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 ..

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

Does case management work? Journal article.

Rosen A, Teesson M. Does case management work? The evidence and the abuse of evidence-based medicine. ANZJ Psych 2001 35;6:731-746

Dear Colleagues,

This paper is long and complex, but its essence seems to be that to in order to be effective, 'case management' needs to be used for high risk subjects and only when implemented by professionals in the field. As a working definition, case management might be termed: "active and assertive community treatment" or better still: "patient care co-ordinated by a single professional using a multi-disciplinary approach". With minor changes, this is believed to apply to dependency matters just as it does to community psychiatry where most of the current evaluative research has been done. More than twelve randomised controlled studies comparing case management with 'standard therapy', from a variety of countries - including Australia - contributed to a Cochrane database on the subject.

Some have considered case management (CM) as a 'motherhood' subject, ineligible of criticism or modification. So much so that I once considered it an imaginary concept, like Falstaff's "honour" monologue. But as long as it is seen in concert with good quality medical care it is a useful way of examining and implementing psychosocial supports.

If not by name, case management comes naturally to GPs since this is just what they do as a matter of course. Hospital specialists and clinic based health workers may have more clearly demarcated duties and thus be less likely to address a patient 'holistically'. It is still possible, however, for any health professional to take the time to examine various aspects of the patient's life and coordinate an approach to address those areas needing attention. It is sometimes straightforward but at other times the high risk areas need to be teased out of a difficult presentation by subjects who may be 'in denial' or unable to recognise the issues themselves due to the circumstances.

Of fundamental importance is the aspect of medical treatment and its quality in relation to the current evidence base. Addiction treatment is in these respects possibly even clearer than in community mental health. There is some debate as to who is responsible for appropriate medical care. Courts generally find that it is the doctor who is responsible for inadequate medical care. It might be argued, however, that other health care workers are almost equally responsible in matters of diagnosis and treatment, despite sometimes their having no training in therapeutics. The doctor may not always be involved in the first instance. Thus to this point others must take the responsibility for assessments and treatment given (or not given). In the community it is normally the patient who decides when to go to the doctor (or the dentist, or the hairdresser for that matter). But in the health care system, there often needs to be a key worker who does significantly more than a travel clerk booking a ticket on request.

comments by Andrew Byrne ..

References:

Pringle JL, Edmondston LA et al. The Role of Wrap Around Services in Retention and Outcome in Substance Abuse Treatment: Finding From the Wrap Around Service Impact Study. Addictive Disorders Their Treat (2002) 1;4:109-118

Addiction journal goes 'troppo con molto prezzo'.

Dear Colleagues,

The (UK) Society for the Study of Addiction has sent out a somewhat apologetic note with the normal subscription notice this month. Under the name of Christine Godfrey, SSA President, we are informed of the excellent news that all members, for the yearly rate of 75 pounds or US$150 will now receive 4 copies of Addiction Biology in addition to the 12 issues of Addiction and special 'supplements' each year. For an additional 12 pounds, we are told that members can also have on-line access. For us in the distant antipodes, where mails take up to six weeks, this on-line bonus is indeed welcome.

The management is to be congratulated for these moves. That said, similar promises have been made in the past. In March 1998 Addiction's blue cover proudly announced "available online". But it wasn't. Not to me, anyway. I know as I tried all year unsuccessfully punching passwords and down-loading software to make it all happen. To this day, the cover bears that same caption 'AVAILABLE ONLINE'. Apparently it can be down-loaded by enterprising librarians and other institutional subscribers. My library did not seem able to do so.

Another enticing piece nearly 5 years ago, in May 1997 was entitled: "Join the Society for the Study of Addiction" ... "A World Wide Web site is under development and it is proposed in the near future to set up an Internet bulletin board for members to exchange ideas and request information. These are exciting times for the Society ... ". [Vol 92(5) p636]. I should have contained my excitement since recent editions still state the same! "A World Wide Web site is under development and it is proposed in the near future ...". [Vol 96 (10) p1530]. One is tempted to wonder whether the Society is really serious about encouraging debate.

