Are Children the Better Placebo Analgesia Responders? An Experimental Approach

Wrobel, Nathalie; Fadai, Tahmine; Sprenger, Christian; Wiech, Katja; Bingel, Ulrike

doi:10.1016/j.jpain.2015.06.013

Cited by 16 publications

(27 citation statements)

References 33 publications

(37 reference statements)

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“…Even in adolescents it was possible to experimentally induce placebo effects in the context of analgesia (25,26). In the context of cognitive performance, the experimental induction of placebo effects may not be as easy to perform as analgesia or possibly just under special circumstances (25,26). The lack of a placebo effect supports other findings that also could not induce placebo effects on cognition in a paradigm with methylphenidate which also used subjects, who have had no experience with this substance.…”

Section: Discussionmentioning

confidence: 59%

“…The latter describes their expectancy induced placebo analgesia response as substantially higher than those typically found in adults, yet a control group was not used. Contrary effects have not been more distinct compared to an adult control group (25). This finding raises the question whether the placebo effect in children or adolescents might depend on their disease and developmental state (25,27).…”

Section: Introductionmentioning

confidence: 78%

“…Contrary effects have not been more distinct compared to an adult control group (25). This finding raises the question whether the placebo effect in children or adolescents might depend on their disease and developmental state (25,27). Concerning the mechanisms of placebo effects in children and adolescents, higher learning capacities, associative learning, and learning capacities in general might play a more important role.…”

Section: Introductionmentioning

confidence: 83%

“…As mentioned in Introduction, the placebo effect in the context of analgesia is a well replicated phenomenon (1). Even in adolescents it was possible to experimentally induce placebo effects in the context of analgesia (25,26). In the context of cognitive performance, the experimental induction of placebo effects may not be as easy to perform as analgesia or possibly just under special circumstances (25,26).…”

Section: Discussionmentioning

confidence: 99%

“…In general, placebo responses in clinical trials tend to be higher in children and adolescents (24). In two of the few experimental studies on the placebo effect in children with similar designs, it was possible to induce placebo effects in healthy children in a heat placebo analgesia design (25,26). The latter describes their expectancy induced placebo analgesia response as substantially higher than those typically found in adults, yet a control group was not used.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Expectancy on Cognitive Performance, Mood, and Psychophysiology in Healthy Adolescents and Their Parents in an Experimental Study

Watolla¹,

Mazurak²,

Gruss

et al. 2020

Front. Psychiatry

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Objective: Placebo effects on cognitive performance and mood and their underlying mechanisms have rarely been investigated in adolescents. Therefore, the following hypotheses were investigated with an experimental paradigm: (1) placebo effects could be larger in adolescents than in adults, (2) parents' expectations influence their adolescents' expectations and placebo effects, and (3) a decrease in stress levels could be an underlying mechanism of placebo effects.Methods: Twenty-six healthy adolescents (13.8 ± 1.6 years, 14 girls) each with a parent (45.5 ± 4.2 years, 17 mothers) took part in an experimental within-subjects study. On two occasions, a transdermal patch was applied to their hips and they received an envelope containing either the information that it is a Ginkgo patch to improve cognitive performance and mood, or it is an inactive placebo patch, in counterbalanced order. Cognitive performance and mood were assessed with a parametric Go/No-Go task (PGNG), a modification of California Verbal Learning Test, and Profile of Mood Scales (POMS). Subjects rated their expectations about Ginkgo's effects before patch application as well as their subjective assessment of its effects after the tests. An electrocardiogram and skin conductance levels (SCLs) were recorded and root mean square of successive differences (RMSSD), high-frequency power (HF), and the area under the curve of the SCL (AUC) were analyzed as psychophysiological stress markers.Results: Expectations did not differ between adolescents and parents and were correlated concerning reaction times only. Overall, expectations did not influence placebo effects. There was only one significant placebo effect on the percentage of correct inhibited trials in one level of the PGNG in adolescents, but not in parents. RMSSD and HF significantly increased, and AUC decreased from pre-to post-patch application in adolescents, but not in parents.Conclusion: With this experimental paradigm, we could not induce relevant placebo effects in adolescents and parents. This could be due to aspects of the study design such as application form and substance, and that healthy subjects were employed. Nevertheless, we could show that adolescents are more sensitive to psychophysiological reactions related with interventions which could be part of the underlying mechanisms of placebo effects in adolescents.

