31 December 2003

To crush or not to crush - buprenorphine tablet administration

Drug and Alcohol Review (2003) 22;4:471-2

Muhleisen P, Spence J, Nielsen S. Crushing buprenorphine tablets.

In Australia, as in most of the research reports, buprenorphine is generally given under supervision of the nurse or pharmacist. As with methadone, there is more supervision for new and unstable patients with take-away dosing permitted to some degree for stable patients after periods in treatment. For example in South Australia up to 5 days may be dispensed in a week with 2 supervised doses after 18 months in stable treatment. In NSW up to two doses may be given per week for those needing daily doses under certain conditions, and for emergencies, travel, etc. Reports from France show that a proportion of doses there are also given under supervision although this is not by regulation but just �good practice�. The issue of whether tablets should be given whole, bisected or crushed is debated.

A report in this month's Drug and Alcohol Review covers this area from a practical perspective from a team which has been using the drug for over 5 years (originally running a trial). This group in Melbourne initially crushed tablets for some patients who they suspected were diverting the drug. Others requested crushed tablets to reduce administration time. Then the Victorian Health authorities, who are not known for their liberal attitudes, nor strong evidence base, advised all buprenorphine to be 'substantially broken or crushed'. Too fine crushing, however, is reported by these authors to sometimes result in a 'powder' which may be swallowed and thus remain largely unabsorbed. Thus crushing can cause problems in the attempt to avoid them.

These authors quote reports of about a quarter of buprenorphine patients attempting to inject their drug on at least one occasion but only less than 5% continuing to do so when they could. This is probably not too different from rates of injecting of methadone syrup.

"Merely crushing doses does not stop diversion or injecting..." <snip>

"Adequate supervision is still the basis of good treatment in this field, and is not replaced by dose-crushing. All professionals involved in the treatment should be diligent in their responsibilities in ensuring that the treatment is safe and effective. Clients who continue to misuse their buprenorphine could be considered unsuitable for treatment with this more expensive and time-consuming drug and an option to minimize potential harm to the client and the treatment itself is to suggest transfer to dosing with methadone, which is still the gold standard opioid substitution treatment."

My personal feeling is that the drug was approved by the TGA in the current tablet forms and most patients should receive the doses in that form. The tablets should only be crushed for good clinical reasons, and then only with the consent and understanding of the patients involved. Otherwise it could be seen as another paternalistic manoeuvre perpetuating the 'them and us' attitude so prevalent in drug clinics around the world.

comments by Andrew Byrne ..

12 December 2003

60 year follow-up of Boston drinkers.

Vaillant GE. A 60-year follow-up of alcoholic men. Addiction 2003 98:1043-1051

Dear Colleagues,

In a staggering feat, veteran alcohol researcher George Vaillant has followed the classic Boston study groups of Glueck & Glueck for up to 60 years from enrolment. These two groups included over 700 citizens either from poor inner city areas or from Harvard University undergraduates, most born in the 1920s. There are significant findings on the natural histories of alcohol abuse, dependence, abstinence and controlled drinking in relation to other medical problems, employment, self-help and mortality. Most importantly there is information on the onset of alcohol problems since the subjects were chosen young and at random. There is some bias since alcoholics are less likely to comply with such research but the differences in responses were not significant in this case.

There is more in this paper than could be included in a brief review. However, the main finding given by Vaillant in his abstract is that despite major differences in the groups in terms of IQ, social background and ethnicity, the main outcomes were very similar in four important domains by age 70. As also found by Drew, chronic alcohol dependence was rare in the older age groups. Controlled drinking was exceptional (1%). Just over half the subjects had died in both groups and around 10% were abusing alcohol (but not dependent) with most of the remainder abstinent.

‘Surprisingly, in both samples, alcohol abuse could persist for decades without remission, death or progression to dependency.’ [of 29 college alcohol abusers 13 surviv(ed) to age 80]. But there were some differences between the groups: ‘The average age of onset of alcohol abuse was a decade later for the college men (40 vs. 30) than it was for the core city men.’

