patient support where the transfer was done some years ago (eg. NSW prisons; Rankin Court, Langton Centre, Clinic 36, Regent House, etc). At a recent health department forum at North Sydney some senior salaried clinicians described every barrier to improved treatment except themselves!

Next I moved to the session on intervention outcomes where Richard Hallinan reported our own 6 year experience prioritising hepatitis C assessments in OTP cases in Redfern (http://www.apsad2008.com/abstract/270.asp). We used some simple criteria devised by Greg Dore to indicate the likelihood of disease progression with liver fibrosis or cirrhosis. Some findings were given from 315 consecutive assessments with follow-up results for 30 cases having anti-viral treatment. Pegylated interferon alpha plus ribavirin were monitored in a shared care model with specialist hepatology services, with encouraging results thus far showing an overall 74% sustained viral response.

Comments by Andrew Byrne ..

Surgery web page: http://www.redfernclinic.com/#news

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

New York in 2008: http://ajbtravels.blogspot.com/

New York diaries 1922: http://bpresent.com/harry/code/10b_bowery.php

Travel log: http://www.redfernclinic.com/c/2007/10/lord-howe-island-naturalists.php4

Vincent Dole in Nepal Diary: http://vincentdolehimalaya.blogspot.com/

Old photos of Sand Souci: http://sanssouciphotos.blogspot.com/

Pinto H, Rumball D, Maskrey V, Holland R. A pilot study for a randomized controlled and patient preference trial of buprenorphine versus methadone maintenance treatment in the management of opiate dependent patients. Journal of Substance Use 2008 13;2:73-82

�Current policy puts too much emphasis on protecting society from methadone, and not enough on protecting society from the epidemic of addiction, violence and infections that methadone can help reduce.�

Institute of Medicine 1995

Tiny tobacco "tea-bags" commonly used in USA, unregulated!


Dear Readers,

This contains some information which is quite interesting. In some American states there are currently significant numbers of tobacco �suckers� compared with traditional smokers (eg. West Virginia 16% vs. 27%). Apparently these products have not been formally approved yet they were never banned and thus are legal and marketable. We await some good research on their use but most believe that they are probably safer than smoking.

Comment by Andrew Byrne .. (see excerpt below). http://www.redfernclinic.com/#news

MORGANTOWN, W.Va. (AP) -- They're discreet, flavorful and come in cute tin boxes with names like ''frost'' and ''spice.'' And the folks who created Joe Camel are hoping Camel Snus will become a hit with tobacco lovers tired of being forced outside for a smoke.

But convincing health officials and smokers like Ethan Flint that they're worth a try may take some work.

Snus -- Swedish for tobacco, rhymes with ''noose'' -- is a tiny, tea bag-like pouch of steam-pasteurized, smokeless tobacco to tuck between the cheek and gum. Aromatic to the user and undetectable to anyone else, it promises a hit of nicotine without the messy spitting associated with chewing tobacco. Just swallow the juice.

21 November 2008

Publications from Byrne Surgery in Redfern, New South Wales.

Byrne A, Hallinan R. HIV seroconversion. [letter] ANZ J Pub Health 2002 26;2:182

Byrne A, Hallinan R, Love A. Administration of a lighter-coloured methadone liquid. D&A Review 2002 21;4:405

Byrne A, Hallinan R. The introduction of buprenorphine into a medical practice treating addiction. Monograph Byrne Surgery March 03

Hallinan R, Byrne A, Amin J, Dore GJ. Hepatitis C virus incidence among injecting drug users on opioid replacement therapy. ANZ Journal Public Health 2004 28;6:576-578

Byrne A, Hallinan R. Evaluation of accreditation of methadone clinics in NSW - Survey of clinics. Poster presentation 29;112 APSAD conference November 2004, Perth WA.

Hallinan R, Byrne A, Amin J, Dore GJ. Hepatitis C virus prevalence and outcomes among injecting drug users on opioid replacement therapy. J Gastro Hepatology 2005 20;7:1082-1086

Hallinan R, Ray J, Byrne A, Agho K, Attia J. Therapeutic thresholds in methadone maintenance treatment: A receiver operating characteristic analysis. Drug Alc Dep 2006 81:129-136

Byrne A, Graham G, Hallinan R, Murnion B. Naltrexone implants as treatment for heroin dependence: Part I. Addiction Biology 2005 10:201

Hallinan R, Ray J, Byrne A, Agho K, Attia J. Therapeutic thresholds in methadone maintenance treatment: A receiver operating characteristic analysis. Drug and Alcohol Dependence 2006 81;2:129-136

Byrne A, Hallinan R. Methadone is still needed in addiction treatments. BMJ 2006;332:53

Hallinan R, Byrne A, Dore G. Harm reduction, hepatitis C and opioid pharmacotherapy: an opportunity for integrated HCV-specific harm reduction. Drug Alc Rev 2007 26:437-443

Byrne A. Safe and effective opioid prescribing in addiction treatment. Monograph of article commissioned, accepted and rejected by Advances in Psychiatric Treatment journal 2008

Hallinan R, Byrne A, Agho K, Dore GJ. Referral for chronic hepatitis C treatment from a drug dependency treatment setting, D&A Dependence 2007 88;1:49-53

12 November 2008

Methadone safe in young uncomplicated patients; check QT in older folk and those taking other drugs or alcohol, or with HIV.

Electrocardiogram characteristics of methadone and buprenorphine maintained subjects. Athanasos P, Farquharson AL, Compton P, Psaltis P, Hay J. Journal of Addictive Diseases 2008 27;3:31-35

Dear Colleagues,

These authors from Adelaide, South Australia report a relevant and reassuring ECG study from a 'normal' addiction clinic setting.

We are presented with a comparison of 35 methadone maintained patients, 19 on buprenorphine and 17 controls. Methadone doses varied from 15-145mg daily, being in the common range used clinically around the world. Most subjects were in their 30s and 28 of 71 subjects (39%) were female.

They report no significant difference between the mean corrected QT interval (QTc) of the three groups (407, 407 and 397 milliseconds). There was also no correlation found between methadone dose and QT interval. The QTc in those taking more than 60mg daily were slightly longer (405ms or 6.3%) than for those taking less than 60mg (381ms) (p=0.02). There were also some 'U' waves reported in the methadone patients. Two methadone patients and one control had prolonged QTc when defined as 430ms or longer for males (450 for females). No result was over 475ms. The threshold above which risk of torsade rises significantly is believed to be 500ms.

These findings are all consistent with the report of Lipsky et al. 35 years ago linking methadone prescription with QT prolongation and U waves. The clinical significance of these findings is still uncertain. These authors report no cases of torsade arrhythmia.

They conclude: 'Although an association is thought to exist between high methadone doses and elongated QTc, methadone and buprenorphine, at commonly used daily doses, remain safe agents for opioid substitution therapy.'

As a further exercise I contacted two prominent addiction experts in Adelaide (pop 1.2 million) on this subject. One had seen no cases and the other was aware of one possible case some years before. This is on a long background of good quality methadone treatment, both private and public, in that city.

It may be timely to examine the evidence for claims that methadone prescription in addiction treatment is accompanied by a significant risk from arrhythmias, including death. Despite there being no body of case reports in such guideline-treated subjects (or perhaps because of it) a number of authors have attempted to assess methadone's role in cardiotoxicity by using indirect and unconventional methods.

For example, Fanoe (ref below) prefers QT/torsade as an explanation for up to 30% of his subjects reporting syncope on MMT in Copenhagen. Since the incidence of torsade is certainly less than 1% annually, this explanation is not credible, especially coming from a country with extremely high alcohol statistics.

Chugh (ref below) used a methodology looking at post mortem structural heart disease in those dying suddenly with or without therapeutic levels of methadone in the blood. Their deduction for QT changes without a single case report seems hard to understand.

