Sham device v inert pill: randomised controlled trial of two placebo treatments
(Published 16 February 2006)
Cite this as: BMJ 2006;332:391
- Ted J Kaptchuk, assistant professor of medicine ()1,
- William B Stason, lecturer in health policy and management2,
- Roger B Davis, associate professor of medicine3,
- Anna R T Legedza, instructor of medicine3,
- Rosa N Schnyer, research associate1,
- Catherine E Kerr, instructor in medicine1,
- David A Stone, director4,
- Bong Hyun Nam, fellow in medicine1,
- Irving Kirsch, professor of psychology5,
- Rose H Goldman, associate professor of medicine6
- 1 Osher Institute, Harvard Medical School, Boston, MA, 02215 USA
- 2 Harvard School of Public Health, Boston, MA 02215, USA
- 3 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
- 4 South-East European Research Centre, University of Sheffield, Thessaloniki, 54624 Greece
- 5 School of Applied Psychosocial Studies, University of Plymouth, Plymouth, Devon PL4 8AA
- 6 Cambridge Health Alliance, Cambridge Hospital, Harvard Medical School, Cambridge, MA 02139, USA
- Correspondence to: T J Kaptchuk
- Accepted 8 November 2005
Objective To investigate whether a sham device (a validated sham acupuncture needle) has a greater placebo effect than an inert pill in patients with persistent arm pain.
Design A single blind randomised controlled trial created from the two week placebo run-in periods for two nested trials that compared acupuncture and amitriptyline with their respective placebo controls. Comparison of participants who remained on placebo continued beyond the run-in period to the end of the study.
Setting Academic medical centre.
Participants 270 adults with arm pain due to repetitive use that had lasted at least three months despite treatment and who scored ≥3 on a 10 point pain scale.
Interventions Acupuncture with sham device twice a week for six weeks or placebo pill once a day for eight weeks.
Main outcomemeasures Arm pain measured on a 10 point pain scale. Secondary outcomes were symptoms measured by the Levine symptom severity scale, function measured by Pransky's upper extremity function scale, and grip strength.
Results Pain decreased during the two week placebo run-in period in both the sham device and placebo pill groups, but changes were not different between the groups (−0.14, 95% confidence interval −0.52 to 0.25, P = 0.49). Changes in severity scores for arm symptoms and grip strength were similar between groups, but arm function improved more in the placebo pill group (2.0, 0.06 to 3.92, P = 0.04). Longitudinal regression analyses that followed participants throughout the treatment period showed significantly greater downward slopes per week on the 10 point arm pain scale in the sham device group than in the placebo pill group (−0.33 (−0.40 to −0.26) v −0.15 (−0.21 to −0.09), P = 0.0001) and on the symptom severity scale (−0.07 (−0.09 to −0.05) v −0.05 (−0.06 to −0.03), P = 0.02). Differences were not significant, however, on the function scale or for grip strength. Reported adverse effects were different in the two groups.
Conclusions The sham device had greater effects than the placebo pill on self reported pain and severity of symptoms over the entire course of treatment but not during the two week placebo run in. Placebo effects seem to be malleable and depend on the behaviours embedded in medical rituals.
We thank Peter Goldman, Fred Mosteller, and John Hedley-Whyte for scientific mentorship; Melbeth Marlang, Lin Nulman, Patricia Muldoon, and Pat Wilkinson for research assistance; Joe Kay, Claire McManis, Bella Rosner, Ellen Highfield, Jonathan Ammen, Nancy Jenkins, Marks Mills, Karen Kirchoff, and Dinah Shatz for performing the sham acupuncture treatments; Sidney Klawansky, Dan Moerman, Robert Scholten, Frank Miller, Julie Buring, Marnie Naeser, and the university seminar on effective and affordable health care at Harvard University for input on study design and analysis; and Jacqueline Savetsky, Andrea Hrbek, Robb Scholten, and Sally Andrews for administrative coordination.
Contributors TJK is guarantor and led the conception, design and analysis of the study. WBS, RHG, RBD, RNS, CEK, DAS, and IK contributed to the conception and design. RHG, WBS, RNS, and CEK were especially important for developing treatments and assessments. RBD and ATRL performed statistical analysis with input from WBS, RHG, BHN, and IK.
Funding This study was made possible by Grant No 1RO1 AT00402-01 from the National Center for Complementary and Alternative Medicine (NCCAM) at the NIH.
Competing interests TJK works as a consultant for Kan Herbal Co, Scotts Valley, Ca.
Ethical approval The institutional review boards of Cambridge Health Alliance, Beth Israel Deaconess Medical Center, Harvard Medical School, and Harvard School of Public Health approved the study.