Pharmacopsychiatry 2021; 54(01): 5-17
DOI: 10.1055/a-1288-1061
Review

Review and Consensus on Pharmacogenomic Testing in Psychiatry

Chad A. Bousman
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
,
Susanne A. Bengesser
5   Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Austria
,
Katherine J. Aitchison
6   Departments of Psychiatry, Medical Genetics and the Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada
,
Azmeraw T. Amare
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
,
Harald Aschauer
9   Biopsychosocial Corporation (BioPsyC), non-profit association, Vienna, Austria
,
Bernhard T. Baune
10   Department of Psychiatry and Psychotherapy, University of Münster, Germany
4   Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia
11   The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia
,
Bahareh Behroozi Asl
6   Departments of Psychiatry, Medical Genetics and the Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada
,
Jeffrey R. Bishop
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
,
Margit Burmeister
13   Michigan Neuroscience Institute and Departments of Computational Medicine & Bioinformatics, Human Genetics and Psychiatry, The University of Michigan, Ann Arbor MI, USA
,
Boris Chaumette
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
,
Li-Shiun Chen
16   Departments of Psychiatry and Genetics, Washington University School of Medicine in St. Louis, USA
,
Zachary A. Cordner
17   Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
,
Jürgen Deckert
18   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, Würzburg, Germany
,
Franziska Degenhardt
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
,
Lynn E. DeLisi
21   Department of Psychiatry, Harvard Medical School, Cambridge Health Alliance, Cambridge, Massachusetts, USA
,
Lasse Folkersen
22   Institute of Biological Psychiatry, Capital Region Hospitals, Copenhagen, Denmark
,
James L. Kennedy
23   Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
24   Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
,
Teri E. Klein
25   Department of Biomedical Data Science, Stanford University, Stanford, California, USA
,
Joseph L. McClay
26   Department of Pharmacotherapy and Outcome Science, Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA
,
Francis J. McMahon
27   Human Genetics Branch, National Institute of Mental Health, Bethesda, MD, USA
,
Richard Musil
28   Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany
,
Nancy L. Saccone
16   Departments of Psychiatry and Genetics, Washington University School of Medicine in St. Louis, USA
,
Katrin Sangkuhl
25   Department of Biomedical Data Science, Stanford University, Stanford, California, USA
,
Robert M. Stowe
29   Departments of Psychiatry and Neurology (Medicine), University of British Columbia, USA
,
Ene-Choo Tan
30   KK Research Centre, KK Women’s and Children’s Hospital, Singapore, Singapore
,
Arun K. Tiwari
23   Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
24   Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
,
Clement C. Zai
23   Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
24   Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
,
Gwyneth Zai
23   Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
24   Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
,
Jianping Zhang
31   Department of Psychiatry, Weill Cornell Medical College, New York-Presbyterian Westchester Division, White Plains, NY, USA
,
Andrea Gaedigk
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
,
Daniel J Müller
23   Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
24   Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
› Institutsangaben
Funding: The work was supported in part by an Alberta Innovates Strategic Research Project G2018000868 (Drs. Aitchison and Bousman), the Neuroscience and Mental Health Institute and Department of Psychiatry, University of Alberta (Ms. Behroozi Asi), NARSAD Young Investigator Grant from the Brain & Behaviour Research Foundation (Dr. Amare), the Foundation Bettencourt-Schueller (Dr. Chaumette), the European COST Action EnGagE CA17130 (Dr. Degenhardt), the German Federal Ministry of Education and Research e:Med programme (Dr. Degenhardt), the NIH/NHGRI U24 HG010615 (Drs. Klein and Sangkuhl), the NIH/NIGMS R24 GM123930 (Dr. Gaedigk), the NIDA R01 DA038076 (Dr. Li-Shiun), and the NIMH Intramural Research Program (Dr. McMahon).

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.



