Deceptive and non-deceptive placebos to reduce sadness: A five-armed experimental study

Background: Placebo effects play an important role in psychopharmacological treatment of depression. Among the most potent mechanisms are positive treatment expectations. However, there is large heterogeneity in how they are induced. We studied the protective effects against sadness of deceptive (DP) and open-label placebos (OLP) combined with one of two new rationale styles. Methods: Healthy participants (N = 147) were randomly assigned to one of five groups. In this ”2x2+1” design, two factors were varied: The rationale style (personal-emotional style vs. scientific-matter-of-fact style) and the type of placebo (DP vs. OLP). The placebo was introduced as a protection from sadness. In addition, there was a no-treatment control group (CG). Participants viewed a sad movie scene after placebo application. The primary outcome was pre-post change in sadness, a major component of depression. Results: Participants in the DP groups showed a significant protective effect against sadness, whereas sadness increased in both the OLP groups and the CG. There were no differences between the rationale styles. Limitations: Short-term induced sadness has limited external validity in a heterogeneous long-term mental disorder like depression. Conclusions: In line with other OLP studies, no OLP effect could be observed in this healthy sample. In contrast, DP significantly reduced sadness. While placebo effects contribute substantially to antidepressant treatment, the potential of OLP in the treatment of depression appears to be limited in non-clinical samples. In addition, our results suggest that different ways to induce treatment expectations are possible.