Placebo nonresponders: An experimental investigation on their unreliability over time.

In order to disentangle the effects of drugs from placebo responses, several approaches have been used, such as a placebo run-in phase in which only placebo nonresponders, or poor responders, are considered for further randomization to either placebo or active treatment. This study is aimed at investigating the variability of placebo nonresponders obtained through the classical placebo run-in paradigm (group RUN) and through mismatch conditioning (group MIS), as done in our previous study. To do this, we simulated a real clinical trial in the laboratory, in which the placebo responders of both groups were discarded and the remaining nonresponders of both groups RUN and MIS were randomized to either continuing on placebo (groups RUN-P and MIS-P, respectively) or receiving topical 0.

Creating Placebo Nonresponders in the Lab.

Conditioning and expectation are known to be the main mechanisms of placebo analgesia. They may operate together, so that expectations may be enhanced by a conditioning procedure. Although most of the studies have tried to potentiate expectations through conditioning in order to generate good placebo responders, a few studies have tried to mismatch conditioning and expectations in order to investigate the subsequent administration of a placebo.