Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses: Implications for Clinical Trials and Clinical Practice

Schedlowski, Manfred; Enck, Paul; Rief, Winfried; Bingel, Ulrike

doi:10.1124/pr.114.009423

Cited by 266 publications

(306 citation statements)

References 407 publications

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“…This could give rise to concerns about the influence of demand characteristics. However, since previous studies did find the effects of pain‐focused imagery on pain and placebo analgesia to be associated with corresponding effects on the autonomic nervous system and with the activation of brain responses that are known to be involved in pain experiences and expectancies (Kosslyn et al., 2001; McNorgan, 2012; Atlas and Wager, 2014; Fardo et al., 2015; Schedlowski et al., 2015), it is likely that the autonomic nervous system was also involved in the effects of response imagery on pain in the current studies. The existing evidence for the involvement of the endocrine system is less convincing (Flaten et al., 2006; Schmid et al., 2015).…”

Section: Discussionmentioning

confidence: 79%

Placebo‐like analgesia via response imagery

Peerdeman

Laarhoven

Bartels

et al. 2017

European Journal of Pain

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BackgroundPlacebo effects on pain are reliably observed in the literature. A core mechanism of these effects is response expectancies. Response expectancies can be formed by instructions, prior experiences and observation of others. Whether mental imagery of a response can also induce placebo‐like expectancy effects on pain has not yet been studied systematically.MethodsIn Study 1, 80 healthy participants were randomly allocated to (i) response imagery or (ii) control imagery. In Study 2, 135 healthy participants were randomly allocated to (i) response imagery with a verbal suggestion regarding its effectiveness, (ii) response imagery only, or (iii) no intervention. In both studies, expected and experienced pain during cold pressor tests were measured pre‐ and post‐intervention, along with psychological and physiological measures.ResultsParticipants rated pain as less intense after response imagery than after control imagery in Study 1 (p = 0.044, ηp2 = 0.054) and as less intense after response imagery (with or without verbal suggestion) than after no imagery in Study 2 (p < 0.001, ηp2 = 0.154). Adding a verbal suggestion did not affect pain (p = 0.068, ηp2 = 0.038). The effects of response imagery on experienced pain were mediated by expected pain.ConclusionsThus, in line with research on placebo effects, the current findings indicate that response imagery can induce analgesia, via its effects on response expectancies.SignificanceThe reported studies extend research on placebo effects by demonstrating that mental imagery of reduced pain can induce placebo‐like expectancy effects on pain.

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Section: Discussionmentioning

confidence: 79%

Placebo‐like analgesia via response imagery

Peerdeman

Laarhoven

Bartels

et al. 2017

European Journal of Pain

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“…In contrast to nocebo effects, placebo effects are the beneficial effects of a treatment, caused not by the drug itself but by psychological mechanisms (including positive expectations) that are elicited through the treatment context [10,11]. Seeing others' response to treatment can influence the viewer's expectations about how effective the treatment is, and conversely, the modeling of adverse events can influence expectations about treatment side effects and cause an increase in nocebo responding [12].…”

Section: Introductionmentioning

confidence: 99%

The Influence of Social Modeling, Gender, and Empathy on Treatment Side Effects

Faasse

Parkes

Kearney

et al. 2018

Annals of Behavioral Medicine

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Background Social modeling has the capacity to shape treatment outcomes, including side effects. Purpose This study investigated the influence of social modeling of treatment side effects, gender, and participant empathy, on side effects of a placebo treatment. Methods Ninety-six participants (48 females) completed a study purportedly investigating the influence of modafinil (actually placebo) on alertness and fatigue. The participants were randomly seated with a male or female confederate and saw this confederate report experiencing side effects or no side effects. Participant empathy was assessed at baseline. Changes in modeled and general symptoms, and misattribution of symptoms, were assessed during the session and at 24-hr follow-up. Results During the experimental session, seeing side effect modeling significantly increased modeled symptoms (p = .023, d = 0.56) but not general or misattributed symptoms. Regardless of modeling condition, female participants seated with a female model reported significantly more general symptoms during the session. However, response to social modeling did not differ significantly by model or participant gender. At follow-up, the effect of social modeling of side effects had generalized to other symptoms, resulting in significantly higher rates of modeled symptoms (p = .023, d = 0.48), general symptoms (p = .013, d = 0.49), and misattributed symptoms (p = .022, d = 0.50). The experience of modeled symptoms in response to social modeling was predicted by participants' levels of baseline empathy. Conclusions Social modeling of symptoms can increase the side effects following treatment, and this effect appears to generalize to a broader range of symptoms and symptom misattribution over time. Higher baseline empathy seems to increase response to social modeling.

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“…Previous studies show that placebo effects also vary across drug treatment trials for the same diseases, suggesting that placebo-drug interactions may exist (41). Knowledge about placebo-drug interactions is important for clinical trial design, as a placebo is commonly used in clinical trials as the direct, comparative arm for the treatment arm.…”

Section: Resultsmentioning

confidence: 99%