Wedam (ref below) wrote 'To compare the effects of [methadone] on the corrected QT (QTc), we conducted a randomized, controlled trial of opioid addicted subjects.' In fact they performed a retrospective re-analysis of old analogue ECG tracings from a 1990s RCT, finding more than 10% had QTc over 500ms. This is not consistent with other reports on the subject. No torsade cases were reported in the study groups.

A review of the world literature by Justo (ref below) found only 40 documented cases, 85% of whom had two or more risk factors. Few of these reported cases bear much similarity to those commencing 'normal' clinic or community addiction treatment. The QT/torsade cases tend to be significantly older, female sex, and to involve co-medications, very high methadone doses (up to 1200mg daily or ten-fold 'normal' doses) as well as certain metabolic (potassium or magnesium deficiencies) and genetic states (familial long QT syndrome).

I believe that it is now possible to restate unequivocally that 'normal', guideline-based methadone treatment is safe and effective. The cardiac arrhythmia issue appears to be based on a combination of factors rather than a consequence of standard methadone treatment. Knowing the other risk factors, most cases could probably be avoided using good clinical practice (see Sticherling). Routine pre-treatment cardiographs would have been unlikely to have detect any of these latter cases.

Even in the face of a dearth of relevant case reports, some have given advice to avoid methadone without due consideration of its benefits and the absence of a suitable alternative in a large proportion of cases, especially high-dose subjects (see Kakko). While methadone-induced torsade clearly can occur, the numbers appear to be exceedingly low and would probably be swamped statistically by reductions in endocarditis cases alone in those taking methadone (these and other benefits are eloquently reported by Krantz in 2001 - ref below).

In practical terms, this means that existing methadone patients needing other strong medications, methadone doses over 200mg or who develop HIV and/or have other risk factors should be recommended a cardiograph, just as they should have electrolytes, liver function tests, etc performed as a matter of clinical course.

We need to ensure that as clinicians we continue to ask the question: what is the evidence?

Comments by Andrew Byrne ..



Fanoe S, Hvidt C, Ege P, Jensen GB. Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen. Heart 2007;93;1051-1055

Chugh SS, Socoteanu C, Reinier K, Waltz J, Jui J, Gunson K. A Community-Based Evaluation of Sudden Death Associated with Therapeutic Levels of Methadone. American Journal of Medicine 2008 121: 66-71

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

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

Sticherling C, Schaer BA, Ammann P, Maeder M, Osswald S. Methadone-induced Torsade de Pointes tachycardias. Swiss Med Wkly 2005;135:282-285

Kakko J, Gronbladh L, Svanborg KD, von Wachenfeldt J, R�ck C, Rawlings B, Nilsson L-H, Heilig M. A Stepped Care Strategy Using Buprenorphine and Methadone Versus Conventional Methadone Maintenance in Heroin Dependence: A Randomized Controlled Trial. Am J Psychiatry 2007 164;5:797-803

Krantz MJ. Clinical Concepts- Cardiovascular Health in MMT Patients. Addiction Treatment Forum 2001 No 4 http://www.atforum.com/SiteRoot/pages/current_pastissues/fall2001.shtml

8 November 2008

Dr Mori Krantz on cardiac protections in methadone treatment. 2001.

Krantz MJ. Clinical Concepts- Cardiovascular Health in MMT Patients. Addiction Treatment Forum 2001 No 4 http://www.atforum.com/SiteRoot/pages/current_pastissues/fall2001.shtml (Archive accessed on 25/10/08 excerpt herewith)

A.T.F. Volume X #4 Fall 2001

Clinical Concepts- Cardiovascular Health in MMT Patients

By Mori J. Krantz, MD*

According to current estimates nearly 61 million Americans have one or more types of cardiovascular disease, including coronary artery disease (CAD), congestive heart failure, and hypertension.[1] Methadone maintenance treatment (MMT) patients are clearly part of this larger demographic, and there are unique clinical characteristics in this group warranting special attention.

High Risk, Less Access

Patients entering MMT are a very high-risk population from a general health maintenance standpoint. As a rule, patients who use illicit drugs expose themselves to a number of health risks, and are less likely to regularly interface with the healthcare system. An increased reliance on emergency services and a lack of integration into healthcare delivery systems create a backdrop for poor outcomes.

The literature confirms that barriers to high quality care for cardiovascular disease are greater in vulnerable patient populations, such as minorities and the poor. A great many MMT patients fall into both of those categories.

For example, African Americans and low-income patients are less likely to receive care by a cardiologist. In contrast, white race, higher income, and college education independently predict care by a cardiologist.[2]

Available data suggest that the gap in cardiovascular disease mortality between the poor and uneducated versus the wealthy and well educated has not lessened and may be widening. The National Conference on Cardiovascular Disease Prevention concluded that to attain the goals set forth by the U.S. Surgeon General�s Healthy People 2010 initiative, we should focus on reducing disparities in health status on the basis of race, ethnicity, and socioeconomic status.[3]

To make matters worse, mainstream physicians often stigmatize MMT patients. This further distances these patients from regular, preventive health care services.

Some Specific Cardiac Risks


Intravenous drug users (IVDUs) are at high risk for developing infections of their heart valves (infective endocarditis). These infections are a direct result of bacteria entering the bloodstream at the skin site of injection.

Acute infection accounts for the majority of hospital admissions among IVDUs and endocarditis is found in 10% of these episodes.[4] Most of these patients have no pre-existing cardiovascular disease.

The symptoms of this disorder may include persistent fever, chills, sweats, muscle and joint aches, malaise, and back pain.[5] These symptoms are invariably preceded by an episode of intravenous drug use.

Endocarditis has very high morbidity and mortality. It can necessitate extended intravenous antibiotic therapy and in many patients will require complex heart valve surgery or even valve replacement. Other consequences of endocarditis include brain abscess, kidney failure, and death.

MMT offers substantial protection from this deadly disease by eliminating or dramatically reducing the amount of illicit drug use. In our local hospital experience during 2000-2001, practically none of the heroin-abusing patients admitted with endocarditis were in methadone treatment programs.

Furthermore, in my oversight of hundreds of MMT patients during nearly a decade, I have encountered only 3 cases of endocarditis in that population. This evidence is anecdotal and retrospective, but supports the common sense notion that methadone treatment dramatically reduces the risk of endocarditis in IVDUs.

Coronary Artery Disease (CAD)

CAD is the number one cause of death in the Western world [1] and MMT patients are no exception. These patients may be at particularly high risk given that as many as 90% of them smoke tobacco, which is a known risk factor for CAD.[6]

Additionally, cocaine abuse is seen with some frequency in this population. Cocaine use has been linked to the development of arrhythmias, CAD, heart attack, and death.[7]

Despite the uses of tobacco and cocaine in MMT patients there have been no published reports documenting a higher overall incidence of cardiovascular disease in these patients. In my MMT practice, there are very few patients with established CAD. This is remarkable, given the fact that a significant proportion are beyond 50 years of age and many continue to smoke cigarettes.

Is there a possible explanation for this relatively low incidence of CAD in MMT patients?

The evidence is not clear. However, there is some pharmacologic data suggesting that methadone may exert a calcium channel blocking effect.[8] Calcium channel-blocking medications lead to slower heart rates and reduced cardiac work, and these agents are effectively used to treat CAD patients who develop symptoms of angina (chest pain).[9]

Also, opiates, including methadone, are known to reduce blood pressure and slow the heart rate. Morphine, for instance, is a commonly used medication to treat hospitalized patients who experience a heart attack.

Thus, due to these properties, methadone is theoretically protective in preventing or reducing cardiac ischemia (lack of blood supply to the heart).

Cardiac Arrhythmias

There is no compelling evidence in the literature to suggest that methadone treatment is a direct cause of sudden cardiac death or fatal heart rhythm disturbances.

