Comparison of maintenance treatments in UK, Victoria and NSW. Drug dilution, crushing, take-aways: the practice versus the evidence

5 Feb 2008

Presenter: Dr Nicholas Lintzeris.

Dear Colleagues,
Dr Lintzeris began by describing his shock at the state of skin and veins in a large proportion of drug users in England when he started a sabbatical session at the National Addiction Centre and Maudsley Hospital in 2003. He showed some unflattering photographs of lower limb �war-wounds� inflicted by hypodermic needles, infections, impure brown heroin and neglect. Most of these people had �worked through� their upper limb then moving to the legs so that 20 to 50% of patients in maintenance treatments were using their groin veins for access.
The street heroin used was of the Afghan or �brown� variety, needing lemon juice or acetic acid to make it soluble. Even then it was still caustic to the veins. Dr Lintzeris noted that there were very high rates of crack cocaine use in English patients, up to 40% smoking it regularly whilst in treatment. He quoted the mental and physical toll this took on the lives of addicts and their families. Alcohol and sedative use was also common. Notably, one common drug of abuse was amitriptyline (�Tryptanol�, �Endep�), an antidepressant not known for recreational use in Australia.
Balancing the intravenous damage to some extent (and perhaps because of it) there was a high proportion of drug users who did not inject at all. Up to 40% were smoking, snorting or swallowing their drug of choice at the time of entering treatment. In Australia about 90% of addicts entering treatment are injectors.
Dr Linzeris noted two main differences in maintenance therapies. Dose levels were generally in the low range (30-50mg daily) and the medication was usually given as �take away� bottles of weak solution rather than being taken under supervision. The use of 1mg per 1ml solution had parallels with the common practice in Victoria of �topping up� take-away bottles with up to 100ml of water or cordial to discourage injecting.Some graphs were shown of methadone treatment in Victoria from 1985 when there were only about 100 patients in treatment. By 1996 there were nearly 4000, and by 2003 about 8000 patients on maintenance treatments. An early experience of 10 deaths in patients starting methadone has shaped the Victorian approach to treatment ever since (see Drummer 1990). Mean dose levels in Victoria have always been in the low range, around 40mg, and only reaching 50mg daily in recent years (NSW is around 70mg). We were told that there were essentially no public clinics in Melbourne and nearly all patients were treated in pharmacies from GP prescribers. This means no capacity for subsidised methadone treatment since all patients must pay for pharmacy dispensing which is normally from 3-5 dollars daily. Very few take-away doses were permitted (originally 3 single doses per month) although this is changing now under more flexible health department rules.
Next we were informed that 33% of 193 authorised prescribers had no active patients. Another 33% had from 1 to 10 patients only while just 15% of the busier prescribers were treating 69% of Victoria�s patients. Thus most of the dependency treatment service in Victoria relies on just 27 individual doctors! By contrast in 2005 NSW had over 500 prescribers and 16,000 patients with no one doctor prescribing for more than 150 patients. In England all doctors can prescribe methadone if they wish to.
Buprenorphine has had significantly greater uptake in Victoria than in the other states. After the first year of use (Jan 2002) there was just 10% of the total on buprenorphine according to some bar charts we were shown. By 2004 it rose to over 50% briefly and then dropped back slightly to 40:60 bup:meth since that time. One may speculate on the reasons, but they probably include the rigidity of the original methadone regulations in Victoria. There was widespread use of second daily buprenorphine even though this is not shown to be as effective as daily use.
In Victoria even the more complex patients with extensive needs and poor resources were still mostly managed by GPs and pharmacists as there are no comprehensive clinics with access to counsellors, psychology, vocational support, social work, etc. Dr Lintzeris called this the �minimalist� model. On the other hand, he told us that considering the state of play in Great Britain, there was simply no model or �system� at all! This was not quite fair since he then showed a pie chart demonstrating that one quarter of patients in GP prescribing (nearly all �NHS�), another quarter in �shared care� between formal clinics and GPs with fully 50% of all patients now in formal �specialist programs� (Community Drug Teams). While some of these latter can formally supervise doses, few pharmacies give witnessed doses.
Treatment access across the UK was highly variable and depended on GP willingness to prescribe. Waiting times for GPs is usually about 2 weeks but up to 3 months for Community Drug Team assessments. Proper, evidence based maintenance treatment (as per UK treatment guidelines) is the exception with most patients on low and reducing doses with sadly predictable results. A common practice is for 40mg daily to start with and reductions from there.
GPs in the UK also commonly prescribe codeine, dihydrocodeine and buprenorphine but more due to personal preference rather than patient need. This applies equally to injectable methadone which comprised 10% of all opioid treatment prescriptions 10 years ago but is less than that now, partly due to the 1999 �Orange� guidelines which were sent to every practising GP in the UK. Methadone tablets are also less used now with about 95% of maintenance medication being methadone in liquid form, mostly the watery and bulky 1mg/1ml solution. Injecting of methadone is rare, as in Victoria, presumably due to dilution of doses which is almost universal. Whether such measures have more benefits than drawbacks on balance has never been tested scientifically. Thus it would seem prudent to consider diluting (�expanding�) doses in special cases but not �across the board� until such evidence is presented.
Another disadvantage of non-supervised consumption in the UK is that the �black-market is flooded�. There is now a scheme whereby pharmacists are paid 1 to 2 pounds daily to administer doses of methadone; patients usually pay nothing. Over a third of patients attend once weekly (6 or 7 bottles dispensed) with a third attending daily (except Sunday) often taking a bottle home. Most of the reminder attend 2, 3 or 4 times weekly. There are no hard and fast rules to addiction treatment in the UK allowing much more professional freedom. Whether that is a good thing overall is a moot point considering the poor adherence to good prescribing practice over many years.
The scientific evidence shows that if take-away doses and less supervision were linked to demonstrated progress, such as urine test results, this was the most effective intervention as �contingency management� by another name.
Dr Lintzeris mentioned the various risks of injecting methadone, overdoses, child deaths and the public perception of the drug treatment system generally. We were told that people could successfully inject the buprenorphine combination drug with naloxone, Suboxone (unpublished comparative study by Leslie Amass, CPDD 2000). Also Dr Lintzeris quoted reductions in the injecting of methadone in NSW and said that the reason behind this was not clear.
Crushing of buprenorphine tablets has been advised by some parties yet evidence is limited on the practice. It would seem logical in some patients who had been caught diverting tablets, yet it clearly will not solve all the problems of buprenorphine administration.
This returned us to some questions posed by Dr Hallinan before the seminar: Why do we have public clinics, private clinics and pharmacy dosing for supervised treatment in NSW? Along with prison programs, is this serendipitously world's best practice, or a �clumsy and vestigial hybrid�? Are we using a number of flexible treatment models for people in various circumstances, or limiting access to opioid maintenance treatments which could be given more effectively in another way? Later discussion and case studies dealt with issues surrounding "access block" in NSW.

Summary by Andrew Byrne based on Dr Lintzeris� power point presentation, questions on the night and some comments from Dr Richard Hallinan.

Buprenorphine "abuse" reported to be rare, despite reportedly commonplace on some American streets.

Abuse of Buprenorphine in the United States: 2003-2005. Smith MY, Bailey JE, Woody GE, Kleber HD. Journal of Addictive Diseases 2007 26;3:107-111 [Editorial on same subject: Buprenorphine Misuse, Abuse, and Diversion: When Will We Ever Learn’ Stimmel B.]

Dear Colleagues,

This report finds that across 20 states in America over a 2 year period only 77 individual cases of buprenorphine abuse occurred based on toxico-surveillance data.

The paper goes into detail about how much ‘abuse’ was of the combination product (Suboxone) and how much the pure (Subutex) finding about two per 10,000 prescriptions for the former and one per 10,000 prescriptions for the latter. Yet it is hard to take any of this data seriously with such small numbers. From street reports it is clear that buprenorphine ‘abuse’ (at least diversion) is happening wholesale in some American cities and such abuse is unlikely to be detected in a study of this nature.

