Anticraving drugs - boring or breakthrough?" Dr Stephen Jurd at Concord Seminar Series 4th Feb 2003.
Dr Stephen Jurd spoke eloquently about the use of anti-craving drugs foralcohol dependence at our first Concord Dependency Seminar for 2003.
We were reminded of the history of this field and the poor uptake of the two approved drugs, acamprosate and naltrexone both in Australia and overseas. Well under 5% of target subjects are currently being prescribed the drugs for reasons which are not at all clear.
Our speaker detailed the now copious research data on these medications individually as well as one very recent trial using both together, a non-approved but promising innovation.
Dr Jurd described his own personal way of choosing whether to try acamprosate or naltrexone initially. He feels that one can score most alcoholics between two extremes, one end tending to drink to get the blood levels up to high levels and attain pleasurable experiences, the other end drinking to maintain a blood level, thereby avoiding unpleasant and negative feelings, including physical/mental withdrawals. From opiate research we know quite a deal about the pleasure centres, opioid receptors, naltrexone blockers, etcetera, which probably dominate as a causal mechanism in the first type of alcohol dependent subjects. The GABA and glutamate systems are in a rough balance, modulating the level of arousal in the CNS. Acamprosate is active at both GABA and glutamate receptors, in an opposite way to alcohol (decreasing glutamate activity and increasing GABA activity). Thus naltrexone decreases the positive feelings associated with alcohol and acamprosate reduces the negative feelings associated with the lack ofalcohol. Naltrexone decreases positive reinforcement and caproate probably decreases negative reinforcement.
The research on naltrexone and acamprosate has been performed in numerous ways in different countries. A common end point in American studies was 'time to relapse' where this was defined as '5 standard drinks on one day' or '5 drinking days' (of any quantity). [And to confuse further, an American 'standard' drink has 15g alcohol, not 10!]
Some European acamprosate research used 'time to first drink' (ANY drink) which made interpretation and comparison more difficult but all trials showed substantially higher numbers retained in treatment and abstinent at 3 months with approximately double the numbers being retained. Graphs of treatment population 'decay' are most impressive, showing an even greater response to both drugs used simultaneously. Outcomes have varied widely in different studies, but there have been so many positive studies that it is beyond doubt that these drugs exert an active effect, presumably on cravings.
The Concord audience was also reminded of the definition of the "intention to treat" research principle: It is a preferable way to analyse outcomes in research studies to include the results from all subjects included in the study, not just those who complete the study. In this way, the survival curve displaying the decay of sobriety over the months will have different sample sizes at each point on the graph. Starting say, with 50 subjects in each of the active and placebo group, after a week 4 may have dropped out of the placebo group and 5 may have dropped out the active drug group. What is compared in the graphing of the results is the PROPORTION of sober subjects at 1 week, say 40 out of 45 (or .89) and the PROPORTION of sober subjects in the placebo group, say 35 out of 46 (or .76). Thus at each point on the graph, all available data are used. As each subject drops out, the denominator decreases.
The anti-serotonin (5HT) drug ondansetron (Zofran) seems to act in a manner opposite to SSRI drugs (which had negative effects in alcoholics in the small number of trials so far performed). Ondansetron doses are modest, being only a fraction of the usual anti-emetic dose of 4mg (300µg taken twice daily). Further studies on this are needed before it could be accepted as a standard alcoholism treatment. The drug appears to be more effective for the "genetic" type of alcoholism rather than the later onset 'reactive' type.
'Rimonabant' is a French-developed cannabis receptor blocker. It seems to have some effect on alcohol cravings in animals but human research is still quite limited.
General practice was the ideal setting to implement these new drug treatments. Both naltrexone and acamprosate are available on the PBS for alcohol dependence when the patient is 'in a treatment program' (such as a general practice setting) - one month supply and repeats allowed. Naltrexone is a simple once daily administration with few side effects in alcoholics. It is contraindicated with opioid analgesics, unlike acamprosate which needs to be taken as two tablets, three times daily. Acamprosate equally has a low side effect profile and few significant drug interactions. The important issue of when to stop therapy was also broached - without a general consensus. Since most relapses occurin the first 2 to 3 months, by 6-12 months it is probably safe to rely on non-drug means to maintain abstinence in most patients.
We should always remember to utilise support services such as self help groups, counselling and psychological services and liver clinics when appropriate.
comments by Andrew Byrne ..
3 March 2003
2 February 2003
Urine testing in drug treatments: Is it effective? Is it ethical? Is it necessary?
re: Goldstein A, Brown BW. Urine testing in methadone maintenance treatment: applications and limitations. J Substance Abuse Treatment 2003 25; 2: 61-63
Commentaries by Coppola; Dupont; Heaps and Lurigio; Parrino.
In addressing urine testing in methadone treatment, these authors seem to have forgotten that methadone prescription by doctors is a time-honoured practice in which compulsory urine testing is not only unnecessary, but also possibly unethical. There is no scientific evidence cited by them or anyone else to my knowledge to show that such testing reduces drug use or improves treatment outcomes in other respects. Indeed, the concept runs contrary to behavioural theory as well as to Hippocratic principles. That is not to say urine testing should not be done. It should. But it should be voluntary. Urine testing may be a valuable measure of outcome for practitioners in evaluating their own practices, rather than necessarily judging their patients. Further, it might be reasonable to suppose that testing improves outcomes if it is part of an environment that promotes communication with patients, even if there is no evidence currently. In this way, urine testing may be a better judge of treatment programs than of the patients in them.
The article by veteran researchers Goldstein and Brown and the series of commentaries published with it show the complete ‘divide’ which exists between good medical treatment and American drug treatment program protocols. Rather than a considered description of the subject, these authors write an ‘introduction’ followed immediately by ‘conclusions’. Neither the authors, nor their commentators give a clear description of how the use of such testing fits into the ethical framework of addiction treatment. We treat obesity and weigh people. We treat diabetes and measure the patients’ sugar levels. We treat tobacco addiction and alcoholism with a variety of means and outcome measures. A treatise on when and how to order these measures would be based on practical experience with the modalities available and their costs/effectiveness. Nobody would suggest withholding or altering treatment substantially if a patient declined to submit to testing on one or two occasions. At the same time, treatment would be fraught if there were no outcome measures.
Each of these authors appears to assume that urine testing reduces drug use and that to be effective, urine testing must be random and frequent, with an implication that it must be compulsory. None of them seriously broach the sensitive but important subject of ‘supervision’ or ‘witnessing’ of urine samples for accuracy and to prevent substitution. This should be implemented in close cooperation with consumer groups, needing scrupulous care in maximising privacy while maintaining the integrity of the process. In some American states it is considered illegal to ‘witness’ such testing. Patients who refuse testing should not be denied treatment although other means need to be sought to demonstrate their progress.
A senior colleague once said to me that the only unquestioned purposes of urine testing is in the course of research and practice evaluation, as well as to make money for pathologists. This should involve consent of the subjects. Most authorities would probably agree that a full dependency assessment also includes urine toxicology. Indeed, it is probably as fundamental as taking the blood pressure and urine test as components of a full cardiovascular assessment. But patients should never be forced to do such testing and the results should only ever be used in their direct best interests.
From the two misconceptions above, these learned American experts delve ever deeper into the realm of speculation, moving further away from science and ethics. How can we justify doctors ordering compulsory expensive and intrusive tests which have never been proven to be of any benefit? Indeed, in many programs the results may directly cause patients to be deprived of take-away doses … and this is lauded by one of the commentators as a ‘benefit’ to the long suffering patient! Such actions could lead to the loss of a job or prevent children getting to school on time. Take-home dosing should only be denied in cases where is it is causing greater risks than benefits, and it should never be withdrawn based on an individual urine test result. It is clear that with improved education that American treatment programs can respond to evidence and improve the quality of the treatment given (d’Aunno 1999). It is difficult to do so, however, when state mandated practice guidelines conflict with the evidence, as with take-home dose provisions, dose levels, counselling and urine testing frequency in some jurisdictions.
These authors seem to be learning things well known to every young medical student, yet they ignore some of the refinements of urine testing which can indeed be very useful for patient care. Results can be wrong for a variety of reasons such as labelling, storage, substitution, ‘inhibitors’, lab errors etc. Doctors’ usual response to unexpected results is to have them repeated. Such testing usually takes 24 hours. While some clinics now do them on site, few can provide a result and a medical opinion in the short time a patient is present for medication. Dupont seems to have realised that urine testing is not ‘delivering’ what we might like, has suggested the role for hair or saliva or sweat tests. These research tools are of interest, but are hardly near implementation, being without a solid research base nor current clinical guidelines.
These authors all seem to believe that a positive methadone result is an important finding to confirm compliance with treatment. Yet these patients are nearly all receiving one or two doses per week under supervision, making such testing superfluous as methadone remains detectable in the body for several days. Indeed, a negative test result is far more likely to be from a tampered urine sample or a lab error than a case of a patient not taking their medicine in my experience. Another unusual but interesting finding is a specimen which is positive for methadone but negative for methadone metabolites. This usually indicates a substituted specimen from a non-methadone patient with a soupcon of medicinal methadone added to the urine. Such unusual but worrisome results should be used with the utmost sensitivity and in the patient’s best interests. Why would patients be driven to do such things in a caring treatment program? How can there be a productive outcome to such a seemingly distrusting environment? Obviously repeated episodes would indicate a change of treatment, but a single such event may lead to a watershed if it leads to improved communication and/or more frank discussion in the therapeutic milieu.
Goldstein and Brown’s response to poor outcomes with standard testing is to do it more frequently and introduce true randomisation so clients could be urine tested on ANY day (even two days in a row). Also recognising the limitations of urine testing, Dupont suggests that hair testing is ‘impervious to cheating’, although goes on to say it is not without problems, as well. We have heard similar claims for drugs in sport or the workplace, equally without any serious evidence of safety nor effectiveness of the intervention.
My own attitude is that urine testing can and should be used by patients to demonstrate their progress in treatment. This should be used, along with evidence of employment or education, a drug ‘diary’, rent receipts, healed veins and other indicators of stability in order to qualify for less supervision in treatment, and thus more ‘normalisation’ of their lives.
