Today it seems clear that the experimental manipulation used to induce placebo analgesia plays a fundamental role in the magnitude of the response. Among the different manipulations that have been performed, both the type of verbal suggestions and the individual’s previous experience have been found to be important.
Verbal suggestions that induce certain expectations of analgesia induce larger placebo analgesic responses than those that induce uncertain expectations. This is illustrated by a study carried out in the clinical setting that investigated the differences between the double-blind and the deceptive paradigm (Pollo et al., 2001).
Postoperative patients were treated with buprenorphine, on request, for 3 days consecutively, and with a basal infusion of saline solution. However, the symbolic meaning of this saline basal infusion was varied in three different groups of patients: the first group (natural history or no-treatment group) was told nothing; the second was told the infusion was either a potent analgesic or a placebo (classic double-blind administration); and the third was told that the infusion was a potent painkiller (deceptive administration).
The placebo effect of the infusion was measured by recording the doses of buprenorphine requested over the 3-day treatment. It is important to stress once again that the double-blind group received uncertain verbal instructions (“It can be either a placebo or a painkiller. Thus we are not certain that the pain will subside”) whereas the deceptive administration group received certain instructions (“It is a painkiller. Thus pain will subside soon”).
Compared to the natural history group, a 20.8% decrease in buprenorphine intake was seen with the double-blind administration. An even greater decrease (33.8%) was found in the deceptive administration group. It is important to point out that the time-course of pain was the same in all three groups over the 3-day treatment period. The same analgesic effect was obtained with different doses of buprenorphine, thus subtle differences in the verbal context of the patient may have a significant impact on the magnitude of the response.
In chronic headache pain, a similar effect has been found by using an active treatment (Kam-Hansen et al., 2014). Each patient received either placebo or rizatriptan administered under three information conditions ranging from negative to neutral to positive (told placebo, told rizatriptan or placebo, told rizatriptan). Rizatriptan was superior to placebo for pain relief.
When patients were given placebo labeled as (1) placebo, (2) rizatriptan or placebo, and (3) rizatriptan, the placebo effect increased progressively. Rizatriptan had a similar progressive boost when labeled with these three labels. The efficacies of rizatriptan labeled as placebo and placebo labeled as rizatriptan were similar.
Therefore, increasing positive information incrementally boosted the efficacy of both placebo and medication in headache, which indicates that the information provided to patients and the ritual of pill taking are important components of care.
Benedetti, Fabrizio. Placebo Effects (p. 113). OUP Oxford.
Kam-Hansen S, Jakubowski M, Kelley JM et al. (2014). Altered placbeo and drug labeling changes the outcome of episodic migraine attacks. Science Translation Medicine, 6(218), 218ra5.
Pollo A, Amanzio M, Arslanian A et al. (2001). Response expectancies in placebo analgesia and their clinical relevance. Pain, 93, 77-84.