Expectancies in Double-Blind Randomised Placebo-Controlled Trials and Placebo-Induced Side Effects

Abstract

The majority of research on the placebo effect has focused on beneficial effects in patients or participants told to expect an active treatment, but who are actually given a placebo. Two important and relatively understudied aspects of the placebo effect are the extent to which expectancies influence outcomes in double-blind randomised placebo-controlled trials (RCTs) and whether the placebo effect contributes to treatment side effects. The current project investigated these two issues in both clinical and experimental settings. The first study involved reanalysing a double-blind RCT of naltrexone and acamprosate for alcohol dependence based on whether participants believed they had been allocated to receive active treatment or placebo (perceived treatment). The second study extended on this by developing an experimental model for these effects using dummy (placebo only) double-blind RCTs for cognitive performance. This allowed for the manipulation of observable changes in the form of false feedback. The third study investigated whether warning participants about side effects increases their occurrence, frequency, and/or severity in three dummy trials for sleep difficulty in healthy volunteers. The final study complemented this by examining whether first time chemotherapy patients’ expectancies for nausea were associated with their post-chemotherapy nausea. The studies on perceived treatment in double-blind RCTs indicated that participants’ beliefs about their treatment allocation can influence their actual treatment outcomes via the placebo effect and that these beliefs are affected by the feedback they receive about their performance. The studies on placebo-induced side effects indicated that the placebo effect may contribute to treatment side effects but that this effect is generally likely to be small. These findings confirm that the placebo effect can influence treatment outcomes and emphasise the importance of considering patient expectancies when delivering medical treatment. They also highlight some general limitations associated with research on the placebo effect, which include, whether conveying uncertainty undermines the placebo effect and whether measuring or manipulating expectancies is the best way to evaluate the placebo effect.