Subscribe to RSS
DOI: 10.1016/j.homp.2010.02.001
The placebo effect and homeopathy
Subject Editor:
Publication History
Received13 July 2009
revised15 January 2010
accepted04 February 2010
Publication Date:
16 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00034926/201002/lookinside/thumbnails/10-1016-j-homp-2010-02-001-1.jpg)
Background: Like other forms of medicine, including Complementary and Alternative Medicine (CAM), homeopathy elicits expectations in patients. The physician–patient relationship, personal and comprehensive treatment and lack of adverse effects are elements in creating positive expectations. Other elements may be associated with negative expectations.
Methods: We conducted a systematic literature review on placebo and nocebo effects in acupuncture and homeopathy using Medline.
Results: Findings on the psychophysiological and neuromediating mechanisms of the placebo–nocebo phenomenon are reviewed. Studies of these effects reveal how expectations and unconscious conditioning can be measured by imaging and EEG methods. They result in significant, non-specific therapeutic effects, which may confuse the evaluation of the specific therapeutic effects treatment, hampering selection of the simillimum.
Conclusions: Directions for future research on non-specific therapeutic effects of homeopathy to improve clinical practice and clinical research are discussed.
-
References
- 1 Hahnemann S. Organon of medicine. [Boericke W, Trans.] 6th edn. New Delhi: B Jain Publishers; 1991.
- 2 Teixeira M.Z. Ensaio clínico quali-quantitativo para avaliar a eficácia e a efetividade do tratamento homeopático individualizado na rinite alérgica perene [tese]. Quali-quantitative clinical trial to evaluate the efficacy and the effectiveness of individualized homeopathic treatment in perennial allergic rhinitis (thesis). São Paulo: School of Medicine, University of São Paulo; 2009. Available from: http://www.teses.usp.br/teses/disponiveis/5/5159/tde-10062009-102220/
- 3 Teixeira M.Z. Bases psiconeurofisiológicas do fenômeno placebo–nocebo: evidências científicas que valorizam a humanização da relação médico–paciente. Psyconeurophysiologic bases of the placebo–nocebo phenomenon: scientific evidences that value the humanization of the doctor–patient relationship. Rev Assoc Med Bras 2009; 55 (01) 13-18.
- 4 Kaptchuk T.J., Kelley J.M., Conboy L.A. et al. Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome. BMJ 2008; 336 (7651): 999-1003.
- 5 Paterson C., Dieppe P. Characteristic and incidental (placebo) effects in complex interventions such as acupuncture. BMJ 2005; 330 (7501): 1202-1205.
- 6 Benedetti F., Lanotte M., Colloca L. When words are painful: unraveling the mechanisms of the nocebo effect. Neuroscience 2007; 147 (02) 260-271.
- 7 de Craen A.J., Kaptchuk T.J., Tijssen J.G., Kleijnen J. Placebos and placebo effects in medicine: historical overview. J R Soc Med 1999; 92 (10) 511-515.
- 8 Su C., Lichtenstein G.R., Krok K., Brensinger C.M., Lewis J.D. A meta-analysis of the placebo rates of remission and response in clinical trials of active Crohn's disease. Gastroenterology 2004; 126 (05) 1257-1269.
- 9 Cho H.J., Hotopf M., Wessely S. The placebo response in the treatment of chronic fatigue syndrome: a systematic review and meta-analysis. Psychosom Med 2005; 67 (02) 301-313.
- 10 Patel S.M., Stason W.B., Legedza A. et al. The placebo effect in irritable bowel syndrome trials: a meta-analysis. Neurogastroenterol Motil 2005; 17 (03) 332-340.
- 11 Ilnyckyj A., Greenberg H., Bernstein C.N. Quantification of the placebo response in ulcerative colitis. Gastroenterology 1997; 112 (06) 1854-1858.
- 12 Walsh B.T., Seidman S.N., Sysko R., Gould M. Placebo response in studies of major depression: variable, substantial, and growing. JAMA 2002; 287 (14) 1840-1847.
- 13 Sysko R., Walsh B.T. A systematic review of placebo response in studies of bipolar mania. J Clin Psychiatry 2007; 68 (08) 1213-1217.
- 14 Macedo A., Baños J.E., Farré M. Placebo response in the prophylaxis of migraine: a meta-analysis. Eur J Pain 2008; 12 (01) 68-75.
- 15 Hrobjartsson A., Gotzsche P.C. Is the placebo powerless? Update of a systematic review with 52 new randomized trials comparing placebo with no treatment. J Intern Med 2004; 256 (02) 91-100.
- 16 Wampold B.E., Minami T., Tierney S.C., Baskin T.W., Bhati K.S. The placebo is powerful: estimating placebo effects in medicine and psychotherapy from randomized clinical trials. J Clin Psychol 2005; 63 (04) 373-377.
