Placebo effect stronger if you pay more

With so much written here lately about placebos and drug effectiveness, I would not want to leave out this remarkable study: Placebo effect is stronger, apparently, if you pay more for the placebo.

This is a fascinating study described in a letter to the Journal of the American Medical Association. A crudely shortened version: Some researchers at MIT (none of them Bill Murray, as far as I can tell) gave light shocks to volunteers, then gave them some placebos that were costly and some that were cheap. The costly ones worked better.

It sounds like a bit of a stunt, but as Respectful Insolence points out in a nice write-up, the finding is perfectly consistent with what we know about placebos. It would seem to have unsettling implications for lowering health-care costs.

An excerpt is below the break; study is here, but behind a pay firewall.

Commercial Features of Placebo and Therapeutic Efficacy

To the Editor: It is possible that the therapeutic efficacy of medications is affected by commercial features such as lower prices. Because such features influence patients' expectations,1 they may play an unrecognized therapeutic role by influencing the efficacy of medical therapies, especially in conditions associated with strong placebo responses.2-3 To investigate this possibility, we studied the effect of price on analgesic response to placebo pills.

In 2006 we recruited 82 healthy paid volunteers in Boston, Massachusetts, using an online advertisement. Each participant was informed by brochure about a (purported) new opioid analgesic approved by the Food and Drug Administration; it was described as similar to codeine with faster onset time, but it was actually a placebo pill. After randomization, half of the participants were informed that the drug had a regular price of $2.50 per pill and half that the price had been discounted to $0.10 per pill (no reason for the discount was mentioned). All participants received identical placebo pills and were paid $30. Participants were blinded to the study purpose, and researchers were blinded to group assignment. The study was approved by the Massachusetts Institute of Technology institutional review board, and all participants provided written informed consent and were debriefed after the study.



Commercial Features of Placebo and Therapeutic Efficacy

The protocol followed an established approach for studying pain. Electrical shocks to the wrist were calibrated to each participant's pain tolerance. After calibration, participants received the test shocks, rating the pain on a computerized visual analog scale anchored by the labels "no pain at all" and "the worst pain imaginable." Participants received all possible shocks in 2.5-V increments between 0 V and their calibrated tolerance. Stimulation at each intensity level was carried out twice for each participant (before and after taking the pill), and the change in reaction to the stimulation was assessed. Visual analog scale ratings were converted to a 100-point scale, the postpill score for each voltage was subtracted from the prepill score, and the mean of these differences was calculated for each participant.

The percentage of participants experiencing a mean score reduction vs increase was compared between the 2 groups using a 2-tailed {chi} test. Because stronger pain may be associated with stronger placebo responses, we also compared results for the 50% most painful shocks for each participant. In addition, mean differences at each voltage between the 2 groups were compared overall with a sign test and individually with F tests. A P value of .05 was considered statistically significant. Analyses were performed using SPSS version 15 (SPSS Inc, Chicago, Illinois).

Considering all voltages tested, pain reduction was greater for the regular-price pill (P < .001). In addition, for 26 of 29 intensities (from 10 to 80 V), mean pain reduction was greater for the regular-price pill (Figure).

Comment

These results are consistent with described phenomena of commercial variables affecting quality expectations and expectations influencing therapeutic efficacy. Placebo responses to commercial features have many potential clinical implications. For example, they may help explain the popularity of high-cost medical therapies (eg, cyclooxygenase 2 inhibitors) over inexpensive, widely available alternatives (eg, over-the-counter nonsteroidal anti-inflammatory drugs) and why patients switching from branded medications may report that their generic equivalents are less effective. Studies of real-world effectiveness may be more generalizable if they reflect how medications are sold in addition to how they are formulated. Furthermore, clinicians may be able to harness quality cues in beneficial ways,6 for example, by de-emphasizing potentially deleterious commercial factors (eg, low-priced, generic).

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