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      Clinical Pharmacogenetics Implementation Consortium Guideline for Cytochrome P450 ( CYP ) 2D6 Genotype and Atomoxetine Therapy

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          Abstract

          Atomoxetine is a nonstimulant medication used to treat attention-deficit/hyperactivity disorder (ADHD). Cytochrome P450 (CYP)2D6 polymorphisms influence the metabolism of atomoxetine thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for atomoxetine based on CYP2D6 genotype (updates at www.cpicpgx.org).

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          Prevalence of Parent-Reported ADHD Diagnosis and Associated Treatment Among U.S. Children and Adolescents, 2016

          Melissa L. Danielson, Rebecca Bitsko, Reem Ghandour … (2018)
          The purpose of this study is to estimate the national prevalence of parent-reported attention deficit/hyperactivity disorder (ADHD) diagnosis and treatment among U.S. children 2–17 years of age using the 2016 National Survey of Children’s Health (NSCH). The NSCH is a nationally representative, cross-sectional survey of parents regarding their children’s health that underwent a redesign before the 2016 data collection. It included indicators of lifetime receipt of an ADHD diagnosis by a health care provider, whether the child currently had ADHD, and receipt of medication and behavioral treatment for ADHD. Weighted prevalence estimates were calculated overall and by demographic and clinical subgroups ( n = 45,736). In 2016, an estimated 6.1 million U.S. children 2–17 years of age (9.4%) had ever received an ADHD diagnosis. Of these, 5.4 million currently had ADHD, which was 89.4% of children ever diagnosed with ADHD and 8.4% of all U.S. children 2–17 years of age. Of children with current ADHD, almost two thirds (62.0%) were taking medication and slightly less than half (46.7%) had received behavioral treatment for ADHD in the past year; nearly one fourth (23.0%) had received neither treatment. Similar to estimates from previous surveys, there is a large population of U.S. children and adolescents who have been diagnosed with ADHD by a health care provider. Many, but not all, of these children received treatment that appears to be consistent with professional guidelines, though the survey questions are limited in detail about specific treatment types received. The redesigned NSCH can be used to annually monitor diagnosis and treatment patterns for this highly prevalent and high-impact neurodevelopmental disorder.
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            The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype.

            A Gaedigk, S Simon, R Pearce … (2008)
            Inferring CYP2D6 phenotype from genotype is increasingly challenging, considering the growing number of alleles and their range of activity. This complexity poses a challenge in translational research where genotyping is being considered as a tool to personalize drug therapy. To simplify genotype interpretation and improve phenotype prediction, we evaluated the utility of an "activity score" (AS) system. Over 25 CYP2D6 allelic variants were genotyped in 672 subjects of primarily Caucasian and African-American heritage. The ability of genotype and AS to accurately predict phenotype using the CYP2D6 probe substrate dextromethorphan was evaluated using linear regression and clustering methods. Phenotype prediction, given as a probability for each AS group, was most accurate if ethnicity was considered; among subjects with genotypes containing a CYP2D6*2 allele, CYP2D6 activity was significantly slower in African Americans compared to Caucasians. The AS tool warrants further prospective evaluation for CYP2D6 substrates and in additional ethnic populations.
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              Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update.

              K Crews, A Gaedigk, H. Dunnenberger … (2014)
              Codeine is bioactivated to morphine, a strong opioid agonist, by the hepatic cytochrome P450 2D6 (CYP2D6); hence, the efficacy and safety of codeine are governed by CYP2D6 activity. Polymorphisms are a major cause of CYP2D6 variability. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for codeine based on CYP2D6 genotype. This document is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP2D6 genotype and codeine therapy.
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                Author and article information

                Journal
                Title: Clinical Pharmacology & Therapeutics
                Abbreviated Title: Clin. Pharmacol. Ther.
                Publisher: Wiley
                ISSN (Print): 0009-9236
                ISSN (Electronic): 1532-6535
                Publication date Created: April 13 2019
                Publication date (Electronic): April 13 2019
                Affiliations
                [1 ]Department of Pharmacy Practice and Pharmaceutical SciencesUniversity of Minnesota College of Pharmacy Duluth Minnesota USA
                [2 ]Department of Experimental and Clinical PharmacologyCollege of PharmacyDepartment of PsychiatryMedical SchoolUniversity of Minnesota Minneapolis Minnesota USA
                [3 ]Department of Biomedical Data ScienceStanford University Stanford California USA
                [4 ]Division of Child and Adolescent PsychiatryDepartment of Psychiatry and Biobehavioral SciencesUniversity of California Los Angeles California USA
                [5 ]Campbell Family Mental Health Research InstituteCentre for Addiction and Mental Health Toronto Ontario Canada
                [6 ]Department of PsychiatryUniversity of Toronto Toronto Ontario Canada
                [7 ]Division of Clinical Pharmacology, Toxicology & Therapeutic InnovationDepartment of PediatricsChildren's Mercy Kansas City Kansas City Missouri USA
                [8 ]School of MedicineUniversity of Missouri‐Kansas City Kansas City Missouri USA
                [9 ]Department of Pharmaceutical SciencesSt. Jude Children's Research Hospital Memphis Tennessee USA
                [10 ]University of Kentucky Mental Health Research CenterEastern State Hospital Lexington Kentucky USA
                Article
                DOI: 10.1002/cpt.1409
                PMC ID: 6612570
                PubMed ID: 30801677
                SO-VID: e94d4920-4898-46b1-86e1-91a9039c8298
                Copyright © © 2019
                License:

                http://doi.wiley.com/10.1002/tdm_license_1.1

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