In clinical practice, the risk of cardiac arrhythmias attributable to these treatments currently appears to be quite small. Future research and accurate incidence data will help clarify any contribution of opioid-agonist therapies to arrhythmia risk.

MMT Minimizes Cardiac Risks

Ongoing participation in MMT affords patients many heart health benefits. For one thing, these patients have significantly greater access to preventive cardiac-health services than opioid-dependent persons not in treatment.MMT patients are provided periodic monitoring of their blood pressure and pulse. Vital signs are obtained upon admission, during yearly physical exams, and during dose changes.

In my experience, this has offered a tremendous opportunity to screen patients for hypertension and then provide adequate treatment. Hypertension afflicts 50 million Americans; it is a leading contributor to CAD and the number one cause of stroke.

In my practice, a full lipid panel is obtained annually in all patients to check cholesterol levels. Those with elevated levels can be offered effective treatment with cholesterol-lowering medications, which have clearly been shown to reduce the risk of heart attack and death in patients who are at high risk.[10-12]

Finally, patients in MMT have access to frequent professional counseling, which presents ideal opportunities for discussing the importance of smoking cessation for long term cardiac health. The most common cause of death in smokers is coronary artery disease (CAD).

Stopping smoking dramatically reduces the risk of future heart attack or death. We regularly counsel patients on tobacco risks and many are able to quit or significantly reduce tobacco consumption as part of comprehensive treatment plans.

In conclusion, from a cardiovascular perspective, methadone is a safe medication and MMT program staff can perform vital roles in providing effective cardiac risk-reduction services.


1. American Heart Association. Heart and Stroke Statistical Update; 1999.

2. Auerbach AD, Hamel MB, Califf RM, et al. Patient characteristics associated with care by a cardiologist among adults hospitalized with congestive heart failure. J Am Coll Cardiol. 2000;36:2119-2125.

3. Cooper R, Cutler J, Desvigne-Nickens P, et al. Trends and disparities in coronary heart disease, stroke and other cardiovascular diseases in the United States. Findings of the National Conference on Cardiovascular Disease Prevention. Circulation. 2000;102:3137-3147.

4. Murphy JG. Mayo Clinic Cardiology Review. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2000:412.

5. Mandell GL. Principles and Practice of Infectious Diseases. 4th ed. Churchill Livingstone; 1995:748.

6. Practitioner panel: methadone and heart health. Addiction Treatment Forum. 2001;10(3):5.

7. Lange RA, Hillis LD. Cardiovascular complications of cocaine use. N Engl J Med. 2001;345:351-358.

8. Lee CH, Berkowitz BA. Calcium antagonist activity of methadone, l-acetylmethadol and l-pentazocine in the rat aortic strip. J Pharmacol Exper Ther. 1980;215(1):259-265.

9. ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina. J Am Col Cardiol. 1999;33:2092-2190

10. Long term treatment with pravastatin in ischaemic disease (LIPID) study group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349-1357.

11. Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: The 4S trial. Lancet. 1994;344:1383-1389.

12. Sacks FM, Pfeffer MA, Moye LA, et al. Cholesterol and Recurrent Events Trial Investigators. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996;335:1001-1009.

*Mori Krantz, MD is Director of the Cardiovascular Risk Reduction Program, Denver Health Medical Center, and Assistant Professor of Medicine and Cardiology, University of Colorado.

6 October 2008

More alarmist speculation on QT 'problems' yet still no incidence of actual complications. Smoke and mirrors.

QTc Interval Prolongation and Opioid Addiction Therapy. Baker WA, Krantz MJ. Archives Internal Medicine (letter) 2008 168;14:1502

Dear Colleagues,

In this letter Baker and Krantz applaud Wedam et al's 'commendable' 'addition to the medical literature' which found QT prolongation in 23% of methadone subjects. In fact these researchers found much the same as Janet Lipski's report from 1973 (34%). Thus it is clear that a substantial minority of methadone patients have modest prolongation of QT intervals of uncertain significance.

Baker and Krantz then express the unsurprising deduction that if a lower cut-off for QT prolongation were used, a correspondingly higher proportion of prolongation subjects will result (up to 50%). The clinical significance of these observations, if any, is not detailed. And none developed tachycardia.

Krantz has wrongly cited Lipski's study as being (at least in part) to investigate sudden deaths in methadone patients. In fact, Lipski and colleagues were concerned about heroin deaths and the QT findings in methadone patients were incidental. When this mistake was pointed out in Lancet, Krantz in reply ignored the matter and turned to increasing deaths of non-addiction treatment (pain) cases in America more recently (Mehler 2007).

Specifically, Krantz writes that Lipski's study was aimed at investigating 'a perceived increase in the risk of sudden death in heroin addicts, even in those successfully treated with methadone' in 1973 in New York (Krantz MJ 2006). From the title and opening lines it is clear that Lipski and colleagues were actually concerned over deaths in heroin users where sometimes blood levels were not particularly high, an issue raised by long time city coroner Dr Milton Helpern (see ref). They performed cardiographs in new methadone applicants who had used street heroin in the previous hours or day(s) to see if there were any electrical disturbances which might explain the sudden deaths in heroin users.

Unlike in his first paper on this subject, Krantz now treats QT prolongation in isolation as if it were a complication in itself, avoiding discussion of torsades or other cardiac events. And like most of the other studies, Wedam and colleagues report no symptomatic heart disease whatever and, most importantly, no sudden deaths. Over a period of 30 years of intensive, supervised prescription of methadone only one single case of arrhythmia was reported to the FDA (Pearson). So while torsades or ventricular fibrillation occur in methadone patients, the prevalence must be very low and possibly near to the rate in the general population (estimated to be 1 in 2000 - see Smith W).

This laudatory letter is just another 'weak link' in the case put by Krantz that due to potential cardiac complications, methadone treatment needs to be reviewed, especially when used in high doses. He recently noted 'with consternation' (hardly a scientific term) that higher doses were being used in addiction clinics in his own state, something most public health specialists would have applauded (D'Aunno). Many rigorous studies indicate that higher doses protect dependency patients from significant and measurable events (overdose, viral disease, criminal behaviour, depression, etc). Dole's seminal study of methadone treatment reported up to 180mg daily with excellent results and no serious side effects.

To my knowledge there have still been no reported series of confirmed case reports of cardiac complications (eg. torsades-de-pointes) in patients receiving methadone treatment for addiction under existing guidelines. Krantz emphasises the proven benefits of MMT yet at the same time questions this established, evidence-based practice, emphasising a difficult therapeutic 'trade-off'. Yet this is before there is documented evidence of a problem existing and despite 30 years of careful research showing safety and effectiveness. Further, there has been no analysis of the costs and benefits of any suggested alternative strategies such as low dose methadone or transfer to buprenorphine. Krantz has also apparently had minimal input from dependency specialists. Few non-cardiologists would be so bold regarding advice on heart treatments.
Dr Krantz's widely publicized views have had the consequence of denigrating methadone as a treatment for both addiction and chronic pain. I can find no evidence suggesting that any cases of cardiac complications resulting from methadone treatment have been avoided as a result. The literature reveals only flimsy and conflicting evidence - most of it retrospective - of an association of methadone and cardiac events. Some have reported a lower cardiac risk (Marmor 2004).

Krantz's articles, letters and personal communications show a clear 'disconnect' between his earlier findings and the sentiments he has expressed more recently. While his earlier findings relate mostly to pain patients, he has strongly targeted an addiction treatment audience for his communications and further research (eg. Krantz 2007). His advice, which has changed over the years, has involved (1) the need (or otherwise) for a cardiograph before starting treatment, (2) the avoidance of methadone where possible and (3) the avoidance of high doses where methadone is used. His other recommendations are purely generic in recommending careful history and physical on each patient and acting on any evidence of cardiac risk. While this is important, it is probably no more important than acting on evidence of infectious disease, overdose risk, liver disease, allergies, mental illness, etc, etc.

