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

https://doi.org/10.1016/j.jpsychores.2018.11.009Get rights and content

Highlights

  • Open-label placebos lead to pain reduction in healthy participants.

  • Impact of optimism on subjective pain intensity ratings in deceptive placebos.

  • Personality-related variables are not associated with open-label placebo analgesia.

  • Individual differences in placebo analgesia may depend on the administration route.

Abstract

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.

Introduction

Although findings about a general influence of personality traits on placebo responses are inconsistent [1,2], it has been repeatedly shown that higher levels of optimism are positively associated with analgesic placebo responses [[3], [4], [5]]. Indeed, optimism is a notable marker of physical health – primarily in subjective reports but also for objective markers [6]. With regard to placebo responses, dispositional optimism is the only personality variable found to affect placebo effects consistently, in that individuals with higher levels of dispositional optimism experience higher analgesic placebo responses [7]. Single studies also reveal that other personality traits seem to be linked to placebo outcomes, although the available data is controversial. Hence, higher levels of trait openness were found to be associated with enhanced placebo responses, yet principally in an interaction with resting-state connectivity and certain genetic dispositions [8], which is in line with other research indicating that openness merely has an impact on placebo responses in combination with certain situational and interpersonal cues [9]. Also, positive attitudes towards pharmaceutical or complementary medicine are currently discussed to influence individual placebo responses [10]. In fact, different experimental placebo studies point out that placebo responses are context-specific, occur primarily in interactions with further environmental- or person-related cues (e.g., [11]), and that there is not one but rather many placebo effects [2,12]. For instance, optimism and empathy show opposite associations with placebo responses – depending on whether the placebo was meant to reduce the experience of stress [13] or pain [3,4,11,14].

Given the limited applicability of placebo administration in practice due to non-compliance with the ethical key principles of informed consent and autonomy, open-label placebos offer a new approach to harness placebo effects. Different studies corroborate the promising effect of openly administered placebos for several clinical conditions [[15], [16], [17], [18], [19]] as well as for experimentally induced heat pain [20]. Here, patient-empowerment is assumed as a possible mechanism of the open-label placebo responses [21]. However, to date, no trial examined the influence of personality-related variables on outcome measures in the field of open-label placebos. Since placebos depend on several contextual factors [5], it is questionable whether findings regarding certain personality traits from studies with deceptive placebos can be transferred to open-label placebo responses.

Therefore, we set out to examine the influence of personality traits on placebo analgesia in a standardized heat pain experiment with open-label placebos [[22], [23], [24]]. We compared an open-label placebo administration with a rationale (OPR+) and without a rationale (OPR) to deceptive placebo (DP) administration and to no treatment (NT). We tested four assumptions: First, we predicted that the association between optimism and participants' heat pain analgesia (i.e., an increase in heat pain tolerance and a decrease of corresponding intensity and unpleasantness ratings) differ among the four treatment groups (NT, OPR, OPR+, and DP) (first hypothesis). Second, we expected that in particular the association between optimism and heat pain analgesia is stronger in the OPR+ group compared to the NT group (second hypothesis), but does not differ between OPR+ and DP groups (third hypothesis). Based on the previous findings indicating that the variable optimism affects placebo analgesia, we a priori selected optimism as the primary personality outcome of interest.

Finally, the association between additional personality traits (i.e., pessimism, openness to experience, locus of control, and positive attitudes towards alternative and complementary medicine) and participants' heat pain analgesia among the four treatment groups were explored. Accordingly, these exploratory analyses were calculated post hoc in order to generate initial hypotheses.

Section snippets

Study design and population

The trial protocol as well as detailed inclusion and exclusion criteria were previously described [20]. Briefly, the randomized-controlled trial (RCT) was conducted at the Division of Clinical Psychology and Psychotherapy at the University of Basel, Switzerland. The Local Ethics Committee approved the design and informed consent of the study. The study is registered at ClinicalTrials.gov: NCT02578420.

160 healthy adult women and men were recruited via advertisements for “a novel mind-body

Sample characteristics

In total, 151 participants were included in this secondary analysis (NT: N = 40, OPR: N = 37, OPR+: N = 37, and DP: N = 37). Reasons for exclusion (N = 9) were previously described [20]. Participants had a mean age of 27.15 (SD 9.51) years and were mostly women (68%). The four groups did not significantly differ in demographic variables (i.e., age, sex, family status, educational level, and employment level).

Association between optimism and objective heat pain tolerance by group

Primary analyses revealed that the groups did not differ regarding their association

Discussion

The present analysis is the first investigation of the impact of personality-related variables on an analgesic open-label placebo response. In line with former research on personality traits and placebo responses, trait optimism was the only personality-related variable displaying a substantial interaction with treatment group for subjective heat pain ratings. However, in the open-label placebo group (OPR+), no effect of trait optimism on the subjective open-label placebo response was found.

Declarations of interest

The authors declare no financial interest or potential conflicts of interest. Supported by a grant project (325130_170117) awarded to JG by the Swiss National Science Foundation.

Acknowledgements

The authors wish to thank Prof. Irving Kirsch for his helpful inputs regarding the statistical analyses of the study. The authors are also very grateful for the support of Linda Kost.

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