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molecular determinants and correlates of pain and analgesic response have been demonstrated, and endogenous biochemical and psychological mechanisms of modulation have been continually elucidated. Nonetheless, it is a little disappointing to read a progressive opinion that passes over the ‘whole-body’ pharmacological approach first applied more than 30 years ago. Dionne and colleagues [1] ask the reasonable question: ‘Individual responder analyses for pain: does one pain scale fit all?’ In the same context, is it not reasonable to ask a supplementary question: ‘Individual responder analyses for pain: does one dose fit all?’ References 1 Dionne, R.A. et al. (2005) Individual responder analyses for pain: does one pain scale fit all? Trends Pharmacol. Sci. 26, 125–130 2 Mather, L.E. et al. (1975) Pethidine revisited: plasma concentrations and effects after intramuscular injection. Br. J. Anaesth. 47, 1269–1277 3 Mather, L.E. et al. (1975) Meperidine kinetics in man. Intravenous injection in surgical patients and volunteers. Clin. Pharmacol. Ther. 17, 21–30 4 Glynn, C.J. et al. (1981) Peridural meperidine in man: analgetic response, pharmacokinetics and transmission into CSF. Anesthesiology 55, 520–526
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5 Erstad, B.L. et al. (1997) Site-specific pharmacokinetics and pharmacodynamics of intramuscular meperidine in elderly postoperative patients. Ann. Pharmacother. 31, 23–28 6 Peng, P.W. et al. (2005) Review article: perioperative pain management of patients on methadone therapy. Can. J. Anaesth. 52, 513–523 7 Austin, K.L. et al. (1980) Relationship between blood meperidine concentrations and analgesic response. Anesthesiology 53, 460–466 8 Austin, K.L. et al. (1980) Multiple intramuscular injections: a major source of variability in analgesia response to meperidine. Pain 8, 47–62 9 Glynn, C.J. and Mather, L.E. (1982) Clinical pharmacokinetics applied to patients with intractable pain: studies with pethidine. Pain 13, 237–246 10 Klepstad, P. et al. (2005) Genetic variability and clinical efficacy of morphine. Acta Anaesthesiol. Scand. 49, 902–908 11 Hill, H.F. and Mather, L.E. (1993) Patient-controlled analgesia: pharmacokinetic and therapeutic considerations. Clin. Pharmacokinet. 24, 124–140 12 Woodhouse, A. and Mather, L.E. (2000) The minimum effective concentration of opioids: a revisitation with patient controlled analgesia fentanyl. Reg. Anesth. Pain Med. 25, 259–267 0165-6147/$ - see front matter Q 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tips.2005.09.001
Homeopathy: a complementary view Elaine Weatherley-Jones Health Services Research, School of Health and Related Research, University of Sheffield, Regent Court, 30 Regent Street, Sheffield S1 4DA, UK
I was disappointed to read Professor Ernst’s opinion of the evidence base for homeopathy (published in this issue of Trends in Pharmacological Sciences [1]) because he did not discuss some of the interesting questions that have arisen from research in homeopathy. In addition, he did not take the opportunity to inform a readership, who are probably unfamiliar with the processes of homeopathic treatment, that homeopathy is a profoundly more complex intervention than simply prescribing a medicine. The features of homeopathic treatment have important implications for the design and interpretation of trials (are placebo trials of homeopathy a genuine test of the intervention?) and also for treatment (is there something about the ‘placebo effect’ in homeopathy that is unique to homeopathy?). The homeopathic consultation is a purposeful enquiry into physical, emotional and mental symptoms and wellbeing, and has a particular structure and intention, including the prescription of a homeopathic medicine. During individualised homeopathic treatment for chronic conditions, the patient and practitioner review symptoms periodically, and the form and content of the consultation is influenced by the patient’s earlier reaction to Corresponding author: Weatherley-Jones, E. (
[email protected]). Available online 16 September 2005 www.sciencedirect.com
homeopathic medicines (remedies): that is, the specific effects of remedies can have an impact on practitioner conduct. The specific effects of an intervention are those that are considered to cause the outcomes of treatment and are unique to a specific therapeutic modality, for example, a drug. Nonspecific effects, such as the credibility of the practitioner and the setting of treatment, are those that form the context within which the specific effect is applied, and also affect the outcome. Kleijnen et al. [2] documented the interaction between the specific effects of treatment and the nonspecific effects and illustrated that these are not independent of each other and each can moderate the impact of the other. For example, one study showed that the method of administering naloxone (an opioid peptide receptor antagonist) to patients with impacted third molars affected the outcome [3]. Patients given naloxone by a person at the bedside (open infusion) or a person in an adjacent room (hidden infusion) experienced more pain than those receiving vehicle, whereas patients who received vehicle by a preprogrammed infusion pump experienced more pain than those who were given naloxone by the same route. Kleijnen and colleagues explain that the nonspecific effects have turned a specific effect from positive to negative. The placebo randomized controlled trial (RCT)