The potential risk of cardiac side effects must be balanced against the unequivocal benefits of methadone maintenance to those who need and want it for their condition. There need be no 'competition' with buprenorphine which is an excellent alternative with certain benefit and certain disadvantages in the opiate treatment population.

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

Krantz MJ, Mehler PS. QTc prolongation: methadone's efficacy-safety paradox. Lancet 2006 368:556-557

Byrne A, Stimmel B. Methadone and QTc prolongation. Lancet 2007 369:366

Mehler PS, Krantz MJ. Authors' reply. Methadone and QTc prolongation. Lancet 2007 369:366-7

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

Lipski J, Stimmel B, Donoso E. The effect of heroin and multiple drug abuse on the electrocardiogram. American Heart J 1973 86:663-8

Pearson EC, Woosley RL. QT prolongation and torsades de pointes among methadone users: reports to the FDA spontaneous reporting system. Pharmcoepidemiol Drug Saf. 2005 14;11:747-753

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

Dole VP, Nyswander ME. A medical treatment for diacetylmorphine (heroin) addiction. J Amer Med Assoc 1965;193:646-50 '193(8) 80-84'

Helpern M. Fatalities from narcotic addiction in New York City: incidence, circumstances and pathologic findings. Human Pathology 1972 2:13-21

Krantz MJ, Rowan SB, Schmittner J, Bucher Bartelson B. Physician Awareness of the Cardiac Effects of Methadone: Results of a National Survey. Journal of Addictive Diseases 2007 26;4:79-85

Marmor M, Penn A, Widmer K, Levin R, Maslansky R. Coronary artery disease and opioid use. Am J Cardiol. 2004;93:1295-1297

Leavitt S. Methadone: facts and fiction ... http://www.atforum.com/SiteRoot/pages/current_pastissues/2007winter.html

[This summary has been up-dated, omitting an incorrect sentence.]

3 September 2008

Subject: Methadone works in American prisoners who are addicted - no surprise.

A randomized clinical trial of methadone maintenance for prisoners: findings at 6 months post-release. Gordon MS, Kinlock TW, Schwartz RP, O'Grady KE. Addiction 2008 103;8:1333-1342

Dear Colleagues,

These researchers found, predictably, that offering methadone maintenance treatment (MMT) to released prisoners with a history of opiate addiction was feasible, safe and effective, just like it is in the community generally when done according to established guidelines. They compared counselling with/without MMT, finding less heroin use and less criminal activity at 6 months after release in those offered MMT. Treatment retention was also higher.

This is yet another example of American clinical practice which is decades behind other countries. And this is despite heroin addiction has been accepted as a �brain disease� by the White House and methadone/agonist treatments are now approved in every state. However, for those in the US prison system these maxims do not apply for some reason. Note that this study was not published in an American journal.

Almost uniquely, in New South Wales, prisoners have had access to methadone treatment for over 20 years. It was initially introduced in the 1980s as a pre-release measure to address the high rate of overdoses in that group. There is now a copious world literature on the subject, largely very positive. Methadone for prisoners has now been introduced in many other jurisdictions, although rarely �across the board� as occurs in New South Wales.

Thus a trial which gave some subjects no access to such treatment would be unethical, unnecessary and cruel in a �normal� jurisdiction. Yet in America, despite a large drug budget and constitutional protections, denying prisoners appropriate treatment seems to be �business as usual�. These researchers should be commended for trying to buck the trend. They write that there is an �urgent treatment need� and one only hopes that something is done for the sake of the prisoners, their families and the general community where the adverse consequences currently must be enormous.

Comments by Andrew Byrne ..

Surgery web page: http://www.redfernclinic.com/

21 August 2008

Lofexidine for withdrawal symptoms works ... (but detoxification usually doesn't).

A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal. Yu E, Miotto K, Akerele E, Montgomery A, Elkashef A, Walsh R, Montoya I, Fischman MW, Collins J, McSherry F, Boardman K, Davies DK, O�Brien CP, Ling W, Kleber H, Herman BH. Drug and Alcohol Dependence 2008 97;1-2:158-168

Dear Colleagues,
This may be a world record for delays in clinical research. Dr Kleber first wrote about the possible effectiveness of lofexidine for withdrawals in 1981 (ref 1). Now, with a stellar cast of senior American colleagues he has produced a small and unsatisfactory report (n = 68, only 17 completers) in the course of attempting to have the drug registered in the United States. With modest but apparently significant benefits noted in a 4 day regimen using the drug, the trial was dramatically called off just over half way thru. This is normally only done where it is considered unethical to continue to using placebo. However those receiving lofexidine also suffered 4 significant side effects, each probably related to hypotension. The benefit of lofexidine was a reduction in withdrawal symptoms/signs from 30 to 20 and an increase in retention from 15 to 38%. While these differences are substantial, the same or better might have been obtained with clonidine, diazepam or even �hospital brandy�. Additionally we know that this intervention (detoxification from opioids) has a ~90% failure rate and also a substantial mortality in the period following.

Doctors and health workers can recommend established, effective treatments, yet detoxification should only be initiated by the patient in my view � both due to its inherent dangers and the lack of a proven strategy to achieve this noble goal. It is hard to justify detoxification from opioids in pregnancy, for example, and some would say it is unethical. On the other hand, patients are perfectly entitled to request services which doctors would not normally actively recommend (abortion, contraception, euthanasia, circumcision, etc). As long as the detoxification is patient-initiated, and the patients are aware of the alternatives and the relative risks then there can be no ethical problem.

The authors give a comprehensive literature review, pointing out that there is little current evidence favouring lofexidine over clonidine regarding effectiveness yet the former seems to have less hypotensive side effects in some trials. Some quoted trials compared lofexidine with buprenorphine, a ludicrous comparison in my view. It would be like comparing aspirin with penicillin for bronchitis. So after 25 years I am still not convinced that lofexidine is a sure-thing in detoxification. One might also think that if it were indeed effective that there might be more anecdotal evidence as well as a possible black market in the drug (at least in the UK).

Comments by Andrew Byrne .. http://www.redfernclinic.com/

Washton AM, Resnick RB, Perzel JF, Garwood J, Gold MS, Pottash AC, Annitto WJ, Extein I, Kleber HD. Lofexidine, a clonidine analogue effective in opiate withdrawal. Lancet 1981 317;8227:991-993

Concord Seminar summary on Adult ADHD in those with substance use disorder.

Concord Dependency Seminar Tuesday 22nd July 2008

Adult ADHD & Substance Use Disorders � Dr Julian Trollor

Dr Julian Trollor is Senior Staff Specialist Neuropsychiatrist at the Neuropsychiatric Institute, Prince of Wales Hospital and Senior Research Fellow of the Brain Ageing Program at the University of New South Wales. He established a clinic for the assessment of adults with possible ADHD in 1995. This clinic now operates as a tertiary service, providing second opinions in difficult cases.

Dr Trollor began his presentation by recounting his own experience of filling out a pop-up box which once appeared unbidden on his computer screen. Dr Trollor (who does not have ADHD) was informed...."the responses you have provided indicate that your symptoms may be consistent with Adult ADD. It may be beneficial for you to talk with your healthcare professional about an evaluation.� The pop-up was sponsored by a manufacturer of a pharmaceutical for ADHD.

Dr Trollor pointed to the growing popular awareness of Adult ADHD (A-ADHD), with �self diagnosis� being common, shared controversy with its childhood counterpart, and community fears about treatment with a potential "drug of abuse".

ADHD is a "neurodevelopmental disorder of childhood onset characterised by impairments in cognitive function (inattentiveness), excessive motor behaviour (hyperactivity) and impaired behavioural regulation (impulsivity).� It is common, with high co-morbidity, and it is often overlooked, despite being relatively easily treated, with treatment improving outcomes.

