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Rapid responses are electronic letters to the editor. They enable our users to debate issues raised in articles published on Although a selection of rapid responses will be included online and in print as readers' letters, their first appearance online means that they are published articles. If you need the url (web address) of an individual response, perhaps for citation purposes, simply click on the response headline and copy the url from the browser window. Letters are indexed in PubMed.

Re: Inappropriate use of sumatriptan: population based register and interview study Birthe K Rasmussen, Jakob Kragstrup, Lars F Gram, et al. 316:doi 10.1136/bmj.316.7141.1352
The problem of sumatriptan overuse has been raised by others(1, 2) and as reported by Gaist and colleagues(3) is of considerable concern, particularly in the context of Chronic Daily Headache(4). It has been suggested that sumatriptan may replace ergotamine in overuse syndromes(5) and indeed the issue of sumatriptan overuse has been raised in these pages(6). We have now seen in our clinic daily use for each of sumatriptan, naratriptan and zolmitriptan, and although thus far only sumatriptan overuse has been observed de novo without a switch from another acute anti-migraine compound, it seems reasonable to speculate that the problem may be seen with any triptan. The core of this problem, which deserves emphasis here, is that daily or near-daily use of any triptan is, with very few exceptions, inappropriate. Moreover, daily or near-daily use of any acute anti-migraine compound in use in the UK may lead to significant management problems, in particular analgesic-associated headache(7). The commonest cause of this we see in our Headache Clinic at the National is overuse of compound analgesics, particularly those which include codeine phosphate. If daily or very frequent headache is as common in the UK as it is in Spain(8) or the United States(9), at 4-5% of the population, overuse of various pain-killers is likely to be a considerable public health issue that has not hitherto received adequate attention. Our experience suggests that the issues raised by Gaist and colleagues(3) are the tip of the overuse iceberg that represents a modern and perhaps man-made epidemic.

1. Pini LA, Trenti T. Does chronic use of sumatriptan induce dependence? Headache 1994;34:600.

2. Catarci T, Lenzi GL, Cerbo R, Fieschi C. Sumatriptan and daily headache. J. Neurol. Neurosurg. Psychiatry 1995;58:508.

3. Gaist D, Tsiropoulos I, Sindrup SH, et al. Inappropriate use of sumatriptan: population based register and interview study. BMJ 1998;316:1352-1353.

4. Silberstein SD, Lipton RB, Sliwinski M. Classification of daily and near-daily headaches: a field study of revised IHS criteria. Neurology 1996;47:871-875.

5. Catarci T, Fiacco F, Argentino C, Sette G, Cerbo R. Ergotamine-induced headache can be sustained by sumatriptan daily intake. Cephalalgia 1994;14:374-375.

6. Kaube H, May A, Diener HC, Pfaffenrath V. Sumatriptan. BMJ 1994;308:1573-1574.

7. Mathew NT. Drug-induced headache. Neurologic Clinics 1990;8:903-912.

8. Pascual J, Castillo J, Guitera V, Munoz P. Epidemiology of chronic daily headache in the general population. Neurology 1998;50.

9. Scher A, Stewart WF, Liberman J, Lipton RB. Prevalence of frequent headache in a population sample. Headache 1997;37:330.

Competing interests: No competing interests

16 May 1998
Peter J Goadsby
Reader in Clinical Neurology/Wellcome Senior Research Fellow
Institute of Neurology, Queen Square London WC1N 3BG UK
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Re: Identifying asthma and chronic obstructive pulmonary disease in patients with persistent cough presenting to general practitioners: descriptive study J C van Houwelingen, M P Springer, D S Postma, et al. 316:doi 10.1136/bmj.316.7140.1286
EDITOR -- Thiadens, et al examined 192 patients presenting to their general practitioner with persistent cough and discovered a high prevalence of asthma (39%) and chronic obstructive pulmonary disease (7%). These researchers and the editors of the BMJ are to be congratulated on tackling a common and challenging problem in primary care practice and applying it to scientific scrutiny. Articles such as this one are what maintain the BMJ at the forefront of medical literature and information.

I was disappointed that Thiadens et al did not provide a control group for examination, i.e. asymptomatic individuals in the community. Specifically, what is the prevalence of abnormal pulmonary function tests in their general population? If it is high, with a prevalence
approaching that found in this coughing population,
an alternative conclusion might be offered: that asthma and chronic obstructive pulmonary disease are common and not significantly more so in the population of coughers.