Addiction once devoted a column to ME! But rather than robust academic discourse it was a clumsy attempt at 'ad hominem' sarcasm following a critical letter on 'decrimalization'. In fact it was hard to understand the meaning of the swagger by Susan Savva in 'News and Notes', but she was clearly enjoying herself at my expense [Vol 95 p1875-6]. Interestingly, the British government seems not to agree with her line of argument as they are now making minor cannabis possession a non-arrestable offence.

On even more serious matters, I have written to the editor, sub-editors and other esteemed members at various times in recent years about the pressing need to improve the quality of methadone and other treatments in the UK and Australia. I pointed out that the Journal had not broached this issue, nor what might be done about it. I was politely told that this issue was being looked into and that a piece was proposed.

All I have seen to date has been a somewhat pompous and contradictory editorial on the possible mischief attended by harm reduction, "quo vadis", by a savant from Montreal. It stated magnanimously that when given properly, methadone treatment 'worked' and was not questioned by leaders in the field. The author then proceeded to question agonist treatments (!). Two recent letters-in-reply were politely critical ... personally, I find it hard to be polite about curbs on simple measures which save lives.

Despite all, I will probably be renewing my subscription to this venerable organ which is nearly into its hundredth year.

comments by Andrew Byrne ..

Comparison of urine toxicology with self-report.

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

Dear Colleagues,

'Confidential' comparisons of urine testing with self-report outside the clinical setting have shown close accuracy (Darke 1998). However, when responses are given to clinicians in the naturalistic setting, as this study finds, they are less likely to be as accurate, at least this is so in the clinic setting where treatment termination based on such results is possible. It is the experience of most who work in the behavioural area that self report is less accurate than objective findings. This probably applies to weight reduction programs, ("the scales are wrong, doctor"), smoking cessation, etc. Urine toxicology always introduces some tension, just like the scales, but it should never cause treatment to be terminated and *taken alone* such testing should not cause patients' treatment schedules to be altered. The most serious consequence of a positive test should be a counselling visit in which 'punishment' should not be an issue.

Despite the lack of surprise in these overall results, it is always gratifying to have ones own experiences documented in a careful scientific study.

These results are hard to generalise to other practices since the patients were all male, ex-service personel, aged 50.4 years (mean) and three quarters were African American.

These authors use exhaustive statistical analysis comparing urine tests results (EMIT tests for opiates and cocaine) and a structured ASI (addiction severity index) including questions on drug use in the previous 30 days. These showed a degree of concordance, but not nearly as much as previous reports of confidential studies where the information was assured to be kept private from treating doctors. What a remarkable state of affairs when patients are apparently afraid for their own doctor to know more about their case!

Comments by Andrew Byrne ..

Addiction: April 2001

Editorial and debate on injectable methadone by Zador. Addiction (2001) 96:547-553.

Zador's perfectly sensible description on the prescribing of injectable methadone by British doctors is challenged by others on some of the most spurious grounds. Both Malcolm Lader and Jerome Jaffe state that it is medico-legally fraught, being non-evidence based medicine. But they ignore the 'out' that this treatment may be the only reasonable alternative for certain heroin dependent folk in whom other treatments have proven unsuccessful or unacceptable. In such a case it may be possible be prove medical negligence by NOT continuing such apparently effective treatment. This may also be the case in a small number of previous trial subjects in Queensland who were given this treatment some years ago. Much treatment given by doctors currently is not strictly evidence based, such as antibiotics for 'bronchitis'.