These authors have overlooked the gravity of their subject by taking a narrow and unrealistic definition of ‘abuse’, finding data which is (1) favourable to the drug manufacturer, (2) well out of line with common knowledge in the field and (3) of limited benefit in assessing the utility of buprenorphine in the community. Two of the authors are experienced addiction authorities and so it is surprising to find such patently inferior science under their names. The first author is a PhD who works for Purdue Pharmaceuticals and I assume that the ‘study‘, such as it was, complies with part of the manufacturer‘s conditions of post-marketing surveillance.

These authors take as their ‘abuse’ yardstick formal toxicity reports to a Poisons Bureau. Yet they know full well that buprenorphine intrinsically has one of the lowest acute toxic profiles of any drug in the pharmaceutical repertoire. Both combination and pure forms of buprenorphine have a wide scope for “abuse” which was not reported here. These would include taking more/less than the prescribed dose, injecting after spitting, combining with other drugs, on-selling, smoking, giving to minors, prison diversions, cross-border trade, etc. Clinical toxicity is extremely rare when buprenorphine is taken alone, even at very high doses. The standard analgesic dose is 0.2mg where doses up to 32mg daily are commonplace. So even 160 times the starting dose may cause no toxicity at all in some subjects.

The term “abuse” in the title may mean different things to different people, but the average person would probably understand it to mean use outside of doctor’s prescription instructions under accepted treatment guidelines. Health workers in detox services, addiction clinics or emergency rooms in the Boston area attest to this drug being used by a large proportion of addicts coming to notice. For unknown reasons, such use still appears to be rare in New York City. Whether these addicts are ‘drug-seeking’ or ‘treatment-seeking’ is not really the point of this investigation. Nor indeed can it determine any positive aspects of such drug consumption. “Thirteen years ago in France buprenorphine was also introduced for unsupervised prescription. Yet the big difference was that under their health system it was freely available to most who needed it, so there was no place for a black market (except at the borders). There were substantial benefits to both drug users and the wider community.

I believe that this finding of only 77 reports of inappropriate use in a large part of the USA must be one of the most irrelevant findings ever published in a peer reviewed journal. It gives no confidence about this drug’s scope for abuse, nor about its expected benefits in the American context. And it is this context which is being touted in other countries for its introduction, despite no substantial evidence of safety and effectiveness when unsupervised from a doctor‘s office.

‘Street’ buprenorphine has been reported as a drug of choice in many places in the past eg. Wellington, New Zealand in 1991 (where both pure and combination products were banned); Perth; Melbourne; Dublin; Finland; France; Vermont, USA. In his related editorial, Stimmel puts the abuse of opiates and casual attitude of some drug companies into historical perspective, although he takes this study more seriously than I did.


Comments by Andrew Byrne .. (whose practice prescribes maintenance buprenorphine successfully to 30 out of 160 dependency patients). http://www.redfernclinic.com/


References:
Stimmel B. Buprenorphine Misuse, Abuse, and Diversion: When Will We Ever Learn. Journal of Addictive Diseases 2007 26;3:

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

Quigley AJ, Bredemeyer DE, Seow SS. A case of buprenorphine abuse. Medical Journal of Australia 1984 140:425-426

O'Connor JJ, Moloney E, Travers R, Campbell A. Buprenorphine Abuse Among Opiate Addicts. British Journal of Addiction 1988 83:1085-1087

Alho H, Sinclair D, Vuori E, Holopainen A. Abuse liability of buprenorphine–naloxone tablets in untreated IV drug users. Drug Alc Depend 2007 81;1:75-78

Anand G. Illegal diversion of buprenorphine to State. The Hindu 5 Apr 2006

Guichard A, Lert F, Calderon C et al. Illicit drug use and injection practices among drug users on methadone and buprenorphine maintenance treatment in France. Addiction (2003) 98: 1585-1597

Jenkinson RA, Clark NC, Fry CL, Dobbin M. Buprenorphine diversion and injection in Melbourne, Australia: an emerging issue? Addiction (2005) 100;2:197-205

Dr Stella Dalton recognised for services to rehabilitation.

Tuesday, 18 December 2007

Dear Reader,

It is not often that our field receives recognition from the government so it was a pleasure to attend the investiture of Dr Stella Dalton as a Member in the General Division of the Order of Australia. This was undertaken by State Governor Professor Marie Bashir at Government House, Sydney on 21st September 2007.

Along with others who were commended for their bravery, philanthropy, public service or contributions to dentistry, medicine, Egyptology and other disciplines, Dr Dalton was recognised for her pioneering work in treating addictions using methadone when this was still in its infancy in 1969. As a psychiatrist, she recognised that addicts were not morally bereft but that some of them may progress well with prescribed doses of a safe, long acting opioid given under supervision with psychosocial supports.

Research in the meantime has proven her to be completely correct and now this treatment is being introduced into every corner of the globe to stem some of the most serious harms from drug addiction, most notably HIV/AIDS.

The ceremony was delightful and I just regret that I was not able to meet more of the distinguished Australians present. After the ceremony drinks and canapés were served in the beautiful gardens above the Sydney Opera House while a naval band played on. I met Professor Naguib Kanawati who had been honoured for his years of service to the field of Egyptology.

I join in others by saluting all these great Australians, including Dr Stella Dalton OA.

Andrew Byrne ..

Withdrawal management and detoxification.

Concord Seminar 25 September 2007

Presenter: Dr Joanne Ferguson, FRANZCP, FAChAM, staff specialist psychiatrist, Rozelle Hospital. Medical Director, McKinnon Unit.