Evidence for the validity of the entity A-ADHD has increased greatly in the last decade and is found in cross sectional, longitudinal and epidemiological studies, family & genetic studies, and neuro-psychological, -physiological, -endocrine and -anatomical studies.

Despite progress in understanding of A-ADHD, clinical diagnosis remains problematic: there is no single criterion marker; the core symptoms are dimensional (or spectrum) rather than categorical; co-morbidity can confound diagnosis; the requirement for retrospective childhood diagnosis may create difficulties; the key descriptors are ubiquitous; and the requirement for �significant impairment� is arbitrary. Diagnostic tests are often used but they lack specificity.

The DSM IV CRITERIA are listed in the appendix (see Redfern Clinic website). Briefly, the person must have (for the primarily inattentive type) six or more inattention symptoms as well as (for the combined type) six or more hyperactivity/impulsivity items for at least 6 months to a degree that is maladaptive. Some symptoms must be present before 7 years of age, impairment must be present in at least two settings, and symptoms do not occur exclusively during the course of a pervasive developmental disorder, psychotic disorder and (as always in DSM-IV) are not better accounted for by another mental disorder.

Symptoms can be grouped in four types:

1. attentional, with difficulty sustaining attention (during lectures, reading, in conversation, at work), easily distractability (eg by extraneous sounds, activity), day-dreaming, making careless mistakes - the primarily inattentional type is more common among women.
2. organisational, often losing things, forgetting day to day activities or appointments, having difficulty organising tasks, following verbal instructions - these may be more pronounced in unstructured settings, and therefore may become more problematic in adults, upon leaving a structured setting like school/college.
3. hyperactivity, being always �on the go� physically, being fidgety or restless, having difficulty relaxing, having racing thoughts or many ideas, taking on multiple tasks at once without finishing many.
4. impulsivity, talking excessively, making tactless comments, interrupting conversations, difficulty waiting turn, taking risks (eg driving, thrill seeking, financial risks), explosive temper, irritated easily by minor frustrations, quick mood changes.

Hyperactivity may be less marked in adults in whom the hyperactivity may be more a phenomenon of mental cluttering, akin to a sense of continuous "noise" - quite distinct from anxiety. A meta-analysis of follow-up studies of children with ADHD showed an age-dependent decline in ADHD symptoms: 65% experienced partial remission in adulthood, with full ADHD diagnosis persisting in approximately 15%. The severity of ADHD symptoms in childhood appears to predict persistence into adulthood.

A large cross-national survey estimated adult ADHD prevalence across ten countries to be 3.4% (range 1.2-7.3%); one US study estimated current prevalence of adult ADHD at 4.4%. As Dr Trollor pointed out, these estimates suggest that A-ADHD is one of the more common mental disorders.

ADHD is a condition with a high genetic loading - family studies suggest 80% of ADHD symptoms can be attributed to genetic factors - with genetic-environmental interactions also playing a role, especially disrupted attachment, early abuse, and chaotic environment. The candidate genes are those involved in motor activity and attentional processes, and include DAT gene (SLC6A3), COMT (Catechol-O-methyltransferase), DBH (Dopamine beta-hydroxylase) and dopamine receptors (especially DRD4), however no single gene accounts for more than 5% of the phenotypic variance of ADHD.

Adult ADHD has major consequences: adults with ADHD are less likely to be employed full-time and more likely to have unstable work records, have significantly lower household income, have fewer close friends, more difficulty sustaining relationships and higher likelihood of having contracted a sexually transmitted disease. They are more accident prone (more traffic violations, severe accidents, more likely to be �at fault�), and have higher medical costs.


In making a diagnosis, it is important to consider the motive/catalyst for presentation, whether owing to legal & forensic issues, a transition from a more to a less structured environment, or on cessation of substance use. Some adults come forward for assessment following diagnosis of their children. Self diagnosis is not a reliable indicator of the presence or absence of ADHD

The diagnostic pathway is to assess current symptom profile, severity and impact, to establish and corroborate childhood diagnosis (from self-report, parental and school reports, previous psychological or medical assessments) and to evaluate co-morbid (or diagnostically confounding) conditions - people with ADHD have increased risk of a diagnosis of antisocial personality disorder, of anxiety disorders, major depression and substance use disorders.

Bearing in mind the partial remission of ADHD in many or even most adults, it is important to consider the actual impact of symptoms on the patient's social, occupational, educational or family life as well as their current coping strategies. Many people cope well with or are untroubled by having features of ADHD and it is not uncommon for people with ADHD to be less likely to complain than their partners or family.

Establishing a retrospective childhood diagnosis is often a challenge, especially for people with major psychosocial problems including substance use disorder (SUD) who may have chaotic histories and be estranged from family. Where possible, informant interview can provide corroboration of the nature and extent of both current and past symptoms. Evidence can be gleaned from academic records, number and type of jobs, history of impulsive infringements, self esteem and interpersonal problems (resulting from impulsivity, poor anger control and organisational skills), and patterns of drug use which may suggest self-medication of symptoms. Sometimes there is a suggestive �paradoxical response� to street amphetamine - ie a calming effect rather than stimulation.

Further assessment may include the use of rating scales, and require physical examination, bloods testing including thyroid function, urine toxicology, EEG, CT/MRI of the brain (a history of head injury may be common in people ADHD owing to their accident proneness, but brain injury may also sometimes mimic ADHD symptoms), and neuropsychological examination including CPT. Not all of these will be required in every case.

Substance Use Disorders and A-ADHD

The epidemiological relationship between substance use disorders (SUD) and A-ADHD is bi-directional, with increased rates of SUD in ADHD clinic samples (for alcohol 17-45%, other drugs 9-30%) and of ADHD in SUD clinic samples (around 25%).

Relative risk of SUD in follow-up of ADHD cohorts is increased up to five-fold, with earlier and increased use of alcohol, tobacco and other substances in adolescents with ADHD compared to controls, and ADHD in childhood and adolescence a significant predictor for later substance use - the risk is greater if the individual has conduct disorder or mood disorder. The relationship of with childhood ADHD is strongest for tobacco smoking, and it is likely a sub-group of individuals with ADHD self-medicate with tobacco: nicotine has been successfully trialled as an intervention.

People who have both SUD and ADHD have poorer outcomes. However, people treated with stimulants in childhood and/or adolescence have an equivalent or lower incidence of SUD compared to those untreated, and the use of stimulant medication to treat people with ADHD does not increase the risk of developing substance use disorder.

It is preferable to perform diagnostic assessment during long-term abstinence (whereby opioid substitution treatment with abstinence from other problematic substance use can be considered abstinence) and, as with other co-morbidities, active SUD should be addressed prior to specific ADHD treatment. It should be borne in mind that ADHD medications have no demonstrated efficacy for the treatment of ADHD where there is co-morbid SUD, nor have studies been conducted of use of psychosocial interventions.

Dr Trollor recommended (and feedback is welcome about) the Draft Guidelines for the Assessment and Management of Attention Deficit Hyperactivity Disorder (National Health and Medical Research Council and the Royal Australasian College of Physicians) accessible at http://www.racp.edu.au/ ( follow link under �announcements�).

From these guidelines, the following are some key recommendations for best practice for assessment and diagnosis of ADHD in adults when co-morbid SUD is present:

People with personality disorder and/or substance abuse should be referred for evaluation of ADHD if they present with a significant level of hyperactivity / impulsivity accompanied by inattention.
Medication treatment for ADHD co-morbid with substance misuse should only be provided by a medical practitioner with expertise in both conditions.
ATX should be the first medication trialled if there is co-morbid substance abuse.

Management of A-ADHD

Dr Trollor's approach to management is to create a hierarchy for interventions, generally treating pressing co-morbid conditions first, as these may increase the expression of ADHD symptoms, and providing for further observation in cases where the diagnosis is uncertain.