Patients should be able to volunteer for a supervised (witnessed) urine test at a point when they wish to have it known that they are moving away from illicit drug use. In my experience, a person who uses a significant quantity of street heroin has a positive ‘EMIT’ opiate test (Syva Corporation, California) for at least 5 and often 6 days. Such a positive test may, however, equally indicate the use of codeine, cough suppressants or even poppy seeds. Hence a positive test is less ‘useful’ than negative one or the negative predictive value of the test is higher than its positive predictive value for heroin use. A confirmed test for morphine is suggestive of, but not proof of illicit heroin use. And in some countries heroin is not always illicit. The use of buprenorphine is directly parallel to methadone maintenance and urine testing principles should be the same in nearly all respects. To date most tests cannot detect buprenorphine, but this does not reduce their utility significantly unless there is no supervision of doses. Even in America, doctors may request pharmacists to supervise some buprenorphine sublingual doses - although for unknown reasons this has not been widely recommended, despite nearly all the excellent American research on buprenorphine using dose supervision.
I have discussed the effect of urine testing on treatment outcomes with an Australian expert who has confirmed that there is no good evidence in his experience and reading either for or against it. He pointed out further, that ‘punishment’ rarely has a beneficial affect on behaviour. On the other hand, there is ample evidence in the literature that ‘reward’ mechanisms do have a positive effect on outcomes. It is a tragedy that so many modern experts appear to be convinced of the utility of unproven modalities and that many such practices which may be outmoded, expensive and even dangerous are persisted with, despite the evidence.
An enquiry of the corresponding author about these matters yielded a reminder that the main thrust of the article was to point out that the probability of detecting a "dirty" urine is ‘vanishingly small’ in most cases of illicit drug use. This rather simplistic piece of mathematics was based on the unreferenced premise that negative tests only indicate an absence of heroin use in the previous 24 hours. The one area we seem to agree on is that most patients, even long term, stable people, should have up to 8 urine tests per year as a part of their normal treatment. But in my view such testing should be patient-initiated and the results should only be used as a guide to the patients’ level of stability along with other clinical indicators.
There is also a political reality that in most countries where addiction treatment is state-funded, community expectations are that urine testing, along with other safeguards and supports, be used as part of a strict and effective system of ethical health care delivery for those addicted to drug and alcohol.
While it can sometimes be disheartening to read superficial and unscientific research in our field, it is always uplifting and reassuring to receive feedback from so many caring and intelligent colleagues who are working effectively with dependent patients in their practices, clinics, hospitals, etc in many different parts of the world. More strength to you all!
Comments by Andrew Byrne ..
Commentaries by Coppola; Dupont; Heaps and Lurigio; Parrino.
In addressing urine testing in methadone treatment, these authors seem to have forgotten that methadone prescription by doctors is a time-honoured practice in which compulsory urine testing is not only unnecessary, but also possibly unethical. There is no scientific evidence cited by them or anyone else to my knowledge to show that such testing reduces drug use or improves treatment outcomes in other respects. Indeed, the concept runs contrary to behavioural theory as well as to Hippocratic principles. That is not to say urine testing should not be done. It should. But it should be voluntary. Urine testing may be a valuable measure of outcome for practitioners in evaluating their own practices, rather than necessarily judging their patients. Further, it might be reasonable to suppose that testing improves outcomes if it is part of an environment that promotes communication with patients, even if there is no evidence currently. In this way, urine testing may be a better judge of treatment programs than of the patients in them.
The article by veteran researchers Goldstein and Brown and the series of commentaries published with it show the complete ‘divide’ which exists between good medical treatment and American drug treatment program protocols. Rather than a considered description of the subject, these authors write an ‘introduction’ followed immediately by ‘conclusions’. Neither the authors, nor their commentators give a clear description of how the use of such testing fits into the ethical framework of addiction treatment. We treat obesity and weigh people. We treat diabetes and measure the patients’ sugar levels. We treat tobacco addiction and alcoholism with a variety of means and outcome measures. A treatise on when and how to order these measures would be based on practical experience with the modalities available and their costs/effectiveness. Nobody would suggest withholding or altering treatment substantially if a patient declined to submit to testing on one or two occasions. At the same time, treatment would be fraught if there were no outcome measures.
Each of these authors appears to assume that urine testing reduces drug use and that to be effective, urine testing must be random and frequent, with an implication that it must be compulsory. None of them seriously broach the sensitive but important subject of ‘supervision’ or ‘witnessing’ of urine samples for accuracy and to prevent substitution. This should be implemented in close cooperation with consumer groups, needing scrupulous care in maximising privacy while maintaining the integrity of the process. In some American states it is considered illegal to ‘witness’ such testing. Patients who refuse testing should not be denied treatment although other means need to be sought to demonstrate their progress.
A senior colleague once said to me that the only unquestioned purposes of urine testing is in the course of research and practice evaluation, as well as to make money for pathologists. This should involve consent of the subjects. Most authorities would probably agree that a full dependency assessment also includes urine toxicology. Indeed, it is probably as fundamental as taking the blood pressure and urine test as components of a full cardiovascular assessment. But patients should never be forced to do such testing and the results should only ever be used in their direct best interests.
From the two misconceptions above, these learned American experts delve ever deeper into the realm of speculation, moving further away from science and ethics. How can we justify doctors ordering compulsory expensive and intrusive tests which have never been proven to be of any benefit? Indeed, in many programs the results may directly cause patients to be deprived of take-away doses … and this is lauded by one of the commentators as a ‘benefit’ to the long suffering patient! Such actions could lead to the loss of a job or prevent children getting to school on time. Take-home dosing should only be denied in cases where is it is causing greater risks than benefits, and it should never be withdrawn based on an individual urine test result. It is clear that with improved education that American treatment programs can respond to evidence and improve the quality of the treatment given (d’Aunno 1999). It is difficult to do so, however, when state mandated practice guidelines conflict with the evidence, as with take-home dose provisions, dose levels, counselling and urine testing frequency in some jurisdictions.
These authors seem to be learning things well known to every young medical student, yet they ignore some of the refinements of urine testing which can indeed be very useful for patient care. Results can be wrong for a variety of reasons such as labelling, storage, substitution, ‘inhibitors’, lab errors etc. Doctors’ usual response to unexpected results is to have them repeated. Such testing usually takes 24 hours. While some clinics now do them on site, few can provide a result and a medical opinion in the short time a patient is present for medication. Dupont seems to have realised that urine testing is not ‘delivering’ what we might like, has suggested the role for hair or saliva or sweat tests. These research tools are of interest, but are hardly near implementation, being without a solid research base nor current clinical guidelines.
These authors all seem to believe that a positive methadone result is an important finding to confirm compliance with treatment. Yet these patients are nearly all receiving one or two doses per week under supervision, making such testing superfluous as methadone remains detectable in the body for several days. Indeed, a negative test result is far more likely to be from a tampered urine sample or a lab error than a case of a patient not taking their medicine in my experience. Another unusual but interesting finding is a specimen which is positive for methadone but negative for methadone metabolites. This usually indicates a substituted specimen from a non-methadone patient with a soupcon of medicinal methadone added to the urine. Such unusual but worrisome results should be used with the utmost sensitivity and in the patient’s best interests. Why would patients be driven to do such things in a caring treatment program? How can there be a productive outcome to such a seemingly distrusting environment? Obviously repeated episodes would indicate a change of treatment, but a single such event may lead to a watershed if it leads to improved communication and/or more frank discussion in the therapeutic milieu.
Goldstein and Brown’s response to poor outcomes with standard testing is to do it more frequently and introduce true randomisation so clients could be urine tested on ANY day (even two days in a row). Also recognising the limitations of urine testing, Dupont suggests that hair testing is ‘impervious to cheating’, although goes on to say it is not without problems, as well. We have heard similar claims for drugs in sport or the workplace, equally without any serious evidence of safety nor effectiveness of the intervention.
My own attitude is that urine testing can and should be used by patients to demonstrate their progress in treatment. This should be used, along with evidence of employment or education, a drug ‘diary’, rent receipts, healed veins and other indicators of stability in order to qualify for less supervision in treatment, and thus more ‘normalisation’ of their lives.
Patients should be able to volunteer for a supervised (witnessed) urine test at a point when they wish to have it known that they are moving away from illicit drug use. In my experience, a person who uses a significant quantity of street heroin has a positive ‘EMIT’ opiate test (Syva Corporation, California) for at least 5 and often 6 days. Such a positive test may, however, equally indicate the use of codeine, cough suppressants or even poppy seeds. Hence a positive test is less ‘useful’ than negative one or the negative predictive value of the test is higher than its positive predictive value for heroin use. A confirmed test for morphine is suggestive of, but not proof of illicit heroin use. And in some countries heroin is not always illicit. The use of buprenorphine is directly parallel to methadone maintenance and urine testing principles should be the same in nearly all respects. To date most tests cannot detect buprenorphine, but this does not reduce their utility significantly unless there is no supervision of doses. Even in America, doctors may request pharmacists to supervise some buprenorphine sublingual doses - although for unknown reasons this has not been widely recommended, despite nearly all the excellent American research on buprenorphine using dose supervision.
I have discussed the effect of urine testing on treatment outcomes with an Australian expert who has confirmed that there is no good evidence in his experience and reading either for or against it. He pointed out further, that ‘punishment’ rarely has a beneficial affect on behaviour. On the other hand, there is ample evidence in the literature that ‘reward’ mechanisms do have a positive effect on outcomes. It is a tragedy that so many modern experts appear to be convinced of the utility of unproven modalities and that many such practices which may be outmoded, expensive and even dangerous are persisted with, despite the evidence.
An enquiry of the corresponding author about these matters yielded a reminder that the main thrust of the article was to point out that the probability of detecting a "dirty" urine is ‘vanishingly small’ in most cases of illicit drug use. This rather simplistic piece of mathematics was based on the unreferenced premise that negative tests only indicate an absence of heroin use in the previous 24 hours. The one area we seem to agree on is that most patients, even long term, stable people, should have up to 8 urine tests per year as a part of their normal treatment. But in my view such testing should be patient-initiated and the results should only be used as a guide to the patients’ level of stability along with other clinical indicators.
There is also a political reality that in most countries where addiction treatment is state-funded, community expectations are that urine testing, along with other safeguards and supports, be used as part of a strict and effective system of ethical health care delivery for those addicted to drug and alcohol.
While it can sometimes be disheartening to read superficial and unscientific research in our field, it is always uplifting and reassuring to receive feedback from so many caring and intelligent colleagues who are working effectively with dependent patients in their practices, clinics, hospitals, etc in many different parts of the world. More strength to you all!
Comments by Andrew Byrne ..
Methadone syrup vs. sugar-free solution, buprenorphine availability in pharmacies and clinics.
Dear Esteemed Colleagues,
After over a decade of being almost a "one product shop", our addiction practice has moved to try each new form of opiate pharmacotherapy as it was made available. In most cases initial reservations were dispelled by the positive feedback regarding patient acceptability, stability and retention from the new drugs. We have also noted a proportion withdrawing successfully from all opioids. Professor Vincent P. Dole suggests that addiction pharmacotherapy should be considered the same as any other prescription medicine.