Jaffe goes through several possible reasons why such prescribing is not appropriate (cost, political acceptability, evidence base) yet he accepts that research might show that it could be so! He even uses the old peccadillo about supplying alcohol to alcoholics and tobacco to smokers 'all paid for indefinitely by the taxpayers'. Of course these drugs ARE CURRENTLY made available by all our governments at reasonable cost to all addicts, and to the very great benefit of the public purse through taxes. It is unusual for this respected researcher to inject such irrelevancies into this otherwise very serious discussion.

Jaffe writes for three pages, his arguments sounding more like those of a politician or a journalist-with-a-mission. He implies that the issue is enormously complex which is simply not the case. This prescribing is either defensible as good medical practice, or it is not. If it MIGHT be, we need more research. Simple!

The limited research that does exist is virtually all encouraging. Prescribing injectables to addicts appears to 'work' in a similar manner to oral methadone, and it may do so in some patients who fare poorly with existing treatments, thus enshrining it as ethical, if of uncertain application.

The article by Strang and Sheridan on relative dosing practices between private and public sectors in England is also of interest (Addiction (2001) 96:567-576).

These authors have conducted yet another elegant and useful study documenting the poor quality of care received by English dependent patients on methadone under the NHS. It is possible that private doctors also are guilty of giving poor treatment but these surveys did not question concurrent prescription of stimulants, or if they did we are not enlightened on the findings. Some private practices are notorious for multiple, gross over-prescribing, including stimulants and one was even the subject of an episode of "The Bill" a few years back.

Since supervised consumption, even in new patients, is exceptional in England, it is not possible to know how much methadone in private of public sector was actually consumed. It is certain, however, that some public sector patients received markedly inadequate doses.

As they point out, there are weaknesses to the study, but one strength is that it is clearly shows that the mean dose of oral methadone in public patients is around 50mg daily, a finding which is consistent with other British reports. As Strang's own guidelines point out, effective doses are usually in the range of 60mg to 120mg daily with only a small proportion of patients requiring more or less than this range. Even allowing for some patients on reducing doses, a mean dose of 50mg would imply that more than half of these patients may be receiving inadequate and therefore ineffective doses. This regrettable situation is still not acknowledged by the authors despite the unfolding tragedy which is dependency treatment in England and Wales in recent years.

Editorial by Juan Negrete, Montreal. Addiction (2001) 96:543-5

This is intriguingly slanted piece heaps scorn on the large proportion of the professional community which perceives benefits in harm reduction principles. The author fails to carefully define what he means by harm reduction which makes his article almost worthless.

It outlines an unscientific and near hysterical viewpoint on harm reduction, a policy most now consider close to 'motherhood' and which has been shown to save countless lives in its various implementations.

Juan Negrete criticises supporters of harm reduction in a most unflattering manner. He says that harm reductionists' aims towards improving methadone treatment only make it easier to get by removing barriers. But he fails to accept that like every other medical intervention, methadone treatment and any variations on its implementation, are subject to rigorous evaluation and hence improvements should only follow normal research findings, not the arbitrary views of any individual parties.

Negrete roundly criticises the Swiss heroin trial, but accepts that if benefits were found, he would review his opinion. How elegantly he contradicts himself, since only by running such a trial could benefits be demonstrated? And they were! The outcomes clearly showed that among 1146 treatment refractory patients there were very high retention rates and low mortality rates along with benefits regarding employment and housing. It is inescapable that this treatment attracted large numbers of otherwise 'treatment-refractory' patients into treatment and kept them alive over the three years of the trial. Is preventing death a 'benefit to patients'?

After faintly praising methadone treatment, Negrete says that maintenance therapies are 'irreversible' and he implies that they prevent addicts attaining drug free status. But people come off methadone successfully all the time! His emotive terminology reveals his clear unhappiness with the field: "harm reduction ideologues"; "compulsive toxicophilia" (is this English?); "drug reward slavery"; [addicts are] "much diminished human beings"; "primitive self-centredness of their pursuit"; "well meaning harm reduction workers who do not assign much importance to the problem of addiction". These are not the usual terms of clear scientific writing and if applied to those dependent on legal drugs would be considered offensive and outrageous by many such people.