I felt very proud when I completed a ten year follow-up of opiate dependent patients a few years ago. But my achievement is dwarfed by this monumental piece of work in the case of alcohol since Vaillant has now carefully examined outcomes over more than an average adult lifetime of three score years and ten.

comments by Andrew Byrne ..

Oral lofexidine versus naloxone injections for detox. American Journal of Addiction.

The Effectiveness of Combined Naloxone/Lofexidine in Opiate Detoxification: Results from a Double-blind Randomized and Placebo-controlled Trial. Beswick T, Best D, Bearn J, Gossop M, Rees S, Strang J. American Journal of Addiction 2003 12;4:295-305

Dear Colleagues,

This intriguing trial from a London based group gave frequent injections of naloxone to addicts in a detoxification ward.

The authors state that methadone ‘has been the standard treatment for in-patient opioid detoxification’. This may be the case in England but not necessarily elsewhere. There seems to be an assumption that lofexidine (and/or clonidine) are safe and effective in outcomes of opioid withdrawal episodes. Although there are apparently fewer hypotensive side effects with lofexidine (‘Brit-Lofex), a recent study from England, a generation of experience and the absence of a reported black market would seem to cast some doubt on their efficacy in successful heroin withdrawals. Next comes the rather controversial and little-researched use of naloxone in drug withdrawal. These researchers gave most subjects over 30 hypodermic injections, a behaviour which most of us are actively trying to discourage.

After finding that there were no significant differences in overall outcomes in those randomised to receive the antagonist naloxone, the authors come to the surprising conclusion that more research is needed on this treatment modality for those trying to quit heroin. With the increasing use of buprenorphine for detoxification, it would seem almost outlandish to support the use of injectable, short acting antagonists like naloxone.

About half of the 33 references are from the authors themselves which may indicate their pre-eminence in the field of opioid detoxification.

Comments by Andrew Byrne ..

Article on inheritance of addiction in Iran. One in 15 offspring opioid-dependent.

Ahmadi J, Arabi H, Mansouri Y. Prevalence of substance abuse among offspring of opioid addicts. Addictive Behaviors (2003) 28:591-595

Dear Colleagues,

This fascinating study from Iran tells us some basic facts about drug use and inheritance in that population. With major differences with western experience in drug and alcohol use there, the significance for our own populations is somewhat limited.

The authors interviewed 500 randomly chosen adult offspring of 2000 addicts in treatment in Shiraz, Iran. Evidently the average age of those in treatment is much higher than our patients since 28% of their offspring were over 40 years of age and 80% married (but still living under the one roof, a condition of the survey).

The authors remind us of the ‘old tradition of drug use’ in Persia, including opium which is used for pleasure as well as as a medicine. While all these drugs are currently illegal, and penalties severe, drug use and dependency are still common. Even alcohol, which is ‘both religiously and legally prohibited’ has significant reported use and dependency. In the first degree relatives of opioid addicts there was substantial ‘ever used’, ‘current use’ and ‘dependency’. There was no reported use of cocaine or psychodelics. Stimulants were not mentioned.

In short, the findings were that among the offspring of opioid addicts in Iran, 20% had ‘ever used’ opium or heroin and 6.4% were currently opiate dependent. Tobacco was ‘ever used’ by 36% with 24% being currently dependent by DSM-IV criteria. In 95% of the opioid used was opium and 5% heroin. Males greatly outnumbered females for most forms of drug use by up to 9:1. The survey was evenly split, however.

Alcohol was ‘ever used’ by 18.2% and cannabis products by only 4.2%. Thus over half of the population had used a psychoactive drug (56.4%) excluding caffeine.

These researchers asked the respondents the reason for their drug use. ‘Enjoyment’ was the prime answer (57%). Next came ‘modeling’ (50%) [which I take to be something akin to ‘peer pressure’] and then ‘release of tension’ (34%).

In our own patient population in Redfern we have a median age of 37 years. On cursory exmination, we could identify only twelve patients out of 328 from the past three years who had adult children and only two of these had a known drug dependency history. Hence, while this paper shows distinct differences between drug use in different countries, drug use can certainly run in families as with other habits, partially as a result of genetics and partly environmentally induced (see elegant twin studies from Minneapolis St Paul).

