Rapid Responses to:
|
|
Rapid Responses: Rapid Responses published:
-
![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
Postmarketing surveillance is present in the UK, but under-used
- John S Watts (2 July 2004)
-
Epidemiologists’ long-term underestimation of harm from hormones
- Ellen C G Grant (3 July 2004)
-
"Bangs for backfires" - a useful measure of benefits and harms? E.g. Rosuvastatin.
- David R Purdy (5 July 2004)
-
Randomized controlled trials: the hijacking of basic sciences by mathematical logic
- Vinod K Gupta, M.D. (6 July 2004)
-
Research and practice - two sides of same coin
- Arun S Nanivadekar (7 July 2004)
-
Re: Randomized controlled trials: the hijacking of basic sciences by mathematical logic
- Ellen C G Grant (8 July 2004)
-
Re: Re: Randomized controlled trials: the mythical hypomagnesaemia -- intrinsic noradrenergic activation -- cortical spreading depression nexus in migraine
- Vinod K Gupta, MD (8 July 2004)
-
Re: Re: Re: Randomized controlled trials: the mythical hypomagnesaemia -- intrinsic noradrenergic activation -- cortical spreading depression nexus in migraine
- Ellen C G Grant (9 July 2004)
|
|
|||
|
John S Watts, Locum Associate Specialist, Child Psychiatry CAMHS Dartford. Unit 1 Twisleton Court, Dartford DA1 2EN
Send response to journal:
|
EDITOR - I read with interest the letter by Srinivas in this week's issue (BMJ 2004;329;51 (3 July)). I agree with the request for a central body to collect adverse drug reaction data and communicate to all doctors. The United Kingdom has a system in place whereby prescribers should report "Suspected adverse reactions to any therapeutic agent ..." (BNF 47 page 10)to a central agency (the MHRA), which then communicates with prescribers - the so-called Yellow Card system. Such a system is not present in many other countries, and provides valuable data regarding adverse drug reactions. However, I understand the response rate is rather low. There is also a bias for reporting severe or unusual reactions, and also for reactions to newer treatments. Until such reporting becomes more widespread and routine, and present in all countries, the data collected will remain unrepresentative of the true picture. This subject is touched upon in the editorial by Vandenbroucke in the same issue (BMJ 2004;329:2-3 (3 July)), where there is a discussion of observational and randomised studies and their collection of data. The problem with relying on clinical studies to produce data regarding adverse drug reactions is one of numbers and representation. The number of patients exposed to drugs in studies is obviously far smaller than the number of patients who take the drug - a problem when a reaction is rare. Additionally, there is also often a difference in studied patient groups and the groups that receive the treatment in the wider community. Until a worldwide adverse drug reaction reporting scheme is in place, delays will occur in the reporting and recognition of serious adverse treatment events. Competing interests: JW worked for a pharmaceutical company for 3 years |
|||
|
|
|||
|
Ellen C G Grant, physician and medical gynaecologist 20 Coombe Ridings, Kingston-upon-Thames, KT2 7JU, UK
Send response to journal:
|
I think it extraordinary that epidemiologists, who have been consistently miscalculating the risks of hormone use since the 1960s, to the detriment of millions of women world-wide, should now be congratulating themselves, on belatedly getting it right. Jan Vandenbourke credits Skegg and Doll with the recommendation in 1977 that all adverse effects should be monitored in a randomised trial.1 The original Family Planning Association’s Council for the Investigation of Fertility Control oral contraceptive trial in the UK, which was started in 1962, attempted to record every single event. Women kept records and every headache, bleeding, and pill consumed, was written down daily. The results of testing seven progesterones and two oestrogens were so disastrous that, although published in the BMJ and Lancet, the evidence was virtually never referred to again. It was clear that the formulations most likely to cause headaches and migraine were also more likely to cause more serious vascular events like strokes and heart attacks. The endometrial pathology, which was examined before, after and at six monthly intervals duration exposures, clearly showed an adverse effect on blood vessels in women having vascular adverse reactions. In my annonymous Editorial for the BMJ in 1969 I said that it was