Placebo effects in children: a review

Weimer, Katja; Gulewitsch, Marco Daniel; Schlarb, Angelika; Schwille‐Kiuntke, Juliane; Klosterhalfen, Sibylle; Enck, Paul

doi:10.1038/pr.2013.66

Cited by 147 publications

(140 citation statements)

References 76 publications

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“…It has been suggested that children and adolescents generally show larger PR than adults (6,8). Our experimental approach clearly confirms this age effect.…”

Section: Placebo Analgesia Responsessupporting

confidence: 86%

“…The literature regarding gender difference of PR is sparse and equivocal (62), and analyses of gender-specific PR in the pediatric population have been especially neglected (8). Whereas some reviews failed to find differences (63) others have reported a slight placebo susceptibility advantage for girls in a migraine headache review (64).…”

Section: Gender-dependent Differences In Pamentioning

confidence: 99%

“…This is especially noteworthy since evidence from the small number of pediatric clinical trials studies suggests that PR might be even more pronounced in children compared to adults (6)(7)(8). Clinical trials of local anesthetics (9,10) as well as a venipuncture study (11) emphasize the significance of PR in children.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Expectancy-Induced Placebo Analgesia in Children and the Role of Magical Thinking

Kempler

Kossowsky

Schwarz

et al. 2014

The Journal of Pain

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Expectations and beliefs shape the experience of pain. This is most evident in context-induced, placebo analgesia, which has recently been shown to interact with the trait of magical thinking (MT) in adults. In children, placebo analgesia and the possible roles that MT and gender might play as modulators of placebo analgesia have remained unexplored. Using a paradigm in which heat-pain stimuli were applied to both forearms, we investigated whether MT and gender can influence the magnitude of placebo analgesia in children. Participants were 49 right-handed children (aged 6-9 years) who were randomly assigned -stratified for MT and gender -to either an analgesia-expectation or a controlexpectation condition. For both conditions, the placebo was a blue-colored hand disinfectant that was applied to the children's forearms. Independent of MT, the placebo treatment significantly increased both heat pain threshold and tolerance. The threshold placebo effect was more pronounced for girls than boys. In addition, independent of the expectation treatment, low-MT boys showed a lower tolerance increase on the left compared to the right side. Finally, MT specifically modulated tolerance on the right forearmside: low-MT boys showed an increase, whereas high-MT boys showed a decrease in heat pain tolerance. This study documented a substantial expectation-induced placebo analgesia response in children (girls > boys) and demonstrated MT and gender-dependent laterality effects in pain perception. The findings may help improve individualized pain management for children. PERSPECTIVE: The study documents the first experimental evidence for a substantial expectancy-induced placebo analgesia response in healthy children from 6 to 9 years of age. Moreover, the effect was substantially higher than the placebo response typically found in adults. The findings may help improve individualized pain management for children. Conflicts of Interest and Source of FundingThe authors declare that there is no conflict of interest. This research was supported by the University of Basel.Running Title: Placebo Analgesia and Magical Thinking in Children Krummenacher et al., 2014 1 Abstract Objective: Higher brain functions such as expectations and beliefs shape the experience of pain. This is most evident in context-induced placebo analgesia (PA), which was recently shown in adults to interact with the trait of magical thinking (MT).In children, PA and the possible relationship between PA and MT has remained unexplored.Methods: Using a lateralized heat-pain paradigm, we investigated the possible modulatory role of PA expectation and MT in response to nociceptive stimuli on the right and left forearm.Participants were 49 right-handed children (6-9 years). In a between-subjects design, half of them were either randomly -stratified for MT and gender -assigned to an analgesia-expectation or a control-expectation condition. Results:Results indicate that, independent of MT, the placebo procedure significantly increased both heat pain threshold (...

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“…It has been suggested that children and adolescents generally show larger PR than adults (6,8). Our experimental approach clearly confirms this age effect.…”

Section: Placebo Analgesia Responsessupporting

confidence: 86%

Section: Gender-dependent Differences In Pamentioning

confidence: 99%

See 1 more Smart Citation

Expectancy-Induced Placebo Analgesia in Children and the Role of Magical Thinking

Kempler

Kossowsky

Schwarz

et al. 2014

The Journal of Pain

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“…While studies have reported a significant placebo response in adult patients (such as those with Parkinson's Disease [293]), placebo response rates are particularly high among children and adolescents in a subset of disorders, including psychiatric (anxiety, major depression, and obsessive compulsive and attention deficit disorders), medical (asthma), and painful (migraine, gastrointestinal) conditions [294,295]. As the current RCTs of CBD primarily target children with severe epilepsy, this may be an important issue.…”

Section: Placebo Effectmentioning

confidence: 99%

Cannabinoids and Epilepsy

et al. 2015

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Cannabis has been used for centuries to treat seizures. Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabisbased antiepileptic therapies. In this study, we review current understanding of the endocannabinoid system, characterize the pro-and anticonvulsive effects of cannabinoids [e.g., Δ9-tetrahydrocannabinol and cannabidiol (CBD)], and highlight scientific evidence from pre-clinical and clinical trials of cannabinoids in epilepsy. These studies suggest that CBD avoids the psychoactive effects of the endocannabinoid system to provide a well-tolerated, promising therapeutic for the treatment of seizures, while whole-plant cannabis can both contribute to and reduce seizures. Finally, we discuss results from a new multicenter, open-label study using CBD in a population with treatment-resistant epilepsy. In all, we seek to evaluate our current understanding of cannabinoids in epilepsy and guide future basic science and clinical studies.

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“…The reason for this is unknown, requiring further investigation, but study design is known to influence clinical trial success as well. Higher placebo responses have been observed in studies where the chances of receiving active treatment exceed 50% because there is a high expectation of improvement, [30,31] thus leading to poor discrimination between treatment groups. This study randomized subjects 2:1 active to placebo (67% chance of receiving active treatment) in part because of the observation that prospective participants in other food therapy trials with 1:1 randomization schemes were declining participation due to a high likelihood of receiving placebo treatment.…”

Section: Discussionmentioning

confidence: 99%