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animal studies should be acknowledged, since some PBM has received payment for lectures or advisory board membership from reports11 have suggested that rimonabant might have AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, and Lundbeck in the past 3 years. MJM declares that she has no confl ict of interest.
antidepressant or anxiolytic actions. Another obser- Di Marzo V, Matias I. Endocannabinoid control of food intake and energy vation that might provide an alternative physio logical balance. Nat Neurosci 2005; 8: 585–89.
Cooke D, Bloom S. The obesity pipeline: current strategies in the development basis for increased mood disorders seen with greatest of anti-obesity drugs. Nat Rev Drug Disc 2006; 5: 921–31.
weight-loss comes from evidence that leptin, the 3 Curioni C, Andre C. Rimonabant for overweight or obesity. Cochrane Database
Syst Rev 2006; 4: CD006162.
adipose-derived hor mone, had an antidepressant action 4 Padwal RS, Majumdar SR. Drug treatments for obesity: orlistat, sibutramine, after intrahippocampal but not hypothalamic injec tion.12 and rimonabant. Lancet 2007; 369: 71–77.
Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A. Effi However, direct clinical correlates are diffi safety of the weight-loss drug rimonabant: a meta-analysis of randomised What is the signifi cance of the fi ndings reported by trials. Lancet 2007; 370: 1706–13.
Onyike CU, Crum RM, Lee HB, et al. Is obesity associated with major Christensen and colleagues? First, their meta-analysis has depression? Results from the Third National Health and Nutrition raised major questions about the safety of rimonabant Examination Survey. Am J Epidemiol 2003; 158: 1139–47.
Food and Drug Administration Endocrinologic and Metabolic Advisory. in obese people, who are already at an increased risk of June 13, 2007. Briefi ng Information, NDA 21-888 ZIMULTI (rimonabant)—Sanofi -Aventis. 2007. http://www.fda.gov/OHRMS/DOCKETS/AC/07/ sion, especially since the FDA review suggests briefi ng/2007-4306b1-00-index.htm (assessed Aug 6, 2007).
that the risk of suicide is increased by use of this agent. 8 Gobbi G, Bambico FR, Mangieri R, et al. Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of More over, at least four other companies have CB antag- anandamide hydrolysis. Proc Natl Acad Sci USA 2005; 102: 18620–25.
onists in phase II or III development. The fi ndings of 9 Hill MN, Ho WS, Sinopoli KJ, et al. Involvement of the endocannabinoid system in the ability of long-term tricyclic antidepressant treatment to Christensen and colleagues’ meta-analysis suggest that suppress stress-induced activation of the hypothalamic-pituitary-adrenal phase III studies of such CB antagonists should monitor axis. Neuropsychopharmacology 2006; 31: 2591–99.
10 Moreira FA, Kaiser N, Monory F, et al. Reduced anxiety-like behaviour induced psychiatric complications very carefully. Second, the link by genetic and pharmacological inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) is mediated by CB1 receptors. between depression and this CB -receptor blocker raises Neuropharmacology 2007; published online July 19. DOI: 10.1016/j.neuropharm.
theoretical questions about a potential central role for Griebel G, Stemmelin J, Scatton B. Eff ects of the cannabinoid CB1 receptor the endocannabinoid system in both normal and clinical antagonist rimonabant in models of emotional reactivity in rodents. Biol Psychiatry 2005; 57: 261–67.
12 Lu X-Y, Kim CS, Frazer A, et al. Leptin: a potential novel antidepressant. Proc Natl Acad Sci USA 2006; 103: 1593–98.
*Philip B Mitchell, Margaret J Morris
13 Vinod KY, Hungund BL. Role of the endocannibinoid system in depression and suicide. Trends Pharmacol Sci 2006; 27: 539–45.
School of Psychiatry and School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australiaphil.mitchell@unsw.edu.au Benefi ts and risks of homoeopathy
Five large meta-analyses of homoeopathy trials have Similarly, modern medicine can off er little for conditions been done. All have had the same result: after excluding such as many types of back pain, stress at work, medically methodo logically inadequate trials and accounting for unexplained fatigue, and most com mon colds. Going publication bias, homoeopathy produced no statistically through a theatre of medical treatment, and trying every signifi cant benefi t over placebo.1–5 And yet homoeopathy drug in the book, will only elicit side-eff ects. An inert pill in these circumstances seems a sensible option.
During the cholera epidemic in the 19th century, However, just as homoeopathy has unexpected death rates at the London Homoeopathic Hospital benefi ts, so it can have unexpected side-eff ects. The very were three times lower than those at the Middlesex act of prescribing a pill carries its own risks: medicalisation, Hospital.6 The reason for homoeopathy’s success in this reinforcement of counterproductive illness behaviours, See Special Report page 1677
epidemic is even more interesting than the placebo and promotion of the idea that a pill is an appropriate eff ect. At the time, nobody could treat cholera, and response to a social problem, or a modest viral illness.
while medical treatments such as blood-letting were Similarly, when a health-care practitioner of any actively harmful, the homoeopaths’ treatments were at description prescribes a pill which they know is no more eff ective than placebo—without disclosing that fact to www.thelancet.com Vol 370 November 17, 2007
their patient—then they disregard both informed consent Every criticism I have made could be managed and their patient’s autonomy. Some could argue that this with clear and open discussion of the problems. cost is accept able, but such old-fashioned paternalism can But homoeopaths have walled themselves off from ultimate ly undermine the doctor–patient relationship.