unlikely that merely changing strengths and doses of hormones could solve the problems, because these were an inevitable part of hormone use with peak complaints varying with different hormone balances.2 In 1971 Vessey, Doll and Sutton published a paper claiming that oral contraceptives prevented benign breast disease.3 The evidence was that significantly fewer longer users had breast disease. This ignored the fact that sore breasts and vascular reactions were reasons for early discontinuation. More of the longer pill takers had breast cancer but the study was too small for this to be statistically significant. The flawed “prevention” reasoning prevailed and gave rise to equally spurious claims of hormone use preventing heart disease and ovarian and endometrial cancers. What followed was basic research into how hormone use caused immunosuppression, and therefore an increase in all illnesses, was sidelined and ignored. An exact “safe” hormone balance was sought for individual conditions that could be neutralised, for example by finding a combination of HRT that would not cause endometrial hyperplasia and endometrial cancer, even although a progesterone dominant combination is more likely to cause breast cancer. As oestrogens and progesterones can have opposite effects on fat levels, years were spent in finding “beneficial” combinations. The aim seemed to be to claim as many “benefits” as possible in numerous epidemiological international trials, whether observational or randomised, without actually investigating what was really happening by using the most informative tests. 1. Vandenbroucke JP. Benefits and harms of drug treatment. BMJ 2004; 329: 2- (3 July), doi:10.1136/bmj.329.7456.2 2. Grant ECG. Changing oral contraceptives. Editorial BMJ 1969; 4; 789-91. 3. Vessey MP, Doll R, Sutton PM. Investigation of the possible relationship between oral contraceptives and benign breast disease. Cancer 1971: 28: 1395-99. Competing interests: None declared |
|||
|
|
|||
|
David R Purdy, GP prescribing lead, Northamptonshire Heartlands PCT Rushden Medical Centre, Adnitt Rd, Rushden. NN10 9TR.
Send response to journal:
|
In his editorial, Jan Vandenbroucke discusses the importance of observational data in relation to assessing drug safety.1 On 26th June, The Lancet published a letter from Sidney Wolfe of Public Citizen calling for the withdrawal of Rosuvastatin2 that made UK national news.3 This seems premature and based on incomplete consideration of risk and benefit, but represents a contemporary (if flawed) attempt to incorporate later observational data into a view based on existing trial data. A simple and intelligible measure allowing meaningful comparisons between “me-too” drugs is clearly needed. Using the rhabdomyolysis and script volume data Wolfe reports for the US market,2 I estimate a rate of between 8 - 20 cases per million scripts in the first full year for the 10mg dose, the low end of the range being most likely (unless reports increase). Since rhabdomyolysis is a dose- related side-effect, comparison of statin strengths equipotent in reducing LDL-C would be logical, whereas the crude rates of the other statins reported by Wolfe are very likely skewed downwards by their lower efficacies. Not to be forgotten is an established death rate from statin- induced rhabdomyolysis of 1 per 10 million scripts.4 In these consumer days of “bangs for bucks”, we surely need to be comparing “bangs for backfires” as well; serious vascular events avoided for each serious adverse event incurred through statin treatment. A 10y CHD risk of 30% is a reasonable indication for a statin. If 1mM decrease in LDL-C reduces CHD events by at least 33% from the 3rd year of treatment5 and Rosuvastatin 10mg daily reduces LDL-C by 2.1mM,5 then 10y CHD risk would be reduced to around 10%. So if 10,000 patients were treated for 10 - 12 years, current data would imply around 2,000 avoided CHD events (including deaths) at a cost of 8 – 20 cases of rhabdomyolysis – better than 100:1 “bangs for backfires”, but in need of consideration by both patient and clinician. Some patients will want higher benefit at higher risk, or will require so to reach treatment targets. So does the market need another statin? Well, yes, if it can better address the needs of higher risk patients at an acceptable level of extra risk. In the UK, only Atorvastatin and Rosuvastatin currently achieve LDL -C reductions greater than 50%. That sector of the market (our highest risk patients) is probably not best served by a single product. Their UK pricing structures clearly reveal the value of competition to the NHS. More robust and comparable safety data are required, together with meaningful ways of communicating treatment risk. (Above estimations are presented in good faith for purpose of example and argument only.) 1 Vandenbroucke JP. Benefits and harms of drug treatments. BMJ 2004; 329: 2-3. 