Publikationsverlauf

Eingereicht: 09. Juli 2020
Eingereicht: 05. Oktober 2020

Angenommen: 07. Oktober 2020

Artikel online veröffentlicht:
04. November 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Hiemke C, Bergemann N, Clement HW. et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: Update 2017. Pharmacopsychiatry 2018; 51: e1
  • 2 Müller DJ, Rizhanovsky Z. From the origins of pharmacogenetics to first applications in psychiatry. Pharmacopsychiatry 2020; 53: 155-161
  • 3 Haga SB, Kantor A. Horizon scan of clinical laboratories offering pharmacogenetic testing. Health Aff (Millwood) 2018; 37: 717-723
  • 4 Bousman CA, Hopwood M. Commercial pharmacogenetic-based decision-support tools in psychiatry. Lancet Psychiatry 2016; 3: 585-590
  • 5 Müller DJ, Kekin I, Kao AC. et al. Towards the implementation of CYP2D6 and CYP2C19 genotypes in clinical practice: Update and report from a pharmacogenetic service clinic. Int Rev Psychiatry 2013; 25: 554-571
  • 6 [Anonymous] Genetic testing and psychiatric disorders: A statement from the International Society of Psychiatric Genetics. Brentwood, TN: International Society of Psychiatric Genetics; 2019
  • 7 Henriques B, Lapetina D, Yavorskyy V. et al. How can drug metabolism and transporter genetics inform psychotropic prescribing?. Front Genet in press DOI: 10.3389/fgen.2020.491895.
  • 8 Gaedigk A, Ingelman-Sundberg M, Miller NA. et al. The Pharmacogene Variation (PharmVar) Consortium: Incorporation of the Human Cytochrome P450 (CYP) Allele Nomenclature Database. Clin Pharmacol Ther 2018; 103: 399-401
  • 9 Gaedigk A, Sangkuhl K, Whirl-Carrillo M. et al. The evolution of PharmVar. Clin Pharmacol Ther 2019; 105: 29-32
  • 10 Caudle KE, Dunnenberger HM, Freimuth RR. et al. Standardizing terms for clinical pharmacogenetic test results: Consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC). Genet Med 2017; 19: 215-223
  • 11 Blumenthal D. Pharmacodynamics: Molecular mechanisms of drug action. In: Laurence L, Brunton RH-D, Björn C. Knollmann. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 13th ed. 2018: 31-54
  • 12 Tangamornsuksan W, Chaiyakunapruk N, Somkrua R. et al. Relationship between the HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. JAMA Dermatol 2013; 149: 1025-1032
  • 13 Hicks JK, Bishop JR, Sangkuhl K. et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther 2015; 98: 127-134
  • 14 Jukić MM, Haslemo T, Molden E. et al. Impact of CYP2C19 genotype on escitalopram exposure and therapeutic failure: A retrospective study based on 2087 patients. Am J Psychiatry 2018; 175: 463-470
  • 15 Bråten LS, Haslemo T, Jukic MM. et al. Impact of CYP2C19 genotype on sertraline exposure in 1200 Scandinavian patients. Neuropsychopharmacology 2020; 45: 570-576
  • 16 Sinyor M, Schaffer A, Levitt A. The sequenced treatment alternatives to relieve depression (STAR*D) trial: A review. Can J Psychiatry 2010; 55: 126-135
  • 17 Uher R, Perroud N, Ng MY. et al. Genome-wide pharmacogenetics of antidepressant response in the GENDEP project. Am J Psychiatry 2010; 167: 555-564
  • 18 Investigators G, Investigators M, Investigators SD. Common genetic variation and antidepressant efficacy in major depressive disorder: A meta-analysis of 3 genome-wide pharmacogenetic studies. Am J Psychiatry 2013; 170: 207-217
  • 19 Probst-Schendzielorz K, Scholl C, Efimkina O. et al. CHL1, ITGB3, and SLC6A4 gene expression and antidepressant drug response: results from the Munich Antidepressant Response Signature (MARS) study. Pharmacogenomics 2015; 16: 689-701
  • 20 Biernacka JM, Sangkuhl K, Jenkins G. et al. The International SSRI Pharmacogenomics Consortium (ISPC): A genome-wide association study of antidepressant treatment response. Transl Psychiatry 2015; 5: e553
  • 21 Whirl-Carrillo M, McDonagh EM, Hebert JM. et al. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther 2012; 92: 414-417
  • 22 FDA. The FDA warns against the use of many genetic tests with unapproved claims to predict patient response to specific medications: FDA Safety Communication. Available at: https://www.fda.gov/medical-devices/safety-communications/fda-warns-against-use-many-genetic-tests-unapproved-claims-predict-patient-response-specific 2019