Specific A-ADHD treatments include: education (through internet, books, support groups); drug therapies (methylphenidate 0.3-1.0mg/kd/day; dextroamphetamine 0.2-0.5mg/kg/day, desipramine, imipramine 25-100mg; and others including atomoxetine, buproprion, MAOI, lithium, venlafaxine, SSRI, CBZ, clonidine,); cognitive & other behavioural therapies to increase organisational skills, impulse control, and self monitoring.


Against a backdrop of a rapid rise in prescription rates, unease about use of stimulants arises from several considerations. With continuation of treatment from childhood there are potentially decades of exposure to stimulants. Should this be open-ended? What are the risks of psychological dependence, and harmful use/dependence given the high psychosocial and substance comorbidity in adults with ADHD?

Stimulants are effective in adults with ADHD although the number of studies is small. Available efficacy data for adults give response rates between 25 and 78 percent for methylphenidate (MPH), in a similar dose range as for children, and a modest literature suggest similar efficacy for dexamphetamine (DEX) - there is no direct evidence to support use of high or very high doses of MPH or DEX.

Current evidence suggests the use of stimulant medication to treat people, including children, with ADHD does not increase the risk of developing substance use disorder. However, there is evidence of diversion and misuse of prescription medications for ADHD among school students and college students, with between 16 and 29 percent of students on stimulant medication having been asked to give, sell or trade their medication at some time. While some individuals report using diverted stimulants to self-medicate for ADHD symptoms, others use them to enhance performance, or for their euphorogenic effects.

Dr Trollor advises stimulant treatment should be reserved for people with pervasive symptoms causing significant difficulty, and where clear goals can be identified, the patient is motivated to work on broad range of solutions and where adequate follow-up and monitoring is available.

Stimulant treatment is relatively contraindicated where ADHD symptoms are present but are not the primary problem, where the clinical diagnosis conflicts with patient �self-diagnosis�, where there is severe co-morbid psychosis or mood disorder, or continuing problematic substance use. One warning signal is where the patient has many past prescribers of stimulants.

Non-stimulants, long-acting stimulants or anti-depressants are preferred to short acting stimulants, which are strongly reinforcing drugs. Pharmacotherapy should be trialled for effectiveness on an individual basis and carefully monitored for benefits and adverse effects; a contract for stimulant treatment may include regular review (possibly including urine toxicology - a moot point at this seminar) and an ongoing goal of abstinence.

Atomoxetine is a predominantly presynaptic noradrenaline transporter inhibitor without euphorigenic and reinforcing properties, with several studies showing benefit in children and adults. There is also a small number of studies for buproprion (an indirect NA & DA agonist), likewise with a low �abuse potential�.

Stimulant Dose

There are no trials of �high� or �very high� stimulant doses in adults with ADHD, and low dosing appears to be appropriate for most individuals. Dr Trollor recommends cautious titration eg commencing at DEX 0.15mg/kg/day or MPH 0.3mg/kg/day and aiming for DEX < 0.5mg/kg/day or MPH <1.0mg/kg/day. For the stimulant-naive patient, Dr Trollor recommends commencing DEX 5mg mane & midi (or MPH 10mg mane & midi). Smaller doses may also be required if patient on other psychotropics or has comorbid anxiety or sleep disorder.

Animal models demonstrate a biphasic response to DEX: low doses (DEX < 1.0mg/kg) reduce, and higher doses DEX 1.0-5.0mg/kg increase, locomotor activity, which may correspond to a �high� in humans.

As stimulants lower the seizure threshold in animals, are associated with (transient) emergent �tics� in 10% of stimulant treated children, elevate pulse and blood pressure (low dose stimulants increase BP by an average of 3-5mmHg) low doses and close monitoring are indicated where there is co-morbid tic disorder, hypertension or seizure disorder. Although psycho-stimulants can induce paranoid delusions, auditory & visual hallucinations, this is mainly seen with intravenous use.

Inter-individual pharmacokinetic variability (especially for MPH, where peak serum levels vary up to five-fold) provides an argument for a trial of higher doses in some individuals with non response to low doses - monitoring stimulant levels may be helpful, as may a second opinion.

One difficulty is how to monitor response, whether subjectively or using self rating scales, observer rating scales, or neuropsychological/neurophysiological testing. Many people will feel better using low dose stimulants, regardless of whether they have ADHD or not. This conundrum was illustrated in a complex case study presented in the second half (see separate posting).

Some parting questions: how can such a prevalent condition, especially in children, be conceived of as a disorder? In an evolutionary sense, does ADHD confer an individual or collective biological advantage? In an anthropological sense, does it represent a failure of adaptation to modern life?

Summary by Richard Hallinan, based on Dr Trollor's presentation and powerpoint file.

7 July 2008

Concord Dependency Seminar Series, Tues 20th May 2008.

Treating the Addicted Brain: Agonists, Antagonists and Modulators.

Speaker: Stephen Jurd, Psychiatrist, RNSH and RANZCP director of training.

Dear Colleagues,

Dr Jurd commenced by almost stating the obvious: the problem of addiction starts with the brain. The origin of the behaviour does not lie in reasoned thoughts, which are late in evolution, but in reward pathways, organised in the hind-brain. From this ancient part of the nervous system, the responses are transferred to the frontal lobes where conscious thoughts, decisions and deductions are made regarding diverse ways to satisfy the more primitive urges. While most reward pathways are related to survival and procreation, drug use mimics such responses chemically, causing satisfaction, pleasure and desire to repeat the experience. The concept of craving was discussed in depth - it is not easy to define and perhaps best to simply call it ‘the motivation to use the drug’.

Equally, a definition of clinical or behavioural ‘salience’ is difficult, yet it is crucial to understanding and defining addiction, first clearly done by the redoubtable Griffith Edwards. Dr Jurd suggested one way to define ‘salience’ is to look at the person’s ‘top-40’ items of interest which for non-addicted people would range across a variety of things from food to music to work, family and hobbies. For the compulsive drug user or alcoholic, gambler, etc this would be a very short list, largely related to their drug or behaviour of interest. This is the ‘narrowed repertoire’ of drug use behaviour.

We were told of a recent pivotal study by Anne Rose Childress working at Philadelphia with Charles O’Brien’s group. They found significant brain responses on real-time PET scanning from ‘split-second’ projections of drug-related images, despite them not being seen or recognised consciously in a group of 22 long term cocaine users. These were also closely correlated with drug, violence or sexually explicit images shown several days later in relevant cases (and not in controls). So, despite not realizing it at the time, these long-term cocaine users’ brains had registered the brief images unconsciously and committed them to memory. Thus for the first time we have evidence of addiction related cues and/or priming occurring ‘outside awareness’. There was also some corroboration of this remarkable finding from another study involving similar brain responses to cues for ‘‘unseen’’ monetary rewards (Pessiglione). The advertising industry may have known of these matters for years!

Decisions in adolescence are agreed to be most important in learning and memory, and some regard drug addiction as an ‘illness of youth’ [cf Stanton Peele ref below]. We were told that there are maximal numbers of synapses in the adolescent brain which then decrease with age. Synaptic structures are highly dynamic, and adult brains are able to make new cells. Both exercise and stroke can lead to increased neural production and brain cells move towards the injury site. All of this is contrary to traditional teaching about the CNS being unable to repair or replace damaged areas.

Addiction is not simply withdrawal, but craving, the inclination to use, the very nature of dependence and a whole clinical syndrome which persists, sometimes well after drug/alcohol use has ceased. DSM defines ‘early remission’ as up to 12 months. We were told that addiction is common, has social and medical impacts, as well as numerous psychiatric complications.