2 Wolfe SM. Dangers of rosuvastatin identified before and after FDA approval. Lancet 2004; 363: 2189-90. 3 http://news.bbc.co.uk/1/hi/health/3838915.stm 4 Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis. N Engl J Med 2002; 346: 539-40. 5 Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 2003; 326: 1423-30. Competing interests: None - unless as a result of a future prescribing incentive scheme |
|||
|
|
|||
|
Vinod K Gupta, M.D., Physician, Dubai Police Medical Services, Dubai, United Arab Emirates P.O. Box 12005, Dubai, United Arab Emirates
Send response to journal:
|
The randomized controlled trial (RCT) has embedded itself into the psyche of the medical researcher as the evidentiary gold standard, which inclination is not entirely without justification. Vandenbroucke’s editorial,1 nevertheless, does not allude to any of the significant limitations of the RCT.2,3 By unquestioningly embracing mathematical logic, the RCT has empowered the clinical investigator to ignore the logic of the basic sciences. No longer is it necessary to evolve a logically defensible theoretical background, because whatever the numbers tell us is the truth. Mathematical logic, however, is itself incomplete.4 Herein lies the unexposed Achilles heel of the RCT, one of the major factors for the flight of clinical research from basic sciences and reason. Rennie bemoans the quality of published papers.5 In effect, mathematics has hijacked biological sciences. Questioning the validity of the premise or performance of the RCT evokes surprise and is often regarded as being unnecessarily contentious in clinical circles. Just like democracy reigns for want of a better political system, the final decapitating scorn heaped on those who remain biologically attuned rather than being overawed mathematically is the challenge and the onus of offering a better investigative “system”. No longer are scientists immersed in the disinterested pursuit of the truth.6 Now investigators purse and publish papers; the truth can take care of itself at its own pace in its own time. In direct contrast to Vandenbroucke’s assertion,1 small effects of treatment will never be resolved by the RCT. The success of the RCT depends on sharply defined end-points such as death in acute myocardial infarction or definitive decline in cognition in Alzheimer’s disease.2,3 Symptomatic well-being, including pain is less suited for the RCT. Migraine is a classic example where the RCT is being used without restraint and without regard to pharmacological absolutes.7 Trials of use of magnesium supplementation for prophylaxis of migraine headache or aura are absolutely without any theoretical basis.8,9 RCTs of botulinum toxin (BT) -- completed and ongoing -- for prevention of migraine for up to 3 months or longer ignore: (i) the inability of BT to cross the blood-brain barrier to influence brain / brain stem function or aura of migraine as well as the short-lasting analgesic behaviour in animals lasting maximally up to 2 weeks;10 (ii) the absence of dose-dependent responses in migraine patients,11 (iii) absence of direct or genuine peripheral antinociceptive effect in humans;12-14 and (iv) the ability of donepezil, with effects on cholinergic function that are diametrically opposite to BT, to provide effective prophylaxis comparable to propranolol.15 Migraine research resonates, unfortunately in reverse, with the mathematical power of statistics that in turn power the RCT. A subtle double standard is always at work in medicine, making the envisaged “marriage” of RCT and observational studies1 less likely than a mirage. Highly critical of data of others, scientists rarely maintain a healthy criticism of their own data. Remarkably, Watson and Crick excelled in and questioned different areas of research, reviewed critically and dampened each other’s over-enthusiasm, or appropriately spurred each other on.16 The need for a RCT or sham-lumbar puncture (LP) was never felt while recommending LP for benign-cough induced headache for approximately five decades.17 As long as the scientist or the research group or the institution or the pharmaceutical