 

It is surprising to find such items in 'Addiction', the world's oldest scientific journal on dependency.

Comments by Andrew Byrne ..

"Confessions of an English Opium-Eater" (Thomas de Quincey)

Written in 1821, this is an intense and pertinent portrayal of narcotic dependence from the addict's viewpoint. De Quincey addresses the constant conflict between intoxication and abstinence. Similar sentiments are related by our patients today, but rarely with as much eloquence and insight as Thomas De Quincey. This classic work is essential reading for all involved in drug and alcohol studies and who admire beautiful language.

With so many patients now on maintenance programs (mostly methadone), and illicit opioids still ubiquitous, it is timely to re-examine this work, probably the oldest account of its kind in English.

The 'Confessions' presents us with several episodes in the author's life. He recounts privileged public school days, subsequent hostile truancy, still later poverty in London squats and, some years afterward, a comfortable country existence. But this story is not just biographical. The disparate scenes each place his drug-taking into vivid context.

As a 36-year-old addict, the writer states that his drug of choice was laudanum (tincture of opium), a medicine first prescribed him for recurrent dyspepsia aged 28. It was then that he also discovered its pleasurable qualities. He consumed up to 320 grains of opium daily, equal to around 20g of raw opium, a large, but not unbelievable quantity. Though he claims to have given up opium, history tells us that he continued heavy use for another 35 years. He did not live long enough to 'enjoy' the discovery of heroin and the hypodermic needle.

The original 'Confessions' was published as a series of articles in the "London Magazine" in 1821. Some parts had been written previously, and the series may have been pieced together hastily out of financial necessity. The author pleads for patience, explaining that his prose follows his own train of thought so closely that it sometimes may appear wandering or disjointed. The American author, William Burroughs suffered the same 'malady', (and possibly for the same reason) but, far from craving his readers' indulgence, he has capitalized on it and has made it his trade-mark.

De Quincey apologises needlessly for his narrative style. Seemingly embroidered or wordy descriptions are well balanced by other elegantly succinct poetic portraits.

"Thou only givest these gifts to man; and thou hast the keys of Paradise, oh, just, subtle, and mighty opium!" Every page of this work contains language of beauty, humanity and frequently, humour.

The subject of this book was taboo at the time of writing, and the very title would have shocked its public. It was then widely believed that Europeans could not become addicted to opium.

As well as 'Preliminary Confessions', he writes chapters on the pleasures and the pains of opium. He affirms his belief in the unique healing powers of the drug, and the benefits of doctor's prescriptions which contain opium. De Quincey reveals that he used opium only intermittently for several years, before developing a daily proclivity. He took it regularly before going to the Covent Garden opera. A proportion of today's narcotic users employ the drug to enhance other pleasurable activities.

Based on personal knowledge as well as information from apothecaries he patronized, De Quincey correctly deduces that opium addiction was extremely widespread in Regency England. He expresses some remorse over his addiction, but devotes much space to explaining his extenuating personal circumstances. Unlike simple pleasure seekers, the reader is told, he took it initially for medical reasons. He also compares it with the pernicious effects of alcohol. He identifies some other prominent opium users: first mentioned is the poet laureate and playwright, Thomas Shadwell (1642-92), a confirmed addict. Of his own contemporaries, he identifies Samuel Taylor Coleridge, William Wilberforce, Dr Abernethy, and several others in public life.

He revised and enlarged the confessions 35 years later, as if to prove opiate addiction and longevity are not mutually exclusive. Most modern editions give some passages from the revisions, but wisely keep the original as a discrete work. The revisions are longer than the entire original work. Although some central issues are clarified in the revisions, other tangential ones are drawn out and examined in excruciating detail.