Topic: Withdrawal management and detoxification-with a focus on complicated patients. [Although this was based on a talk given by Dr Ferguson, the summary also includes audience discussion and input from the three authors.]
Dr Ferguson stressed that the McKinnon Unit is not a �detoxification� ward but a medical unit which manages drug and alcohol withdrawals. The term detoxification is commonly used to refer to "chemicals, drugs, and food additives in the processed foods that we eat....", so that the general public, as well as our patients, may conceptualise drug withdrawal as a removal of such toxins: bringing to mind colonic irrigation, detox diets like Lemon Detox, herbal laxatives and high-fibre diets eliminating caffeine, meat and processed food, and associated treatments such as lymphatic drainage and massage.
Dr Ferguson used clinical cases to illustrate principles and pitfalls of withdrawal management. Since this is often undertaken in private with minimal problems and no interventions at all, she chose to deal with the more complicated cases such as those with dual diagnosis, dual or triple dependency and/or chronic illnesses.
The first case was a 47 year old labourer who had relapsed after 3 years opioid abstinence. On presentation he was using MS Contin (slow-release morphine) 100mg to 500mg injected each day, to a maximum of up to 800mg in the 16 hrs before admission, with no withdrawal symptoms. He was also taking 10-15 x 5mg diazepam tabs daily (50-75mg daily). He was agitated and tremulous on arrival at the detox unit.
The early signs of irritability, anxiety and enlarged pupils (possibly due to general sympathomimetic arousal) were attributed to benzodiazepine withdrawal, where onset of symptoms is typically after 16 hours or so. Tremor is unusual as a symptom of opioid withdrawal, and might help point to benzodiazepine withdrawal.
The benzodiazepine withdrawal regime at McKinnon Unit is to give 20mg diazepam 2nd hourly, to a maximum of 80mg in 24 hours, reducing to 60mg daily, then 35mg daily, 20mg daily then nil. Dr Ferguson told us that formal scoring of benzodiazepine withdrawal has not been shown to have any predictive value.
Regarding opiate withdrawal there are usually early signs such as enlarged pupils, sweating, pallor, agitation, goose flesh, lacrimation and runny nose. After that, nausea, melancholia and hyperalgesia can occur. At 36-48 hours, abdominal cramps, nausea, diarrhoea, mild leg aches are seen. By this stage, the enlarged pupils usually settle. Beyond this time, at 48-72 hours, there is more prominent aching of the leg and back muscles, abdominal pain and diarrhoea.
For opiate withdrawals at McKinnon Unit the regimen is to give buprenorphine sub-lingual tablets 4mg +4mg+4mg in the first 24 hours. However, with a poor response to this drug initially, this patient needed a further 4mg making 16mg in the first day off heroin. (four-times daily buprenorphine dosing has more to do with service related issues than evidence base).
In this case the patient suffered a protracted withdrawal syndrome, with the need to reintroduce buprenorphine on day 11. This was probably due to the mixed withdrawal syndrome, and possibly inadequately treatment of the opioid withdrawals early on. It may be that buprenorphine doesn't quite have the "grunt" to provide adequate symptom control in some patients.
The second case was a 24 year old methamphetamine-dependent man with schizophrenia, who lived with his family and was on disability support pension. He was taking quetiapine (Seroquel) 600mg bd, amisolpride (Solian) 800mg daily, citalopram (Cipramil) 40 mg daily, and had also been smoking a gram of �ice� daily for 8 months and taking alprazolam (Xanax) 2mg bd � prescribed by a GP.
Withdrawal symptoms of agitation, hallucinations and religious preoccupation settled with diazepam 60mg in 24 hours. He then slept, was quiet and left against medical advice after 4 days, clearly unhappy with continuing treatment (and diazepam had been reduced significantly by then).
Dr Ferguson posed the question of whether there is a withdrawal period from amphetamine use at all, or whether it is just a �recovery period�. Hence symptomatic treatment for agitation and sleeplessness may be provided with medications such as chlorpromazine, olanzapine and/or diazepam: there is some evidence of amphetamine users accessing olanzapine (Zyprexa), as well as the more commonly available benzodiazepines, for self-medication of the amphetamine "come-down". The only thing known to help profound listlessness would be to extend the stimulant use, something Australian doctors are mostly not yet comfortable doing. However, the period of �come-down� is always self limited if the patient can remain drug free.
The third case was a man aged 45 yrs with hep C, cirrhosis, diabetes and leg ulcers who had been drinking 90 to 120g alcohol daily with up to 15 x 5mg tabs diazepam daily. Single and on a pension, he was still looking after his 13 year old daughter. He was a heavy tobacco smoker as well as using injected heroin every 2 weeks on �pay day�.
The case illustrated how comorbid medical problems can have similar signs to alcohol withdrawal, including elevation of body temperature, and how to discriminate with a proper medical evaluation including blood counts and biochemical measures. Other issues were the need for nicotine replacement for tobacco withdrawal; whether agitation might be due to nicotine replacement or nicotine withdrawal; possible advantages of oxazepam over diazepam for severe liver failure with impaired hepatic drug metabolism (risk of over-sedation from accumulation of diazepam); a lower need for diazepam when unwell or drowsy.
A mild Alcohol Withdrawal Syndrome may not need any medication within the first 24 hours, after 2-3 days symptoms of anxiety, sweaty, headaches, insomnia, tremor, mild hypertension and tachycardia may be present. �Generally symptoms are mild and require little in way of medication� however medication eases withdrawal and improves outcomes - diazepam and thiamine are the mainstay. There is no evidence of benefit from more than 100mg thiamine daily, however at least the first dose should be given intramuscularly, as after heavy alcohol use there may be chronic or acute diarrhoea, and oral absorption is often poor. For severe intoxication / withdrawal, for example for drinkers of methylated spirits, 100mg thiamine should be given intramuscularly for at least 3 days.
More severe symptoms are dehydration, diarrhoea, anorexia, nausea, vomiting and weakness and very severe cases may have hypertension (diastolic of 120mmHg or greater can require antihypertensives) panic attacks, marked tremors, fever (however true fever is rare unless with an infectious cause). Seizures and delirium are a sign of treatment failure and should not occur when proper medical treatment available.
Alcohol withdrawals can occur with relatively high blood alcohol levels in heavy drinkers, including those who have reduced their use, so one needs to assess baseline use and more recent use.
Alcohol Withdrawal Scales (AWS) are subjective, with infection/fever and other illnesses as potential confounders, and need to be used thoughtfully and in context. Further, AWS has poor correlation with BP/pulse. Providing diazepam only when AWS >5 means people can be significantly uncomfortable before can get treatment. A kinder alternative may be to treat as soon as the BP is elevated or at the first sign of tremor.
The issue of using vigabantrin (Sabril) for alcohol withdrawal was raised as it may have fewer side effects but is currently only approved for resistant epilepsy.
A fourth case was then described of recurrent withdrawal episodes in a 47 year old alcohol and opiate dependent man on pension living alone in a rental flat, a history of depression and hypothyroidism, and more than 10 admissions to hospitals in 12 months, usually through casualty distressed and unable to cope, out of medication in withdrawal, anxious, but also with several falls and injuries, complicated by MRSA infection, and recently shortness of breath with a possible myocardial infarction.
After prolonged withdrawals (80mgs diazepam for 3 days then reducing over 10 days) he was unable to go to rehabilitation as he was overwhelmed and unable to organise himself.
Issues raise by this case were: therapeutic nihilism - where feelings of despair, hopelessness in treatment providers augment the client's feelings of guilt, shame and hopelessness; and the �GOMER� (get out of my emergency room) syndrome. The patient had some cognitive impairment but not so much to need involvement of the Guardianship Board to manage his affairs. Under the NSW Inebriates Act there has been a trial at Nepean Hospital of compulsory treatment for 2 weeks, with another 2 weeks following where necessary. Patients can also be sent to gazetted Psychiatric Hospital beds. This is not feasible for the great majority.
In general the patient needs to initiate treatment, and we need to recognise and accept the limits of what we can do, focus on symptom management not demand management and have a clear consensus of treatment aims, an agreed plan of treatment and a opt out phase.
Dr Ferguson described protocols for withdrawal management at Rozelle Hospital.
Opiate dependency: - buprenorphine 8-12 mg sublingual per day for 3-5 days, depending on opiate type and quantity. Reduce to 8/6/4/2/2 for last 2days. Symptomatic relief with metoclopramide (Maxalon), hyosine (Buscopan), diazepam (Valium).
Alcohol: - diazepam (Valium), dose not set, related to dispensing and review issues, maybe 40mg/day and metoclopramide (Maxolon) and antihypertensive.
Cannabis/THC: Symptoms of insomnia, agitation, irritable, appetite change, lasting 1-5 days, for which benzodiazepines - at lower doses than for alcohol withdrawal - , olanzapine (Zyprexa), mirtazapine (Avanza) may be used. There seems to be a consensus not to do inpatient withdrawal for THC, but McKinnon will do it for failed (and well documented) outpatient withdrawal.
In order to access their services, there needs to be a phone assessment of demographics (do they live in the right area?); drug use and co-morbidities; negotiation of a treatment plan (which MAY include withdrawal medication options) and then articulation of the plan: for admission (the person must phone daily at 7am until they can secure a place for admission); and/or outpatient appointments; documentation for MMT/BMT; mental health assessment; and/or other requirements eg plans for subsequent rehabilitation programs.
Some predictors of failure ambulatory treatment (as an outpatient) are (1) poor support of abstinence; (2) poor housing (or no housing); (3) multiple drug use, including withdrawal from one substance and use of others (except nicotine); (4) or severe symptoms of withdrawal.
The question was raised why drug and alcohol practitioners in the community may have difficulty "referring" their patients to "detox" units, and do not receive discharge summaries as from most other hospital services. One answer may lie in the historical development of hospital drug and alcohol services using a psychiatric care model, with a primary client orientation and team based case, as well as possibly some resistance among nursing staff to perceived medical paternalism. Another may be that referring doctors have not acquainted themselves with the protocols of the "detox" unit.
In the second half there were a few case vignettes and selected scenarios:
"I went into hospital to come off alcohol and benzos, and they just gave me Normison and sent me home on the 3rd day ...". This was a 41yo woman with history of alcohol withdrawal fits, alcoholic hepatitis. Some questions raised were:
1. If someone has a history of having fits while taking benzodiazepines, do they need admission for withdrawal management? A. not necessarily
2. Why does anyone need to go into a detox unit to come off benzodiazepines? Surely you can just change them over to diazepam and reduce the dose, in the community. A: supervision issues.
Evidently this patient�s symptoms were assessed as mild in the first 48 hours, predicting little risk of complicated benzodiazepine withdrawal. However it appears to be an early discharge for alcohol withdrawal, depending on the alcohol use history given.
"I get fits when I stop alcohol, but I'm not going back to that detox place - can't you just give me some Valium, Doc?" This was a 54 yo man on methadone, with hepatitis C, cirrhosis and ascites, presenting to a doctor in the community, with blood alcohol 0.06 and withdrawal symptoms of agitation and marked tremor. As alcohol withdrawal is dangerous, Dr Ferguson considered it medically strongly indicated to give some diazepam. However, some doctors may feels apprehensive about medico-legal consequences of giving diazepam to an intoxicated patient outside a supervised setting. It may be safest in small quantities, especially if supervised at the surgery, clinic or pharmacy.
"I need to go somewhere to come off cannabis, but the rehab won't take me because I'm on methadone, and the detox unit say they don't do cannabis withdrawal...." - it was agreed that some people may need to remove themselves from a high exposure environment to stop cannabis use, and this may be difficult when the person in on MMT. Some "detox" units offer this service, while for others it is considered low priority.
Andrew Byrne posed the question of when and why detoxification units started giving opiates to opiate addicts. Previously it was rather unusual, if not unheard of, rather like giving hospital brandy to alcoholics who were drying out. This changed the nature of the treatment from detoxification to �re-toxification� in many or even most opiate admissions. This can even be the case in those intent on short-term abstinence. Especially with a very long acting drug such as buprenorphine, it ensures that detoxification does not even start until a few days after leaving the ward, quite the opposite of the traditional position. The practice does offer patients a �taste� of one maintenance treatment yet this they could just as easily obtain as out-patients, and most opiate addicts have tried such approaches already. This change in treatment policy seems to have happened without any discussion or most importantly, input from drug users themselves. Dr Ferguson explained that compliance and retention are now better after the introduction of buprenorphine. Yet it is hard to understand how this brings patients closer to the goal of opiate abstinence.