- 17 Hunsley J., Westmacott R. Interpreting the magnitude of the placebo effect: mountain or Molehill?. J Clin Psychol 2007; 63 (04) 391-399.
- 18 Tilburt J.C., Emanuel E.J., Kaptchuk T.J., Curlin F.A., Miller F.G. Prescribing “placebo treatments”: results of national survey of US internists and rheumatologists. BMJ 2008; 337: a1938.
- 19 Geers A.L., Helfer S.G., Weiland P.E., Kosbab K. Expectations and placebo response: a laboratory investigation into the role of somatic focus. J Behav Med 2006; 29 (02) 171-178.
- 20 de la Fuente-Fernandez R., Schulzer M., Stoessl A.J. Placebo mechanisms and reward circuitry: clues from Parkinson's disease. Biol Psychiatry 2004; 56 (02) 67-71.
- 21 Olness K., Ader R. Conditioning as an adjunct in the pharmacotherapy of lupus erythematosus. J Dev Behav Pediatr 1992; 13 (02) 124-125.
- 22 Goebel M.U., Trebst A.E., Steiner J. et al. Behavioral conditioning of immunosuppression is possible in humans. FASEB J 2002; 16 (14) 1869-1873.
- 23 Benedetti F., Amanzio M., Baldi S., Casadio C., Maggi G. Inducing placebo respiratory depressant responses in humans via opioid receptors. Eur J Neurosci 1999; 11 (02) 625-631.
- 24 Benedetti F., Pollo A., Lopiano L., Lanotte M., Vighetti S., Rainero I. Conscious expectation and unconscious conditioning in analgesic, motor, and hormonal placebo/nocebo responses. J Neurosci 2003; 23 (10) 4315-4323.
- 25 Amanzio M., Pollo A., Maggi G., Benedetti F. Response variability to analgesics: a role for non-specific activation of endogenous opioids. Pain 2001; 90 (03) 205-215.
- 26 Colloca L., Lopiano L., Lanotte M., Benedetti F. Overt versus covert treatment for pain, anxiety, and Parkinson's disease. Lancet Neurol 2004; 3 (11) 679-684.
- 27 Amanzio M., Benedetti F. Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated subsystems. J Neurosci 1999; 19 (01) 484-494.
- 28 Vase L., Robinson M.E., Verne G.N., Price D.D. Increased placebo analgesia over time in irritable bowel syndrome (IBS) patients is associated with desire and expectation but not endogenous opioid mechanisms. Pain 2005; 115 (03) 338-347.
- 29 Sauro M.D., Greenberg R.P. Endogenous opiates and the placebo effect. A meta-analytic review. J Psychosom Res 2005; 58 (02) 115-120.
- 30 Petrovic P., Kalso E., Petersson K.M., Ingvar M. Placebo and opioid analgesia – imaging a shared neural network. Science 2002; 295 (5560): 1737-1740.
- 31 Wager T.D., Rilling J.K., Smith E.E. et al. Placebo-induced changes in fMRI in the anticipation and experience of pain. Science 2004; 303 (5561): 1162-1167.
- 32 Price D.D., Craggs J., Verne G.N., Perlstein W.M., Robinson M.E. Placebo analgesia is accompanied by large reductions in pain-related brain activity in irritable bowel syndrome patients. Pain 2007; 127 (01/02) 63-72.
- 33 Fricchione G., Stefano G.B. Placebo neural systems: nitric oxide, morphine and the dopamine brain reward and motivation circuitries. Med Sci Monit 2005; 11 (05) MS54-MS65.
- 34 Koyama T., McHaffie J.G., Laurienti P.J., Coghill R.C. The subjective experience of pain: where expectations become reality. Proc Natl Acad Sci U S A 2005; 102 (36) 12950-12955.
- 35 Keltner J.R., Furst A., Fan C., Redfern R., Inglis B., Fields H.L. Isolating the modulatory effect of expectation on pain transmission: a functional magnetic resonance imaging study. J Neurosci 2006; 26 (16) 4437-4443.
- 36 Kong J., Gollub R.L., Polich G. et al. A functional magnetic resonance imaging study on the neural mechanisms of hyperalgesic nocebo effect. J Neurosci 2008; 28 (49) 13354-13362.
- 37 Pollo A., Torre E., Lopiano L., Rizzone M., Lanotte M., Cavanna A. Expectation modulates the response to subthalamic nucleus stimulation in Parkinsonian patients. Neuroreport 2002; 13 (11) 1383-1386.
- 38 de la Fuente-Fernandez R., Ruth T.J., Sossi V., Schulzer M., Calne D.B., Stoessl A.J. Expectation and dopamine release: mechanism of the placebo effect in Parkinson's disease. Science 2001; 293 (5532): 1164-1166.