Thus the first patients to be considered for any new modalities might best be those who are unhappy with current options (usually moderate-dose methadone 'syrup'). While staff considerations are important, patient considerations should be paramount. Hence despite our reticence, we have tried each new product in patients who seemed appropriate. I now believe that buprenorphine and 'Biodone' (and probably diazepam and naltrexone) should be available in every addiction treatment service dispensary. And they should be available during the same hours, and from the same experienced staff as other supervised pharmacotherapies (and if possible, at the same price). To do otherwise is unduly disruptive to couples or associates who may be on different treatments, of for those changing from one to another. It also adds to the stigmatisation of addiction treatments and may increase congestion.
Staff may feel reluctant to introduce new medications in addiction treatment but they can yield enormous rewards for both patients and staff. I recommend starting with the most frustrating and unhappy cases and one may find that with some manipulation of the medication such folk can become the most devoted and grateful patients, and they often attain stability surprisingly rapidly. We thought that having buprenorphine cases would take longer but in fact it now saves us time. People are more likely to be getting what they need and are thus less likely to be in the 'unstable' category who take up so much of our time.
In our practice (~150 patients) about 75% now choose 'Biodone' sugar-free solution of methadone. About 10% are grateful that we still supply the old 'syrup' being as yet unable to tolerate the sugar-free medicine. And we have about 20 patients on buprenorphine currently, nearly all previously unhappy with methadone. There are also a number on methadone who were very unhappy with buprenorphine, which is no surprise considering personal preferences.
Some say that it is more difficult to dose different medications but I remember the frustrating cases who previously took time to 'gag down' their medicine - as well as those with nausea and vomiting who needed reassessments, anti-emetic injections, supplementary dosing and other time-consuming consultations and procedures. In community pharmacies, hospital wards, ambulance and psychiatric crisis teams, the staff members dispense and administer a variety of different medications without difficulty, sometimes to large numbers of patients.
With some places being still "one product" establishments, I hope that we can "normalize" these pharmacotherapies since what is happening at present is less than satisfactory for a great many patients and is certainly no good for staff morale. My staff and I have found the new options have made our lives easier and more rewarding professionally. I estimate that the proportion we can retain in treatment has increased substantially to perhaps 85%.
Andrew Byrne ..
After over a decade of being almost a "one product shop", our addiction practice has moved to try each new form of opiate pharmacotherapy as it was made available. In most cases initial reservations were dispelled by the positive feedback regarding patient acceptability, stability and retention from the new drugs. We have also noted a proportion withdrawing successfully from all opioids. Professor Vincent P. Dole suggests that addiction pharmacotherapy should be considered the same as any other prescription medicine.
Thus the first patients to be considered for any new modalities might best be those who are unhappy with current options (usually moderate-dose methadone 'syrup'). While staff considerations are important, patient considerations should be paramount. Hence despite our reticence, we have tried each new product in patients who seemed appropriate. I now believe that buprenorphine and 'Biodone' (and probably diazepam and naltrexone) should be available in every addiction treatment service dispensary. And they should be available during the same hours, and from the same experienced staff as other supervised pharmacotherapies (and if possible, at the same price). To do otherwise is unduly disruptive to couples or associates who may be on different treatments, of for those changing from one to another. It also adds to the stigmatisation of addiction treatments and may increase congestion.
Staff may feel reluctant to introduce new medications in addiction treatment but they can yield enormous rewards for both patients and staff. I recommend starting with the most frustrating and unhappy cases and one may find that with some manipulation of the medication such folk can become the most devoted and grateful patients, and they often attain stability surprisingly rapidly. We thought that having buprenorphine cases would take longer but in fact it now saves us time. People are more likely to be getting what they need and are thus less likely to be in the 'unstable' category who take up so much of our time.
In our practice (~150 patients) about 75% now choose 'Biodone' sugar-free solution of methadone. About 10% are grateful that we still supply the old 'syrup' being as yet unable to tolerate the sugar-free medicine. And we have about 20 patients on buprenorphine currently, nearly all previously unhappy with methadone. There are also a number on methadone who were very unhappy with buprenorphine, which is no surprise considering personal preferences.
Some say that it is more difficult to dose different medications but I remember the frustrating cases who previously took time to 'gag down' their medicine - as well as those with nausea and vomiting who needed reassessments, anti-emetic injections, supplementary dosing and other time-consuming consultations and procedures. In community pharmacies, hospital wards, ambulance and psychiatric crisis teams, the staff members dispense and administer a variety of different medications without difficulty, sometimes to large numbers of patients.
With some places being still "one product" establishments, I hope that we can "normalize" these pharmacotherapies since what is happening at present is less than satisfactory for a great many patients and is certainly no good for staff morale. My staff and I have found the new options have made our lives easier and more rewarding professionally. I estimate that the proportion we can retain in treatment has increased substantially to perhaps 85%.
Andrew Byrne ..
Sugar-free methadone acceptable to a majority of patients
Byrne A. Methadone ‘solution’ (Biodone) survey. APSAD Annual Conference, Wesley Centre, Sydney. October 2001 p41 (published conference abstract)
METHADONE 'SOLUTION' (BIODONE) SURVEY
INTRODUCTION: In November 2000 a new formulation of methadone became available in Australia, a red coloured, solution without the sugars, preservative, gum and alcohol of the current syrup. Patient responses have shown a low level of satisfaction with the existing product and it is not necessarily safe from a dental point of view. Comments on the flavour such as 'disgusting' and 'foul' have been made.
In some patients, side effects such as dyspepsia, vomiting and reflux are given as reasons for patients either dropping out of treatment or taking inadequate doses to abolish cravings for 24 hours. Such patients may be assisted by an alternative formulation.
METHODS: We offered the new methadone 'solution' to 125 patients (31 female, 82 male) who had been receiving the 'syrup' prescribed at an inner city dependency practice. Most patients received their medication at the Redfern practice while 14 (11%) attended a variety of pharmacies and clinics. Patients were surveyed about whether it was preferred and if any changes were noted after taking the new preparation.
RESULTS: The new 'solution' was tried by 116 (93%) at least once. The preparation was preferred by 57 (46%) patients with a further 24 (19%) having no preference. Thirty five patients (28%) sought to return to the 'syrup' product, finding the solution unacceptable, largely because of the foul taste. Many patients described the taste as being unpleasant, but that it went away more rapidly than with the syrup.
For those on high dose (>150mg daily, n = 30) the acceptance rate was higher, 60% favouring the new formulation. For those on less than 80mg, the rates were almost evenly divided into thirds: (1) favouring the Biodone solution, (2) favouring the Glaxo syrup and (3) no preference.
Reports from 6 patients indicated that clinically significant side effects from the syrup were either completely or largely abolished with the solution. These included morning sickness, reflux, dyspepsia and a 'heavy' feeling in the upper abdomen after dosing.
Four patients (3%) reported that the new solution did not seem to last as long and withdrawal symptoms occurred prior to 24 hours. This was addressed by increased dose in one case, splitting doses in another, returning to the syrup in one case. The fourth case persevered with the symptoms which settled after a number of weeks.
DISCUSSION: It is possible that sorbitol, alcohol and the other constituents of the 'syrup' may impede absorption in some cases. The 'non-core' constituents may be responsible for reducing gastric emptying time, thus increasing the effective half-life. The simple 'solution' thus may be absorbed faster in some cases and its elimination slightly faster. The syrup is thought to induce nausea and vomiting in some cases since changing to the simple solution caused such symptoms to cease in several cases.
CONCLUSIONS: It is recommended that all patients who have symptoms from the current formulation are given access to the new water based solution ('Biodone Forte'). If experience proves positive in practice, the benefits of a sugar-free medicine should be a consideration for all patients.
METHADONE 'SOLUTION' (BIODONE) SURVEY
INTRODUCTION: In November 2000 a new formulation of methadone became available in Australia, a red coloured, solution without the sugars, preservative, gum and alcohol of the current syrup. Patient responses have shown a low level of satisfaction with the existing product and it is not necessarily safe from a dental point of view. Comments on the flavour such as 'disgusting' and 'foul' have been made.
In some patients, side effects such as dyspepsia, vomiting and reflux are given as reasons for patients either dropping out of treatment or taking inadequate doses to abolish cravings for 24 hours. Such patients may be assisted by an alternative formulation.
METHODS: We offered the new methadone 'solution' to 125 patients (31 female, 82 male) who had been receiving the 'syrup' prescribed at an inner city dependency practice. Most patients received their medication at the Redfern practice while 14 (11%) attended a variety of pharmacies and clinics. Patients were surveyed about whether it was preferred and if any changes were noted after taking the new preparation.
RESULTS: The new 'solution' was tried by 116 (93%) at least once. The preparation was preferred by 57 (46%) patients with a further 24 (19%) having no preference. Thirty five patients (28%) sought to return to the 'syrup' product, finding the solution unacceptable, largely because of the foul taste. Many patients described the taste as being unpleasant, but that it went away more rapidly than with the syrup.
For those on high dose (>150mg daily, n = 30) the acceptance rate was higher, 60% favouring the new formulation. For those on less than 80mg, the rates were almost evenly divided into thirds: (1) favouring the Biodone solution, (2) favouring the Glaxo syrup and (3) no preference.
Reports from 6 patients indicated that clinically significant side effects from the syrup were either completely or largely abolished with the solution. These included morning sickness, reflux, dyspepsia and a 'heavy' feeling in the upper abdomen after dosing.
Four patients (3%) reported that the new solution did not seem to last as long and withdrawal symptoms occurred prior to 24 hours. This was addressed by increased dose in one case, splitting doses in another, returning to the syrup in one case. The fourth case persevered with the symptoms which settled after a number of weeks.
DISCUSSION: It is possible that sorbitol, alcohol and the other constituents of the 'syrup' may impede absorption in some cases. The 'non-core' constituents may be responsible for reducing gastric emptying time, thus increasing the effective half-life. The simple 'solution' thus may be absorbed faster in some cases and its elimination slightly faster. The syrup is thought to induce nausea and vomiting in some cases since changing to the simple solution caused such symptoms to cease in several cases.
CONCLUSIONS: It is recommended that all patients who have symptoms from the current formulation are given access to the new water based solution ('Biodone Forte'). If experience proves positive in practice, the benefits of a sugar-free medicine should be a consideration for all patients.
12 December 2002
No evidence for cannabis 'gateway' causation of hard drug use.
