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Randomized Controlled Trial
. 2018 Mar;27(1):e1572.
doi: 10.1002/mpr.1572. Epub 2017 Jun 30.

Placebo response and its determinants in children with ADHD across multiple observers and settings: A randomized clinical trial

Weam Fageera  1   2 , Alexandru Traicu  3 , Sarojini M Sengupta  1   3 , Marie-Eve Fortier  1   2 , Zia Choudhry  1   2 , Aurélie Labbe  3   4 , Natalie Grizenko  1   3 , Ridha Joober  1   2   3
Affiliations
Randomized Controlled Trial

Placebo response and its determinants in children with ADHD across multiple observers and settings: A randomized clinical trial

Weam Fageera et al. Int J Methods Psychiatr Res. 2018 Mar.

Abstract

This study aims to quantify placebo response (PR) in children with attention deficit hyperactivity disorder (ADHD) as assessed by parents and teachers and to explore some of its determinants. Five hundred and forty children with ADHD (ages 6-12) were recruited to a randomized, double-blind, placebo-controlled crossover trial with methylphenidate. The main outcome variable was Conners' Global Index (CGI), based on assessment of behaviour by parents (CGI-P) and teacher (CGI-T). PR was calculated as the difference between CGI-P/T scores at baseline and placebo week. There was a highly significant PR as assessed by the parents' and teachers' (p < 0.001). The magnitude of PR as assessed by parents was greater (10.57 points) compared to that assessed by teachers (3.93 points). The determinants of PR were different between parents and teachers. For parents, income, marital status, education, maternal smoking during pregnancy, and prior psychostimulant exposure (PPE) showed a significant effect on PR. For teachers, only ethnicity and PPE had an effect. The pattern of PR revealed two distinct profiles that may shed some light on the mechanisms involved in PR. PR in children with ADHD varies depending on the setting of the observations and the evaluator. Several psychosocial factors have been identified as modulators of PR. This is relevant for the design and interpretation of clinical trials and for clinical practice.

Trial registration: ClinicalTrials.gov NCT00483106.

Keywords: ADHD; parents; placebo response; predictors; teachers.

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Figures

Figure 1
Figure 1
Study participants CONSORT flowchart
Figure 2
Figure 2
Changes in attention deficit hyperactivity disorder (ADHD) symptoms between baseline, placebo, and active‐medication week according to (a) the parents and (b) the teachers. A – Shows a significant difference between baseline week and placebo week scores (i.E. placebo response) as assessed by the Conners' Global Index for parents and teachers (CGI‐P and CGI‐T, respectively) (p < 0.001). B – Shows a significant difference between active‐medication week and placebo week scores (p < 0.001). C – Shows a significant difference between baseline week and acive‐medication week scores (i.E. treatment response) (p < 0.001). Error bars represent the standard deviation
Figure 3
Figure 3
Differences in CGI‐P and CGI‐T trajectories in groups stratified by factors associated with the placebo response. (A) to (C) show significant interactions between ethnicity and previous treatment with medication, respectively. (D) to (G) show significant interactions between parental marital status, parental income, maternal smoking during pregnancy, and maternal education, respectively, and the change in parents' CGI‐P scores between the baseline and placebo weeks
Figure 4
Figure 4
Components of placebo response
See this image and copyright information in PMC

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