There must be a system of reward, hard-wired into the mammalian brain where intuitively certain people and/or events are memorable, striking and causing a ‘yearning’. And such a system would just be normal. Dopamine has been identified as the relevant neurotransmitter.

However one defines them, ‘cravings’ lead to the conscious motivation to seek and use the drug, with a euphoric recall, and with often pleasant associations. “This feels sooo … good”. This is the case for both stimulatory and sedating drugs. Dopamine from the nucleus accumbens is crucial for reinforcement and reward; attention, memory and learning. These mesolimbic pathways are not unique to opiates but are similar for nicotine, alcohol, benzodiazepines, stimulants, etc.

The next result is to trigger ‘yearning’ for the experience to be repeated. Drugs excite the reward pathway and this then leads to addiction. At a certain point the individual becomes aware of the dangers and the illogical nature of their behaviour, yet continues with it. Similarly, they may be able to rationalise with a counsellor, doctor or family member that it is harmful to continue (cortical), yet the behaviour persists (driven by limbic pathways).

We were shown a familiar brain diagram from The New England Journal of Medicine: Neural Reward Circuits Important in the Reinforcing Effects of Drugs of Abuse [Cami J, Farre M. 2003 349:975-986].

Stimulants may also cause direct stimulation of dopamine production. On the other hand, sedatives inhibit the production of inhibitors of dopamine and so lead to increased dopamine concentrations. Thus in the reward pathway all drugs lead to increased dopamine at critical points in the hind-brain and so lead to increased learning, attention and focus on the drug use.

Aversive Agents

Disulfiram does not affect the dopamine pathway, but has its action through the frontal lobe using logic and reasoning. With this the person learns that “it is dumb to take alcohol with this”, and so even when cravings are strong the addict may choose not to consume alcohol, knowing the likely consequences.


Most of these provide a longer acting form of the drug which avoids the cycle of intoxication and withdrawal. For example methadone is a long half life drug, decreasing heroin use and improving quality of life. The person learns that they simply do not need to use additional opiates as there is little gain.

Nicotine is the same drug, with a safer delivery of drug via patches, gums and inhalers. Post-myocardial infarct patients do better on patches.

Dexamphetamine - there is no pharmacological basis to change to this from methamphetamine as the half-life of ‘dex’ is 10-12 hours compared to 9-15 hours for methamphetamine. A longer acting form may be more appropriate for addiction treatment.

Benzodiazepines – theoretically for alcohol but they are not satisfactory, both are disinhibitory agents, acting on GABA receptors.

Partial agonists

Buprenorphine (for opiate dependence).
Varenicline (a nicotine receptor blocker).


Naltrexone – a long acting opioid antagonist, works when taken but does not chemically modulate cravings for opioids (might do so psychologically according to Brewer). For alcohol with time it can modulate cravings but unlike disulfiram the person will not become ill if alcohol is consumed.

Rimonaband – cannabinoid antagonist - not yet available in Australia – used overseas for obesity(?).

Odansetron (Zofran) – serotonin-3 antagonist with promise for alcohol abuse in very low dose [see RCT Bankole Johnson link below].


These take time to work, and act less on receptors but modulate other areas which then lead to change in receptors and/or their neurotransmitters.

Acamprosate modulates the balance of GABA. We were reminded that this drug is really only of benefit for those wishing to cease alcohol use completely whereas those on naltrexone are more likely to be able to manage controlled drinking better (although this is not approved under PBS prescribing criteria). In a similar way in depressives, SSRI drugs also take time to have their clinical effects, rather than a chemical effect on receptors which theoretically occurs straight away.

We were then brought back to the traditional in-patient treatment of alcoholism and drug addiction, something which is now rare as authorities have closed down many detox and rehab wards. The justification has often been that they were “not cost-effective”. Dr Jurd quoted the highly reputed “Project Match” which found double the rate of abstinence at one year in those who received an in-patient stay as part of their treatment when compared with those who only received out-patient services. Note that entrants were not randomised so the significance is limited to an non-causal association.

Two case histories were then presented and ‘work-shopped’ in some detail:

Case 1: A youth with excess alcohol use causing serious health, legal, and social problems.

Case 2: A middle-aged set-in-his-ways professional with smoking and alcohol excess with hypertension. He stopped nicotine after 12 months but unable to decrease his alcohol.

Summary written by Judith Meldrum and Andrew Byrne. Further details of the case histories and workshop discussion will be sent as a supplement later when time allows. See our summary of “The neurobiology of addictive behaviours” on web page: http://www.redfernclinic.com/c/2005/12/alcohol-pharmacotherapy-macquarie.php4 Web site: http://www.redfernclinic.com/concord/

References: Childress AR, Ehrman RN, Wang Z, Li Y, Sciortino N,,, O’Brien CP. (2008) Prelude to Passion: Limbic Activation by "Unseen" Drug and Sexual Cues. PLoS ONE 3(1): e1506

Johnson BA, Roache JD et al. Ondansetron for Reduction of Drinking Among Biologically Predisposed Alcoholic Patients. A Randomized Controlled Trial. JAMA (2000) 284:963-97

Peele S. The Surprising Truth About Addiction. Psychology Today (2004) May-June: 43-46 http://www.peele.net/lib/surprising.html

Pessiglione M, Schmidt L, Draganski B, Kalisch R, Lau H, et al. (2007) How the brain translates money into force: a neuroimaging study of subliminal motivation. Science 316: 904–906 http://www.sciencemag.org/cgi/content/abstract/316/5826/904

6 July 2008

Concord Seminar summary: 'How not to be sued'. Speaker Prof Bob Batey.

Subject: “Practising in Addiction Medicine: how not to be sued!”
Speaker: Professor Robert Batey.
Concord Seminar Tuesday 18th March 2008 7pm.
Held at Concord Hospital (Western Sydney, Australia), Conference Room No 1.

Professor Batey began by asking his audience to consider why this subject was being covered and also why he had been asked to speak on it. He pointed out that despite doctors being of a certain age and seniority, mistakes and miscalculations could still occur. A prevention strategy was essential using established safeguards. However, when these failed, such errors need to be dealt with appropriately and openly. This applies to doctors, nurses and all allied health professionals.
No amount of renown could avoid this issue. No connection with great physicians, great institutions or fine academic reputation could help when things go wrong. We were told that despite a love of the profession and hitherto keeping out of the way of lawyers, none of us should become complacent or over-confident that it would remain that way.
Connections with great physicians could help in one respect: by following their examples in what they taught about good medical practice.
The art and practice of medicine.
The value of spending time with patients.
The need to be ‘vulnerable’ rather than ‘all-knowing’.
The absolute necessity to know what you are doing while admitting any areas of uncertainty.
The reality that you might appear to be rude while still acting consistently and fairly.
Patients may accept mistakes if you demonstrate that your are sincere and competent.

We can all name some great physicians we have worked with but it would be hard to match Dr Batey’s list of mentors: Allan McGuiness, Charles Ruthven Blackburn, Sheila Sherlock, Mr Michael Stephens, Dr Dick Richards. Those who worked at Sydney’s Prince Alfred Hospital or Sydney University may know three of these.
Some behaviours which patients and colleagues may sometimes overlook include:
Use of long phrases no one can understand.
Gruffness to the point of rudeness.
Late for rounds but never missing them.
However, this is contingent on the clinician displaying consistent excellence and reliability in the longer term, leading to the earning of respect.
In the field of Addiction Medicine there is another credential needed: A capacity to set boundaries. At this we were shown a slide of the Great Wall of China!
In order to demonstrate some ways NOT to practise we were shown some cases from 2007:
Presents with female partner
Both on methadone: 65mg and 50 mg respectively for >10 yrs
Receiving 4 take away doses.
Neither are employed at present but both had been working in local area 12 months ago.
No children at home

SO far so good but
They want to switch to oral Physeptone (methadone tablets) so they can just pick up scripts for 2 weeks supply.
They also admit to not sleeping well and to using benzodiazepines regularly.
No other major issues.