industry is perceived as being more important than science itself, the RCT will remain as a frequently misused tool for shoddy science and self-serving activities. Just like democracy without recall, RCT without acknowledgement of possibility of initial conceptual error (not terminal cosmetic methodological end-of-study excuses, as is commonly practiced) is a farce. Whenever challenged in correspondence columns, the protagonists of the RCT muster their collective formidable intellectual clout to obfuscate or to equivocate or to maintain (un)dignified silence. Because the RCT is performed by humans on humans, the scope for error is endless. It is, perhaps, too much to expect any researcher to contribute willingly (or even grudgingly) in the crucifixion of a personal or favoured scientific belief, but an uncompromising search for the truth precisely demands just that. References: 1. Vandenbroucke JP. Benefits and harms of drug treatments. BMJ 2004;329:2-3. 2. Gupta VK. Randomized controlled trials versus clinical realities: prostate cancer screening. BMJ [Online] 11 February 2004. Available at: http://bmj.bmjjournals.com/cgi/eletters/328/7435/301#50002 3. Gupta VK. Donepezil and Alzheimer’s disease: seeking simplistic therapies for a complex disorder. BMJ [Online] 2 July 2004. Available at: http://bmj.bmjjournals.com/cgi/eletters/329/7456/9-a#65621 4. Sleigh JW. Evidence-based medicine and Kurt Godel. Lancet 1995;346:1172. 5. Rennie D. Editors and authors. JAMA 1989;261:2543-45. 6. Kassirer JP. The frustrations of scientific misconduct. N Engl J Med 1993;328:1634-36. 7. Gupta VK. Migraine following haemorrhage in brain stem cavernous angioma: pathophysiological considerations. Published electronic response to Afridi S, Goadsby PJ. New onset migraine with a brain stem cavernous angioma. J Neurol Neurosurg Psychiatry 2003;74: 680-1. Available at: http:www.jnnp.com/cgi/eletters/74/5/680#55 8. Gupta VK. Management of migraine aura: basic theoretical and clinical reconsiderations. Headache (In press). 9. Gupta VK. Magnesium therapy for migraine: do we need more trials or more reflection? Headache 2004;44: 445. 10. Cui M, Khanijou S, Rubino J, Kei Roger Aoki KR. Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. Pain 2004;107:125-33. 11. Silberstein S, Mathew N, Saper J, Jenkins S. Botulinum toxin type A as a migraine preventive treatment. Headache 2000;40:445-50. 12. Voller B, Sycha T, Gustorff B, et al. A randomized, double-blind, placebo controlled study on analgesic effects of botulinum toxin A. Neurology 2003;61:940-4. 13. Kramer HH, Angerer C, Erbguth F, Schmelz M, Birklein F. Botulinum Toxin A reduces neurogenic flare but has almost no effect on pain and hyperalgesia in human skin. J Neurol 2003;250:188-93. 14. Blersch W, Schulte-Mattler WJ, Przywara S, May A, Bigalke H, Wohlfarth K. Botulinum toxin A and the cutaneous nociception in humans: a prospective,double-blind, placebo-controlled, randomized study. J Neurol Sci 2002;205:59-63. 15. Nicolodi M, Galeotti N, Ghelardini C, Bartolini A, Sicuteri F. Central cholinergic challenging of migraine by testing second-generation anticholinesterase drugs. Headache 2002;42:596-602. 16. Watson JD. The double helix. New York: Signet Books, New American Library, 1968. 17. Gupta VK. Is benign cough headache caused by intraocular haemodynamic aberration? Med Hypotheses. 2004;62:45-48. Competing interests: None declared |
|||
|
|
|||
|
Arun S Nanivadekar, Independent Medical Research Consultant C-2 Flushel Apts, 21 Road, Bandra (W), Mumbai 400050, India
Send response to journal:
|
Research is an attitude combined with purposeful activity to back it. I believe practice with an open and curious mind, and the desire to make and record observations of planned or unplanned interventions, is at the heart of research. Every practising doctor has access to patients who are unique in some way, and an opportunity to do the so-called n-of-1 trials of modern and alternative interventions in an effort to help the patient achieve his own health goals. Cultivating the habit to document such observations or n-of-1 trials in a standardized manner can help generate a vast amount of information that is unfortunately lost to medicine. Internet has now made it possible to form worldwide networks of doctors who are interested in some specific area of their practice: be it prevalence, incidence, exposure to risk factors, new drugs, new diagnostic tests, new procedures, alternative therapies, outcome of an intervention, or whatever. If an