Summary of the evening written by Richard Hallinan, Andrew Byrne, Judith Meldrum with help from Dr Joanne Ferguson�s power point presentation.

Advances in assessment and treatments for infection with hepatitis C virus (HCV)

Concord Seminar 20th November 2007

Presenter: Professor Greg Dore, Viral Hepatitis Clinical Research Program, National Centre in HIV Epidemiology and Clinical Research.

Topics: HCV epidemiology; treatment assessment; HCV treatment among methadone patients and current injecting drug users (IDU); strategies to improve HCV treatment outcomes; advances in HCV treatment and new research.
Although there has been a drop in annual HCV notifications in Australia from 15,000 in the mid 1990s to 13,000 recently, it is unsure how much of this reflects a fall in incidence (new infections) and thus a success for existing harm reduction policies. As most HCV infections in injecting drug users (IDU) occur within the first few years of injecting, some more significant indicators may be reductions in new HCV notifications in the 15-19 year age group, and in HCV prevalence in young male IDUs attending needle syringe programs (NSPs) from 2001-2006. Such figures do indeed show a marked reduction, which is reassuring that overall notifications should decline further.
It is possible that the lack of a fall in HCV prevalence in young female IDUs may reflect their "going second" in shared injecting situations, and/or sometimes having older male partners already at higher risk of having HCV.
IDUs still constituted the majority (62%) of all acute or newly acquired infections in Australia (n = 474 in 2006), however this may be an underestimate as the source of infection is reported as unknown in 15%, and sexual in 5% (sexual transmission may occur where sexual practices involve blood but is unlikely in most "vanilla" sexual encounters / relationships). Tattoos account for about 8% and occupational exposure 2.5% of new cases.
Overall HCV seroprevalence in people attending NSP remains high at 65%, and is somewhat higher again (75%) in MMT/BMT populations: ie about 30,000 of the circa 40,000 people in opioid replacement treatment in Australia. Of these, probably about 20,000 (50%) have chronic HCV (RNA-positive), about 10% of the total in Australia, making this an important point of access for HCV treatment.
Mortality among people with HCV in Australia has a bimodal distribution, in the 5th and 8th decades of life, the former largely related to drug-related deaths among IDUs and the latter liver disease-related deaths in people born overseas, in HCV endemic areas. Liver disease-related deaths have risen since 1999, a trend perhaps "unmasked" by a fall of direct drug-related deaths as a result of the "heroin shortage".
With cases of HCV cirrhosis in Australia predicted to rise to 12,000 by 2010, and twice that number by 2020, an aim is to be treating 6,000 people/year for HCV. Since April 2006, when the liver biopsy requirement for interferon-based treatment was dropped, treatment figures have risen from about 2,000 to 3,000/year. Liver biopsy was a major disincentive for many people.
Sustained viral response SVR (persisting absence of viral RNA 6 months after treatment) is usually considered a cure of the viral infection, although not necessarily of the underlying liver damage. Occasional later relapses of HCV may represent reinfection with HCV in IDU. Over the last decade response rates to interferon-based treatment have improved, from about 10% SVR for interferon monotherapy to overall to over 60% SVR for combined pegylated interferon/ribavirin (PEG-IFN/RBV), ranging from 50 � 80% depending on genotype.
Early studies of PEG-IFN�2a/RBV showed benefit of longer treatment (48 versus 24 weeks) and bodyweight-adjusted ribavirin dosing (up to 1200mg/day) for genotype 1, but not for genotypes 2 and 3. While early viral response (EVR) - defined as RNA undetectable or >99% decline in viral load at 12 weeks - increases the chances of SVR for genotype 1 to 72%, failure to achieve EVR almost inevitably predicts treatment failure.
The bottom line for treatment is: 24 weeks PEG-IFN/RBV for genotypes 2 and 3; 48 weeks for genotype 1 if the person achieves EVR at 12 weeks. There is no evidence of any difference in efficacy between PEG-IFN�2a (Roche) and PEG-IFN�2b (Schering-Plough).
Recent analysis suggests that people with genotype 1 who have a Rapid Viral Response (RVR) - HCV RNA undetectable at 4 weeks - may do just as well with 24 weeks as 48 weeks of PEG-IFN�2a/RBV, achieving SVR rates above 80%.
At St Vincent�s Hospital in Darlinghurst, treatment completion rates rose from 55% 2000-02 to 74% in 2003-04, with drops in treatment discontinuations due to both non-response and to toxicity. This appears a trend to improvements in delivery of treatment.
Results of treatment in current injectors are comparable to results among non injectors, and abstinence from IDU is not a pre-condition for subsidised treatment in Australia: nor are stage of fibrosis (was pre-2006); elevated ALT (was pre-2006); the presence of symptoms; low alcohol intake.
There is some evidence of poorer treatment outcomes in people who continue to drink alcohol, but whether this is related to worsened treatment adherence or effects on viral replication is unclear.
The current conditions for subsidised treatment eligibility in Australia (S100 Criteria) are:
� 18 years or older
� No evidence of de-compensated cirrhosis
� Must have chronic HCV infection (>6 months)
� Use double contraception where the patient is either a woman of child-bearing years or their male partner.
� No prior IFN-based HCV treatment
Subsidised treatment costs the patient about A$30/month, (A$5/month for concession card holders) and this is probably as cheap as anywhere in the world.
To be balanced against the curative potential of PEG-IFN/RBV are its toxicity (flu-like symptoms, depression, anaemia, lethargy) and the requirement for contraception during and 6 months following treatment. Apart from treatment eligibility, the stage of liver disease and prognosis the genotype and viral load, presence of co-morbidities, and work and family obligations have to be considered in treatment decision-making. There needs to be at least some treatment willingness and relative socio-behavioural stability, however with persistence and good support people with relative treatment contraindications can often be successfully brought through treatment.
Greg Dore advocates some targeting of individuals with higher risk of progressive disease:
Higher likelihood of cirrhosis is predicted by:
� older age (> 40 years)
� duration of infection > 20 years
� heavy alcohol intake
� HIV or chronic HBV coinfection
� peripheral stigmata of CLD (spider naevi, palmar erythema)
� impaired hepatic synthetic function (low albumin, prolonged PT)
� AST / ALT ratio > 1.0
� AST / platelet ratio > 1.0 (<0.5 very unlikely to have cirrhosis)
At the Byrne Surgery, about 50% of people with chronic HCV met similar criteria for higher risk of HCV progression, and have been specifically targeted for treatment, with 27 people having been treated since 2003. Of 20 liver biopsies among these higher risk people, 18 had at least moderate liver fibrosis.
Although HIV and HBV co-infection are relatively uncommon in people with HCV infection, they are definite indicators of higher risk, and in many cases HCV treatment should be undertaken before HIV or HBV treatment.
