The therapeutic oxymoron: exploring the mechanisms of open-label placebo

Placebos have emancipated themselves from earlier, often unethical or merely research- based practices, toward an open and thereby ethical administration. Despite a plethora of efficacy studies and nearly two decades of empirical research on open-label placebos (OLPs), little to nothing is known about the circumstances under which they realize their potential. While the underlying processes of deceptive placebos are fairly well understood, these findings cannot simply be transferred to the field of OLPs, given that the two areas most probably operate through distinct mechanisms. To address this research gap, this thesis aims to identify potential explanatory forces behind OLPs. To do the unexploredness justice, a multi-method approach was adopted to shed light on the topic: A network meta-analysis of OLPs (study 1) supports the notion that OLPs can be an efficacious intervention for nonclinical and clinical populations. In particular, this study highlights the importance of inducing positive treatment expectancies, for example, by providing a treatment rationale. The mere administration of a pill without embedding it in a narrative apparently is insufficient, implying that the pill itself might not be a necessary component for OLP effects. This finding was confirmed in a three-week randomized controlled trial (study 2) in which OLPs and the sheer imagination of a pill intake both led to significantly lower test anxiety in students compared to a control group. The presence of a placebo effect solely through means of imagination implies that the daily therapeutic ritual itself evoked beneficial effects. Although these two studies provide valuable insights into OLP mechanisms, they leave the question unanswered as to which participant-related factors play a role in distinct OLP effects. Therefore, a qualitative analysis (study 3) was conducted, in which a central finding was the great extent to what an individual's desire for relief determines the magnitude of the OLP effect. OLP effects can therefore be understood as a relief of symptoms that occurs within the framework of a plausible narrative and a ritual that corresponds to the individual's desire for relief when seeking treatment. Taken together, these three studies suggest, that the words and rituals, as well as the patient's desire for relief, are key determinants responsible for the effect of OLP. A better understanding of the relative weight of each of these components can inform research regarding underlying mechanisms. This, in turn, can assist clinicians in considering or utilizing these mechanisms more frequently in their clinical practice and, where appropriate, communicate the therapeutic value of each element openly