Reassessing the marijuana gateway effect. Morral AR, McCaffrey DF, Paddock SM. Addiction (2002) 97;1493-1504
Dear Colleagues,
These authors use a meticulously designed formula for detecting whether household survey figures of drug use can be explained without using the a proposed effect that previous cannabis use makes an individual more likely to use other illicit drugs (the 'gateway' theory). The authors make a simple assumption about drug use behaviour and then look to see if the comprehensive age-group, annual data available can be made to fit without a 'gateway' or 'enhancing' factor involving prior cannabis use. This exercise reminds me of the elegant mathematical demonstration that the square root of two is an irrational number and cannot be represented by a fraction such as p/q where p and q are integers.
For the exercise, the authors assumed that each individual has a given propensity to try drugs to which they are exposed at a given age (this survey only looked at "ever tried" criteria). Thus some were quite vulnerable to drugs they came across while others would be less likely to use them. They assumed further that such individuals would be equally likely to use any drug they came across (ie. that there was no such thing as the 'gateway' theory) and then compared their calculations with the comprehensive drug prevalence figures together for each age 12 to 22 years from the US National Household Survey of Drug Abuse (NHSDA).
After complex statistical computations for both cannabis and 'hard' drugs, the authors conclude that the drug use prevalence figures are consistent with their assumptions, needing no 'priming' or 'gateway' effect for the increases seen in drug use prevalence from the household surveys. Rather than claiming that this disproves the 'gateway' theory (which remains to be supported by any specific evidence to my knowledge), the authors are very modest in their conclusions. They state that a gateway 'priming' effect may still exist but that their figures do not support it. It would appear that if such a gateway effect did in fact exist, that there would have to be an equal and opposite effect keeping the numbers using hard drugs constant. This latter would require some subjects to have a decreased propensity or 'immunity' to drug use. Such an interpretation would be curious or even spurious and thus, the reader is left to seriously question the gateway theory based on these data and the original assumption.
In this study, perhaps for the first time, the 'gateway' theory of enhanced vulnerability has been put to scientific scrutiny and found wanting.
Starting a series of commentaries by selected experts James Anthony writes a long yet rather unconvincing plea that we not abandon the gateway theory, in spite of these results. Rather than giving cogent reasons, he calls on an odd comparison with the shared viral causes of chickenpox and shingles. This seems a weak analogy, as behavioural problems such as drug use do not have a single origin like a virus (although there are occasionally similarities between drug epidemics and those caused by infectious disease, see Frischer M).
Kenkel and Mathios call for economic examinations of the supply and demand situations for drugs, forgetting that this has been done 'de facto' in Holland and South Australia for 20 years. But the trove of interesting evidence from decriminalised areas, including independent statistics is once again ignored, even by serious commentators on drug policy.
Lynskey claims that Morral et al's work is inconsistent with other findings but the two studies he quotes do not seem to address causation of 'progressive' drug use, merely its existence (including alcohol and tobacco). He then states that his own and other work shows that there is a strong genetic component (~50%) to drug use and/or dependence, and that such a common factor may explain Morral's findings. But such a propensity to all drug use is precisely what Morral's group assumed ... and then deduced that this fitted the detailed serial drug prevalence findings without the need for an additional 'priming' or gateway effect. Indeed, a gateway effect would have produced very different prevalence figures from those found by the household surveys.
The study authors reply with the only really robust statements of the otherwise bland 'debate' regarding the existence of the 'gateway' or stepping-stone theory of drug use. Although they say their work does not disprove the gateway theory they are "sceptical about the prospects for any [future] definitive tests [of the validity of the marijuana gateway effect]". They go on to say that US prohibition policies result in 'an enormous black market and over 600,000 arrests annually with associated economic, personal and social consequences. Evaluation of prohibition policies should balance the known and possible harms of legal access to marijuana against the known and possible harms associated with marijuana prohibition." An American president propounded the same sentiment 20 years ago, but without any moves on the official, lignified American stance on strict cannabis prohibition. It is interesting that cannabis for medical treatment is now gaining popular interest again. It was widely used in the first half of the twentieth century (eg. 'cannabis tincture').
There have been claims that a new study by Lynskey et al. in JAMA 'proves' the gateway theory, however this is not the claim of the authors. They state of their study of adolescent drug use in twins who 'used' or 'did not use' cannabis by age 17 that: "While the findings of this study indicate that early cannabis use is associated with increased risks of progression to other illicit drug use and drug abuse/dependence, it is not possible to draw strong causal conclusions solely on the basis of the associations shown in this study." There are serious limitations in this study which was a cross sectional retrospective study using phone interviews from the twins up to 15 years after the exposure.
Regardless of the existance of a gateway theory and other possible serious dangers of cannabis, our current laws seem not to protect young people. None of the many subjects in these trials was prevented from using cannabis under the current system. As in Holland, it would seem more logical for the authorities to regulate the drug as occurs with alcohol and tobacco, two drugs which are also often called 'gateway' drugs (with some justification). Prohibition may indeed be the main common factor linking cannabis, heroin, cocaine and other illicit drug use. Lynskey et al. support this by writing: ".. access to cannabis use may provide individuals with access to other drugs as they come into contact with drug dealers. ... [Dutch decriminalization of cannabis] may have been partially successful as rates of cocaine use among those who have used cannabis are lower in the Netherlands than in the United States."
comments by Andrew Byrne ..
Dear Colleagues,
These authors use a meticulously designed formula for detecting whether household survey figures of drug use can be explained without using the a proposed effect that previous cannabis use makes an individual more likely to use other illicit drugs (the 'gateway' theory). The authors make a simple assumption about drug use behaviour and then look to see if the comprehensive age-group, annual data available can be made to fit without a 'gateway' or 'enhancing' factor involving prior cannabis use. This exercise reminds me of the elegant mathematical demonstration that the square root of two is an irrational number and cannot be represented by a fraction such as p/q where p and q are integers.
For the exercise, the authors assumed that each individual has a given propensity to try drugs to which they are exposed at a given age (this survey only looked at "ever tried" criteria). Thus some were quite vulnerable to drugs they came across while others would be less likely to use them. They assumed further that such individuals would be equally likely to use any drug they came across (ie. that there was no such thing as the 'gateway' theory) and then compared their calculations with the comprehensive drug prevalence figures together for each age 12 to 22 years from the US National Household Survey of Drug Abuse (NHSDA).
After complex statistical computations for both cannabis and 'hard' drugs, the authors conclude that the drug use prevalence figures are consistent with their assumptions, needing no 'priming' or 'gateway' effect for the increases seen in drug use prevalence from the household surveys. Rather than claiming that this disproves the 'gateway' theory (which remains to be supported by any specific evidence to my knowledge), the authors are very modest in their conclusions. They state that a gateway 'priming' effect may still exist but that their figures do not support it. It would appear that if such a gateway effect did in fact exist, that there would have to be an equal and opposite effect keeping the numbers using hard drugs constant. This latter would require some subjects to have a decreased propensity or 'immunity' to drug use. Such an interpretation would be curious or even spurious and thus, the reader is left to seriously question the gateway theory based on these data and the original assumption.
In this study, perhaps for the first time, the 'gateway' theory of enhanced vulnerability has been put to scientific scrutiny and found wanting.
Starting a series of commentaries by selected experts James Anthony writes a long yet rather unconvincing plea that we not abandon the gateway theory, in spite of these results. Rather than giving cogent reasons, he calls on an odd comparison with the shared viral causes of chickenpox and shingles. This seems a weak analogy, as behavioural problems such as drug use do not have a single origin like a virus (although there are occasionally similarities between drug epidemics and those caused by infectious disease, see Frischer M).
Kenkel and Mathios call for economic examinations of the supply and demand situations for drugs, forgetting that this has been done 'de facto' in Holland and South Australia for 20 years. But the trove of interesting evidence from decriminalised areas, including independent statistics is once again ignored, even by serious commentators on drug policy.
Lynskey claims that Morral et al's work is inconsistent with other findings but the two studies he quotes do not seem to address causation of 'progressive' drug use, merely its existence (including alcohol and tobacco). He then states that his own and other work shows that there is a strong genetic component (~50%) to drug use and/or dependence, and that such a common factor may explain Morral's findings. But such a propensity to all drug use is precisely what Morral's group assumed ... and then deduced that this fitted the detailed serial drug prevalence findings without the need for an additional 'priming' or gateway effect. Indeed, a gateway effect would have produced very different prevalence figures from those found by the household surveys.
The study authors reply with the only really robust statements of the otherwise bland 'debate' regarding the existence of the 'gateway' or stepping-stone theory of drug use. Although they say their work does not disprove the gateway theory they are "sceptical about the prospects for any [future] definitive tests [of the validity of the marijuana gateway effect]". They go on to say that US prohibition policies result in 'an enormous black market and over 600,000 arrests annually with associated economic, personal and social consequences. Evaluation of prohibition policies should balance the known and possible harms of legal access to marijuana against the known and possible harms associated with marijuana prohibition." An American president propounded the same sentiment 20 years ago, but without any moves on the official, lignified American stance on strict cannabis prohibition. It is interesting that cannabis for medical treatment is now gaining popular interest again. It was widely used in the first half of the twentieth century (eg. 'cannabis tincture').
There have been claims that a new study by Lynskey et al. in JAMA 'proves' the gateway theory, however this is not the claim of the authors. They state of their study of adolescent drug use in twins who 'used' or 'did not use' cannabis by age 17 that: "While the findings of this study indicate that early cannabis use is associated with increased risks of progression to other illicit drug use and drug abuse/dependence, it is not possible to draw strong causal conclusions solely on the basis of the associations shown in this study." There are serious limitations in this study which was a cross sectional retrospective study using phone interviews from the twins up to 15 years after the exposure.
Regardless of the existance of a gateway theory and other possible serious dangers of cannabis, our current laws seem not to protect young people. None of the many subjects in these trials was prevented from using cannabis under the current system. As in Holland, it would seem more logical for the authorities to regulate the drug as occurs with alcohol and tobacco, two drugs which are also often called 'gateway' drugs (with some justification). Prohibition may indeed be the main common factor linking cannabis, heroin, cocaine and other illicit drug use. Lynskey et al. support this by writing: ".. access to cannabis use may provide individuals with access to other drugs as they come into contact with drug dealers. ... [Dutch decriminalization of cannabis] may have been partially successful as rates of cocaine use among those who have used cannabis are lower in the Netherlands than in the United States."
comments by Andrew Byrne ..
Administration of a lighter-coloured methadone liquid with unexpected outcomes.