individual or an organization can but act as a catalyst to help these doctors identify their area of interest, form a virtual network, and get on with building up their information base, what a wealth of evidence would it create for everyone! This would also take care of the limitations of randomized controlled trials, such as a highly selected sample and poor generalizability of conclusions. It would also be the most fecund fountainhead of new discoveries, as it has been in the past. But again, this finally depends on people - both doctors and patients: the purpose with which doctors take up their careers, the purpose with which patients see their doctors, how much they try to understand the strengths and limitations of each other, and how freely a community allows them to do so. Competing interests: None declared |
|||
|
|
|||
|
Ellen C G Grant, physician and medical gynaecologist 20 Coombe Ridings, Kingston-upon-Thames, KT2 7JU, UK
Send response to journal:
|
EDITOR – I agree partly with Vinod Gupta’s response to Jan Vandenbroucke’s Editorial. Epidemiologists have often misused mathematics in both observational and in Randomised Controlled Trials to hijack basic science.1 However, I disagree with him that there is lack of scientific evidence for supplementing with magnesium to prevent migraine. Migraine attacks signal disturbed biochemistry. Zinc and/or magnesium deficiencies are usual in most illnesses including migraine and recurrent headaches and are readily diagnosed from red blood cell or white blood cell estimations respectively.2-4 As enzyme co-factor deficiencies appear to increase adverse reactions to common foods and chemicals, it is important to confirm repletion of magnesium and zinc deficiencies.2 To consider a Randomised Controlled Trial of magnesium repletion, without first determining whether magnesium is deficient, seems unscientific to me. Migraine is not due to deficiency of any of the numerous drugs listed by Stephen Silberstein.5 Most migraine attacks occur in women in their child-bearing years, which should contraindicate drug use, as about one in three pregnancies are unplanned. Repletion of essential nutrient deficiencies is an important part of preconception care for the benefit of both mother and child. Women are more susceptible to migraine attacks than non-smoking men probably because of vascular changes, premenstrually, in early pregnancy and when they take hormones or medications derived from the oestrogenic ergot fungus. A key discovery in the 1970s was that the most frequent and severe migraine attacks occurred in patients taking ergot medications, OC (or HRT) steroids or smoking.6 Groups of 30 patients each achieved a ten-fold reduction in monthly migraine attacks when these major precipitants were discontinued. Stopping use of progestagens and oestrogens (OCs or HRT) reduced migraine attacks from 424 to 34, stopping ergotamine from 530 to 52 and stopping smoking from 169 to 16. All patients were also advised to avoid cheese, chocolate, citrus food and alcohol and this reduced migraine attacks from 127 to 67 in the non- user control group. 60 residual patients with headaches followed individually tailored low-allergy high-protein diets. Wheat was the commonest “hidden allergen” to be unmasked after exclusion dieting. All had fewer headaches and 85% became headache free. 15 patients with hypertension became normotensive. Patients took an average of 115 tablets per month before the exclusion diets but 0.5 of a tablet afterwards.7 Pregnancy and exogenous progestagens and oestrogens lower zinc and magnesium concentrations and increase copper concentrations. Copper deficiency is also common among past hormone users and can usually be diagnosed by a blood superoxide dismutase function test. Correcting deficiencies helps to ensure normal cell membrane transport, efficient immune function and balanced cytokine production.8 Tolerance to foods and chemicals improves when nutritional deficiencies have been repleted. Unless these easily reproducible scientific findings, involving the relation between migraine and food allergy, exogenous hormones and smoking and nutritional deficiencies, are taken into account, Randomised Control Trials of magnesium supplementation for migraine prevention could produce misleading and confusing results. Furthermore, severely magnesium deficient patients can have adverse reactions to parenteral magnesium. Basic laboratory investigations need to be included for sense and safety. Ellen C G Grant 20 Coombe Ridings, Kingston-upon-Thames, Surrey KT2 7JU, UK (e-mail: ellencggrant@onetel.net.uk) 1 Vandenbroucke JP. Benefits and harms of drug treatments. BMJ 2004;329:2-3. 