- 39 Kirsch I., Deacon B.J., Huedo-Medina T.B., Scoboria A., Moore T.J., Johnson B.T. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the food and drug administration. PLoS Med 2008; 5 (02) e45.
- 40 Fournier J.C., DeRubeis R.J., Hollon S.D. et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA 2010; 303 (01) 47-53.
- 41 Leuchter A.F., Cook I.A., Witte E.A., Morgan M., Abrams M. Changes in brain function of depressed subjects during treatment with placebo. Am J Psychiatry 2002; 159 (01) 122-129.
- 42 Mayberg H.S., Silva J.A., Brannan S.K. et al. The functional neuroanatomy of the placebo effect. Am J Psychiatry 2002; 159 (05) 728-737.
- 43 Levine J.D., Gordon N.C., Bornstein J.C., Fields H.L. Role of pain in placebo analgesia. Proc Natl Acad Sci U S A 1979; 76 (07) 3528-3531.
- 44 Benedetti F. The opposite effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia. Pain 1996; 64 (03) 535-543.
- 45 De Pascalis V., Chiaradia C., Carotenuto E. The contribution of suggestibility and expectation to placebo analgesia phenomenon in an experimental setting. Pain 2002; 96 (03) 393-402.
- 46 Kirsch I., Sapirstein G. Listening to Prozac but hearing placebo: a meta analysis of antidepressant medication. Prev Treat 1998; 1 (02) ArtID 2a.
- 47 McRae C., Cherin E., Yamazaki T.G. et al. Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial. Arch Gen Psychiatry 2004; 61 (04) 412-420.
- 48 Benedetti F., Amanzio M., Maggi G. Potentiation of placebo analgesia by proglumide. Lancet 1995; 346 (8984): 1231.
- 49 Price D.D. Assessing placebo effects without placebo groups: an untapped possibility?. Pain 2001; 90 (03) 201-203.
- 50 Price D.D., Finniss D.G., Benedetti F. A comprehensive review of the placebo effect: recent advances and current thought. Annu Rev Psychol 2007; 59: 565-590.
- 51 Eisenberg D.M., Kessler R.C., Foster C., Norlock F.E., Calkins D., Delbanco T.L. Unconventional medicine in the United States: prevalence, costs and patterns use. N Engl J Med 1993; 328 (04) 246-252.
- 52 Eisenberg D.M., Davis R.B., Ettner S.L. et al. Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. JAMA 1998; 280 (18) 1569-1575.
- 53 Fisher P., Ward A. Complementary medicine in Europe. BMJ 1994; 309 (6947): 107-111.
- 54 Burg M.A., Hatch R.L., Neims A.H. Lifetime use of alternative therapy: a study of Florida residents. South Med J 1998; 91 (12) 1126-1131.
- 55 Molassiotis A., Scott J.A., Kearney N. et al. Complementary and alternative medicine use in breast cancer patients in Europe. Support Care Cancer 2006; 14 (03) 260-267.
- 56 Weyl Ben Arush M., Geva H., Ofir R., Mashiach T., Uziel R., Dashkovsky Z. Prevalence and characteristics of complementary medicine used by pediatric cancer patients in a mixed western and middle-eastern population. J Pediatr Hematol Oncol 2006; 28 (03) 141-146.
- 57 Buettner C., Kroenke C.H., Phillips R.S., Davis R.B., Eisenberg D.M., Holmes M.D. Correlates of use of different types of complementary and alternative medicine by breast cancer survivors in the nurses' health study. Breast Cancer Res Treat 2006; 100 (02) 219-227.
- 58 Träger-Maury S., Tournigand C., Maindrault-Goebel F. et al. Use of complementary medicine by cancer patients in a French oncology department. Bull Cancer 2007; 94 (11) 1017-1025.
- 59 Laengler A., Spix C., Seifert G., Gottschling S., Graf N., Kaatsch P. Complementary and alternative treatment methods in children with cancer: a population-based retrospective survey on the prevalence of use in Germany. Eur J Cancer 2008; 44 (15) 2233-2240.
- 60 Furnham A., Forey J. The attitudes, behaviors, and beliefs of patients of conventional vs. complementary (alternative) medicine. J Clin Psychol 1994; 50 (03) 458-469.
- 61 Veeramah E.K., Holmes S. Complementary therapy: complement or threat to modern medicine?. J R Soc Health 2000; 120 (01) 42-46.
- 62 Astin J.A. Why patients use alternative medicine: results of a national survey. JAMA 1998; 279 (19) 1548-1553.
- 63 Teixeira M.Z. Homeopatia: prática médica humanística. Homeopathy: a humanistic approach to medical practice. Rev Assoc Med Bras 2007; 53 (06) 547-549.
- 64 Van Wassenhoven M., Ives G. An observational study of patients receiving homeopathic treatment. Homeopathy 2004; 93 (01) 3-11.