Phase II trials suggest benefit from triple therapies of IFN/RBV with protease inhibitors for chronic HCV and Phase II trials are due to start soon.
Acute HCV can be treated with interferon monotherapy, with SVR rates of 80-90% in 3 months treatment, unless there is HIV co-infection or HCV genotype 1 with a high viral load. However, as about 25% of people spontaneously clear the virus (generally in the first 3 months after infection but up to 6 months and even later in a few cases) treatment of acute infection is usually deferred at least 3 months.
Although sustained viral response rates at the Byrne surgery are high (71% overall, 81% for genotype 2/3) a case was presented to show that things are not always easy. This long-term MMT patient received HCV antiviral treatment in the setting of micronodular cirrhosis, Genotype 1a/1b, viral load 360,000 and pre-treatment alcohol use of 30-60g/day. This patient was overweight 105kg, a smoker (10 cigs/day) with shortness of breath on exertion, chronic airflow limitation (not taking medications), hypertension (Enalapril), probable ischaemic heart disease (chest tightness on stress test but no ECG changes; echocardiogram: LVH with moderate dilatation), osteoarthritis (diclofenac prn), a history of peptic ulcer disease (uses omeprazole prn).
Despite these relative contraindications to treatment, this patient ceased drinking alcohol, and started combination treatment with IFN.2a/RBV, achieving rapid viral response (<600 ie qualitative RNA assay) at 5 weeks. RBV dose started with 1200mg/day and reducing to 800mg/day as haemoglobin dropped under 100, and was stopped for 5 weeks when the patient suffered severe nosebleeds (with normal BP 130/80; prothrombin time 1.1 and platelets acceptable at 81). Diclofenac was ceased, and ENT review showed a large vessel on the septum which was cauterised, packed with Chloromycetin for 3 days, with ongoing Vaseline use.
After the patient had stoically endured 36 weeks of IFN.2a/RBV, and in view of the apparent rapid viral response, treatment was stopped at week 36, sadly with a rapid ALT and viral flare. The patient has since maintained alcohol abstinence and long term low dose interferon treatment is being considered.
Issues arising from this case were the feasibility of treatment of "brittle" patients; drying of the nasal mucosa with the IFN/RBV; the pros and cons of NSAIDS for osteoarthritis in this situation; the possibility of viral escape with the interruption to RBV treatment and the wisdom of the decision to stop treatment early; whether endoscopy might have been done to exclude oesophageal varices before treatment; the benefits of going on the front foot in treating HCV in substance dependent people, who may rise to the challenge by achieving abstinence (in this case alcohol abstinence).
Other questions arising in the second half:
Q. What about treating people with persistently high-normal ALT? A: there is some discussion about whether ALT reference ranges should be lowered, especially for women. A single normal ALT measurement is not helpful, as ALT typically waxes and wanes in chronic HCV, so ongoing monitoring at least is required. Although one would rather have a persistently lowish than a persistently very high ALT, ALT correlates poorly with disease activity, and the duration of HCV is an important consideration in assessing risk of disease progression.
Q. What is the role of abdominal ultrasound in assessing chronic HCV? A: mainly to exclude portal hypertension. Greg Dore often does not order this test. Newer methods for assessing fibrosis/cirrhosis by measuring the stiffness of the liver may make ultrasound more useful.

Summary by Richard Hallinan, Greg Dore and Andrew Byrne.

Editorial questions the ethics of naltrexone imlants until they are proven and registered

Degenhardt L, Gibson A, Mattick RP, Hall W. Drug and Alcohol Review 2008 27;1:1-3

Depot naltrexone use for opioid dependence in Australia: large-scale use of an unregistered medication in the absence of data on safety and efficacy.

Dear Colleagues,On page one of Drug and Alcohol Review for January 2008 there is an editorial which condemns the current practice of using customized naltrexone implants before safety and effectiveness data have been obtained. Degenhardt and co-authors reflect the sentiments of many in the field questioning the premature use of various doses of non-standardised pellets of naltrexone sub-cutaneously. After quoting the limited research and normal therapeutic safeguards, they write: �Practitioners who do so run the risk of bringing into disrepute a treatment that we think may well prove to play a useful niche role in the treatment of a small group of highly selected opioid-dependent patients.�In my view it is time to call a moratorium on this treatment. The attractive side of the interest in developing naltrexone implants is that this demonstrates the relentless efforts of researchers to develop more effective, safer and more cost effective treatments for heroin dependence. However, it is important that such a quest follow the basic rules of all medical research, always protecting those taking part in the research.Standard doses of supervised methadone in traditional clinics have always suited a substantial proportion of those addicted to street heroin. Now that we have a second variety of methadone and two types of buprenorphine in Australia, as well as better �matching� of drugs, doses, added supports, etc, these success rates have improved further. Trials utilizing both methadone and buprenorphine as appropriate have shown up to 80% retention at 6 months. About 5% will successfully detoxify each year, still leaving a proportion of drug users either unwilling or unable to cope with existing treatments. Thus these may suit other approaches such as supervised naltrexone tablets, depot injections or implants (or even heroin trials). There are still waiting lists for tradition detoxification services, both medicated and otherwise.Now that John Howard is leaving office Australia may yet get its latter-day drug trial. Even beyond a simple �heroin trial�, we may need some new bold new approaches for alcohol, amphetamine use, depression, suicide and the stresses of modern life. Just as there is some indication that naltrexone may help a certain group of addicts, there has also been some promise in the use of tiagabine, ondansetron, modafinil, long-acting morphine and dexamphetamine. A new drug, varenicline (Champix) is to be released next month on the PBS under similar conditions as Zyban. There is some unconfirmed information that this nicotinic receptor drug may reduce alcohol cravings at the same time.On the subject of the stresses of modern life, I learned of an inspiring talk at the APSAD conference in Auckland last month discussing the �search for wisdom� exemplified by Bob Cloninger in his presentation on "Wellness". This was amplified with great clarity in a lecture on the history of theism by an 89 year old retired professor of theology, Lloyd Geering. He allowed the audience to recognise that in this secular age, we are all now �playing God� ourselves and it is understandably quite stressful. My correspondent said that these �higher themes� spilled out into many of the discussions and set the tone for much of the casual interaction with colleagues at the conference, many of whom were �new� to APSAD being part of the large Kiwi contingent.

