Exploring the ethical use of placebo effects in affective states: current evidence and next steps

Placebo effects have been recognized as essential psychobiological factors that significantly influence mental and physical well-being. Affective states, in particular, have demonstrated substantial placebo responses in clinical trials of antidepressants and a wide range of placebo effects in experimental studies. Nevertheless, utilizing these placebo effects without deceiving patients has only recently been considered, with initial studies showing promising results. However, the current body of research on such open- label placebos (OLPs) in affective states is limited, and conflicting results highlight the need for further research to strengthen and broaden our knowledge in this field. This thesis strives to contribute to addressing this research gap in multiple ways.
Firstly, it expands the existing pool of experimental affect paradigms for conducting basic placebo research by demonstrating its feasibility in a randomized controlled trial involving healthy volunteers (Study I). Besides successfully testing a new paradigm, this study reveals that OLPs can be as efficacious as deceptive placebos in reducing experimentally induced guilt. Secondly, a large randomized controlled trial replicates previous findings on the efficacy of OLPs in the treatment of preclinical test anxiety (Study II). It also provides evidence that placebo effects can be harnessed when participants imagine taking a pill, implying that placebo effects can be harnessed without the ingestion of physical pills. Thirdly, this thesis takes a meta-perspective by synthesizing the results of various studies in a network meta-analysis (Study III). The results of both preclinical and clinical studies provide a robust database demonstrating the efficacy of OLPs in regulating psychological complaints. These analyses further highlight that the treatment rationale provided with OLP interventions is indispensable for their efficacy.
The promising results of the three studies contribute collectively to the growing evidence base supporting the use of OLPs as a viable and ethical approach to harnessing placebo effects in the management of affect-related conditions. Moreover, they provide not only a new experimental paradigm for conducting experimental research but also valuable insights into which components of the OLP treatment regime are most critical. Crucially, they highlight that placebo effects extend beyond the effects of the mere intake of inactive remedies but instead emphasize the importance of both treatment explanations and the power of imagination. As such, these insights can inform future placebo research, leading to more efficacious and ethical interventions for individuals experiencing psychological distress.