I encourage Thiadnes, et al to pursue further examination of their study group as I am sure that much more information can be garnered here. One issue deserving scrutiny is whether these patients are still coughing after six months and thereafter? Also, what diagnoses can be rendered (if any) to the remaining (54%) of coughers and does their prognosis differ from the group diagnosed with asthma and chronic obstructive pulmonary disease? Finally, how do these patients respond to different therapies?

Competing interests: No competing interests

16 May 1998
Joseph M Rothenberg
primary care internist
Jerusalem, Israel
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Re: Can students learn comparable clinical skills in general practice and hospital settings? . 316:doi 10.1136/bmj.316.7143.1531a
It was kind of Elizabeth Murray and her colleagues to cite my book, Cross-over Trials in Clinical Research in their reply. Nevertheless, I have reservations about the use of such trials in assessing the effect of education. The essential feature of a cross-over trial is that subjects are allocated to sequences of treatments in order to study the effects of individual treatments(1). An necessary condition of using such trials is that the effects of treatments be reversible. This is quite plausible when comparing different beta-agonists in asthma, for example. In an educational setting, however, this would mean that students would have to forget what they had previously learned. I have enough confidence in the authors' educational abilities to doubt that this will have been the case.

1. Senn, S.J. Cross-over Trials in Clinical Research, Wiley, Chichester, 1997.

Competing interests: No competing interests

16 May 1998
Stephen Senn
Professor of Pharmaceutical and Health Statistics
University College London
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Re: Secondary prevention in coronary heart disease: baseline survey of provision in general practice John M Rawles, et al. 316:doi 10.1136/bmj.316.7142.1430

I noticed the low usage of lipid lowering agents. Could this be because of the confusion of the upper age limit at which these should be offered? The upper age limit in this trial was 80 which is higher than that used in trials to date. I believe there is also evidence that above a certain age, higher cholesterol is associated with longevity, the reason for which is not clear.(However, nobody has suggested yet that we should ever consider stopping these drugs.)

Competing interests: No competing interests

14 May 1998
M Ramsay
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Re: How should different life expectancies be valued? Norman Waugh, David Scott. 316:doi 10.1136/bmj.316.7140.1316

Diminishing marginal utility of health effects

EDITOR - Recently, Waugh and Scott wrote a letter in which they raised some important questions and proposed to triple or double health effects when total life expectancy is below 6, repectively 12 months taking the ‘duration of life time left’ into account in economic evaluations.1 We feel that they raised a number of issues, in which economic theory may be of help.

Firstly, the principle of attaching more weight to benefits gained when life expectancy is short, seems familiar. This idea corresponds to the economic principle of diminishing marginal utility, reflecting that giving an additional sandwich to someone having few is to be preferred over giving it to someone having many. Applying this principle here implies that giving an additional QALY to a person with a quality adjusted life-expectancy of 20 years, is less valuable than adding one to a person with an expectancy of only 3 months. That this notion implicitly is already used, may be derived from the fact that life-saving lung-transplantation, with a huge costs per QALY, is considered worthwile, while prevention programmes for cholestorol, with much lower costs per QALY are not considered cost-effective. Additionally, the same notion may explain the acceptance of high costs in last year(s) of life, where potential health gains and life-expectancy are oftentimes low. However, we do feel that Waugh and Scott’s proposal to triple or double health effects is as arbitrary as no adjustment and that more research is needed to find the appropriate weights.

Secondly, correcting for diminishing marginal utility may partly solve the problem that persons with a shorter life-expectancy may be more willing to accept a poor quality of life than persons with a longer life-expectancy. However, this also relates to one of the principles underlying QALYs, namely that of constant proportional trade-off, which means that indifference between 10 years in health state A and 5 years in health state B implies indifference between 10 months in A and 5 months in B. Again, more research is needed to indicate how the concept of QALYs should be adapted for situations involving very short life-expectancies.

Finally, in relation to the above, Waugh and Scott mention discounting of future effects. It should be noted that discounting and diminishing marginal utility are two different subjects, with similar consequences, but from completely different backgrounds. Therefore, we feel that they should be treated separately.

