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Genetic Influence on Efficacy of Pharmacotherapy for Pediatric Attention-Deficit/Hyperactivity Disorder: Overview and Current Status of Research

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Abstract

Multiple stimulant and non-stimulant medications are approved for the treatment of attention-deficit/hyperactivity disorder (ADHD), one of the most prevalent childhood neurodevelopmental disorders. Choosing among the available agents and determining the most effective ADHD medication for a given child can be a time-consuming process due to the high inter-individual variability in treatment efficacy. As a result, there is growing interest in identifying predictors of ADHD medication response in children through the burgeoning field of pharmacogenomics. This article reviews childhood ADHD pharmacogenomics efficacy studies published during the last decade (2009–2019), which have largely focused on pharmacodynamic candidate gene investigations of methylphenidate and atomoxetine response, with a smaller number investigating pharmacokinetic candidate genes and genome-wide approaches. Findings from studies which have advanced the field of ADHD pharmacogenomics through investigation of meta-analytic approaches and gene–gene interactions are also overviewed. Despite recent progress, no one genetic variant or currently available pharmacogenomics test has demonstrated clinical utility in pinpointing the optimal ADHD medication for a given individual patient, highlighting the need for further investigation.

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Authors and Affiliations

  1. Division of Developmental and Behavioral Pediatrics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, MLC 4002, Cincinnati, OH, 45229, USA

    Nada A. Elsayed, Kaila M. Yamamoto & Tanya E. Froehlich

  2. Department of Gynecology and Obstetrics, Integrated Research Center for Fetal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Nada A. Elsayed

  3. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Tanya E. Froehlich

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TF is the principal investigator for a National Institutes of Mental Health (NIMH) award relating to methylphenidate. This NIMH funding is awarded to TF’s institution (so she does not receive any funding directly for this grant), and NIMH is a US government agency that does not have any financial stake in methylphenidate. NE and KY have no potential conflicts of interest to report.

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Elsayed, N.A., Yamamoto, K.M. & Froehlich, T.E. Genetic Influence on Efficacy of Pharmacotherapy for Pediatric Attention-Deficit/Hyperactivity Disorder: Overview and Current Status of Research. CNS Drugs 34, 389–414 (2020). https://doi.org/10.1007/s40263-020-00702-y

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