Cognitive Schemas in Placebo and Nocebo Responding: Role of Autobiographical Memories and Expectations

Bartels, D.J.P.; Laarhoven, Antoinette I. M. van; Heijmans, Naomi; Hermans, Dirk; Debeer, Elise; Kerkhof, Peter C M van de; Evers, Andrea W M

doi:10.1016/j.clinthera.2017.02.004

Cited by 13 publications

(12 citation statements)

References 31 publications

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“…Nevertheless, as mentioned elsewhere, numerous studies reveal that expectancies also modulate placebo and nocebo effects (Bartels et al, 2014; Bartels, van Laarhoven, Heijmans, et al, 2017; Bartels, van Laarhoven, Stroo, et al, 2017; Bingel et al, 2011; Bräscher, Witthöft, & Becker, 2018; Fiorio et al, 2012). Expectancies are induced by verbal instructions, social observation (for reviews see, Colloca & Grillon, 2014; Medoff & Colloca, 2015) and distinct forms of learning (for example, Benedetti et al, 2003; Egorova et al, 2015; Morton, El-Deredy, & Jones, 2014; Reicherts, Gerdes, Pauli, & Wieser, 2016).…”

Section: Role and Manipulation Of Expectanciesmentioning

confidence: 85%

Pain Modulation: From Conditioned Pain Modulation to Placebo and Nocebo Effects in Experimental and Clinical Pain

Damien

Colloca

Belleï-Rodriguez

et al. 2018

International Review of Neurobiology

112

107

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Accumulating evidence reveal important applications of endogenous pain modulation assessment in healthy controls and in patients in clinical settings, as dysregulations in the balance of pain modulatory circuits may facilitate pain and promote chronification of pain. This article reviews data on pain modulation, focusing on the mechanisms and translational aspects of pain modulation from conditioned pain modulation (CPM) to placebo and nocebo effects in experimental and clinical pain. The specific roles of expectations, learning, neural and neurophysiological mechanisms of the central nervous system are briefly reviewed herein. The interaction between CPM and placebo systems in pain inhibitory pathways is highly relevant in the clinic and in randomized controlled trials yet remains to be clarified. Examples of clinical implications of CPM and its relationship to placebo and nocebo effects are provided. A greater understanding of the role of pain modulation in various pain states can help characterize the manifestation and development of chronic pain and assist in predicting the response to pain-relieving treatments. Placebo and nocebo effects, intrinsic to every treatment, can be used to develop personalized therapeutic approaches that improve clinical outcomes while limiting unwanted effects.

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Section: Role and Manipulation Of Expectanciesmentioning

confidence: 85%

Pain Modulation: From Conditioned Pain Modulation to Placebo and Nocebo Effects in Experimental and Clinical Pain

Damien

Colloca

Belleï-Rodriguez

et al. 2018

International Review of Neurobiology

112

107

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“…Previous studies regarding nocebo effects on itch have found indications for a role of psychological characteristics in relation to negative outcome expectancies, like worrying or negative affect, however research is extremely scarce [ 50 ]. Moreover, in a recent study by our research group, indications were found that one’s cognitive schemas regarding specificity and valence of memories and expectations regarding itch are related to placebo responding on itch, i.e., participants who were more specific in their memories regarding itch and who had less negative itch-related expectations for the future were more likely to be placebo itch responders [ 33 ]. Future research should further investigate the determinants of (reversing) nocebo responses, like individual differences in psychological characteristics in relation to negative outcome expectancies and cognitive schemas regarding memories and expectations.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, we exploratively tested the extent to which previously reduced nocebo effects would generalize to a different itch stimulus to assess external validity. Furthermore, it was explored whether psychological characteristics related to negative or positive outcome expectancies (e.g., worrying or optimism, respectively) were associated with (reversion of) nocebo responses [ 15 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Minimizing nocebo effects by conditioning with verbal suggestion: A randomized clinical trial in healthy humans