academic medicine, and critique has been all too often There are also more concrete harms. A routine feature met with avoidance rather than argument. The Society of homoeopaths’ marketing practices is to denigrate of Homeopaths (in Europe) has even threatened to sue mainstream medicine. One study found that half of all bloggers,15 and the university courses on alternative homoeo paths who were approached advised patients medicine which I and others have approached have fl atly against the measles, mumps, and rubella vaccine for refused to provide basic information, such as what they their children.7 A television news investigation found teach and how.16 It is hard to think of anything more that almost all homoeopaths who were approached unhealthy.
recom mended ineff ective homoeopathic prophylaxis for To ban homoeopathy would be an over-reaction, as malaria, undermined medical prophylaxis, and did not placebos could have a clinical role. However, whether the even give simple advice on bite prevention.8 Undermining placebo eff ect is best harnessed by homoeopaths will medicine is a wise commercial decision for homoeopaths, remain questionable until these ethical issues and side-because survey data show that a disappointing exper ience eff ects have been addressed. with mainstream medicine is one of the few feat ures to regularly correlate with a decision to use alter native Ben Goldacretherapies. But it might not be a responsible choice.
Homoeopaths can undermine public-health campaigns; leave their patients exposed to fatal diseases; and, in the I am a medical doctor who is also employed by the media as a commentator on pseudoscience and the sociology of medicine.
extreme, miss or disregard fatal diagnoses. There have 1 Kleijnen J, Knipschild P, ter Riet G. Clinical trials of homoeopathy. BMJ 1991; also been cases of patients who died after medically 302: 316–23.
Boissel JP, Cucherat M, Haugh M, Gauthier E. Critical literature review on the trained homoeopaths advised them to stop medical eff ectiveness of homoeopathy: overview of data from homoeopathic treatments for serious medical conditions.9,10 medicine trials. Brussels, Belgium: Homoeopathic Medicine Research Group. Report to the European Commission. 1996: 195–210.
All these problems have been exacerbated by 3 Linde K, Melchart D. Randomized controlled trials of individualized society’s eagerness to endorse the healing claims of homeopathy: a state-of-the-art review. J Alter Complement Med 1998;
4: 371–88.
homoeopaths, and by the lack of a culture of critical 4 Cucherat M, Haugh MC, Gooch M, Boissel JP. Evidence of clinical effi cacy of homeopathy: a meta-analysis of clinical trials. Eur J Clin Pharmacol 2000; self-appraisal in alternative medicine. Publication bias 56: 27–33.
in alternative ther apy journals is high: in 2000, only 5% 5 Shang A, Huwiler-Müntener K, Nartey L, et al. Are the clinical eff ects of homoeopathy placebo eff ects? Comparative study of placebo-controlled of studies published in complementary or alternative trials of homoeopathy and allopathy. Lancet 2005; 366: 726–32.
health journals were negative.11 To my knowledge, the 6 Hempel S. The medical detective. London, UK: Granta Books, 2006.
Schmidt K, Ernst E. Aspects of MMR. BMJ 2002; 325: 597.
ethical issues of autonomy and placebo have never been 8 Jones M. Malaria advice ‘risks lives’. Newsnight, BBC2 July 13, 2006. http://news.
discussed. Homoeopaths routinely respond to negative bbc.co.uk/1/hi/programmes/newsnight/5178122.stm (accessed Nov 8, 2007).
General Medical Council Fitness To Practise Panel. Dr Marisa Viegas. 2007. http://www.gmc-uk.org/concerns/hearings_and_decisions/ftp/20070628_ observational study,12 which amounts to little more than a ftp_panel_viegas.asp (accessed Nov 8, 2007).
10 Sheldon T. Dutch doctor struck off for alternative care of actor dying of cancer. customer-satisfaction survey, has been promoted13 as if it BMJ 2007; 335: 13.
trumps a string of randomised trials.
Schmidt K, Pittler M, Ernst E. Bias in alternative medicine is still rife but is
diminishing. BMJ 2001; 323: 1071.
Homoeopaths can misrepresent scientifi c evidence 12 Spence DS, Thompson EA, Barron SJ. Homeopathic treatment for freely to an unsuspecting and scientifi cally illiterate public, chronic disease: a 6-year, university-hospital outpatient observational
study. J Altern Complement Med 2005; 11: 793–98.
but in doing so they undermine the public understanding 13 Grice E. Keep taking the arsenic. Daily Telegraph Nov 25, 2005. of what it means to have an evidence base for a treatment. http://www.telegraph.co.uk/health/main.jhtml?view=DETAILS&grid=P8&xml=/health/2005/11/25/hhomeo25.xml (accessed Nov 8, 2007).
This approach seems particularly egregious when 14 Evans I, Thornton H, Chalmers I. Testing treatments: better research for better healthcare. London, UK: British Library, 2006.
academics are working harder than ever to engage the 15 Goldacre B. Threats, the homeopathic panacea. Guardian Oct 20, 2007. wider public in a genuine understanding of research,14 and http://www.guardian.co.uk/science/2007/oct/20/homeopathy (accessed Nov 6, 2007).
when most good doctors try to educate and involve their 16 Giles J. Degrees in homeopathy slated as unscientifi c. Nature 2007; patients in the selection of treatment options.
446: 352–53.
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