Effects of likelihood framing on side effect expectations and nocebo side effects: Results from three experimental studies with a placebo analgesic cream

OBJECTIVES: This research examined whether different framings of the likelihood of side effects influence their occurrence in response to a placebo analgesic. DESIGN: Three independent experimental studies in non-clinical samples were performed. METHODS: Study 1 investigated the effects of likelihood framing on side effect expectations, while Studies 2 and 3 investigated the effects of likelihood framing on side effect experiences in terms of nocebo side effects. RESULTS: Study 1 (N = 244) showed that participants had higher side expectations when the side effect likelihood was negatively framed (e.g. 1% occurrence) than positively framed (e.g. 99% no occurrence). Side effect expectations were also more negative when frequencies (e.g. 1 in 100) rather than percentages were used. Study 2 tested the effects of positive vs. negative framing and percentages vs. frequencies on the occurrence of itch as a side effect of a placebo analgesic cream, which was applied in an experimental heat pain paradigm in a non-clinical sample (N = 179). Only 11% reported itch, with no significant differences between conditions. Study 3 (N = 110) increased the stated likelihood of itch, yet only 17% reported experiencing it. Crucially, reports of itch did not differ between experimental groups and a control group where itch was not mentioned as a possible side effect. CONCLUSION: This research failed to induce itch as a nocebo response. While examining likelihood framing in nocebo side effects is valuable, establishing an appropriate experimental model remains challenging. Future research directions and methodological considerations to move forward are discussed.