Main issue is a desire for increased “freedom”
Totally anti-buprenorphine as partner had tried to change and failed miserably
They talk constantly and when one stops to draw breath the other starts up
They have no insight into the issues
It is late in the day

You weaken and write their first script of physeptone tablets, enough for 5 days “to see how they go”.
No no no!
This is dangerous
It is unwarranted
It is indefensible
At this point……
Is there a way forward??
Mr JF:
40 yr old, unemployed hairdresser
Past heavy alcohol intake (120 gm/d as beer) Now nil
Lives alone, no contact with children
Had one admission for pancreatitis 8 yrs ago. Apparently this settled.
Now complains of abdominal pain on a daily basis

Oxycontin 10 mg qid
Oxycontin 20 mg tds
Oxycontin 40 mg prn
Asks for proladone suppository twice a day to add to his pain relief program

You give him proladone

You have no idea what his pain is due to or indeed if he has pain at all.
He is dependent, he has a “dog’s breakfast” of a management plan.
BUT HE LOVES YOU for being so ‘caring’ !!!
The state pharmaceutical authorities may not be sympathetic - although after removal of the 2 month rule on opioid prescription in New South Wales in 2006 this may be ‘legal‘ even though it may be ‘poor medicine’.

Ms GG, aged 38.
Admitted to local hospital semi-conscious with signs of pneumonia.
Uncertain what is happening but assessment reveals:
Pneumonia of right lower lobe.
Obtunded with pin point pupils.
Injection marks L ante cubital fossa.
Poor nutrition.
Lives with husband and 3 children 10, 9 and 4.
She does not work, he is a motor mechanic.
No major past medical problems.
Both she and he are on methadone program.
She is on 80 mg/d and he 90 mg/d.
Both get 6 takeaway doses per week.
No safe storage sites at home
No urine drug screens performed in past year.
Pharmacist concerned regarding stability.
Why does she get 6 T/A’s….. “Well, my husband gets them”.
She responds to Narcan injection subcutaneously.
Admits to injecting her doses.
Assessed for HCV and HBV and has both.
1 Child has evidence of exposure to HBV.
Vaccination program not completed.
Is this all OK?? Should there be a full review of their dependency treatment?
Mr BJ had Crohn’s disease for 15 yrs.
Several recurrences when Inflammatory Bowel Disease (IBD) treatment reduced.
Surgery x 3, fistula complicating this.
Intermittent analgesia when in hospital.
Tried heroin from friend “for pain relief”.
Now on methadone program 50mg/d.
Presents wanting pain relief from IBD.
He convinces you of his pain.
He asks for morphine injections prn.
You are convinced of his need for pain relief.
You write script for morphine ampoules and arrange for him to come in for doses when needed.
He is found dead with signs of O/D. Not a good situation.

Ms HT is a 78 year old widow
Dependent on benzodiazepines you commenced years ago for insomnia.
You become convinced benzos are bad for people and discuss trying to withdraw them which she refuses.
Admitted to hospital for an acute surgical problem
She experiences a significant withdrawal as no-one took a medication history. She decides that she was not adequately informed about the risks and sets a litigation process in motion.
Who should have done more?
The next topic was “WHAT AM I DRIVING AT” which reminded us that it is OUR RESPONSIBILITY to ensure that patients are safe to drive, operate machinery and look after children while taking medication. All patients should be warned that new medication and changes in doses of existing drugs, including alcohol, may affect ability to perform adequately.

Professor Batey’s final advice to us was:
Spend time taking a good history and performing a full physical examination.
Communicate appropriately with your patients.
Document findings and management plans in the notes.
Evaluate progress rationally and regularly.
Do not become enmeshed with patient stories rather than reality.
Set boundaries clearly and compassionately.
Seek peer support.
Adhere to good clinical practice guidelines.
Seek second opinions in unusual circumstances where guidelines may not apply.

27 June 2008

Heroin addicts turn to pain killers in a big way in Sydney since 2006

ABC news item Mon 23/6/08


'Hillbilly heroin' makes its mark on Australian streets.

Doctor shopping: dealers rove from surgery to surgery conning doctors.

Audio: Black market booming for prescription painkillers (AM) There are any number of illegal drugs on Australian streets at any one time, but a relative newcomer, known as 'hillbilly heroin', is becoming more popular - subsidised by taxpayers. Audio: http://mpegmedia.abc.net.au/news/audio/am/200806/20080623-am06-oxycodone.mp3

News story:
There are increasing fears that the use of drugs such as oxycodone is growing and becoming a serious problem in Australia.

Oxycodone and similar drugs such as morphine are restricted and only available by prescription, but ABC Radio's AM program has discovered the legitimate market is being rorted by drug dealers.

Twenty-two-year-old Steven - not his real name - moved to Sydney from the United States several years ago.

He brought with him an addiction to the painkiller oxycodone, which is mostly sold under the brand name OxyContin.

In the United States drugs like OxyContin and morphine, usually sold as MS Contin, are widespread. They are called 'hillbilly heroin'.

However when Steven got to Australia, he initially found it hard to find them. But he says that situation changed very quickly.

"I knew that it was prescribed here, but it just wasn't very prevalent. Over the time since getting here, it became more and more, and I heard about it and finally found people selling it down in Melbourne.

"It has become much more prevalent and people do know what it is now and it is definitely growing."

In the United States, the abuse of oxycodone and morphine is rampant and they cause large numbers of overdose deaths.

In Australia, the drugs are restricted and obtainable only with a prescription from a doctor in cases of severe pain.

But there are strong indications the illegal use of these drugs is increasing in Australia. The Australian Crime Commission's recent Illicit Drug Data Report stated morphine use was rising in Queensland and the ACT.

The director of Sydney's Medically Supervised Injecting Centre, Dr Ingrid Van Beek, says she noticed a change about two years ago.

"Of course these medications have always been injected over the years by injecting drug users, but it was about two years ago that we started to see quite a significant increase."

On average around 220 people use the centre each day. Dr Van Beek says now up to 45 per cent of these people report using either oxycodone or morphine.

They get them from people like Sammy, a longtime drug dealer in Sydney's Kings Cross.

He says oxycodone and morphine are more popular than heroin.

"Heroin only holds you for four hours before it starts coming out of your system; where oxycodone or morphine sulphate holds you for 48 hours and one is cheaper than the other," he said.

Sammy gets his supply by what he calls 'doctor shopping' - that is roving from surgery to surgery conning doctors into believing he needs the drugs for medicinal purposes.

"They'd give me what I needed because I looked respectable. If I went in with tracksuit pants and a t-shirt and an Adidas jacket or something like that you know, typical bogan basically, then they would have had second thoughts about prescribing them to me," he said.

Sammy show he has dozens of used packets of OxyContin and MS Contin that he obtained doctor shopping.

These were often bought for less than $5 for a packet of 20 tablets - a price subsidised by the Pharmaceutical Benefits Scheme.

Dr Andrew Byrne is an addiction specialist operating out of Redfern in inner-city Sydney. He says almost all of his patients now report using either oxycodone or morphine, often to the exclusion of heroin.

He says it is far too easy to obtain legal drugs for illegal purposes.

"Given that the doctor doesn't believe that the patient is a drug addict, the doctor is allowed to write a prescription for strong opiate drugs at any quantity and with any number of repeats that they feel is appropriate," he said.

Dr Byrne says it is effectively an illegal drug trade subsidised by the taxpayer.

Based on a report by Michael Edwards for AM.

Tags: drugs-and-substance-abuse, law-crime-and-justice, crime, drug-offences, australia, nsw, sydney-2000, vic, melbourne-3000

Related stories:
Gulf War veteran admits holding up pharmacies

Health workers asked to help police in prescription drugs crackdown