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      Review and Consensus on Pharmacogenomic Testing in Psychiatry

      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 4 , 11 , 6 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 16 , 25 , 29 , 30 , 23 , 24 , 23 , 24 , 23 , 24 , 31 , 32 , 23 , 24
      Pharmacopsychiatry
      Georg Thieme Verlag KG

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          Abstract

          The implementation of pharmacogenomic (PGx) testing in psychiatry remains modest, in part due to divergent perceptions of the quality and completeness of the evidence base and diverse perspectives on the clinical utility of PGx testing among psychiatrists and other healthcare providers. Recognizing the current lack of consensus within the field, the International Society of Psychiatric Genetics assembled a group of experts to conduct a narrative synthesis of the PGx literature, prescribing guidelines, and product labels related to psychotropic medications as well as the key considerations and limitations related to the use of PGx testing in psychiatry. The group concluded that to inform medication selection and dosing of several commonly-used antidepressant and antipsychotic medications, current published evidence, prescribing guidelines, and product labels support the use of PGx testing for 2 cytochrome P450 genes (CYP2D6, CYP2C19). In addition, the evidence supports testing for human leukocyte antigen genes when using the mood stabilizers carbamazepine (HLA-A and HLA-B), oxcarbazepine (HLA-B), and phenytoin (CYP2C9, HLA-B). For valproate, screening for variants in certain genes (POLG, OTC, CSP1) is recommended when a mitochondrial disorder or a urea cycle disorder is suspected. Although barriers to implementing PGx testing remain to be fully resolved, the current trajectory of discovery and innovation in the field suggests these barriers will be overcome and testing will become an important tool in psychiatry.

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          Most cited references109

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          Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

          Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures.
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            Pharmacogenomics knowledge for personalized medicine.

            The Pharmacogenomics Knowledgebase (PharmGKB) is a resource that collects, curates, and disseminates information about the impact of human genetic variation on drug responses. It provides clinically relevant information, including dosing guidelines, annotated drug labels, and potentially actionable gene-drug associations and genotype-phenotype relationships. Curators assign levels of evidence to variant-drug associations using well-defined criteria based on careful literature review. Thus, PharmGKB is a useful source of high-quality information supporting personalized medicine-implementation projects.
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              Pharmacogenetics: from bench to byte--an update of guidelines.

              Currently, there are very few guidelines linking the results of pharmacogenetic tests to specific therapeutic recommendations. Therefore, the Royal Dutch Association for the Advancement of Pharmacy established the Pharmacogenetics Working Group with the objective of developing pharmacogenetics-based therapeutic (dose) recommendations. After systematic review of the literature, recommendations were developed for 53 drugs associated with genes coding for CYP2D6, CYP2C19, CYP2C9, thiopurine-S-methyltransferase (TPMT), dihydropyrimidine dehydrogenase (DPD), vitamin K epoxide reductase (VKORC1), uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), HLA-B44, HLA-B*5701, CYP3A5, and factor V Leiden (FVL).
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                Author and article information

                Journal
                Pharmacopsychiatry
                Pharmacopsychiatry
                Georg Thieme Verlag KG
                0176-3679
                1439-0795
                January 07 2021
                January 2021
                November 04 2020
                January 2021
                : 54
                : 01
                : 5-17
                Affiliations
                [1 ]Departments of Medical Genetics, Psychiatry, Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada
                [2 ]Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
                [3 ]Alberta Children’s Hospital Research Institute, Calgary, AB, Canada
                [4 ]Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia
                [5 ]Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Austria
                [6 ]Departments of Psychiatry, Medical Genetics and the Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada
                [7 ]Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia
                [8 ]South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia
                [9 ]Biopsychosocial Corporation (BioPsyC), non-profit association, Vienna, Austria
                [10 ]Department of Psychiatry and Psychotherapy, University of Münster, Germany
                [11 ]The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia
                [12 ]Department of Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy and Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA
                [13 ]Michigan Neuroscience Institute and Departments of Computational Medicine & Bioinformatics, Human Genetics and Psychiatry, The University of Michigan, Ann Arbor MI, USA
                [14 ]Institute of Psychiatry and Neuroscience of Paris, GHU Paris Psychiatrie & Neurosciences, University of Paris, Paris, France
                [15 ]Department of Psychiatry, McGill University, Montreal, Canada
                [16 ]Departments of Psychiatry and Genetics, Washington University School of Medicine in St. Louis, USA
                [17 ]Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
                [18 ]Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, Würzburg, Germany
                [19 ]Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany
                [20 ]Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Duisburg, Germany
                [21 ]Department of Psychiatry, Harvard Medical School, Cambridge Health Alliance, Cambridge, Massachusetts, USA
                [22 ]Institute of Biological Psychiatry, Capital Region Hospitals, Copenhagen, Denmark
                [23 ]Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
                [24 ]Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
                [25 ]Department of Biomedical Data Science, Stanford University, Stanford, California, USA
                [26 ]Department of Pharmacotherapy and Outcome Science, Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA
                [27 ]Human Genetics Branch, National Institute of Mental Health, Bethesda, MD, USA
                [28 ]Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany
                [29 ]Departments of Psychiatry and Neurology (Medicine), University of British Columbia, USA
                [30 ]KK Research Centre, KK Women’s and Children’s Hospital, Singapore, Singapore
                [31 ]Department of Psychiatry, Weill Cornell Medical College, New York-Presbyterian Westchester Division, White Plains, NY, USA
                [32 ]Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children’s Mercy Kansas City, Kansas City and School of Medicine, University of Missouri-Kansas City, Kansas City, MO, USA
                Article
                10.1055/a-1288-1061
                33147643
                5271394a-767a-43cb-b6aa-5192ad72cd78
                © 2021
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