et al. 2017

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Nocebo effects, i.e., adverse treatment effects which are induced by patients’ expectations, are known to contribute to the experience of physical symptoms such as pain and itch. A better understanding of how to minimize nocebo responses might eventually contribute to enhanced treatment effects. However, little is known about how to reduce nocebo effects. In the current randomized controlled study, we tested whether nocebo effects can be minimized by positive expectation induction with respect to electrical and histaminic itch stimuli. First, negative expectations about electrical itch stimuli were induced by verbal suggestion and conditioning (part 1: induction of nocebo effect). Second, participants were randomized to either the experimental group or one of the control groups (part 2: reversing nocebo effect). In the experimental group, positive expectations were induced by conditioning with verbal suggestion. In the control groups either the negative expectation induction was continued or an extinction procedure was applied. Afterwards, a histamine application test was conducted. Positive expectation induction resulted in a significantly smaller nocebo effect in comparison with both control groups. Mean change itch NRS scores showed that the nocebo effect was even reversed, indicating a placebo effect. Comparable effects were also found for histamine application. This study is the first to demonstrate that nocebo effects can be minimized and even reversed by conditioning with verbal suggestion. The results of the current study indicate that learning via counterconditioning and verbal suggestion represents a promising strategy for diminishing nocebo responses.

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“…Appendix Table 2 Environmental factors and stimuli modifying placebo/nocebo effects Modifiable Non-modifiable Patient's expectations [13] Previous experiences [14] Pre-treatment verbal and non-verbal suggestions [15,16] Patient's personality [17] Speed of treatment titration [18] Cultural factors [19,20] Safety profile of treatment [21] Age [22] Patient-doctor relation/communication [23] Social Media and Internet information [24] Investigator/physician status [15] Gender [25] Affective and cognitive traits [26] Level of patients' education [22] Generic formulations [27,28] Genetics [29] The appearance of drugs or medical devices, e.g. packaging, color, price, drug taste, etc.…”

Section: Fundingmentioning

confidence: 99%

European Headache Federation recommendations for placebo and nocebo terminology

et al. 2020

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Background and aim Despite recent publications, practitioners remain unfamiliar with the current terminology related to the placebo and nocebo phenomena observed in clinical trials and practice, nor with the factors that modulate them. To cover the gap, the European Headache Federation appointed a panel of experts to clarify the terms associated with the use of placebo in clinical trials. Methods The working group identified relevant questions and agreed upon recommendations. Because no data were required to answer the questions, the GRADE approach was not applicable, and thus only expert opinion was provided according to an amended Delphi method. The initial 12 topics for discussion were revised in the opinion of the majority of the panelists, and after a total of 6 rounds of negotiations, the final agreement is presented. Results/recommendations Two primary and mechanism-based recommendations are provided for the results of clinical trials: [1] to distinguish the placebo or nocebo response from the placebo or nocebo effect; and [2] for any favorable outcome observed after placebo administration, the term “placebo response” should be used, and for any unfavorable outcome recorded after placebo administration, the term “nocebo response” should be used (12 out of 17 panelists agreed, 70.6% agreement). The placebo or nocebo responses are attributed to a set of factors including those that are related to the medical condition (e.g. natural history, random comorbidities, etc.), along with idiosyncratic ones, in which the placebo or nocebo effects are attributed to idiosyncratic, or nonspecific mechanisms, exclusively (e.g. expectation, conditioning, observational learning etc.). To help investigators and practitioners, the panel summarized a list of environmental factors and idiosyncratic dynamics modulating placebo and nocebo effects. Some of them are modifiable, and investigators or physicians need to know about them in order to modify these factors appropriately to improve treatment. One secondary recommendation addresses the use of the terms “placebo” and “nocebo” (“placebos” and “nocebos” in plural), which refer to the triggers of the placebo/nocebo effects or responses, respectively, and which are inert agents or interventions that should not be confused with the placebo/nocebo responses or effects themselves (all panelists agreed, 100% agreement). Conclusion The working group recommends distinguishing the term response from effect to describe health changes from before to after placebo application and to distinguish the terms placebo(s) or nocebo(s) from the health consequences that they cause (placebo/nocebo responses or effects).

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Cognitive Schemas in Placebo and Nocebo Responding: Role of Autobiographical Memories and Expectations

Cited by 13 publications

References 31 publications

Pain Modulation: From Conditioned Pain Modulation to Placebo and Nocebo Effects in Experimental and Clinical Pain

Pain Modulation: From Conditioned Pain Modulation to Placebo and Nocebo Effects in Experimental and Clinical Pain

Minimizing nocebo effects by conditioning with verbal suggestion: A randomized clinical trial in healthy humans

European Headache Federation recommendations for placebo and nocebo terminology

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