Comments by Andrew Byrne ..

Is methadone cardio-protective or cardio-toxic? Probably neither.

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

Dear Colleagues,
Krantz and colleagues� latest foray into the purported cardiac consequences of methadone treatment has mixed messages. Their survey of methadone clinics finds a majority of clinicians have not heard of what might be termed �Krantz syndrome�. The paper states that �only 41% (95% CI, 37- 45) were aware of methadone�s QT-prolonging properties.� Yet further: �emerging evidence suggests [methadone] may � prolong the QT interval.� But then again more forcefully: �methadone is now categorized as a medication definitively linked with torsade de pointes ��. Are they having a bet both ways on causality? The evidence on this is conflicting as Martell apparently found a significant association between dose and QT interval where Peles, Kreek et al found no such correlation, including blood levels, in a large study from Israel. Krantz and colleagues fail to cite the Peles study although it was available on the net in early December 2006.
Most reports of QT prolongation in methadone patients, eg. Pearson; Walker; Krantz; Ehret, involve (1) �mega-doses� (>300mg daily), (2) other cardio-toxic drugs, (3) abnormal metabolic states (such as hypokaloaemia) and/or (4) heart disease. Only a small minority of reported cases could be termed �regular� methadone clinic patients from my reading. And yet it is these very patients for whom Krantz gives advice to avoid methadone if possible and when it is used to avoid �high� doses.
To most dependency researchers, �high dose� means more than 100mg daily. For discussion of QT problems �high dose� would appear to mean more than 300mg daily, with the highest reports nearly 2000mg daily! The mean daily dose in Krantz� original study was 397mg; Pearson 410mg; Walker >600mg. These are not the sort of doses dependency clinics are usually familiar with.
Since so many of the cases quoted by Krantz refer to pain management, it is surprising that this survey only involved addiction centres.
This whole exercise seems to ignore the consequences of NOT giving methadone - which about 1 million people world-wide receive today. For most there is no alternative, at least none that would be affordable. Even if methadone were a cause of cardiac complications, Krantz gives us no clear strategy to prevent them, short of forgoing treatment with methadone altogether or giving lower (and therefore sometimes inadequate) doses. Hence, apart from raising anxiety levels, it is hard to see how Krantz�s long campaign on this subject has contributed to the field. It is likely that his perspective would be broadened if he had collaborated more closely with dependency specialists. The advice he is giving to the field is contrary to almost all established guidelines which stress adequate doses of methadone to reduce harmful injecting behaviour as a high priority public health strategy.
In Lancet Krantz quotes a study of methadone related deaths to justify focusing on this issue. Yet this study finds that only 4% of the deaths occurred in patients in addiction treatment programs (Ballesteros 2003), and there was absolutely nothing to suggest that cardiac effects played any role in those deaths.
It is still likely in my view that the reduced level of cocaine and heroin use with higher methadone doses shown by Dr Lisa Borg some years ago should actually protect against cardiac arrhythmias - to say nothing of the many other life-threatening concomitants of illicit heroin use, most notably overdose. Others have written about the cardio-protective effect of methadone and the opioid system in ischaemic heart disease (Marmor; Dickson).
Adding to the confusion, while stating that doctors should take account of this syndrome when prescribing methadone, Krantz still does not recommend routine ECG before starting methadone treatment. Ellen Pearson agrees with this assessment in her paper with Woosley, stating further that limiting the dose of methadone is unlikely to completely avoid cardiac complications. As far as I am aware nobody has yet reported a series of cases of cardiac arrhythmia in �normal� methadone patients, so how can this be a public health issue?
Although Pearson�s 59 FDA reports did not specify whether methadone was prescribed as part of an addiction program or otherwise, one may deduce that no more than 14 of the cases would likely have been �normal� clinic patients and only one death occurred in this group in a patient reportedly taking 29mg daily. I understand that few clinics would be able to measure out a dose of 29mg, raising the possibility that this is a mistake or a typo on the FDA report. Even as Krantz states that the FDA reports are an underestimate of the prevalence of this complication, there are still only the most sparse number of cases considering well over a million Americans have been on the treatment over the years (~240,000 currently). I also note that of 5 deaths in Pearson�s excellent report, only one of them had torsades, the fatal arrhythmia associated with QT changes, raising the possibility that there was only one cardiac death out of 59 cases over a period of years.
In my view the majority of prescribers in this survey who had not heard of QT changes were more likely to give better treatment to their patients than the �enlightened� minority who may have tried to take heed of Krantz�s sentiments.

Comments by Andrew Byrne ..

I note that of 7 web citations in this paper, 6 did not link to the correct (or indeed any) site. This may be a common problem with changes to web addresses yet it must also be a weakness of a scientific paper when peer-reviewed published citations are always to be preferred where possible in my view.

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

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

Martell BA, Arnsten JH, Krantz MJ, Gourevitch MN. Impact of methadone treatment on cardiac repolarization and conduction in opioid users. Am J Cardiol. 2005;95:915-8

Peles E, Bodner G, Kreek MJ, Rados V, Adelson M. Corrected-QT intervals as related to methadone dose and serum level in methadone maintenance treatment (MMT) patients - a cross-sectional study. Addiction 2007 102;2:289-300

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

Krantz MJ, 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

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

Walker PW, Klein D, Kasze L. High dose methadone and ventricular arrhythimias: a report of three cases. Pain 2003 103:321-4

Ehret GB, Voide C, Gex-Fabry M, Chabert J et al. Drug-Induced Long QT Syndrome in Injection Drug Users Receiving Methadone High Frequency in Hospitalized Patients and Risk Factors. Arch Intern Med 2006 166:1280-1287

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

Dickson E et al. �Runners high� may protect against myocardial infarction. Am J Physiol Heart Circ Physiol 2007; Advance online publication

Management of the Narcotic Addict (Halliday R. 1963)

Below is the text for the VERY FIRST description of methadone in the treatment of addiction, two years before Dole’s publication. Note that Dr Halliday recommends 40mg in divided doses for the first three days then 30, 20 and 10mg over 12 days for detoxification with some patients needing treatment over a longer period of weeks or months under supervision and with appropriate safeguards and psychosocial support. He does not state why he recommends methadone, only that he does and in the absence of any other opioid. I have included a citation and abstract for a subsequent paper co-authored by Halliday describing their experience with methadone in Vancouver from 1959 to 1964 for both short and longer term prescribed patients. This is all insightful and way ahead of their time in my view. Yet it in no way detracts from the work of Dole and Nyswander who I understand were unaware of this work in 1963 when they were doing similar things in New York City - but without the stated aim of abstinence. AB ..


Halliday R. Management of the Narcotic Addict. 1963 British Columbia Medical Journal 5(10):412-414


In recent years there has been a change of opinion as to the nature of problems of the addict, and it is now generally accepted that the addict is a sick person physically, psychologically and socially, and as such requires medical and other treatments. The practising physician should be, as in other areas of medicine, a member of the treatment team, and it is assumed that there will be an increasing demand on his time and skill in this held of treatment.

According to Press and Parliamentary reports, the Minister of National Health and Welfare, Miss Judy La Marsh, has stated there is not any legal barrier against the prescribing of narcotics by a physician for an addicted person, provided that such treatment is directed toward withdrawal from narcotics and eventual abstinence. In other words, treatment is not to be considered as continued maintenance therapy on narcotics unless all other measures have been attempted and have failed. References are frequently made to the so-called “British System’ and it is believed that the small number of drug addicts in the United Kingdom is due to this system — the system being that of drug maintenance. This belief is erroneous and it might be pertinent at this time to state the facts since this might help to clear the confusion that exists in many people’s minds about this situation,

In 1955 Mr. J. H. Walker, who was then the United Kingdom delegate to the United Nations Narcotic Commission referred to his government’s attitude to drug addicts and their treatment in his submission to the Canadian Senate Committee enquiring into the use of narcotic drugs in Canada. He made a number of points quite clear; namely:

1. The policy of the Government was based on the recommendations of the Committee appointed in 1924, and headed by Sir Humphrey Rolleston, to advise the Ministry of Health on the implementation of the Dangerous Drugs Act. (This committee maintained, with few exceptions, addiction to morphine and heroin should be regarded as a manifestation of a morbid state, and not as a mere form of vicious indulgence), That the policy did not include the mistaken notion, held by many people, that addicts should be regularly supplied with drugs on a maintenance basis. A memorandum to physicians from the Ministry of Health included this statement: “the continued supply of drugs to a patient, either direct or by prescription, solely for the gratification of addiction is not regarded as a medical need.”