Werner Brouwer, Research fellow
Ben van Hout, Senior Research Fellow
institute for Medical Technology Assessment
Erasmus University Rotterdam
PO Box 1738, 3000 DR Rotterdam, The Netherlands
phone: + 31 10 408 8584, fax: + 31 10 452 6086

1 Waugh N, Scott D. How should different life-expectancies be valued? BMJ 1998: 316: 1316

(Word count: text including title 399 words)

Competing interests: No competing interests

14 May 1998
Werner Brouwer
Research Fellow (Brouwer) and Senior Research Fellow (Van Hout)
Ben van Hout
institute for Medical Technology Assessment, Erasmus University Rotterdam, The Netherlands
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Re: How the cycle of poverty and ill health can be broken Dan Kaseje, Martin P Wasserman, et al. 316:doi 10.1136/bmj.316.7142.1456

Great to read in a firstclass journal a long overdue attack on poverty,economic globalisation a root cause of illth.I love working in emergency medicine but we've got to get upstream of the swelling flood of disasters before we all drown! More strength to your arms!

Competing interests: No competing interests

14 May 1998
Paul Appleton
A@E Registrar
Nepean Hospital, Penrith Australia
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Re: Drug treatment in heart failure Richard P Steeds, Kevin S Channer. 316:doi 10.1136/bmj.316.7131.567

We would like to offer an alternative interpretation of the sympathetic overdrive in heart failure.

Malliani and Pagani (1) advanced the hypothesis that the augmented sympathetic outflow in this clinical syndrome could be produced by a "positive" (2)
spinal feed back reflex: a sort of Bainbridge reflex.
The afferent fibres start from the atrial volume-receptors stimulated by an high filling pressure; from the spinal cord arise the efferent sympathetic fibres directed again to the heart where they have an excitatory ("positive") effect: tachycardia. An increased heart rate can not work as a compensatory mechanism in a failed heart: this is particulary true in acute heart failure when the baroreflex can not play a role in sympathetic overdrive.
This interpretation could furnish the basis to explain the effectivness of b-blockers in congestive heart disease: these drugs, infact, reduce the abnormal positive feedback and not only heart rate.

1) Malliani A, Pagani M. Cardiovascular reflexes mediated by sympathetic afferent fibers. Eur Heart J 1983 Jan;4 Suppl A:49-54

2) Pagani M, Pizzinelli P, Bergamaschi M, Malliani A A positive feedback sympathetic pressor reflex during stretch of the thoracic aorta in conscious dogs. Circ Res 1982 Jan;50(1):125-132

Competing interests: No competing interests

13 May 1998
Elisabetta Fabris
Alberto Maestroni
University of Milan
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Re: Lithium James W Jefferson. 316:doi 10.1136/bmj.316.7141.1330

EDITOR-Grof and Schou attempt to explain the discepancies in the evidence about lithium by suggesting that the withdrawal syndrome only occurs in those with more broadly defined bipolar disorder.1 Schou has been an enthusiast for lithium and was involved in an influential double-blind lithium discontinuation study, which had remarkably favourable results for lithium (21 placebo patients relapsed and none on lithium).2 In that study patients were not informed they were in a clinical trial and were deceived into believing they had received tablets from an unreliable batch so that concealed trial medication could be reissued. Although this procedure would now be regarded as unethical because of lack of consent, it does have the advantage that patient expectancies are not created if they remain unaware of the trial. Four placebo patients were excluded from the analysis because for some reason they used some of their old tablets or supplementary lithium from outside sources.

Particular detail was paid to methodological issues because of criticism of the inferences made from previous non-blind trials.3 Patients were matched on total number of previous episodes, and assigned randomly to lithium or placebo, although no details were given of the randomisation procedure. Although it was anticipated that side-effects might compromise the blindness of the trial, and the protocol required that patients with side-effects must be excluded, none were eliminated. Lithium blood results were reported to assessors, but care was reported to have been taken to ensure that fictitious values for the placebo patients approximated to those recorded before the trial and showed variations similar to those found in the patients receiving lithium. No attempt was made to measure the degree of unblinding. Despite the lack of evidence for unblinding or incomplete randomisation it is difficult to believe that bias did not in some way affect the results as they are so strikingly favourable to lithium, particularly in the context of the need to counter criticism at the time and produce an unequivocal answer.

