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

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.

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.

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.

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.