Open-label placebo response - Does optimism matter? A secondary-analysis of a randomized controlled trial

Objective: Open-label placebos (OLPs) have been found to elicit significant and clinical meaningful effects, but in comparison to deceptive placebo administration there is a lack of research regarding possible predictors. This study sets out to examine the effects of optimism and other personality-related variables on OLP responses. Methods: We conducted a secondary-analysis of an OLP trial in healthy participants (N = 160), who were randomized to no treatment (NT), OLP without rationale (OPR-), OLP with rationale (OPR+), and deceptive placebo (DP) in an experimental heat pain paradigm. Results: The association between objective posttreatment pain tolerance and optimism did not differ among groups. However, for subjective heat pain ratings at posttreatment, regression analyses showed a significant interaction between group and optimism scores in subjective intensity (F[3, 142] = 3.81, P = 0.012) and unpleasantness ratings (F[3, 142] = 2.95, P = 0.035), indicating that the association between optimism and subjective ratings differed among groups, in particular between OPR+ and NT (intensity: P = 0.012; unpleasantness: P = 0.037), and OPR+ and DP (intensity: P = 0.016). Thus, higher optimism scores were negatively associated with subjective ratings in the NT and DP groups but not in the OPR+ group. Additional exploratory analyses revealed no significant interactions between group and further personality-related variables on heat pain analgesia. Conclusion: Taken together, OLPs are effective, the underlying personality-related variables seem, however, to differ significantly from the deceptive placebo response. Therefore, the concept of "placebo responders" might depend on the route of placebo administration.