Placebos without deception: a randomized controlled trial in irritable bowel syndrome

Ted J Kaptchuk, Elizabeth Friedlander, John M Kelley, M Norma Sanchez, Efi Kokkotou, Joyce P Singer, Magda Kowalczykowski, Franklin G Miller, Irving Kirsch, Anthony J Lembo, Ted J Kaptchuk, Elizabeth Friedlander, John M Kelley, M Norma Sanchez, Efi Kokkotou, Joyce P Singer, Magda Kowalczykowski, Franklin G Miller, Irving Kirsch, Anthony J Lembo

Abstract

Background: Placebo treatment can significantly influence subjective symptoms. However, it is widely believed that response to placebo requires concealment or deception. We tested whether open-label placebo (non-deceptive and non-concealed administration) is superior to a no-treatment control with matched patient-provider interactions in the treatment of irritable bowel syndrome (IBS).

Methods: Two-group, randomized, controlled three week trial (August 2009-April 2010) conducted at a single academic center, involving 80 primarily female (70%) patients, mean age 47 ± 18 with IBS diagnosed by Rome III criteria and with a score ≥ 150 on the IBS Symptom Severity Scale (IBS-SSS). Patients were randomized to either open-label placebo pills presented as "placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes" or no-treatment controls with the same quality of interaction with providers. The primary outcome was IBS Global Improvement Scale (IBS-GIS). Secondary measures were IBS Symptom Severity Scale (IBS-SSS), IBS Adequate Relief (IBS-AR) and IBS Quality of Life (IBS-QoL).

Findings: Open-label placebo produced significantly higher mean (±SD) global improvement scores (IBS-GIS) at both 11-day midpoint (5.2 ± 1.0 vs. 4.0 ± 1.1, p<.001) and at 21-day endpoint (5.0 ± 1.5 vs. 3.9 ± 1.3, p = .002). Significant results were also observed at both time points for reduced symptom severity (IBS-SSS, p = .008 and p = .03) and adequate relief (IBS-AR, p = .02 and p = .03); and a trend favoring open-label placebo was observed for quality of life (IBS-QoL) at the 21-day endpoint (p = .08).

Conclusion: Placebos administered without deception may be an effective treatment for IBS. Further research is warranted in IBS, and perhaps other conditions, to elucidate whether physicians can benefit patients using placebos consistent with informed consent.

Trial registration: ClinicalTrials.gov NCT01010191.

Conflict of interest statement

Competing Interests: AJL has worked as a consultant for Ironwood, GSK, Salix, Alkermes, and Ardelyx. These companies have had no relationship to this study. All other authors report no competing interest or appearance of competing interest.

Figures

Figure 1. Enrollment Flowchart.
Figure 1. Enrollment Flowchart.
Figure 2. Outcomes at the 21-Day Endpoint…
Figure 2. Outcomes at the 21-Day Endpoint by Treatment Group.