De Quincey remains one of the great wordsmiths, and this well-forged story gives a personal aspect to one of mankind's most ancient activities, the pursuit of pleasure from drugs. [De Quincey, T. Confessions of an English Opium-Eater. Penguin English Library 1972, edited with an introduction by Alethea Hayter. First published in the "London Magazine", 1821]

Hulse et al. omit deaths in naltrexone report.

re: Hulse GK, Basso MR. Reassessing naltrexone maintenance as a treatment for illicit heroin users. Drug Alcohol Review 1999 18:263-269

Comment letter published D&A Review 2000 19;3:347

[Note: no reply published from original authors]
Dear Editor,

I support the authors' contention that naltrexone be judged using the same criteria as other treatments to enable fair comparisons of outcomes.

It is self-evident that stricter acceptance criteria will yield lower apparent 'success' rates, but that these will not alter actual patient outcomes. Clinical trials are rarely directly comparable so one of the tasks of clinicians is to determine the significance of each addition to the scientific literature. For dependency treatments this is not difficult since the aims of treatment are relatively straightforward and can be verified by simple means.

Hulse and Basso have reported detailed outcomes of a naltrexone treatment trial using two criteria for reporting six month follow-up details. Despite using tables and text to illuminate these outcomes, they place these results out of clinical context by omitting the two deaths which were previously reported from this cohort [Hulse G. Naltrexone - Defining a framework for use. Australian Professional Society on Alcohol and other Drugs (APSAD) Newsletter 'Summer' 1998, p4].

Mortality is the most fundamental end point in any treatment trial. To ignore, omit or mis-state deaths or other end points makes interpretation of data impossible and is inappropriate in balanced scientific writing.

A comparison of methadone and naltrexone in dependency management should be rigorous and impartial. After twenty years and over 500 peer-reviewed papers demonstrating the benefits of methadone, there has been only very limited research favouring naltrexone treatment in heroin addicts in the same time period. Few if any accredited addiction treatment services use naltrexone as a first line drug although it shows promise in certain selected groups and is effective in alcoholism.

The authors of all scientific research studies should be scrupulous in all reporting, lest they be seen as advocates for particular causes instead of maintaining the detachment which is essential in ethical research.

Yours faithfully,

Andrew Byrne ..

Another effective anti-craving drug for some alcoholics.

Dear Colleagues, In a most interesting development, researchers in Texas have shown significant improvements in drinking behaviour in some alcoholic patients given modest doses of ondansetron (Zofran). This widely used anti-serotonin, anti-nausea drug was given in a 3 month randomised, double-blind, placebo-controlled trial. Compliance was over 90% as measured by history and urine riboflavin tracer. Side effect profile was low with the only significant problem being constipation in 5% of patients. One death occurred in a patient falling down a flight of stairs, unrelated to the treatment (but possibly related to the condition being treated). Patients reported 'drinks per day', 'drinks per drinking day', 'percentage of days abstinent', and 'total days abstinent'. In older onset alcoholics the results were equivocal (n=160). The younger onset group (<25 years, n=161) are believed to comprise those with a stronger genetic component to their alcoholism and appear to have more psychiatric co-morbidity such as antisocial personality traits. In these patients the reductions in alcohol consumed was substantial and significant [those on 4ug/kg twice daily had a dramatic (p<0.001) response compared to placebo. The 'effect sizes' of the benefit of the twice daily medication were up to 0.41 which was in the 'moderate' range. "Patients with early-onset alcoholism who received ondansetron (1, 4, and 16 µg/kg twice daily) compared with those who were administered placebo, had fewer drinks per day (1.89, 1.56, and 1.87 vs 3.30; P = .03, P = .01, and P = .02, respectively) and drinks per drinking day (4.75, 4.28, and 5.18 vs 6.90; P = .03, P = .004, and P = .03, respectively)."

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Self reported drinking frequencies were corroborated using serum carbohydrate deficient transferrin (CDT). Taken along with blood alcohol concentrations at visits, this makes the study very scientifically rigorous.


