A Comprehensive Analysis Examining the Role of Genetic Influences on Psychotropic Medication Response in Children
Jatinder Singh1,2,3, Athina Manginas1,2,3, Georgina Wilkins1,2,3
1Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AE, UK.
Insights
Genetic factors significantly impact how children respond to psychotropic medications. This review highlights the role of non-CYP450 polymorphisms and ABCB1 variants in treatment outcomes for pediatric mental health conditions.
Area of Science:
- Pharmacogenomics and Child Psychiatry
- Precision Medicine in Pediatrics
Background:
- Psychotropic medications are widely used for pediatric mental health conditions.
- Genetic influences on treatment response in children remain under-investigated.
- A systematic review and thematic analysis were conducted to address this knowledge gap.
Purpose of the Study:
- To systematically review and analyze the genetic impact on psychotropic medication response in children.
- To identify key genetic factors and themes influencing treatment outcomes.
- To provide insights for clinical implementation and future research.
Main Methods:
- Systematic review and thematic analysis of 50 articles.
- PRISMA reporting guidelines were followed.
- Study quality assessed using Down and Blacks checklist; health economics by CHEERS checklist.
Main Results:
- Five key themes emerged: non-CYP450 polymorphisms, pediatric CYP450 pharmacogenetics, genetic predictors, implementation insights, and phenoconversion.
- Non-CYP450 variants are linked to epilepsy onset and treatment response.
- ABCB1 variants and phenoconversion of CYP2D6/CYP2C19 substrates affect medication response in mental health conditions.
Conclusions:
- Assessing non-CYP450 polymorphisms is crucial for optimizing psychotropic medication response, particularly in children with autism.
- A multidisciplinary approach can guide clinical decisions for complex neurodevelopmental profiles.
- Findings offer a valuable resource for clinicians, researchers, and policymakers in child psychiatry and pharmacogenomics.
Abstract:
Psychotropic medication is commonly used for the treatment of mental health conditions. However, the genetic factors that influence psychotropic medication responses in children have not been thoroughly investigated. To address this gap, a systematic review and thematic analysis were conducted to examine the genetic impact of psychotropic medication response in children. The Down and Blacks and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklists assessed the quality of studies and health economics, respectively. Using PRISMA reporting guidelines, 50 articles were identified with a sample size ranging from 2 to 2.9 million individuals. Most of the studies reported on ethnicity, and approximately half of the studies (24/50) were performed in North America. Five themes emerged from the thematic analysis: (1) implications of non-CYP450 polymorphisms, (2) paediatric CYP450 pharmacogenetics, (3) genetic predictors of response, (4) insights for implementation and future research and (5) phenoconversion. The thematic analysis revealed that assessment of non-CYP450 polymorphisms and psychotropic medication response, especially in those with mental health conditions such as autism, would be helpful. Epilepsy onset, risk and treatment response were associated with non-CYP450 genetic variants. Phenoconversion of substrates associated with CYP2D6 and CYP2C19 metabolisers is common in individuals with mental health conditions, and ABCB1 variants can influence psychotropic medication responses. A multidisciplinary model could also help guide clinical decision-making in cases involving complex neurodevelopmental profiles. Using the Down and Blacks checklist, the average score from the 50 studies was 17.7 points (min. 14, max. 24). The health economic evaluation of studies using the CHEERS checklist gave an average score of 33.0% (range: 21.4% to 35.7%). The study provides an important resource of information for healthcare professionals, researchers and policymakers working at the intersection of child psychiatry, pharmacogenomics and precision medicine.
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