Administration of a lighter-coloured methadone liquid. Byrne A, Hallinan R, Love A. D&A Review [letter] 2002 21;4:405
We report a naturalistic experiment whereby 88 dependent patients were administered a lighter coloured methadone preparation for 2 weeks with unexpected outcomes.
The methadone liquid was supplied as new batch which was much lighter in colour than usual. Its appearance was consistent with a 1:1 dilution with water. Being a pure solution, free of sugars, flavouring or preservatives, the taste was reported to be not substantially different although some patients felt it was less bitter.
In this medical practice, over a 2 week period, 88 patients were given 1200 doses of the lighter coloured medicine. Of these, 686 were 'take-away' or dispensed doses (56%, mean 3.9 doses per patient per week). Patients had been in treatment an average of 6.3 years and 69 (78%) had consistently clear supervised urine tests for heroin, cocaine and amphetamine. There were 11 who were also prescribed supervised diazepam due to dual dependency.
Approximately 30 of the patients reported withdrawal symptoms from the medicine and two made telephoned reports to the NSW Methadone Advice and Complaint Service. Symptoms included insomnia, cravings, sweating and 'hanging out'. No patient reported using heroin as a result of the new medication but several requested a return to the previous (darker) medicine or the alternative sugar-based syrup, each of which was still available individually on request. One patient became acutely agitated over the change and ultimately moved to another dispensary.
The strength of methadone in both samples was found to be identical on pathology testing. On request, the drug company restored the usual supply after two weeks.
These observations would seem to indicate that minor symptoms may be interpreted incorrectly as a lack of opioid. Thus much of what patients experience from small changes in opiate doses may be psychologically mediated. Illicit drug users often report variable strengths of street drugs. In this case, a batch of medicine with less dye in it caused serious and credible complaints from a large proportion of long-term stable patients despite reassurance at the time. In two cases the feelings were so strong that outside assistance was sought over the matter.
Yours faithfully,
*Andrew Byrne (dependency specialist)
*Richard Hallinan (associate general practitioner)
*Anne Love (registered nurse)
*The Medical Practice, 75 Redfern St, Redfern, NSW, 2016
email for correspondence: ajbyrne@ozemail.com.au
Our thanks for Mr David Ruxton of Sydney Diagnostic Services who performed the drug assays.
We report a naturalistic experiment whereby 88 dependent patients were administered a lighter coloured methadone preparation for 2 weeks with unexpected outcomes.
The methadone liquid was supplied as new batch which was much lighter in colour than usual. Its appearance was consistent with a 1:1 dilution with water. Being a pure solution, free of sugars, flavouring or preservatives, the taste was reported to be not substantially different although some patients felt it was less bitter.
In this medical practice, over a 2 week period, 88 patients were given 1200 doses of the lighter coloured medicine. Of these, 686 were 'take-away' or dispensed doses (56%, mean 3.9 doses per patient per week). Patients had been in treatment an average of 6.3 years and 69 (78%) had consistently clear supervised urine tests for heroin, cocaine and amphetamine. There were 11 who were also prescribed supervised diazepam due to dual dependency.
Approximately 30 of the patients reported withdrawal symptoms from the medicine and two made telephoned reports to the NSW Methadone Advice and Complaint Service. Symptoms included insomnia, cravings, sweating and 'hanging out'. No patient reported using heroin as a result of the new medication but several requested a return to the previous (darker) medicine or the alternative sugar-based syrup, each of which was still available individually on request. One patient became acutely agitated over the change and ultimately moved to another dispensary.
The strength of methadone in both samples was found to be identical on pathology testing. On request, the drug company restored the usual supply after two weeks.
These observations would seem to indicate that minor symptoms may be interpreted incorrectly as a lack of opioid. Thus much of what patients experience from small changes in opiate doses may be psychologically mediated. Illicit drug users often report variable strengths of street drugs. In this case, a batch of medicine with less dye in it caused serious and credible complaints from a large proportion of long-term stable patients despite reassurance at the time. In two cases the feelings were so strong that outside assistance was sought over the matter.
Yours faithfully,
*Andrew Byrne (dependency specialist)
*Richard Hallinan (associate general practitioner)
*Anne Love (registered nurse)
*The Medical Practice, 75 Redfern St, Redfern, NSW, 2016
email for correspondence: ajbyrne@ozemail.com.au
Our thanks for Mr David Ruxton of Sydney Diagnostic Services who performed the drug assays.
Adolescent cannabis use addressed in 'Addiction' supplement December 2002
'Addiction' supplement December 2002. "Treatment of marijuana disorders". Edited by Michael L. Dennis and Thomas F. Babor.
Dear Colleagues,
This edition of Addiction on cannabis is most unusual in several respects, for a scientific journal. Least controversial is that 'cannabis', the normal scientific term, is used interchangeably with the American intrusive term 'marijuana' which should probably now be avoided in serious research writing. Further, some authors appear to assume that cannabis use automatically warrants the term 'disorder' and still further that this is requires treatment in a high proportion of cases. This Addiction 'special issue' was 'made possible by the Center for Substance Abuse Treatment (CSAT) ... US Department of Health and Human Services'. This sort of patronage of a scientific journal is unusual in my experience. I do not know whether 'special editions' or 'supplements' as such are peer reviewed in the normal way.
The two introductory pieces, each including the contributing 'guest editors' (one being a regular Addiction regional editor), repeatedly emphasise the importance and prevalence of cannabis problems and thus the crucial place of good research and translating this into clinical practice. One can only agree. It is only in the third last paragraph of these 15 pages that they concede that existing treatment for cannabis dependence is associated with smaller reductions in drug use than with other drugs, and, especially in adolescents and young adults "in some cases actually increase their [cannabis] use". This important latter statement is written in parentheses for no syntactical reason that I could detect.
Quite rightly, emphasis is given by the authors to the age of first use of cannabis and the likelihood of problems in later life. They state rather cumbersomely: "The likelihood of having tobacco or alcohol problems is highest (39% and 45% respectively) for adolescents who first tried these substances prior to age 15 and the rates decline with later onset. ... For cannabis and other drugs there is a very different pattern: the rate of problems is more than 60% among people who first used prior to age 15. Although the rates decline in the older onset age cohorts, they never fall below 50% for a given substance. (The two exceptions to this pattern are cocaine and heroin, which have a high risk of problems regardless of the age of first use)."
These authors make a bold statement, then contradict it parenthetically for two of the most troublesome drugs in that country. "Never" usually means 'never'. But not, evidently, when followed by a sentence put in parentheses. This subject is too important to use less-than-accurate unscientific or ill defined language. We should use clear, correct and importantly, unemotional language when addressing one of the major problems facing modern society, being drug use in young people. We know that a scientific approach to any subject is more likely to result in optimal outcomes ... be it drug treatment, population control, HIV/AIDS, malaria programs or other endeavours. There are a number of important inconsistencies in this issue of Addiction.
There appear to be unwritten assumptions about cannabis use and its dangers in a section entitled "Beyond Benign Neglect". Referring to those in whom treatment was 'mandated', the authors state: "Even those who are not cannabis-dependent demonstrate a wide range of functional impairment (eg. missing work, school, fighting, arrests, injuries) that varies with their frequency of using cannabis use." Apart from awkward English, this would seem to imply that cannabis use is often associated with delinquency and perhaps (but without any references) in a *causative* manner.
These authors detail the widespread availability, relative cheapness and strength of cannabis in America, but there is only passing reference to the failure of legal sanctions to keep the drug out of the reaches of young people. It is a serious oversight to ignore good research from Holland, a comparable western country which has had virtually legal availability of cannabis for adults for over a generation. I cannot imagine any reason why serious, experienced researchers and commentators would choose to neglect such a major source of evidence on cannabis harms.
There is still a major problem with terminology when some authors consider cannabis use needful of treatment may consist of only weekly drug use episodes. True cannabis dependence is a problem and certainly needs all of our efforts as professionals in the field. But some would consider a program which sought to address once weekly cannabis use in teenagers as rather 'low-priority' in the scheme of drug related harms, and when compared against the major problems of hepatitis C, overdose, depression and dependence (not to mention bush fires and terrorism).
Dennis and colleagues describe the Cannabis Youth Treatment (CYT) experiment in the first research report in this Addiction supplement. They randomly assigned young people referred from a variety of agencies to be treated with one of five behavioural therapies including CBT and family therapy. But when describing 'existing practice' for 150,000 adolescents treated in 1998, it is stated that half used the drug only weekly. It is hard to take the rest of their work seriously when they are 'treating' a large proportion of young people who may not qualify for a DSM IV category for either abuse or dependence.
Dennis and co-authors stress that they were anxious to be able to generalise their results to the American community. It is disappointing, therefore, that they excluded 44% of 1250 referrals on a number of criteria. These included those who (i) had used other drugs/alcohol to a significant degree (ii) had a substantial medical or psychological diagnosis, (iii) were intellectually impaired, (iv) had a severe conduct disorder or impending incarceration, (v) lacked an available English speaking parent. Another 15% declined to be involved while over half of those accepted felt that they did not need treatment for cannabis use. About two thirds were coerced by the American judicial system making the results less meaningful scientifically in other jurisdictions such as Canada, UK or Australia. Fully 80% did not view their cannabis use as 'a problem'. Only 45% were classified as cannabis dependent, yet we are given the intriguing information that this figure rises to 76% if the parents' opinions are included (!).
Self report of cannabis use in the previous month at intake, three and six months was 83%, 59% and 58%. On-site urine testing performed at the same intervals was positive for 76%, 68% and 71%. These hardly give rise to great optimism for the five programs being trialed. Nor is any statistical significance given for these modest and seemingly unimpressive, if downward, trends. No explanation is given for the remarkable finding that up to a quarter of the enrolled subjects were not actually using cannabis at or near the start of 'treatment' by either self report or urine test.
Therapy sessions were taped and reviewed with which some may find a fundamental ethical discomfort. Retention is incompletely reported, eg. 81% completed 2 months or more of a 3 month program (mean 80 days). The average stay in a 5-6 week treatment was 43 days which seems unlikely if not impossible unless there were 'overstayers'. To the credit of these researchers, it appears that over 90% of subjects were interviewed at 3, 6, 9 and 12 months using various extensive means of contact.
With high expectations I read on to find that these researchers, who repeatedly stressed the importance of their work, give no outcome results despite their comparative 'manual' intervention 'treatment phase' ending over two years ago. They whet our appetite by stating that after some preliminary results reported here, "more will be forthcoming in the coming years". Of the copious references fully 37 are from these authors themselves and their own institutions, showing their publishing prowess and perhaps also just how small the cannabis 'treatment' field actually is.