One of the reasons proposed for the striking difference is that all patients had well-diagnosed affective disorders of the endogenous type, the same point about effectiveness as Grof and Schou make about the presence of the withdrawal syndrome. The assumption seems to be that lithium is a specific prophylactic treatment for the biological diseases of manic-depressive and recurrent-depressive disorders. Evidence for lithium withdrawal has not always been found and heightened anxiety, sleep disturbances and irritability have been associated.4 The presence of withdrawal symptoms seems to also be influenced by clinicians and experimenters and not just patients alone. It seems appropriate and timely to propose further research of the implications that drug discontinuation itself contributes to relapse, including the study of nonspecific effects. This is the same conclusion reached by the group, quoted by Grof and Schou, who found that recurrences are greater than before lithium treatment in patients abruptly discontinuing lithium.5

DB Double, Consultant Psychiatrist, Norfolk Mental Health Care NHS Trust, Hellesdon Hospital, Drayton High Road, Norwich NR6 5BE (

1. Grof P, Schou M. Re: Lithium.

2. Baastrup PC, Poulsen JC, Schou M, Thomsen K, Amdisen A. Prophylactic lithium: Double blind discontinuation in manic-depressive and recurrent-depressive disorders. Lancet 1970;ii:326-330

3. Blackwell B, Shepherd M. Prophylactic lithium: another therapeutic myth? Lancet 1968;i:968-971

4. Balon R, Yeragani VK, Pohl RB, Gershon S. Lithium discontinuation: Withdrawal or relapse? Comp Psychiatry 1988;29:330-334

5. Baldessarini RJ, Tondo L, Viguera AC. Forty years of lithium treatment. Arch Gen Psychiatry 1998;55:93

Competing interests: No competing interests

12 May 1998
D B Double
Consultant Psychiatrist
Norfolk Mental Health Care NHS Trust
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Re: Outcome of low back pain in general practice: a prospective study Alan J Silman, et al. 316:doi 10.1136/bmj.316.7141.1356

Dear Sir

The prospective study of low back pain (LBP) in general practice by Croft et al. reminds us of the important fact that non attendance for further care does not equal recovery. They measure morbidity which often remains unrecognised, and their data counter the claim that 90% of patients with LBP have fully recovered by one month.

However, this study is not methodologically robust enough to support the statement that of the non attenders 'most will still be experiencing low back pain and related disability one year after the (index) consultation'. Detailed follow up data analysing patients' experience outside the surgery was only available in a minority of the original group, 170/463 (37%), leaving considerable room for selection bias. Although an attempt was made to quantify this bias, the 'validation group' was too small (44) to be conclusive. Two further factors may have exagerated this bias. Both the original cross sectional survey and the interview process may have altered patients perceptions of their LBP (the Hawthorne effect).

Competing interests: No competing interests

12 May 1998
Alastair Hay
Clinical Lecturer in General Practice
University of Leicester, Leicester General Hospital, Gwendolen Rd, Leicester, LE5 4PW
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Re: Adverse drug reactions Munir Pirmohamed, Alasdair M Breckenridge, Neil R Kitteringham, B Kevin Park. 316:doi 10.1136/bmj.316.7140.1295

EDITOR, - As a pharmacy practice lecturer teaching adverse drug reactions to the pharmacy students, I have found the review article of Pirmohamed et al's 1 to be very informative. I will certainly recommend this article to my students. However, in their article, they defined Type B reactions as idiosyncratic reactions. Professors Rawlins & Thompson who were the originators of Type A and B reactions, did not use "idiosyncratic" as a term to define or describe Type B reaction2. Indeed, Professor Rawlins was against the use of idiosyncrasy as Type B reaction3-4. He referred to the Oxford Dictionary which defines idiosyncrasy" as "abnormal individual sensitivity to a food or drug". Therefore, idiosyncratic adverse reactions, in this context, could equally well be Type A or Type B reaction. I agree with Professor Rawlins that the literature on drug safety is bedevilled by inconsistencies in nomenclature5 and we should try to standardise the terminology.


1 Pirmohamed M, Breckenridge AM, Kitteringham NR, Park BK. Clinical review. Adverse drug reactions. BMJ 1998;316:1295-8.

2 Rawlins MD, Thompson JW. Mechanisms of adverse drug reactions. In: Davies DM, ed. Textbook of adverse drug reactions. Oxford: Oxford University Press, 1991:18-45.

3 Hoigne RV. Should "idiosyncrasy" be defined as equivalent to "Type B" adverse drug reactions [Letter]? Pharmacoepidemiology and Drug Safety 1997;6:213.

4 Rawlins MD. Commentary: Should "idiosyncrasy" be defined as equivalent to "Type B" adverse drug reactions? Pharmacoepidemiology and Drug Safety 1997;6:291.

5 Rawlins MD, Mann RD. Monitoring adverse events and reactions. In: Mann RD, Rawlins MD, Auty RM, eds. A Textbook of Pharmaceutical Medicine. Lancs:Parthenon Publishing Group, 1993:317-22.

Competing interests: No competing interests

11 May 1998
Ian C K Wong
Lectuer of Pharmacy Practice
University of Bradford
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