2 Grant ECG. The pill, hormone replacement therapy, vascular and mood over- reactivity, and mineral imbalance. J Nutr Environ Med 1998; 8: 105-116. 3 Thomas J, Thomas E, Tomb E. Serum and erythrocyte magnesium concentrations in migraine. Magnesium Res 1990; 5: 127-30. 4 Howard J HM. Serum leucocyte, sweat, and hair levels – a correlation study. J Nutr Med 1990; 1 :119-26. 5 Silberstein SD. Migraine. Lancet 2004: 363: 381-91. 6 Grant ECG .Food allergy and migraine. Lancet 1979; 2: 358-59. 7 Grant ECG. Oral contraceptives, smoking, migraine, and food allergy. Lancet 1978; 2:581-582. 8 Sherman AR. Immune dysfunction in iron, copper, and zinc deficiencies. In: Bodgen JD, Klevay LM, eds. Clinical Nutrition of the Essential Trace Elements and Minerals: The Guide for Health Professionals. Totawa, NJ: Humana Press Inc., 2000: 309-331. Competing interests: None declared |
|||
|
|
|||
|
Vinod K Gupta, MD, Physician Dubai Police Medical Services, P.O. Box 12005, Dubai, United Arab Emirates
Send response to journal:
|
Grant offers persuasive defence of the practice of magnesium (Mg) supplementation for prevention of migraine headache. Mg deficiency has been unequivocally established in migraine; at least this aspect is not unscientific, as alluded to by Grant. Nevertheless, Mg deficiency: (i) is not specific to migraine, but a part of the complex, well-orchestrated neuroendocrine-metabolic response to stress in general; and (ii) can neither explain the characteristic lateralization (unilateral, bilateral, or side-shift) of headache nor the typical onset and offset of headache, especially the phenomenon of post-stress migraine headache.1 Moreover, Grant underscores Mg deficiency in pregnancy, but classic or common migraine that begins during pregnancy usually subsides within 3 months.2,3,4 Third, no study has compared the levels of brain Mg of migraine patients against those in significantly stressful clinical situations but without headache. Fourth, as a vasodilator, Mg mirrors the action of nitroglycerine—the human experimental model of migraine. Finally, transport of Mg from blood to cerebrospinal fluid (CSF) across the blood-brain barrier (BBB) is limited in normal humans; intravenous administration of magnesium sulfate does not increase CSF Mg concentration.5 Orally or intravenously administered Mg, therefore, cannot affect brain neuronal function or cortical spreading depression (CSD). 6 In migraine patients, Mg deficiency is believed to trigger CSD.7 CSD is a powerful yet largely benign stimulus that acutely is capable of providing long-lasting ischemic tolerance probably through ischemic preconditioning; there is little evidence to support the popular belief that CSD is an important brain pathophysiological mechanism.8 Insofar as migraine pathophysiology is concerned, the ability of atenolol – that does not cross BBB – to prevent migraine with or without aura heralds the demise of the popular neurological theoretical concept of CSD.9 Even if the BBB permeability of Mg is regarded as a debatable issue, the pathogenetic focus on hypomagnesaemia is maintained at the expense of ignoring fundamental clinical features and pharmacological absolutes. A series of loosely connected assumptions currently constitutes migraine pathophysiology.10 The onus of elucidating the specific mechanisms – other than a vague / non-specific “cellular well-being” -- through which Mg repletion predictably and invariably(?) remits migraine rests with the proponents of the theory. References 1. Gupta VK. Magnesium therapy for migraine: do we need more trials or more reflection? Headache 2004; 44: 445. 2. Critchley M, Ferguson FR. Migraine. Lancet 1933; 1:123-6. 3. Massey EW. Migraine during pregnancy. Obstetric Gynecol 1977;32:693-6. 4. Gupta VK. A clinical review of the adaptive role of vasopressin in migraine. Cephalalgia 1997;17:561-9. 5. Ko SH, Lim HR, Kim DC, Han YJ, Choe H, Song HS. Magnesium sulfate does not reduce postoperative analgesic requirements. Anesthesiology 2001;95: 640-6. 6. Gupta VK. Management of migraine aura: basic theoretical and clinical reconsiderations. Headache (In press). 7. Welch KMA, D’Andrea G, Tepley N, et al. The concept of migraine as a state of central neuronal hyperexcitability. Neurol Clin 1990;8:817-28. 8. Gupta VK. Cortical spreading depression is neuroprotective: the challenge of basic sciences. Headache (In press). 9. Gupta VK. Non-lateralizing brain PET changes in migraine: phenomenology versus pharmacology? Brain. (Online publication in response to Matharu MS, Bartsch T, Ward N, Frackowiak RSJ, Weiner R, Goadsby PJ. Central neuromodulation in chronic migraine patients with suboccipital stimulators: a PET study. Brain Advance Access published on January 1, 2004, DOI 10.1093/brain/awh022. Brain 127: 220--30 [In press]. 10. Gupta VK. Bureaucratisation of migraine. Lancet Neurol 2004;3: 396. Competing interests: None declared |