In this special issue of Addiction there follows a series of 6 "research reports", mostly from the same stable of authors as the initial report and involving one or both guest editors. These mostly document various aspect of the conduct of the same study of 600 American teenagers who chose to use cannabis and came to attention of the treatment fraternity. Once again, the wider field is not always considered in most of these, notably the item on costs which omits to compare the cost of legal sanctions which are the primary option used in some countries for drug control amongst their citizenry. The second part of this Supplement is devoted to the Marijuana Treatment Project looking at long term cannabis users and three treatment interventions. Sadly, this is just a description of the trial (including an interesting 'delayed treatment control') but again, no outcome results!
Considering the widespread use of cannabis and its propensity to cause problems in some users, especially young people, research of this nature is very important. However it is most unusual to publish details and proposals in peer reviewed journals before results are collated. Surely it is putting the cart before the horse - especially when some such programs have shown little, or even negative impact on drug use in the past. Some of the subjects are probably normal adolescents and the chance of 'treatment' improving their outcomes is simply not a consideration. The decision to omit the "no treatment" or 'control' option for treatment interventions was taken for stated reason that "past studies have shown consistently that untreated or minimally treated adolescents become worse or fail to improve". Many would disagree with this deduction and some may even find it spurious. Without controls the rigour of any study is reduced, which is very disappointing for a large, prospective intervention such as this.
comments by Andrew Byrne ..
citations:
Dennis M, Titus JC, Diamond G, Donaldson J, Godley SH, Tims FM, Webb C, Kaminer Y, Babor T, Roebuck MC, Godley MD, Hamilton N, Liddle H, Scott CK & CYT Steering Committee. The Cannabis Youth Treatment (CYT) experiment: rationale, study design and analysis plans. Addiction (2002) 97 (Suppl )1 16-34
Stephens RS, Babor TF, Kadden R, Miller M. Marijuana Treatment Project (MTP). Addiction (2002) 97 (Supp )1 109-124
Dear Colleagues,
This edition of Addiction on cannabis is most unusual in several respects, for a scientific journal. Least controversial is that 'cannabis', the normal scientific term, is used interchangeably with the American intrusive term 'marijuana' which should probably now be avoided in serious research writing. Further, some authors appear to assume that cannabis use automatically warrants the term 'disorder' and still further that this is requires treatment in a high proportion of cases. This Addiction 'special issue' was 'made possible by the Center for Substance Abuse Treatment (CSAT) ... US Department of Health and Human Services'. This sort of patronage of a scientific journal is unusual in my experience. I do not know whether 'special editions' or 'supplements' as such are peer reviewed in the normal way.
The two introductory pieces, each including the contributing 'guest editors' (one being a regular Addiction regional editor), repeatedly emphasise the importance and prevalence of cannabis problems and thus the crucial place of good research and translating this into clinical practice. One can only agree. It is only in the third last paragraph of these 15 pages that they concede that existing treatment for cannabis dependence is associated with smaller reductions in drug use than with other drugs, and, especially in adolescents and young adults "in some cases actually increase their [cannabis] use". This important latter statement is written in parentheses for no syntactical reason that I could detect.
Quite rightly, emphasis is given by the authors to the age of first use of cannabis and the likelihood of problems in later life. They state rather cumbersomely: "The likelihood of having tobacco or alcohol problems is highest (39% and 45% respectively) for adolescents who first tried these substances prior to age 15 and the rates decline with later onset. ... For cannabis and other drugs there is a very different pattern: the rate of problems is more than 60% among people who first used prior to age 15. Although the rates decline in the older onset age cohorts, they never fall below 50% for a given substance. (The two exceptions to this pattern are cocaine and heroin, which have a high risk of problems regardless of the age of first use)."
These authors make a bold statement, then contradict it parenthetically for two of the most troublesome drugs in that country. "Never" usually means 'never'. But not, evidently, when followed by a sentence put in parentheses. This subject is too important to use less-than-accurate unscientific or ill defined language. We should use clear, correct and importantly, unemotional language when addressing one of the major problems facing modern society, being drug use in young people. We know that a scientific approach to any subject is more likely to result in optimal outcomes ... be it drug treatment, population control, HIV/AIDS, malaria programs or other endeavours. There are a number of important inconsistencies in this issue of Addiction.
There appear to be unwritten assumptions about cannabis use and its dangers in a section entitled "Beyond Benign Neglect". Referring to those in whom treatment was 'mandated', the authors state: "Even those who are not cannabis-dependent demonstrate a wide range of functional impairment (eg. missing work, school, fighting, arrests, injuries) that varies with their frequency of using cannabis use." Apart from awkward English, this would seem to imply that cannabis use is often associated with delinquency and perhaps (but without any references) in a *causative* manner.
These authors detail the widespread availability, relative cheapness and strength of cannabis in America, but there is only passing reference to the failure of legal sanctions to keep the drug out of the reaches of young people. It is a serious oversight to ignore good research from Holland, a comparable western country which has had virtually legal availability of cannabis for adults for over a generation. I cannot imagine any reason why serious, experienced researchers and commentators would choose to neglect such a major source of evidence on cannabis harms.
There is still a major problem with terminology when some authors consider cannabis use needful of treatment may consist of only weekly drug use episodes. True cannabis dependence is a problem and certainly needs all of our efforts as professionals in the field. But some would consider a program which sought to address once weekly cannabis use in teenagers as rather 'low-priority' in the scheme of drug related harms, and when compared against the major problems of hepatitis C, overdose, depression and dependence (not to mention bush fires and terrorism).
Dennis and colleagues describe the Cannabis Youth Treatment (CYT) experiment in the first research report in this Addiction supplement. They randomly assigned young people referred from a variety of agencies to be treated with one of five behavioural therapies including CBT and family therapy. But when describing 'existing practice' for 150,000 adolescents treated in 1998, it is stated that half used the drug only weekly. It is hard to take the rest of their work seriously when they are 'treating' a large proportion of young people who may not qualify for a DSM IV category for either abuse or dependence.
Dennis and co-authors stress that they were anxious to be able to generalise their results to the American community. It is disappointing, therefore, that they excluded 44% of 1250 referrals on a number of criteria. These included those who (i) had used other drugs/alcohol to a significant degree (ii) had a substantial medical or psychological diagnosis, (iii) were intellectually impaired, (iv) had a severe conduct disorder or impending incarceration, (v) lacked an available English speaking parent. Another 15% declined to be involved while over half of those accepted felt that they did not need treatment for cannabis use. About two thirds were coerced by the American judicial system making the results less meaningful scientifically in other jurisdictions such as Canada, UK or Australia. Fully 80% did not view their cannabis use as 'a problem'. Only 45% were classified as cannabis dependent, yet we are given the intriguing information that this figure rises to 76% if the parents' opinions are included (!).
Self report of cannabis use in the previous month at intake, three and six months was 83%, 59% and 58%. On-site urine testing performed at the same intervals was positive for 76%, 68% and 71%. These hardly give rise to great optimism for the five programs being trialed. Nor is any statistical significance given for these modest and seemingly unimpressive, if downward, trends. No explanation is given for the remarkable finding that up to a quarter of the enrolled subjects were not actually using cannabis at or near the start of 'treatment' by either self report or urine test.
Therapy sessions were taped and reviewed with which some may find a fundamental ethical discomfort. Retention is incompletely reported, eg. 81% completed 2 months or more of a 3 month program (mean 80 days). The average stay in a 5-6 week treatment was 43 days which seems unlikely if not impossible unless there were 'overstayers'. To the credit of these researchers, it appears that over 90% of subjects were interviewed at 3, 6, 9 and 12 months using various extensive means of contact.
With high expectations I read on to find that these researchers, who repeatedly stressed the importance of their work, give no outcome results despite their comparative 'manual' intervention 'treatment phase' ending over two years ago. They whet our appetite by stating that after some preliminary results reported here, "more will be forthcoming in the coming years". Of the copious references fully 37 are from these authors themselves and their own institutions, showing their publishing prowess and perhaps also just how small the cannabis 'treatment' field actually is.
In this special issue of Addiction there follows a series of 6 "research reports", mostly from the same stable of authors as the initial report and involving one or both guest editors. These mostly document various aspect of the conduct of the same study of 600 American teenagers who chose to use cannabis and came to attention of the treatment fraternity. Once again, the wider field is not always considered in most of these, notably the item on costs which omits to compare the cost of legal sanctions which are the primary option used in some countries for drug control amongst their citizenry. The second part of this Supplement is devoted to the Marijuana Treatment Project looking at long term cannabis users and three treatment interventions. Sadly, this is just a description of the trial (including an interesting 'delayed treatment control') but again, no outcome results!
Considering the widespread use of cannabis and its propensity to cause problems in some users, especially young people, research of this nature is very important. However it is most unusual to publish details and proposals in peer reviewed journals before results are collated. Surely it is putting the cart before the horse - especially when some such programs have shown little, or even negative impact on drug use in the past. Some of the subjects are probably normal adolescents and the chance of 'treatment' improving their outcomes is simply not a consideration. The decision to omit the "no treatment" or 'control' option for treatment interventions was taken for stated reason that "past studies have shown consistently that untreated or minimally treated adolescents become worse or fail to improve". Many would disagree with this deduction and some may even find it spurious. Without controls the rigour of any study is reduced, which is very disappointing for a large, prospective intervention such as this.
comments by Andrew Byrne ..
citations:
Dennis M, Titus JC, Diamond G, Donaldson J, Godley SH, Tims FM, Webb C, Kaminer Y, Babor T, Roebuck MC, Godley MD, Hamilton N, Liddle H, Scott CK & CYT Steering Committee. The Cannabis Youth Treatment (CYT) experiment: rationale, study design and analysis plans. Addiction (2002) 97 (Suppl )1 16-34
Stephens RS, Babor TF, Kadden R, Miller M. Marijuana Treatment Project (MTP). Addiction (2002) 97 (Supp )1 109-124
11 October 2002
Young Australian visits Mayo Clinic in 1924. Lost letters found!
In 1924, my 24 year old maternal grandfather was asked to accompany a family friend to the Mayo Clinic in Rochester, Minnesota. Australian doctors advised the trip for an illness plaguing his friend, Bill Treloar of Tamworth, NSW.
Drs William and Charles Mayo were among the first to use a team approach in medical treatment. Having pioneered the medical specialties and the sharing of medical records, the Mayo Clinic's fame had spread, even downunder.