The Rolleston Committee concluded that morphine or heroin might properly be administered to addicts in the following circumstances:
(a) where patients are under treatment by the gradual withdrawal method with a view to cure;
(b) where it has been demonstrated that after a prolonged attempt at cure that the use of the drug cannot be safely discontinued entirely on account of the severity of the withdrawal symptoms produced;
(c) where it has been clearly demonstrated that the patient, while capable of leading a useful and relatively normal life when a certain minimum dose is regularly administered, becomes incapable of this when the drug is entirely discontinued.

The physician is the only person who interprets these recommendations, particularly the last one, in regard to the treatment of his patient, and it is because of misunderstanding about this that the concept of a “British System” in terms of maintenance therapy for all addicts has become a widely accepted, however erroneous, belief. This belief is another one of the legends that confuse ideas about the problem of narcotic addiction. Other legends include beliefs that British addicts are registered for treatment and that there are ‘drug clinics set up by the Government to which addicts report regularly for their drugs, either by drug supply or by prescription. Reliable investigators like Schur (2) and Brill and Larimore (3) have demonstrated that there is no such thing as a “British System” for these addicts and one agreed that the narcotic problem in the United Kingdom is a relatively minor one, largely owing to social and cultural factors rather than to superior legislative controls. The most significant and different attitude however is that of accepting the addicts as a sick person rather than a criminal.

In this country, as in the United States, the absence of community treatment facilities must he directly related to the social concept of the addict as a criminal first, and a sick person second. All available statistics from the treatment centres located in correctional institutions indicate that not more than 5% - 10% of addicts have been helped to abstain following such treatment alter a suitable follow-up period - say, 5 years. (4) One of the major drawbacks in such treatment programs, which within the institutional setting have been well developed in many instances, has been the lack of adequate follow-up and rehabilitation in the community as well as the lack of community facilities at which the addict might seek treatment in the first instance. The medical practitioner (and this is particularly true in the United States) has been threatened, and in many cases prosecuted, if he prescribed narcotics for addict patients when such patients were not in a hospital or clinic. It is true that it is extremely difficult to treat many addicts unless they are in a dosed setting such as a hospital or clinic and that ambulant treatment, as this has been practised in the past, is unsatisfactory. However it is not illegal to treat the patient on an ambulant basis. This being so, the physician may properly prescribe narcotics or other drugs for the treatment of the addict provided that such treatment is part of a more comprehensive program designed to help the addict eventually abstain from the use of narcotic drugs.

As it is not possible in most areas to admit the addict into a general or psychiatric hospital for the treatment of his addiction as such, it is suggested that the physician should do whatever he can to establish and maintain contact with the addict patients in his practice. The physician may need help from other colleagues, agencies and so on to ensure that a comprehensive treatment program is established for his patient. He can initiate a gradual withdrawal program by the administering of suitable drugs, either directly or by prescription. Such drugs may require to be dispensed on a daily basis or be given to a “sponsor” or “chaperone” where the patient is incapable of proper self administration, and this has been the practice at the Narcotic Addiction Foundation of B.C. A typical drug withdrawal program is as follows:
1.
Tabs. Methadone 10 mgms. q.i.d. x 3 days, then
10 mgms. tid. x 3 days
10 mgms. bid. x 3 days
5 mgms. bid. x 3 days
2.
Tabs. Perphenazine 4 mgms. t.i.d. 6 hourly
4 mgms. x 12 days
3.
Chloral Hydrate Grs 7½ @ H.S. x 12 days

In selected patients a more gradual withdrawal program is set up, during which the patient may have narcotics (methadone) prescribed on a continuing basis over a period of weeks or months. Such a program demands careful selection of patients who are considered to have good motivation and prospects for rehabilitation, and also requires close and continuing supervision of the therapist or therapists concerned. It follows that narcotics are not then being prescribed in such instances ‘solely for the gratification of addiction’, but are being used because they are considered to be necessary in the overall treatment of the patient. A comparable situation might be the continuing and controlled prescription of tranquillisers to severely mentally ill patients, who are thereby able to live and function in the community, rather than to be hospitalized. In the last analysis the responsible physician determines his treatment program in the light of what is considered to be sound and ethical medical practice. Some clarification on this is required from the national and provincial Colleges of Physicians and Surgeons.

During the program of withdrawal medication, whether rapid or prolonged, the medication is constantly under review, and if necessary altered to suit the patient’s needs - e.g. depression may become a prominent and severe symptom, and anti-depressants may require to be introduced to alleviate this condition.

Other needs of the patient are explored by the psychiatric and social work staff of the Narcotic Addiction Foundation, and attempts are made to understand these and to develop a suitable treatment program around meeting these or giving the patient adequate support until his problems can be dealt with in a more satisfactory manner. Where in-patient treatment is desirable, the patient is admitted to the nine bedded unit available for this purpose. With such a small number of beds delays in admission for such treatment are unavoidable.

It is intended to make further communications on this complex problem of drug addiction but it is hoped that this introductory statement may be of some help to those physicians who are interested and are anxious to participate in the treatment of this problem which has made such extensive inroads into our own community.

If further information is desired please address enquiries to:
The Narcotic Addiction Foundation of B-C.
640 West Broadway, Vancouver 9, B.C.
or Telephone TRinity 9-4585

REFERENCES

1. Proceedings of the special committee on the Traffic in Narcotic Drugs in Canada.
Queen’s Printer, Ottawa, 1955, pp. 362-363.

2. Schur, E. M. Narcotic Drug Addiction in Britain and America. Indiana University Press, 1962, p. 316.

3. Larimore, G. W. and Brill, H.
On the Site Study of the British Narcotic System Report to Governor Nelson Rockefeller, New York, 1959, pp. 23-26.

4. Pescor, M. J. Follow-up Study of Treated Narcotic Drug Addicts. U.S. Public Health Report Supplement 170, 1943, pp. 1-18.

5. Hunt, O. H. and Odoroff, M. Follow-up Study of Narcotic Drug Addicts After Hospitalization. U.S. Public Health Services Report, Volume 77, No. 1, Jan., 1962, pp. 41-54.



Paulus I, Halliday R. Rehabilitation and the Narcotic Addict: Results of a Comparative Methadone Withdrawal Program. CMAJ 1967 96:655-659

The purpose of this retrospective study was to compare (1) regular methadone withdrawal treatment and (2) prolonged methadone withdrawal treatment in 105 and 71 voluntary patients respectively, who attended the Narcotic Addiction Foundation (N.A.F.) between 1959 and mid-1964. Treatment consisted of individual counselling and medical care for all, and only residential care and psychiatric assessment for selected cases. The number of treatment sessions and the details of drug therapy are described.

One hundred and fifty-three of 176 patients (87%) were interviewed approximately one to five years after the first clinic contact. Forty-three per cent showed some overall improvement in their behaviour. Rehabilitation was defined as change in a specific area, drug use, work, criminal behaviour, community associations, friendship patterns and family relationships rather than in terms of abstention from drugs only. Age affected comparative results.