- 65 Thompson T.D., Weiss M. Homeopathy – what are the active ingredients? An exploratory study using the UK Medical Research Council's framework for the evaluation of complex interventions. BMC Complement Altern Med 2006; 6: 37.
- 66 Launsø L., Henningsen I., Rieper J., Brender H., Sandø F., Hvenegaard A. Expectations and effectiveness of medical treatment and classical homeopathic treatment for patients with hypersensitivity illnesses –- one year prospective study. Homeopathy 2007; 96 (04) 233-242.
- 67 Marian F., Joost K., Saini K.D., von Ammon K., Thurneysen A., Busato A. Patient satisfaction and side effects in primary care: an observational study comparing homeopathy and conventional medicine. BMC Complement Altern Med 2008; 8: 52.
- 68 Pariente J., White P., Frackowiak R.S., Lewith G.T. Expectancy and belief modulate the neuronal substrates of pain treated by acupuncture. Neuroimage 2005; 25 (04) 1161-1167.
- 69 Lewith G.T., White P.J., Pariente J. Investigating acupuncture using brain imaging techniques: the current state of play. Evid Based Complement Alternat Med 2005; 2 (03) 315-319.
- 70 Bell I.R., Lewis 2nd D.A., Schwartz G.E. et al. Electroencephalographic cordance patterns distinguish exceptional clinical responders with fibromyalgia to individualized homeopathic medicines. J Altern Complement Med 2004; 10 (02) 285-299.
- 71 Bell I.R., Lewis 2nd D.A., Lewis S.E. et al. EEG alpha sensitization in individualized homeopathic treatment of fibromyalgia. Int J Neurosci 2004; 114 (09) 1195-1220.
- 72 Bausell R.B., Lao L., Bergman S., Lee W.L., Berman B.M. Is acupuncture analgesia an expectancy effect? Preliminary evidence based on participants' perceived assignments in two placebo-controlled trials. Eval Health Prof 2005; 28 (01) 9-26.
- 73 Linde K., Witt C.M., Streng A. et al. The impact of patient expectations on outcomes in four randomized controlled trials of acupuncture in patients with chronic pain. Pain 2007; 128 (03) 264-271.
- 74 Dorn S.D., Kaptchuk T.J., Park J.B. et al. A meta-analysis of the placebo response in complementary and alternative medicine trials of irritable bowel syndrome. Neurogastroenterol Motil 2007; 19 (08) 630-637.
- 75 Cherkin D.C., Sherman K.J., Avins A.L. et al. A randomized trial comparing acupuncture, simulated acupuncture, and usual care for chronic low back pain. Arch Intern Med 2009; 169 (09) 858-866.
- 76 Fisher P., McCarney R., Hasford C., Vickers A. Evaluation of specific and non-specific effects in homeopathy: feasibility study for a randomised trial. Homeopathy 2006; 95 (04) 215-222.
- 77 Brien S., Lachance L., Lewith G.T. Are the therapeutic effects of homeopathy attributed to the consultation, the homeopathic remedy, or both? A protocol for a future exploratory feasibility trial in patients with rheumatoid arthritis. J Altern Complement Med 2004; 10 (03) 499-502.
- 78 Bell I.R., Lewis 2nd D.A., Brooks A.J. et al. Individual differences in response to randomly assigned active individualized homeopathic and placebo treatment in fibromyalgia: implications of a double-blinded optional crossover design. J Altern Complement Med 2004; 10 (02) 269-283.
- 79 Myers S.S., Phillips R.S., Davis R.B. et al. Patient expectations as predictors of outcome in patients with acute low back pain. J Gen Intern Med 2008; 23 (02) 148-153.
- 80 Bignamini M., Bertoli A., Consolandi A. et al. A controlled double-blind clinical study of 15 CH barium carbonate vs. placebo in a group of hypertensive inmates of 2 homes for the aged. Clin Ter 1987; 122 (06) 429-436.
- 81 Frei H., Everts R., von Ammon K. et al. Randomised controlled trials of homeopathy in hyperactive children: treatment procedure leads to an unconventional study design. Experience with open-label homeopathic treatment preceding the Swiss ADHD placebo controlled, randomised, double-blind, cross-over trial. Homeopathy 2007; 96 (01) 35-41.
- 82 Hill P.B., Hoare J., Lau-Gillard P., Rybnicek J., Mathie R.T. Pilot study of the effect of individualised homeopathy on the pruritus associated with atopic dermatitis in dogs. Vet Rec 2009; 164 (12) 364-370.
- 83 University of Sao Paulo. Effectiveness of individualized homeopathic treatment in perennial allergic rhinitis. National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT00822406). Available from: http://clinicaltrials.gov/ct2/show/NCT00822406.