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Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Effects of Expectancy on Cognitive Performance, Mood, and Psychophysiology in Healthy Adolescents and Their Parents in an Experimental Study

Watolla¹,

Mazurak²,

Gruss

et al. 2020

Front. Psychiatry

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Selbstheilungskräfte und der Placebo-Effekt

Grams¹

2017

Gesundheit!

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Placebo response rates and potential modifiers in double-blind randomized controlled trials of second and newer generation antidepressants for major depressive disorder in children and adolescents: a systematic review and meta-regression analysis

Meister

Abbas

Antel

et al. 2018

Eur Child Adolesc Psychiatry

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Children and adolescents with major depressive disorder (MDD) appear to be more responsive to placebo than adults in randomized placebo-controlled trials (RCTs) of second and newer generation antidepressants (SNG-AD). Previous metaanalyses obtained conflicting results regarding modifiers. We aimed to conduct a meta-analytical evaluation of placebo response rates based on both clinician-rating and self-rating scales. Based on the most recent and comprehensive study on adult data, we tested whether the placebo response rates in children and adolescents with MDD also increase with study duration and number of study sites. We searched systematically for published RCTs of SNG-AD in children and/or adolescents (last update: September 2017) in public domain electronic databases and additionally for documented studies in clinical trial databases. The log-transformed odds of placebo response were meta-analytically analyzed. The primary and secondary outcomes were placebo response rates at the end of treatment based on clinician-rating and self-rating scales, respectively. To examine the impact of study duration and number of study sites on placebo response rates, we performed simple meta-regression analyses. We selected other potential modifiers of placebo response based on significance in at least one previous pediatric meta-analysis and on theoretical considerations to perform explorative analyses. We applied sensitivity analyses with placebo response rates closest to week 8 to compare our data with those reported for adults. We identified 24 placebo-controlled trials (2229 patients in the placebo arms). The clinician-rated placebo response rates ranged from 22 to 62% with a pooled response rate of 45% (95% CI 41-50%). The number of study sites was a significant modifier in the simple meta-regression analysis [odds ratio (OR) 1.01, 95% CI 1.01-1.02, p = 0.0003, k = 24) with more study sites linked to a higher placebo response. Study duration was not significantly associated with the placebo response rate. The explorative simple analyses revealed that publication year may be an additional modifier. However, in the explorative multivariable analysis including the number of study sites and the publication year only the number of study sites reached a p value ≤ 0.05. The self-rated placebo response rates ranged from 1 to 68% with a pooled response rate of 26% (95% CI 10-54%) (k = 6; n = 396). This meta-analysis confirms a high pooled placebo response rate in children and adolescents based on clinician ratings, which exceeds that observed in the most recent meta-analysis of placebo effects in adults (36%; 95% CI 35-37%) published in 2016. However, and similar to findings in adults, the pooled response rates based on self-ratings were substantially lower. In accordance with previous meta-analyses, we corroborated the number of study sites as significant modifier. In Ramona Meister, Mariam Abbas and Jochen Antel contributed equally to the study.

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Are Children the Better Placebo Analgesia Responders? An Experimental Approach

Cited by 16 publications

References 33 publications

Effects of Expectancy on Cognitive Performance, Mood, and Psychophysiology in Healthy Adolescents and Their Parents in an Experimental Study

Effects of Expectancy on Cognitive Performance, Mood, and Psychophysiology in Healthy Adolescents and Their Parents in an Experimental Study

Selbstheilungskräfte und der Placebo-Effekt

Placebo response rates and potential modifiers in double-blind randomized controlled trials of second and newer generation antidepressants for major depressive disorder in children and adolescents: a systematic review and meta-regression analysis

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