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cannot measure such interactions, and thus we should be cautious in using the double-blind placebo RCT as a satisfactory test of individualised homeopathy. Placebo trials for testing the efficacy of a single component of a complex intervention are potentially flawed [4] and can result in misleading interpretations of data. This might, in part, explain the paradox that, although trials of homeopathic treatment have not yet provided unequivocal evidence for the efficacy of remedies, there are many reports of clinical benefit. It seems premature to dismiss homeopathic treatment as ‘no more’ than placebo without having explored the nature of such nonspecific benefits. Characteristic effects of homeopathic treatment that are of significant clinical benefit and are due neither to the remedies nor to a general effect of time and attention might exist. For example, the structure and content of a homeopathic consultation, although not rigidly defined, have features that are unique to homeopathy and are necessary for the homeopath to decide on an appropriate prescription. Current research in homeopathy using methods from medical anthropology, sociology and psychology are currently underway, and clinical benefits have been reported recently. For example, ‘CAM [complementary and alternative medicine] appears to serve a variety of functions beyond the explicit relief of symptoms.[and] it is important that these wider effects are taken into account when evaluating complementary medicine’ [5]. The high dilution of solutes in the preparation of remedies means that, for many observers, homeopathic medicine is implausible and cannot possibly have any direct effect. However, evidence from in vitro studies [6,7] ‘[show] that high dilutions of histamine may indeed exert an effect on basophil activity’ [6]. These studies, although not directly testing homeopathy, show that it is possible for highly diluted substances to retain the potential to affect biological systems. It is laudable that Ernst raises the issues of safety of homeopathic treatment and the issue of CAM practitioners preventing effective interventions should be addressed to see whether this does happen. The Society of Homeopaths does not encourage its members to advise against vaccination but issues the following guidance to the general public: ‘The Society acknowledges that there is much anecdotal and scientific evidence to support the
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arguments presented for and against vaccination.The Society believes that parents should be supported in making informed decisions on the short and long-term implications of vaccination.’ Peter Fisher, Vice-president of the Faculty of Homeopathy and Clinical Director of the Royal London Homeopathic Hospital is quoted as saying: ‘People who claim homeopathy is against immunisation are not in the homeopathic tradition.’ [8] It is interesting that Ernst refers to ‘homeopathic aggravations’, the phenomenon where, having taken a homeopathic remedy, the patient produces an overreaction to the remedy such that a ‘healing crisis’ occurs. The existence of such ‘adverse effects’ is inconsistent with the thesis that homeopathic remedies are placebos: an inert substance cannot directly cause an adverse effect. Thus, Ernst’s view that the potential benefit of homeopathic treatment (which is due only to the placebo effects) is outweighed by its potential harm (which must be due to aggravations) appears to be logically inconsistent. In summary, until appropriate research methods are applied to homeopathy to provide descriptive data and to test hypotheses fairly, it is premature to dismiss homeopathy as a potentially beneficial treatment. References 1 Ernst, E. (2005) Is homeopathy a clinically valuable approach? Trends Pharmacol. Sci., 26. doi: 10.1016/j.tips.2005.09.003 2 Kleijnen, J. et al. (1994) Placebo effect in double-blind clinical trials: a review of interactions with medications. Lancet 344, 1347–1349 3 Levine, J.D. and Gordon, N.C. (1984) Influence of the method of drug administration on analgesic response. Nature 312, 755–756 4 Weatherley-Jones, E. et al. (2004) The placebo-controlled trial as a test of complementary and alternative medicine: observations from research experience of individualised homeopathic treatment. Homeopathy 93, 186–189 5 Cartwright, T. and Torr, R. (2005) Making sense of illness: the experiences of users of complementary medicine. J. Health Psychol. 10, 559–572 6 Belon, P. et al. (2004) Histamine dilutions modulate basophil activation. Inflamm. Res. 53, 181–188 7 Belon, P. et al. (1999) Inhibition of human basophil degranulation by successive histamine dilutions: results of a European multi-centre trial. Inflamm. Res. 48, S17–S18 8 Sampson, V. (2002) Val A less painful choice? The Times 19 December, p. 2 0165-6147/$ - see front matter Q 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tips.2005.09.004
Free journals for developing countries The WHO and six medical journal publishers have launched the Access to Research Initiative, which enables nearly 70 of the world’s poorest countries to gain free access to biomedical literature through the Internet. The science publishers, Blackwell, Elsevier, the Harcourt Worldwide STM group, Wolters Kluwer International Health and Science, Springer-Verlag and John Wiley, were approached by the WHO and the British Medical Journal in 2001. Initially, more than 1000 journals will be available for free or at significantly reduced prices to universities, medical schools, research and public institutions in developing countries. The second stage involves extending this initiative to institutions in other countries. Gro Harlem Brundtland, director-general for the WHO, said that this initiative was ’perhaps the biggest step ever taken towards reducing the health information gap between rich and poor countries’. See http://www.healthinternetwork.net for more information. www.sciencedirect.com
