Individual Participant Data Meta-Analysis: Moderators of Response to Stimulants for Preschool
Luis C Farhat1, Luisa Shiguemi Sugaya2, Michael H Bloch3
1Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil; School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, United Kingdom.
Insights
Stimulants may be more effective for White children with attention-deficit/hyperactivity disorder (ADHD) compared to Black children. Race, not age or symptom severity, might influence stimulant effectiveness in preschoolers with ADHD.
Area of Science:
- Pediatric Psychiatry
- Neurodevelopmental Disorders
- Pharmacological Treatments
Background:
- Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in preschool children.
- Stimulant medications are frequently prescribed for ADHD, but individual responses can vary.
- Identifying moderators of treatment efficacy is crucial for personalized medicine.
Purpose of the Study:
- To identify factors that predict the effectiveness of stimulant medications versus placebo in preschoolers with ADHD.
- To inform personalized treatment recommendations for young children diagnosed with ADHD.
Main Methods:
- Individual participant data from two randomized placebo-controlled trials (MAPPA and SPD489-347) were analyzed.
- Moderator effects of baseline demographic and clinical characteristics on ADHD symptom severity were evaluated.
- Meta-analyses pooled subgroup data from additional studies (PATS) where possible.
Main Results:
- Stimulant efficacy was greater in White children compared to Black children in US-based studies.
- Older age did not moderate stimulant efficacy and was not linked to worse outcomes.
- Higher baseline ADHD symptom severity predicted greater endpoint severity, irrespective of treatment.
Conclusions:
- Race appears to be a potential moderator of stimulant efficacy in preschool ADHD.
- Age and baseline symptom severity did not emerge as significant moderators in this analysis.
- Findings are exploratory and require confirmation in future research.
Objective:
This study aimed to identify moderators of efficacy of stimulants against placebo to inform personalized recommendations for treatment in preschool children (<6 years of age) with attention-deficit/hyperactivity disorder (ADHD).
Method:
We acquired individual-level participant data from 2 randomized placebo-controlled trials (RCTs) of preschool ADHD: namely, MAPPA (8-week methylphenidate, 102 participants, Brazil) and SPD489-347 (6-week lisdexamfetamine, 148 participants, United States). We evaluated the moderator and predictor effects of baseline demographic (age, sex, race, ethnicity, maternal educational level) and baseline clinical (ADHD symptom severity, intelligence quotient, number of psychiatric comorbidities) characteristics, as available, on endpoint ADHD symptom severity scores. Data from each study were analyzed separately with linear mixed-effects model for repeated measures. For categorical variables, we also computed treatment effects (ie, stimulants vs placebo) within subgroups and, when possible, pooled them alongside subgroup data from the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS) (5-week methylphenidate, 165 participants, United States) in random-effects meta-analyses.
Results:
Stimulants had greater efficacy against placebo in White children compared to Black children when considering data from US studies. Older age was not a moderator of greater efficacy of stimulants against placebo, nor was it associated with worse ADHD symptom severity at endpoint. Greater baseline ADHD symptom severity was associated with higher ADHD symptom severity at endpoint independently of the assigned treatment group.
Conclusion:
Race, but not older age or baseline ADHD symptom severity, may moderate the efficacy of stimulants for preschool ADHD. Given the post hoc nature of subgroup analyses, the findings should be interpreted as exploratory and viewed as hypotheses for confirmation in future studies.
Plain Language Summary:
In this individual participant meta-analysis, the authors obtained data from 2 clinical trials of psychostimulants for preschool children (aged 6 years or younger) with attention-deficit/hyperactivity disorder (ADHD) to investigate associations between demographic, clinical characteristics, and treatment effects. One study was focused on methylphenidate and was conducted in Brazil with 102 participants. The other study focused on lisdexamfetamine and was conducted in the United States with 148 participants. Some analyses also included subgroup data from a study focused on methylphenidate and was conducted in the US with 165 participants. In the US studies, stimulants appeared to work better in White children than in Black children, while older age or clinical severity was not associated with effectiveness of stimulants. The authors emphasize that these findings are exploratory and should be confirmed in future studies before guiding clinical decisions.
Clinical Trial Registration Information:
Safety and Efficacy Study in Preschool Children Aged 4-5 Years With Attention-deficit/Hyperactivity Disorder (ADHD); https://clinicaltrials.gov/study/NCT03260205; Early Interventions in Children With Attention Deficit/Hyperactivity Disorder; https://clinicaltrials.gov/study/NCT02807870.
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