The young Australians' trip of 5 months took in Tahiti, California, Rochester, New York and London, returning via Suez and Perth. The letters excerpted below lay ignored for almost 80 years until I sought them from my uncle Bill Gracie in Muwillumbah, near the Queensland border. A bank teller, Harry Gordon Gracie later became ANZ manager in the Riverina, Hunter and New England regions. The letters are addressed to his family in Artarmon, just north of the Sydney Harbour Bridge (which had yet to be built). They will interest modern medicos, being a young man's observations of a famous medical institution in a period of great change in our profession.
Hotel Campbell, Rochester, Minnesota
23 Sept 1924
My dear mother,
Rochester, Minnesota is where the Mayo Bros are and where I hope Bill will get fixed up. The first part of our long journey from Sydney now over, we are resting for a little while. Bill is attending the clinic, so far with good results. He was up at the Clinic again this morning and when he returned we took a car without a driver to see the sights around the town. The total cost for the hire of a Ford Coupe, nearly new was 9/- so we consider that is dirt cheap.
The Mayo Clinic here just keeps the town. It is a marvellous place with 300 doctors employed all under the direct control of the Mayos. The people flock to them in thousands every day. The town lists its population at 13,000 while there are always at least 25,000 in the place. Of course it is full of hotels and hospitals and cripples of all sorts abound. It is a pitiful sight to stand outside the clinic and watch the hundreds pouring in and out, the whole time suffering from every known form of disease - and some, I suppose, unknown. And they line up in queues to wait their turn. It puts one in mind of Hickson's Mission but on a much larger scale.
The American scenery is very fine their cities large and convenient - their people are all only too willing to explain anything to you and take you about when you come to their home town. But everything in the place is artificial. They talk and think of nothing else but the almighty $ and the shortest way to pack up a stack of them. There is nothing substantial about the places we have so far seen in San Francisco and Los Angeles. They are all jerrybuilt homes and buildings, put up in quick time.
We are both well. Bill is brighter than previously by a long way - while I have put on 5lbs since leaving Sydney!
Often I would give a pound for a long iced lager. One can get lots of spirits in this place - and good stuff too I believe - but not for me, thanks! Everyone laughs at the Prohibition laws here and they drink hard.
[and a subsequent letter ...] after a little over a week Bill is ever so much better - the doctors have now finished their examinations of him. They put him on a diet and he finishes the course today. On Friday next he goes back to the Clinic and has his final instructions. We are hoping to leave then to continue our trip on to Buffalo and New York.
Yesterday called into a stud farm of Holstein cattle owned by the State Hospital. It is a wonderful affair. The patients are all mental cases and they milk 150 cows twice a day by hand. The milk is used in the hospitals around. The bails are enormous as they bail all the cows at the same time and they always go to the same bail. Their milk is tested every time. Last night I went to a village dance in town with some girls from the hotel. They are nurses from the clinic. Bill went to bed.
We have just about seen all there is to see in this place as an old chap who devotes his life to wheeling patients about for the love of it has taken a great fancy to us. Johnny McBride, the "Angel of the Wheelchairs" at Rochester has shown us all over the town. One day he took us to the basement of the Colonial Hospital and from there through a subway to the Kahler Hotel. We went up to the top and saw all over the city from the 14th floor. The Kahler is a combination affair. The basement is set apart for nurses, rest rooms, etc. The first floor is lobby and offices the next six are hotel then to the roof is hospital. In a corner of the roof garden are four operating theatres and while we were up there one of the theatres was in full swing and was full of doctors watching the operation. From the roof we went back to the basement and then more subways to the Damon Hotel across the street. It is practically wholly devoted to hospital uses. More subways from there to the Clinic which is 3 blocks away from the Colonial Hospital where we entered so you can imagine how far we travelled underground.
In Italy all roads lead to Rome but in Rochester all subways lead to the Clinic. From the Clinic I went to St Mary's Hospital by jitney. This is the largest surgical hospital in the world under one roof. You can imagine the size of the place when there are fourteen operating theatres in it. They are all fitted with a gallery for onlookers and the largest of these theatres has a gallery built of marble leading up from the main floor and operating table, that will hold 240 people - and which cost $60,000. One doctor alone did 20 goitre operations in a single day.
St Mary's is run by Catholic sisters and it is here the Mayos' do all their own operations. In fact they refuse to operate elsewhere. They are Protestants but when they first commenced practice in this place these Sisters helped them so much that they stick to them now.
Then there is Worrell Hospital where a lot of the X ray work is done and also the contagious diseases. There are 9,000 cases in one month of one disease alone. These are only a few of the hospitals that keep this place alive. There are also the Curie, Samaritan, Zambro and many others. In fact the town is full of hospitals, drug stores (as they call chemists shops) and undertakers ... not forgetting hotels.
The country around here is the best and prettiest we have yet seen in the States and the weather is all one could wish for.
We are having a great time here and Bill is the best he has yet been although he still has to keep to the vegetarian diet. He does not think he is coming home with me but will stay in England for 3 or 4 months and then come home.
[and a subsequent letter after reaching London ...] I am having a good time here in London but Bill is in dock again. It is nothing serious but he was not improving as rapidly as he thought he should. He attributed it to the old trouble with his nose and so saw a specialist here who advised an operation to remove a septum from the back of his nose. This prevented the normal use of his nostrils and matter was being swallowed and perhaps poisoning his stomach. He went into a private hospital on Sunday last and was operated on last Monday morning. He was pretty sick for a couple of days but yesterday and today has been as fit again as ever. He thinks so too which makes a lot more noise than what I think as now it is only a matter of his mind over his ailment. Hospitals do not exist in the heart of London and I have a long way to go to see him.
Yesterday we had a London fog. It is all we have heard of it and more. To see anything you have to get right on top of it. I went out to lunch at 1.45 and the street lights were on and also the electric signs and the lights of vehicles. It was just like night with gusts of the soupy stuff called fog all around. Bill has been advised to get out of the cities until his nose is quite healed again so he will not now come to Paris with me but go straight to Cornwall. I shall join him down there after seeing Paris and the battlefields of Flanders and Belgium. I will then stay in Cornwall for Xmas and N. Year and come back to London to catch the "Ormonde" on 3rd.
Bill is slowly improving I think but will take some time to regain his normal health and I do not think he will return much before our summer next year, 1925.
View full text of Harry's letters here
Drs William and Charles Mayo were among the first to use a team approach in medical treatment. Having pioneered the medical specialties and the sharing of medical records, the Mayo Clinic's fame had spread, even downunder.
The young Australians' trip of 5 months took in Tahiti, California, Rochester, New York and London, returning via Suez and Perth. The letters excerpted below lay ignored for almost 80 years until I sought them from my uncle Bill Gracie in Muwillumbah, near the Queensland border. A bank teller, Harry Gordon Gracie later became ANZ manager in the Riverina, Hunter and New England regions. The letters are addressed to his family in Artarmon, just north of the Sydney Harbour Bridge (which had yet to be built). They will interest modern medicos, being a young man's observations of a famous medical institution in a period of great change in our profession.
Hotel Campbell, Rochester, Minnesota
23 Sept 1924
My dear mother,
Rochester, Minnesota is where the Mayo Bros are and where I hope Bill will get fixed up. The first part of our long journey from Sydney now over, we are resting for a little while. Bill is attending the clinic, so far with good results. He was up at the Clinic again this morning and when he returned we took a car without a driver to see the sights around the town. The total cost for the hire of a Ford Coupe, nearly new was 9/- so we consider that is dirt cheap.
The Mayo Clinic here just keeps the town. It is a marvellous place with 300 doctors employed all under the direct control of the Mayos. The people flock to them in thousands every day. The town lists its population at 13,000 while there are always at least 25,000 in the place. Of course it is full of hotels and hospitals and cripples of all sorts abound. It is a pitiful sight to stand outside the clinic and watch the hundreds pouring in and out, the whole time suffering from every known form of disease - and some, I suppose, unknown. And they line up in queues to wait their turn. It puts one in mind of Hickson's Mission but on a much larger scale.
The American scenery is very fine their cities large and convenient - their people are all only too willing to explain anything to you and take you about when you come to their home town. But everything in the place is artificial. They talk and think of nothing else but the almighty $ and the shortest way to pack up a stack of them. There is nothing substantial about the places we have so far seen in San Francisco and Los Angeles. They are all jerrybuilt homes and buildings, put up in quick time.
We are both well. Bill is brighter than previously by a long way - while I have put on 5lbs since leaving Sydney!
Often I would give a pound for a long iced lager. One can get lots of spirits in this place - and good stuff too I believe - but not for me, thanks! Everyone laughs at the Prohibition laws here and they drink hard.
[and a subsequent letter ...] after a little over a week Bill is ever so much better - the doctors have now finished their examinations of him. They put him on a diet and he finishes the course today. On Friday next he goes back to the Clinic and has his final instructions. We are hoping to leave then to continue our trip on to Buffalo and New York.
Yesterday called into a stud farm of Holstein cattle owned by the State Hospital. It is a wonderful affair. The patients are all mental cases and they milk 150 cows twice a day by hand. The milk is used in the hospitals around. The bails are enormous as they bail all the cows at the same time and they always go to the same bail. Their milk is tested every time. Last night I went to a village dance in town with some girls from the hotel. They are nurses from the clinic. Bill went to bed.
We have just about seen all there is to see in this place as an old chap who devotes his life to wheeling patients about for the love of it has taken a great fancy to us. Johnny McBride, the "Angel of the Wheelchairs" at Rochester has shown us all over the town. One day he took us to the basement of the Colonial Hospital and from there through a subway to the Kahler Hotel. We went up to the top and saw all over the city from the 14th floor. The Kahler is a combination affair. The basement is set apart for nurses, rest rooms, etc. The first floor is lobby and offices the next six are hotel then to the roof is hospital. In a corner of the roof garden are four operating theatres and while we were up there one of the theatres was in full swing and was full of doctors watching the operation. From the roof we went back to the basement and then more subways to the Damon Hotel across the street. It is practically wholly devoted to hospital uses. More subways from there to the Clinic which is 3 blocks away from the Colonial Hospital where we entered so you can imagine how far we travelled underground.
In Italy all roads lead to Rome but in Rochester all subways lead to the Clinic. From the Clinic I went to St Mary's Hospital by jitney. This is the largest surgical hospital in the world under one roof. You can imagine the size of the place when there are fourteen operating theatres in it. They are all fitted with a gallery for onlookers and the largest of these theatres has a gallery built of marble leading up from the main floor and operating table, that will hold 240 people - and which cost $60,000. One doctor alone did 20 goitre operations in a single day.
St Mary's is run by Catholic sisters and it is here the Mayos' do all their own operations. In fact they refuse to operate elsewhere. They are Protestants but when they first commenced practice in this place these Sisters helped them so much that they stick to them now.