Lancet items relating to cannabis regulation versus cannabis harms

Dear Colleagues,

Degenhardt, Hall and colleagues� Lancet letter is the only one this week to be classified �premium content� and thus is not available to casual �browsers� like myself. Yet once read, it seems to be almost the last word on the subject of cannabis harms. This debate has been raging in England since 1995 when Lancet famously wrote: �The smoking of cannabis, even long term, is not harmful to health.� This was both incorrect and unhelpful in a difficult area needing clarity, not bland over-simplifications. In the past, Hall has written similar sentiments � but in a more guarded and scientific manner along the lines of �For a majority of users, cannabis causes few if any adverse health consequences.� But this is a long way from saying it is harmless.

And from the current state of knowledge, summarised in this week�s insightful letters, we can now say confidently that the legal status of cannabis is not related to the rate of its use, harmful or otherwise. To quote: �Cannabis use changed at similar rates across States irrespective of these [differing] penalties. This finding strongly suggests that other factors - such as social attitudes and perceived harms - are more important drivers of consumption than penalties for use.� Regarding Australian jurisdictions, �about half have criminal penalties for possession or use, and the remainder have fines�.

As Degenhardt and colleagues rightly state, more serious than the small risk of psychosis is the 16% risk of dependence in young people using cannabis. Further, as Macleod points out in his letter, respiratory symptoms both from tobacco mixed with cannabis and even cannabis alone, also loom large as good reasons to advise young people to avoid cannabis.

Comments by Andrew Byrne ..

Degenhardt L, Hall WD, Roxburgh A, Mattick RP. UK classification of cannabis: is a change needed and why? Lancet 2007 370:1541

Zullino DF, Rathelot T, Khazaal Y. Cannabis and psychosis. Lancet 2007; 370:1540

Macleod J, Oakes R, Copello A, et al. The psychosocial sequelae of use of cannabis and other illicit drugs by young people: systematic review of longitudinal, general population studies. Lancet 2004; 363: 1579-1588

Moore THN, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 2007; 370: 319-328 http://www.thelancet.com/journals/lancet/article/PIIS0140673607611623/abstract

Editorial. Rehashing the evidence on psychosis and cannabis. Lancet 2007; 370:292 http://www.thelancet.com/journals/lancet/article/PIIS0140673607611337/fulltext

http://www.thelancet.com/journals/lancet/article/PIIS0140673607611350/fulltext

Drug and Alcohol Dependence, December 2007. Some interesting titles.

Alcoholic monkeys, clinic accreditation, ‘antagonists’ fail opiate and cocaine users (again), methadone success in US prisoners, buprenorphine/benzo interactions and hep C.

Dear Readers,

Some of you have written to enquire after my health. In fact my internet silence in recent weeks is due to the wasteful, costly and time consuming exercise of practice accreditation. Most health care providers are now subject to this exaction, yet few such interventions could be less productive than for addiction treatment providers in New South Wales. We are routinely assessed by well meaning people who have never written a prescription. Imagine a pharmacy or fire brigade being accredited by non-pharmacists or non-fire officers?! And there is no determination as to whether the right patients are getting the right dose of the right drug! That is a state Health Department responsibility, we are told, yet there is only one single inspector for the entire state! Sadly many addiction patients in NSW receive relatively poor care. Some receive inadequate doses and no access to take-away doses, contrary to the Federal treatment guidelines’ advice that such dosing improves outcomes significantly where used appropriately.

So getting back to a list of meaty scientific titles has been a great pleasure, this time the December edition of Drug and Alcohol Dependence, the largest circulation American addiction publication.

It is nice to see familiar names coming up in the research literature. Some one has never met, others one may have met at conferences, others still have become real friends over the years. In this edition alone we find Cicero, Grabowski, Mitchell TB, Lintzeris, Ciraulo, Strang, Schwartz RP, Dolan, Dore, Westcott, Wodak, Vlahov, Inciardi, Degenhardt, Grulich, Kaldor, Kippax, McCance-Katz, Comer and Nunes. This is a breathtaking array of scientific talent and it is quite something that they would all be represented in a single edition of a medical journal.

Several titles immediately caught my eye so I glanced at their abstracts. Hence I would advise those interested to obtain the full article where appropriate. As ever, there are repetitive themes popular with funding authorities despite usually come up with the same outcomes. Many do not learn from history and keep trying the same thing, hoping for different results. Albert Einstein said this was a form of madness.

Various medications have been tried in cocaine users but researchers seem to ignore the fact that most cocaine users are in for a good time. As such, they are unlikely to continue with a drug which gives them a ‘bad time’ (reserpine makes many normal people feel ill, so why give it to cocaine users?). Likewise the same group from the University of Cincinnati, tried tiagabine in yet another costly RCT with no significant difference (placebo does not give much of a predictable ‘good time’ either!).

Next we learn of yet another study showing that oral naltrexone does not work for relapse prevention in heroin users. Yet this new observational study, with some ethical issues to my mind, shows one marginally interesting finding. The failure rate of 70% in those who ‘tested the block’ (relapsed while still taking the naltrexone) was even worse in those who had waited for the block to wear off where a 90% drop-out rate was found. Is this a joke? Or are 70-90% failure rates encouraging enough to warrant more research?

Next we have a report of what should be the very last RCT of methadone treatment, this time in pre-release prisoners in Baltimore. Jail inmates have never been considered quite the same as others regarding medical and psychiatric needs in many parts of the world, including China, Russia, Cuba and America. So now we know that methadone also ‘works’ in pre-release prisoners. And even American prisoners … surprise, surprise! This was introduced into NSW prisons over 20 years ago, initially as a pre-release measure like in this trial. It has consistently produced enormous benefits for the entire community at very modest cost. Along with some other quite backward things in our state, this is one innovation we can be proud of and which is now being slowly copied around the world.

Next we have a fascinating item in which mature monkeys were found to enjoy alcohol with flavouring and to cut down their voluntary intake significantly when accompaniments were altered. Shades of ice-pops and mixers. Hence there seem to be some parallels between us and our close animal cousins. Again, no real surprise here, but gratifying confirmation that humans are not completely unique freaks in the animal kingdom in our desire to be ‘high’.

A group from Australia has done a careful study of the chronological march of the hepatitis C epidemic with very little good news to date. Despite harm reduction measures, treatment availability, education, etc, Australia still has a major public health problem with up to 9,000 new cases each year. More effective interventions might reduce this, as with HIV to hundreds or even dozens.

Another item looks at over 1000 gay men and finds that each year, about 5% started at least once weekly amphetamine use with the same proportion taking up at least once weekly MDMA (ecstasy) use. The proportions would have been very different 10 years ago when ecstasy use would probably have been much more popular. But we now live in the ‘ice age’ as Walter Ling calls it, where Pam Lichty calls it the ‘drug for today’ (which it is!). Yet few researchers have really addressed stimulant use in a logical manner, looking unemotionally at the harms and benefits as perceived by the users and to society generally. This is extraordinary when these drugs have been used across the world for generations now. Anabolic steroids probably fit into the same category and because of their often illicit or unprescribed nature, research is extremely limited and thus advice to the many users of these drugs is necessarily perfunctory: ‘say no to drugs’, keep fit, don’t share needles, don’t use too much, use with a friend, use an injecting room, etc.

Lastly there are two items on drug interactions. We have what might be the first serious report of a significant buprenorphine interaction. Some buprenorphine patients developed sedation on anti-retroviral drugs and needed dose reductions. This is just normal therapeutics, but nice to see it formally reported by a clinical experiment rather than happenstance. Lintzeris reports on giving 20mg diazepam or placebo to methadone or buprenorphine patients in a small RCT with variations in the opioid as well. He concludes: ‘High dose diazepam significantly alters subjective drug responses and psychological performance in patients maintained on methadone and buprenorphine’. No great surprise here, either.

Comments by Andrew Byrne ..

http://www.redfernclinic.com/

http://www.sciencedirect.com/science/journal/03768716

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