  • 23 Hicks JK, Bishop JR, Gammal RS. et al. A call for clear and consistent communications regarding the role of pharmacogenetics in antidepressant pharmacotherapy. Clin Pharmacol Ther 2020; 107: 50-52
  • 24 Hicks JK, Sangkuhl K, Swen JJ. et al. Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther 2016; 102: 37-44
  • 25 Swen JJ, Nijenhuis M, de Boer A. et al. Pharmacogenetics: From bench to byte—an update of guidelines. Clin Pharmacol Ther 2011; 89: 662-673
  • 26 [Anonymous] https://www.knmp.nl/patientenzorg/medicatiebewaking/farmacogenetica/pharmacogenetics-1/pharmacogenetics KNMP Apothekersorganisatie. 2019
  • 27 Zhang L, Brown SJ, Shan Y. et al. CYP2D6 genetic polymorphisms and risperidone pharmacokinetics: A systematic review and meta-analysis. Pharmacotherapy 2020; 40: 632-647
  • 28 Jukic MM, Smith RL, Haslemo T. et al. Effect of CYP2D6 genotype on exposure and efficacy of risperidone and aripiprazole: A retrospective, cohort study. Lancet. Psychiatry 2019; 6: 418-426
  • 29 Cui Y, Yan H, Su Y. et al. Genotype-based dose recommendations for risperidone in Asian people. Front Pharmacol 2020; 11: 936
  • 30 Kapur S, Mamo D. Half a century of antipsychotics and still a central role for dopamine D2 receptors. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27: 1081-1090
  • 31 Lieberman JA. Dopamine partial agonists: A new class of antipsychotic. CNS Drugs 2004; 18: 251-267
  • 32 Yoshida K, Müller DJ. Pharmacogenetics of antipsychotic drug treatment: update and clinical implications. Mol Neuropsychiatry 2020; 5: 1-26
  • 33 Olesen OV, Linnet K. Contributions of five human cytochrome P450 isoforms to the N-demethylation of clozapine in vitro at low and high concentrations. J Clin Pharmacol 2001; 41: 823-832
  • 34 Lesche D, Mostafa S, Everall I. et al. Impact of CYP1A2, CYP2C19, and CYP2D6 genotype- and phenoconversion-predicted enzyme activity on clozapine exposure and symptom severity. Pharmacogenomics J 2020; 20: 192-201
  • 35 Caudle KE, Rettie AE, Whirl-Carrillo M. et al. Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Clin Pharmacol Ther 2014; 96: 542-548
  • 36 Hou L, Heilbronner U, Degenhardt F. et al. Genetic variants associated with response to lithium treatment in bipolar disorder: A genome-wide association study. Lancet 2016; 387: 1085-1093
  • 37 Chen CH, Lee CS, Lee MT. et al. Variant GADL1 and response to lithium therapy in bipolar I disorder. N Engl J Med 2014; 370: 119-128
  • 38 Song J, Bergen SE, Di Florio A. et al. Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder. Mol Psychiatry 2017; 22: 1223
  • 39 Amare AT, Schubert KO, Hou L. et al. Association of polygenic score for schizophrenia and hla antigen and inflammation genes with response to lithium in bipolar affective disorder: A genome-wide association study. JAMA Psychiatry 2018; 75: 65-74
  • 40 Amare AT, Schubert KO, Hou L. et al. Association of polygenic score for major depression with response to lithium in patients with bipolar disorder. Mol Psychiatry DOI: 10.1038/s41380-020-0689-5.
  • 41 Manson L, Swen J, Guchelaar H. Diagnostic Test criteria for HLA genotyping to prevent drug hypersensitivity reactions: A systematic review of actionable HLA recommendations in CPIC and DPWG Guidelines. Frontiers in Pharmacologyin press DOI: 10.3389/fphar.2020.567048.
  • 42 Bloch KM, Sills GJ, Pirmohamed M. et al. Pharmacogenetics of antiepileptic drug-induced hypersensitivity. Pharmacogenomics 2014; 15: 857-868
  • 43 Deng Y, Li S, Zhang L. et al. Association between HLA alleles and lamotrigine-induced cutaneous adverse drug reactions in Asian populations: A meta-analysis. Seizure 2018; 60: 163-171
  • 44 Phillips EJ, Sukasem C, Whirl-Carrillo M. et al. Clinical pharmacogenetics implementation consortium guideline for hla genotype and use of carbamazepine and oxcarbazepine: 2017 update. Clin Pharmacol Ther 2018; 103: 574-581
  • 45 Satapornpong P, Jinda P, Jantararoungtong T. et al. Genetic diversity of HLA class I and class II alleles in Thai populations: Contributions to genotype-guided therapeutics. Front Pharmacol 2020; 11: 78
  • 46 Lin CW, Huang WI, Chao PH. et al. Temporal trends and patterns in carbamazepine use, related severe cutaneous adverse reactions, and HLA-B*15:02 screening: A nationwide study. Epilepsia 2018; 59: 2325-2339
  • 47 Chen Z, Liew D, Kwan P. Effects of a HLA-B*15:02 screening policy on antiepileptic drug use and severe skin reactions. Neurology 2014; 83: 2077-2084