Comments by Andrew Byrne ..

Australian national opioid treatment guideline publications August 2003.

Commonwealth Department of Health and Aging. Australian national treatment guidelines (full citations and internet address below) published Aug 03

Dear Colleagues,

Below are the web contacts for the Australian National treatment guidelines which were distributed in December 2003 by the Department of Health and Aged Care in Canberra. There are four volumes, a full and abbreviated version for both methadone and naltrexone. The authors are to be congratulated on a 'generic' set of instructions for the basic approaches to maintenance treatments, regardless of where this may be given.

http://www.healthyactive.gov.au/internet/main/publishing.nsf/Content/phd-illicit-methadone-treatment (old 1997 version)

http://www.health.gov.au/internet/main/publishing.nsf/Content/phd-illicit-methadone-cguide-s (abbreviated version 2003)

(link to other guidelines available for buprenorphine, naltrexone, methadone, etc)

Australia’s eight different jurisdictions have eight different sets of treatment rules, from quite liberal (South Australia) to almost barbaric (Northern Territory). However, doctors do not normally have the liberty of giving sub-standard treatment because of the jurisdiction they practice in. According to the British Medical Journal, where there is clear research evidence, doctors are normally required to follow it. Hence, as these Guidelines point out, all Australian opioid dependent residents should have access to appropriate dose levels of the right drug in the right setting. Also, in all community treatment settings there should be some level of take-away dosing available for stable patients as this improves compliance and retention rates, according to these Guidelines. In the absence of regular take-away doses one of the most important ‘incentives’ of supervised methadone treatment is lost and patients may feel condemned to almost daily attendance indefinitely (as apparently sometimes happens in Victoria as well as the NSW public sector clinics). If local rules should impinge on appropriate dosing, they should be addressed and overcome in the interests of making treatment safe, effective and humane (for example the ACT rules on daily methadone doses of over 100mg; the Victorian DOH will allow waivers for take-home doses under certain circumstances if doctors apply appropriately).

An area of major difficulty in these and other guidelines remains induction protocol for methadone. Mortality from overdose in the first week has caused a knee-jerk reduction in starting doses from 40mg to 20mg in some settings. However, there has been no evaluation of this rather dramatic change and it may well have caused an increase in treatment drop-outs. Despite the stated wide variations in methadone metabolism in these guidelines, no clinical protocol is given for determining who is a fast metaboliser and thus may need higher doses. In one paper it is stated that due to variable absorption and metabolism of methadone, “the rate of clearance from the body has been reported to vary by a factor of almost 100” [Ward J, Bell J, Mattick RP, Hall W. Methadone Maintenance Therapy for Opioid Dependence. A guide to appropriate use. (1996) CNS Drugs. 6;6:440-449]. Thus increasing doses by only 10mg per week may take many months to reach optimal levels in some folk who may need 200mg or even more to achieve ‘normal’ or therapeutic blood levels.

There is no substitute for careful clinical assessment and gradual dose adjustments for this drug, as with insulin, digoxin or Dilantin in unstable folk at the commencement of treatment. Perhaps somebody should describe a ‘sliding scale’ for methadone inductions. The American Health Department “TIP” protocols allow up to 60mg on the first day in three divided doses under very close clinical supervision. Few clinics can support the clinical supervision necessary for this, hence 40mg is the usual starting dose in many cases in the USA. Most Australian drug services now apparently use a standard 30mg starting dose in the great majority of cases.

I hope this is of assistance for colleagues involved in methadone and buprenorphine treatments. Naltrexone should only be prescribed for opioid dependency in specialist settings, whereas for alcoholism all primary care physicians should be familiar with it.

Andrew Byrne ..

Clinical guidelines and procedures for the use of methadone in the maintenance treatment of opioid dependence - Abbreviated version (pdf file 176Kb) Date Published: 2003 ISBN: 0 642 82263 8
Author: National Drug Strategy Australian Government Department of Health and Ageing.