Then there is Worrell Hospital where a lot of the X ray work is done and also the contagious diseases. There are 9,000 cases in one month of one disease alone. These are only a few of the hospitals that keep this place alive. There are also the Curie, Samaritan, Zambro and many others. In fact the town is full of hospitals, drug stores (as they call chemists shops) and undertakers ... not forgetting hotels.
The country around here is the best and prettiest we have yet seen in the States and the weather is all one could wish for.
We are having a great time here and Bill is the best he has yet been although he still has to keep to the vegetarian diet. He does not think he is coming home with me but will stay in England for 3 or 4 months and then come home.
[and a subsequent letter after reaching London ...] I am having a good time here in London but Bill is in dock again. It is nothing serious but he was not improving as rapidly as he thought he should. He attributed it to the old trouble with his nose and so saw a specialist here who advised an operation to remove a septum from the back of his nose. This prevented the normal use of his nostrils and matter was being swallowed and perhaps poisoning his stomach. He went into a private hospital on Sunday last and was operated on last Monday morning. He was pretty sick for a couple of days but yesterday and today has been as fit again as ever. He thinks so too which makes a lot more noise than what I think as now it is only a matter of his mind over his ailment. Hospitals do not exist in the heart of London and I have a long way to go to see him.
Yesterday we had a London fog. It is all we have heard of it and more. To see anything you have to get right on top of it. I went out to lunch at 1.45 and the street lights were on and also the electric signs and the lights of vehicles. It was just like night with gusts of the soupy stuff called fog all around. Bill has been advised to get out of the cities until his nose is quite healed again so he will not now come to Paris with me but go straight to Cornwall. I shall join him down there after seeing Paris and the battlefields of Flanders and Belgium. I will then stay in Cornwall for Xmas and N. Year and come back to London to catch the "Ormonde" on 3rd.
Bill is slowly improving I think but will take some time to regain his normal health and I do not think he will return much before our summer next year, 1925.
Submitted by Andrew Byrne ..
View full text of Harry's letters here
1 July 2002
Benzodiazepine addiction - trial of 2 methods of treatment from Finland
Treatment of out-patients with complicated benzodiazepine dependence: comparison of two approaches. Vorma H, Naukkarinen H, Sarna S, Kuoppasalmi K. Addiction (2002) 97: 851-859
Dear Colleagues,
These authors randomised 76 benzodiazepine dependent patients to receive 'traditional' dose taper treatment or an experimental protocol involving fixed rates of withdrawal and psychosocial supports.
The patients presented to four addiction clinics in Finland with the experimental condition being implemented by one such clinic. This presumably entailed some patients having their treatment moved and standardised to the experimental protocol.
There was daily or binge drinking in about 30% of subjects. About half had used 40mg diazepam equivalent daily or more. Patients used sedatives for an average of 7 years and over 80% had previously tried to quit. About one in seven had used recreational drugs in the previous year. 80% of each group has a current axis I disorder (anxiety, depression, alcohol abuse). Two thirds had a personality disorder, leaving only 5-10% without a formal psychiatric diagnosis. There were no significant differences between the randomized groups.
The experimental plan included a fixed diazepam or equivalent taper based on the patient's dose and proportionate reductions of about one tenth each week. The time taken for tapering was thus longer for higher doses. They also included a drug/alcohol diary, video film on withdrawals, sleep advice, printed material on reductions, 'assessment of benzodiazepine functions' and relaxation exercises. About a third of subjects in each group was prescribed fluoxetine for depression. 'Control' treatment involved traditional sedative reductions, 'supervised by a physician'.
Subjects had monthly urine and/or blood drug screens plus interviews including an AUDIT questionnaire after abstinence was attained, or at 12 months, where possible.
Judging by abstinence or 12 months of treatment attendance the experimental group had a 46% completion rate while the control group yielded 70%, a significant difference. One subject who had been accepted but dropped out, committed suicide some months later. The authors state that if they excluded patients who did not participate in treatment or left treatment 'for reasons unrelated to the treatment' the differences become insignificant. [But if patients did not participate in the treatment as offered, then would normally be considered 'failures' in any fair assessment of an experimental intervention.]
The reductions in benzo use were impressive, all tending to be better in the 'control' taper group (but apparently not significantly). Fully 27% achieved abstinence in the control group, 13% in the experimental. There were reductions in overall benzo use by 45-80% across the groups. One in six subjects demonstrated no reductions over 12 months despite the treatment interventions. It would appear that all of the patients were followed up at some point, a remarkable feat for benzo users, or any drug treatment subjects.
This study tells us that trying to standardise an approach to treatment in a way which is not based on sound research findings does not lead to improvements in outcomes. Indeed, it may be that the lack of prescribing flexibility even reduced successes for some patients in this difficult area.
Unlike heroin addiction, there is still no 'gold standard' treatment for tranquillizer addiction. But despite this, most in the field seem to approve some degree of diazepam (or similar) prescribing with reductions as tolerated in a setting of medical care and psychosocial supports. These authors did not use diazepam in every case, nor do they describe supervised or daily dosing which is now recommended in certain unstable cases (see Strang J. UK Dependency Treatment Guidelines 1999 p31-33).
comments by Andrew Byrne ..
4 April 2002
Urine testing in treatment - how often?
Fellous J, Lowenstein W, Gourarier L, Bonan B, et al. Relevance of urinalysis monitoring of methadone maintenance patients: a clinical-biological agreement on 41 patients. Addiction Biology (2000) 5:313-318
This interesting report from a Paris addiction treatment service tells us much about good medical treatment with methadone as well as showing the benefits and limitations of urine drug testing in the clinical environment. These researchers reiterate that urine testing should never be used punitively but more as a clinical guide or reminder. They state that such testing is 'still used by some as a disciplinary measure despite recommendations of clinicians and epidemiologists'. 'It should not be performed as a repressive imposition which will probably lead drug abusers to falsify their urine samples' (6 references given).
The study's sub-group of the clinic population comprised 41 long term methadone maintenance treatment (MMT) patients with mean age 33, 57% male, 92% injectors. Dose ranges were also typical with 90% receiving between 30 and 120mg daily (mean dose 72mg). 5% were prescribed in excess of 120mg. The overall clinic's annual retention rate appeared to be a staggering 96%.
All patients had at least one test every 2 months during the 12 months of the trial which examined results in comparison with clinical history given to health professionals. The simplified addiction severity measure used self-report of drug use and medical/social consequences. There was a 'very poor agreement' with urine test results. The authors conclude that urine test results should be used as a surveillance to alert the physician to early relapse and to schedule earlier consultations for action to be taken such as dose adjustment, counselling, etc.
This report underlines that urine testing has still not been proven to have any effect on the outcomes of treatment or prevention, despite popular belief of a therapeutic benefit from such surveillance. Urine testing, as long as it is (1) supervised (witnessed and/or temperature tested) and (2) tested by reliable and sensitive methods and (3) used without any threats of adverse consequences on treatment - is an accurate way of determining a subject's recent intake of drugs. This provides evidence for research into medical, legal or epidemiological aspects of psychoactive drug use. It probably also has a place in improving clinical outcomes but this remains to be proven by comparative research.
I was intrigued to learn this week that the Australian Health Insurance Commission has increased from 21 to 36 the maximum rebateable number of urine toxicology tests per annum. Why ever would they fund additional tests per year when there is no evidence that they are of any benefit? Could politics have influenced matters?
comments by Andrew Byrne ..
further references:
Chutuape MA, Silverman K, Stitzer ML. Effects of urine testing frequency on outcome in a methadone take-home contingency program. D&A Dependence 62 (2001) 69-76
Chermack ST, Roll J, Reilly M, Davis L, Kilaru U, Grabowski J. Comparison of patient self-report and urinalysis results obtained under naturalistic methadone maintenance conditions. D&A Dependence (2000) 59:43-49
Ditton J, Cooper GAA, Scott KS et al. Hair testing for 'ecstasy' (MDMA) in volunteer Scottish drug users. Addiction Biology (2000) 5:207-213
This interesting report from a Paris addiction treatment service tells us much about good medical treatment with methadone as well as showing the benefits and limitations of urine drug testing in the clinical environment. These researchers reiterate that urine testing should never be used punitively but more as a clinical guide or reminder. They state that such testing is 'still used by some as a disciplinary measure despite recommendations of clinicians and epidemiologists'. 'It should not be performed as a repressive imposition which will probably lead drug abusers to falsify their urine samples' (6 references given).
The study's sub-group of the clinic population comprised 41 long term methadone maintenance treatment (MMT) patients with mean age 33, 57% male, 92% injectors. Dose ranges were also typical with 90% receiving between 30 and 120mg daily (mean dose 72mg). 5% were prescribed in excess of 120mg. The overall clinic's annual retention rate appeared to be a staggering 96%.
All patients had at least one test every 2 months during the 12 months of the trial which examined results in comparison with clinical history given to health professionals. The simplified addiction severity measure used self-report of drug use and medical/social consequences. There was a 'very poor agreement' with urine test results. The authors conclude that urine test results should be used as a surveillance to alert the physician to early relapse and to schedule earlier consultations for action to be taken such as dose adjustment, counselling, etc.
This report underlines that urine testing has still not been proven to have any effect on the outcomes of treatment or prevention, despite popular belief of a therapeutic benefit from such surveillance. Urine testing, as long as it is (1) supervised (witnessed and/or temperature tested) and (2) tested by reliable and sensitive methods and (3) used without any threats of adverse consequences on treatment - is an accurate way of determining a subject's recent intake of drugs. This provides evidence for research into medical, legal or epidemiological aspects of psychoactive drug use. It probably also has a place in improving clinical outcomes but this remains to be proven by comparative research.
I was intrigued to learn this week that the Australian Health Insurance Commission has increased from 21 to 36 the maximum rebateable number of urine toxicology tests per annum. Why ever would they fund additional tests per year when there is no evidence that they are of any benefit? Could politics have influenced matters?
comments by Andrew Byrne ..
further references:
Chutuape MA, Silverman K, Stitzer ML. Effects of urine testing frequency on outcome in a methadone take-home contingency program. D&A Dependence 62 (2001) 69-76
Chermack ST, Roll J, Reilly M, Davis L, Kilaru U, Grabowski J. Comparison of patient self-report and urinalysis results obtained under naturalistic methadone maintenance conditions. D&A Dependence (2000) 59:43-49
Ditton J, Cooper GAA, Scott KS et al. Hair testing for 'ecstasy' (MDMA) in volunteer Scottish drug users. Addiction Biology (2000) 5:207-213
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