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JAMA also contains an enthusiastic editorial by Dr Henry Kranzler from Connecticut ('Medications for Alcohol Dependence. New Vistas'). He waxes about the significance and importance of these findings in the context of disulfiram, naltrexone and acamprosate treatment. In addition, he mentions that SSRI drugs have a positive effect in the older age onset alcoholics, linking the serotonergic basis for much surrounding cravings, reward pathways and other still ill-understood areas.


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This may be a landmark paper. It allows us to match diagnosis with an effective treatment in a way not previously imaginable in alcohol dependency. The findings are consistent with a smaller study (Sellers, Sobell et al. Ontario, 1994) and animal experiments, according to the authors.


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These new findings place an even greater burden on the medical profession to be equal to the 'therapeutic challenge'. Society stands to gain enormously if these research findings can be widely implemented. It is a great tragedy and a travesty that naltrexone uptake has been so slow when it is so very effective in alcoholism, doubling the rates of abstinence. Many physicians still seem to take the line that there is 'nothing you can do for an alcoholic' and 'they have to help themselves'. comments by Andrew Byrne ..

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Johnson BA, Roache JD, Javors MA, DiClemente CC, Cloninger CR, et al. Ondansetron for Reduction of Drinking Among Biologically Predisposed Alcoholic Patients. A Randomized Controlled Trial. JAMA (2000) 284:963-971

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http://jama.ama-assn.org/issues/v284n8/rfull/joc00147.html


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Kranzler H. Medications for Alcohol Dependence. New Vistas. Editorial. JAMA (2000) 284
http://jama.ama-assn.org/issues/v284n8/ffull/jed00057.html

Could additional methadone increase cravings? 'Addiction' thinks so!

Curran HV, Bolton J, Wanigaratne S, Smyth C. 'Additional methadone increases craving for heroin: a double blind, placebo controlled study of chronic opiate users receiving methadone substitution treatment. Addiction 1999 94(5), 665-674


Rather than a useful contribution to the literature this small study confirms much of what is known about methadone behavioural pharmacology. It has one surprising finding of increased cravings in those given a one third extra methadone dose on one day, blind, with a week 'wash-out' period. This finding, being based on surveys of 18 patients and which, although statistically significant (p=0.03), was based on questions of a like nature concerning heroin craving on a small number of cases in a purely subjective area. This finding has been used in the title as though a highly important new finding despite a lack of further statitsical analysis possible and perhaps desirable on such series. The finding is out of keeping with much of what we know of methadone and the methods require closer scrutiny before being accepted. The reviewers had a difficult task as the findings would be considered controversial and rather outlandish by some.

While this is a little pedantic, I would also dispute the part of the title which states these are patients 'receiving methadone substitution treatment'. The text reveals that the patients were indeed on a treatment with a policy of 'reductions' and eventual abstinence rather than 'methadone substitution' which I use synonymously with 'maintenance'. According to the latest UK dependency guidelines, 'methadone substitution treatment' requires an effective dose of 60mg to 120mg with only exceptional cases needing less or more. These patients were not doing particularly well, judging by the frequent reported use of illicit drugs by the group. The authors state that the patients were chosen on the basis that they were on stable doses, but that the clinic had a policy of reductions to abstinence. In this cohort the average dose was 43mg, about half the level found in good quality methadone treatment services generally (and these include some patients on reductions). Hence these patients were either on inappropriate, ineffective 'methadone substitution' as defined by the UK
Guidelines or they were on reduction treatment with evidence of instability. For these reasons any conclusions as delicate as whether additional methadone could affect cravings over a few hours are based on the most shaky grounds and should be received by the academic community only with great caution.

The authors chose not to develop discussion about the most glaring finding of the study which is that a proportion of English addicts seem to be receiving sub-standard and ineffective treatment in publicly funded clinics. Some would see this as scandalous.

Comment by Andrew Byrne ..