Is the perceived placebo effect comparable between adults and children? A meta-regression analysis

Abstract

Background: A potential larger perceived placebo effect in children compared with adults could influence the detection of the treatment effect and the extrapolation of the treatment benefit from adults to children. This study aims to explore this potential difference, using a meta-epidemiological approach. Methods: A systematic review of the literature was done to identify trials included in meta-analyses evaluating a drug intervention with separate data for adults and children. The standardized mean change and the proportion of responders (binary outcomes) were used to calculate the perceived placebo effect. A meta-regression analysis was conducted to test for the difference between adults and children of the perceived placebo effect. results: For binary outcomes, the perceived placebo effect was significantly more favorable in children compared with adults (β = 0.13; P = 0.001). Parallel group trials (β = −1.83; P < 0.001), subjective outcomes (β = −0.76; P < 0.001), and the disease type significantly influenced the perceived placebo effect. conclusion: The perceived placebo effect is different between adults and children for binary outcomes. This difference seems to be influenced by the design, the disease, and outcomes. Calibration of new studies for children should consider cautiously the placebo effect in children.

Is Placebo Response Responsible for Many Phase III Failures?

“…A 2013 review indicated only 2.5% of articles discussed placebo response in pediatrics . A meta‐regression analysis showed a difference in placebo response between adults and children for binary outcomes (i.e., percent of responders), but not for continuous outcomes …”

Efficacy and Safety of Selective Serotonin Reuptake Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors, and Placebo for Common Psychiatric Disorders Among Children and Adolescents

“…While in line with older reviews in children 69 , this is in contrast to adult studies that found no significant differences in placebo effect size between depression and anxiety 70 . This contrast is not unique: placebo responses between children and adults differ significantly for binary outcomes across a wide variety of diseases 71 . One explanation might be that children and adolescents with MDD may be more demoralized than patients with anxiety disorders and are therefore more sensitive to changes in hope and favorable meanings 69 .…”

Adolescent and adult differences in major depression symptom profiles

“…In particular, selective serotonin reuptake inhibitors (SSRIs) and tricylic antidepressants show smaller effect sizes in treating depression in adolescents compared to adults (Hazell et al, 1995;Hazell & Mirzaie, 2013;Locher et al, 2017;Thapar et al, 2012). This may be partly due to a higher placebo response for depression in young people (Janiaud et al, 2017). Third generation antidepressants such as SNRIs and mirtazapine have not shown to be significantly better than placebo Locher et al, 2017).…”