References

    1. Miller FG, Colloca L, Kaptchuk TJ. The placebo effect: illness and interpersonal healing. Perspectives in Biology and Medicine. 2009;52:518–39.
    1. Finniss DG, Kaptchuk TJ, Miller F, Benedetti F. Placebo effects: biological, clinical and ethical advances. Lancet. 2010;375:686–95.
    1. Miller FG, Colloca L. The legitimacy of placebo treatments in clinical practice: evidence and ethics. American Journal of Bioethics. 2009;9:39–47.
    1. American Medical Association Placebo Use in Clinical Practice. 2006. CEJA Report 2-I-2006. Accessed online 05/16/07 at . Assessed 2010 January 5.
    1. Tilburt JC, Emanuel EJ, Kaptchuk TJ, Curlin FA, Miller FG. Prescribing “placebo treatments:” results of a national survey of US internists and rheumatologists. BMJ. 2008;337:a1938.
    1. Fassler M, Meissner K, Schneider A, Linde K. Frequency and circumstances of placebo use in clinical practice – a systematic review of empirical studies. BMC Medicine. 2010;8:15.
    1. Saito YA, Schoenfeld P, Locke GR. The epidemiology of irritable bowel syndrome in North American: a systematic review. American Journal of Gastroenterology. 2002;97:1910–5.
    1. Drossman DA, Camilleri M, Mayer EA, Whitehead WE. AGA technical review on irritable bowel syndrome. Gastroenterology. 2002;123:2108–31.
    1. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, et al. Functional bowel disorders. Gastroenterology. 2006;130:1480–91.
    1. Gralnek IM, Hays RD, Kilbourne A, Naliboff B, Mayer EA. The impact of irritable bowel syndrome on health-related quality of life. Gastroenterology. 2000;119:654–60.
    1. Drossman DA, Morris CB, Schneck S, Hu YJ, Norton NJ, et al. International survey of patients with IBS: symptom features and their severity, health status, treatments, and risk taking to achieve clinical benefit. Journal of Clincal Gastroenterol. 2009;2009
    1. Pare P, Gray J, Lam S, Balshaw R, Khorasheh S, et al. Health-related quality of life, work productivity, and health care resource utilization of subjects with irritable bowel syndrome: baseline results from LOGIC (Longitudinal Outcomes Study of Gastrointestinal Symptoms in Canada), a naturalistic study. Clinical Therapy. 2006;28:1726–35.
    1. Brandt LJ, Chey WD, Foxx-Orenstein A, Schiller LR, Schoenfeld P, et al. An Evidence-Based Systematic Review on the Management of Irritable Bowel Syndrome. American Journal of Gastroenterology. 2009;104:S1–S34.
    1. Kaptchuk TJ, Kelley JM, Conboy LA, Davis RB, Kerr CE, et al. Components of the placebo effect: a randomized controlled trial in irritable bowel syndrome. BMJ. 2008;336:999–1003.
    1. Patel SM, Stason WB, Legedza A, Ock SM, Kaptchuk TJ, et al. The placebo effect in irritable bowel syndrome (IBS) trials – a meta-analysis. Neurogastroenterology & Motility. 2005;17:332–340.
    1. Kaptchuk TJ, Shaw J, Kerr CE, Conboy LA, Kelley JM, et al. “Maybe I made up the whole thing:” Placebos and patients' experiences in a randomized controlled trial. Culture Medicine and Psychiatry. 2009;33:382–412.
    1. Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, et al. Functional bowel disorders and functional abdominal pain. Gut. 1999;(45 Suppl 2):II 43–7.
    1. Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Alimentary Pharmacology & Therapeutics 1997; 1997;11:395–502.
    1. Hammer J, Eslick GD, Howell SC, Altiparmak E, Talley NJ. Diagnostic yield of alarm features in irritable bowel syndrome and functional dyspepsia. Gut. 2004;53:666–72.
    1. Vanner SJ, Depew WT, Paterson WG. Predictive value of the Rome criteria for diagnosing the irritable bowel syndrome and functional dyspepsia. Gut. 2004;53:666–72.
    1. Lembo AJ, Wright RA, Bagby B. Alosetron controls bowel urgency and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome. American Journal of Gastroenterology. 2001;96:2662–70.
    1. Gordon S, Ameen V, Bagby B, Shahan B, Jhingran P, et al. Validation of irritable bowel syndrome Global Improvement Scale: an integrated symptom end point for assessing treatment efficacy. Digestive Disease Science. 2003;48:1317–23.
    1. Mangel AW, Hahn BA, Heath AT. Adequate relief as an endpoint in clinical trials in irritable bowel syndrome. Journal of Internal Medical Research. 1998;26:76–81.
    1. Drossman DA, Patrick DL, Whitehead WE. Further validation of the IBS-QOL: a disease-specific quality-of-life questionnaire. American Journal of Gastroenterology. 2000;95:999–1007.
    1. Glaser BG, Strauss A. Edison, N.J.: Aldine Transactions; 1967. Discovery of Grounded Theory: Strategies for Qualitative Research. 1967.
    1. Denzin NK, Lincoln YS, editors. Thousand Oaks, CA: Sage Publications; 2003. Collecting and Interpreting Qualitative Materials.
    1. Park LC, Covi L. Nonblind placebo trial. Archives of General Psychiatry. 1965;12:336–345.
    1. Sandler AD, Bodfish JW. Open-label use of placebos in the treatment of ADHD: a pilot study. Child Care and Health Development. 2008;34:104–10.
    1. Kaptchuk TJ. Intentional ignorance: a history of blind assessment and placebo controls. Bulletin for the History of Medicine 1998; 1998;72:389–433.
    1. Cohen J. A power primer. Psychological Bulletin. 1992;112:155–159.
    1. Camillleri M, Northcutt AR, Kong S, Dukes GE, McSorley D, et al. Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomized, placebo controlled trial. Lancet 2000; 355:1034–40.
    1. Novick J, Miner P, Krause R, Glebas K, Bliesath H, et al. A randomized, double-blind, placebo-controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation. Alimentary Pharmacology & Therapeutics 2002; 2002;16:1877–88.
    1. Rahimi R, Nikfar S, Abdollahi, M Efficacy and tolerability of alosetron for the treatment of irritable bowel syndrome in women and men: A meta-analysis of eight randomized, placebo-controlled,12-week trials. Clinical Therapeutics. 2008;30:884–901.
    1. Hróbjartsson A, Gotzsche PC. Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. New Eng J Med. 2001;344:1594–1602.
    1. Hróbjartsson A, Gotzsche PC. Placebo interventions for all clinical conditions. Cochrane Database of Systematic Reviews. 2010; 2010;1:CD003974. doi: .
    1. Gryll SL, Katahn M. Situational factors contributing to the placebo effect. Psychopharmocology. 1978;57:129–43.
    1. Spiro HM. New Haven, CT: Yale University Press; 1986. Doctors, Patients, and Placebos.

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