What Is the benefit of adding placebo side-effect information to positively framed patient leaflets?

Background: Positively framing side-effect risk in patient information leaflets (PILs) can reduce side-effect expectations and resulting nocebo effects (nonspecific medication side effects unrelated to the drug’s pharmacological action). There is scope to educate patients about nocebo effects in PILs to minimize their occurrence further.

Aims: To investigate if incorporating information on placebo-reported side effects reduces side-effect expectations compared to a positively framed-only or standard PIL.

Methods: Participants (N = 443) completed an online study and were randomized to read one of three PILs for a hypothetical antibiotic: standard PIL (n = 140), positively framed PIL (n = 151), or positively framed PIL with placebo side-effect information (n = 152). Participants’ side-effect expectations, absolute risk perceptions, and intended adherence were recorded.

Results: The standard PIL resulted in significantly higher side-effect expectations compared to the positively framed + placebo side-effect information PIL. Including the placebo side-effect results had no effect on side-effect expectations compared to the positive framing only PIL, however, there was a significant interaction between health literacy and PIL condition on side-effect expectations. Both positively framed PILs produced more accurate risk estimates for the more common side effects. There was no difference in intended adherence between the three PILs.

Limitations: Our findings are limited by the highly educated sample and hypothetical context.

Conclusions: There was no benefit of adding placebo side-effect information, however alternative ways of explaining nocebo effects in PILs should be explored utilizing clinical contexts and samples with a wider range of participant ages, and health literacy.