|06/02/2006 - All placebos not created alike. |
The debate about the existence of a placebo effect has heated up over the past year as more and more lab experiments are detecting immediate physiological responses to placebos. A new study takes placebo investigations out of the lab and into a clinical trial, showing a discernible placebo effect over time, according to an article in the Feb. 1 British Medical Journal.
While researchers usually use placebos in clinical trials to test the effectiveness of a new treatment, this trial pitted one placebo against another. "It's upside down research," said Ted Kaptchuk, assistant professor of medicine and associate director of the Division for Research and Education in Complementary and Integrative Medical Therapies and the Osher Institute at Harvard Medical School. "We investigated whether a sham acupuncture device has a greater placebo effect than an inert pill."
The study of 270 individuals with chronic arm pain had two phases. In the first phase, 135 patients were given sham acupuncture, and another 135 patients were given a placebo pill for two weeks. During this period, investigators found no strong evidence for an enhanced effect with placebo devices compared with placebo pills.
In the second phase of the study, the same patients were randomized again, with half the patients entered in a sham acupuncture device versus real acupuncture trial, and the other half in a placebo pill vs. real pain pill trial. The acupuncture trial extended four more weeks (the length believed needed to see improvement), and the pill trial lasted six more weeks (the length needed to have the real drug in the bloodstream).
In the second phase of the study, patients receiving sham acupuncture reported a more significant decrease in pain and symptom severity than those receiving placebo pills for the duration of the trials. The results of this study show that the placebo effect varies by type of placebo used.
"These findings suggest that the medical ritual of a device can deliver an enhanced placebo effect beyond that of a placebo pill. There are many conditions in which ritual is irrelevant when compared with drugs, such as in treatment of a bacterial infection," said Kaptchuk, "but the other extreme may also be true. In some cases, the ritual may be the critical component."
The enhanced placebo effect illustrated in this study applied only to subjective reports from patients about their perception of pain and the severity of their condition. More objective measures of grip strength showed no difference in improvements between the two placebos.
The results also provided evidence that what doctors tell patients about side effects directly influences their experience of them. Prior to participating in the study, doctors provided informed consent forms alerting the patients as to the side effects they might experience: temporary soreness for acupuncture and fatigue and dry-mouth for the pills. Of those receiving placebos, 25 percent of sham acupuncture and 31 percent of placebo pill patients reported experiencing the very side effects suggested to them even when nothing was administered to cause them.
This study takes the first step away from examining the placebo effect as a generalized phenomenon to one investigating how it varies in specific clinical environments. Kaptchuk and his colleagues have initiated other National Institute of Health funded studies that will explore the placebo phenomenon in clinical trials for different illnesses and in laboratory experiments that focus on underlying neurobiological, biochemical, genetic and psychological mechanisms.
Though the results of this study add evidence pointing to the existence of a placebo effect in a clinical environment, Kaptchuk does not recommend the use of placebos with patients or deception in the doctor-patient encounter. The aim is to understand how the ritual of healing affects health outcomes.
Source : Harvard Medical School
Research Title: Sham device v inert pill: randomised controlled trial of two placebo treatments
Ted J Kaptchuk 1*, William B Stason 2, Roger B Davis 3, Anna R T Legedza 3, Rosa N Schnyer 1, Catherine E Kerr 1, David A Stone 4, Bong Hyun Nam 1, Irving Kirsch 5, Rose H Goldman 6
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
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 outcome measures: 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.