|||
|
|
|||
|
Ellen C G Grant, physician and medical gyanecologist 20 Coombe Ridings, Kingston-upon-Thames, KT2 7JU, UK
Send response to journal:
|
EDITOR - I would be the last person to deny that pregnancy changes the risk of migraine as Vinod Gupta comments in his second response to Jan Vandenbroucke’s Editorial, which includes the harms and benefits of hormone therapy.1 My first pregnancy was heralded by an alarming hemianopia, when I could only see half of a tree during a walk after Sunday lunch. I had cooked a roast using gas in a basement flat. The prodromal visual disturbances were followed by a sickenly severe migraine. Three times, with each pregnancy, I endured sickness, vomiting and headaches. Although working at the time in the Obstetrics Department and Fertility Clinic at University College Hospital, I was not told that these symptoms were likely to be due to nutritional deficiencies and accumulated toxic metals, such as dental mercury, precipitating over-reactions to common foods and chemicals. It is now 45 years later and how many pregnant women are given this information? The appropriate diagnostic tests are now available. Such valuable knowledge can not only help prevent pregnancy symptoms but can also minimise health problems in the children. Like most pregnant women at 12-14 weeks, when the placenta began to take over the production of higher levels of immunosuppressant steroid hormones, both the sickness and headaches stopped. However, during the 10 years I worked at Charing Cross Migraine clinic, one woman had suffered such severe daily migraine attacks that she had been given pethedine throughout her entire pregnancy. When she followed the high protein, low- allergy diet which is described in my “Food allergy and migraine” paper, her next pregnancy was completely pain-free.2 It is the immunosuppressive actions of progesterones and oestrogens that have caused the confusion over the harms, and now unsubstantiated medical benefits, of contraceptive and menopausal hormone use. Taking hormones can increase harmful nutritional deficiencies while simultaneously suppressing warning symptoms like headaches. It is not generally agreed that magnesium does not pass through the blood brain barrier and it is the second most abundant cation in neurones. The best defined manifestation of magnesium deficiency is impirment of neuromuscular function; examples include hyperirritability, tetany, convulsions, and electrocardiographic changes. I do not use parenteral magnesium therapy as adverse reactions can occur, especially when magnesium has been chronic. I prefer to supplement magnesium orally. It can take several weeks or months to normalise sweat and red cell magnesium levels and selenium supplementation may also be required.4 Magnesium deficiency is common in hormone takers and absorption problems may need treating. Magnesium is an essential co-factor more than 300 enzymes and no one should be deficient. However, magnesium deficiency is so common that it is found in numerous conditions. This fact is not an argument against magnesium deficiency contributing, along with the equally common zinc, copper, B vitamins and essential fatty acid deficiencies, to headaches and migraine by increasing adverse reactions to common foods and chemicals. All essential nutrients are required for normal cell functioning. What is so difficult to understand? A single cause and a single magic bullet for every single medical condition may be a pharmacologist or microbiologist’s dream but the dominance of such thinking has given nightmares to many of us. 1 Vandenbroucke JP. Benefits and harms of drug treatments. BMJ 2004;329:2-3. 2 Grant ECG .Food allergy and migraine. Lancet 1979; 2: 358-59. 3. McLaren Howard J, Davies S, Hunnisett AG. Red cell magnesium and glutathione peroxidase in infertile women – effects of oral supplementation with magnesium and selenium. Mag Res 1994; 7: 49-57. Competing interests: None declared |
|||