Placebo Analgesic Effect Stronger in Patients vs Healthy Individuals

Though placebo analgesia has been observed in both healthy individuals and patient groups, a lack of data exists comparing the effect between the two groups within the same study. Norwegian researchers aimed to explore this relationship in a meta-analysis published in December 2016 in Psychosomatic Medicine.¹

Studies have demonstrated the effectiveness of placebo treatment for clinical pain, chronic pain, and experimentally induced pain.^2-4 Some findings, including those from a study of patients with low back pain, suggest that the effect is stronger in clinical vs experimental pain. When the same patients received placebo treatment for both clinical and experimental pain (back pain and pain induced by a cold pressor test, respectively), a larger effect was found for the clinical pain.⁵

In order to optimize the use of the placebo analgesic effect in clinical practice, it is necessary to identify any potential differences in this effect between patients and healthy individuals, as well as between different types of pain. In the current analysis, the authors’ search of the literature on placebo analgesia resulted in 71 studies — 55 consisting of healthy individuals and 16 involving patients — with a total of 4239 participants. Five of the patient studies focused on clinical pain, while the remaining 11 involved experimentally induced pain.

The results show average effect sizes of ḡ=1.24 and ḡ=1.49 for healthy individuals and patients, respectively. The average effect sizes of placebo treatment in the patient studies were ḡ=1.05 and ḡ=1.73 for clinical pain and experimentally induced pain, respectively. A greater number of studies showing significant pain reduction involved patients vs healthy participants, according to a chi-square test (P =.040).

“We know that the placebo analgesic effect often increases in correlation with the magnitude of the pain and when motivation for pain relief is high,” explained study co-author June T. Forsberg, MA, a PhD student at the Norwegian University of Science and Technology. Healthy participants in an experimental study know that the pain is only temporary, unlike patients, who do not know if or when the pain will stop. “Therefore, we assume that the motivation for pain relief is higher in patients compared with healthy individuals,” she told Clinical Pain Advisor.

More studies of patient groups are needed before these findings can be generalized to patients, and they should examine a variety of pain conditions. “The significance of these findings is the major impact that our expectations have on the treatment effect — when we expect pain relief it will increase the treatment effect, and clinicians should take advantage of that,” said Ms Forsberg.

Summary and Clinical Applicability

Compared with healthy individuals, patients respond to placebo analgesia to a greater extent for both clinical and experimentally induced pain.  

References

1. Forsberg JT, Martinussen M, Flaten MA. The placebo analgesic effect in healthy individuals and patients: a meta-analysis [published online December 2, 2016]. Psychosom Med. doi: 10.1097/PSY.0000000000000432
2. Benedetti F, Amanzio M, Baldi S, et al. The specific effects of prior opioid exposure on placebo analgesia and placebo respiratory depression. Pain. 1998;75:313-319. 
3. Lee HF, Hsieh JC, Lu CL, et al. Enhanced affect/cognition-related brain responses during visceral placebo analgesia in irritable bowel syndrome patients. Pain. 2012;153:1301-1310.
4. Price DD, Craggs J, Verne GN, Perlstein WM, Robinson ME. Placebo analgesia is accompanied by large reductions in pain-related brain activity in irritable bowel syndrome patients. Pain. 2007;127:63-72.
5. Charron J, Rainville P, Marchand S. Direct comparison of placebo effects on clinical and experimental pain. Clin J Pain. 2006;22:204-211.