  • 48 Sukasem C, Chantratita W. A success story in pharmacogenomics: genetic ID card for SJS/TEN. Pharmacogenomics 2016; 17: 455-458
  • 49 Finsterer J, Segall L. Drugs interfering with mitochondrial disorders. Drug Chem Toxicol 2010; 33: 138-151
  • 50 Seo T, Nagata R, Ishitsu T. et al. Impact of CYP2C19 polymorphisms on the efficacy of clobazam therapy. Pharmacogenomics 2008; 9: 527-537
  • 51 de Leon J, Spina E, Diaz FJ. Clobazam therapeutic drug monitoring: A comprehensive review of the literature with proposals to improve future studies. Ther Drug Monit 2013; 35: 30-47
  • 52 Sohn DR, Kusaka M, Ishizaki T. et al. Incidence of S-mephenytoin hydroxylation deficiency in a Korean population and the interphenotypic differences in diazepam pharmacokinetics. Clin Pharmacol Ther 1992; 52: 160-169
  • 53 Tomasi J, Lisoway AJ, Zai CC. et al. Towards precision medicine in generalized anxiety disorder: review of genetics and pharmaco(epi)genetics. J Psychiatr Res 2019; 119: 33-47
  • 54 Brown JT, Bishop JR, Sangkuhl K. et al. Clinical pharmacogenetics implementation consortium guideline for cytochrome P450 (CYP)2D6 genotype and atomoxetine therapy. Clin Pharmacol Ther 2019; 106: 94-102
  • 55 Stage C, Dalhoff K, Rasmussen HB. et al. The impact of human CES1 genetic variation on enzyme activity assessed by ritalinic acid/methylphenidate ratios. Basic Clin Pharmacol Toxicol 2019; 125: 54-61
  • 56 Saccone NL, Baurley JW, Bergen AW. et al. The value of biosamples in smoking cessation trials: a review of genetic, metabolomic, and epigenetic findings. Nicotine Tob Res 2018; 20: 403-413
  • 57 Salloum NC, Buchalter ELF, Chanani S. et al. From genes to treatments: a systematic review of the pharmacogenetics in smoking cessation. Pharmacogenomics 2018; 19: 861-871
  • 58 Chen LS, Hartz SM, Baker TB. et al. Use of polygenic risk scores of nicotine metabolism in predicting smoking behaviors. Pharmacogenomics 2018; 19: 1383-1394
  • 59 Lerman C, Schnoll RA, Hawk LW. et al. Use of the nicotine metabolite ratio as a genetically informed biomarker of response to nicotine patch or varenicline for smoking cessation: A randomised, double-blind placebo-controlled trial. Lancet Respir Med 2015; 3: 131-138
  • 60 Dennis BB, Bawor M, Thabane L. et al. Impact of ABCB1 and CYP2B6 genetic polymorphisms on methadone metabolism, dose and treatment response in patients with opioid addiction: A systematic review and meta-analysis. PLoS One 2014; 9: e86114
  • 61 Crist RC, Reiner BC, Berrettini WH. A review of opioid addiction genetics. Curr Opin Psychol 2019; 27: 31-35
  • 62 Liu M, Jiang Y, Wedow R. et al. Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. Nat Genet 2019; 51: 237-244
  • 63 Berrettini W. A brief review of the genetics and pharmacogenetics of opioid use disorders. Dialogues Clin Neurosci 2017; 19: 229-236
  • 64 Schwantes-An TH, Zhang J, Chen LS. et al. Association of the OPRM1 Variant rs1799971 (A118G) with non-specific liability to substance dependence in a collaborative de novo meta-analysis of European-Ancestry cohorts. Behav Genet 2016; 46: 151-169
  • 65 Bousman C, Maruf AA, Müller DJ. Towards the integration of pharmacogenetics in psychiatry: a minimum, evidence-based genetic testing panel. Curr Opin Psychiatry 2019; 32: 7-15
  • 66 Chua EW, Kennedy MA. Current state and future prospects of direct-to-consumer pharmacogenetics. Front Pharmacol 2012; 3: 152
  • 67 Fan M, Bousman CA. Commercial pharmacogenetic tests in psychiatry: do they facilitate the implementation of pharmacogenetic dosing guidelines?. Pharmacopsychiatry 2020; 53: 174-178
  • 68 Bousman CA, Jaksa P, Pantelis C. Systematic evaluation of commercial pharmacogenetic testing in psychiatry: A focus on CYP2D6 and CYP2C19 allele coverage and results reporting. Pharmacogenet Genomics 2017; 27: 387-393
  • 69 de Leon J, Spina E. What is needed to incorporate clinical pharmacogenetic tests into the practice of psychopharmacotherapy?. Expert Rev Clin Pharmacol 2016; 9: 351-354
  • 70 Pratt VM, Cavallari LH, Del Tredici AL. et al. Recommendations for clinical CYP2C9 genotyping allele selection: A joint recommendation of the Association for Molecular Pathology and College of American Pathologists. J Mol Diagn 2019; 21: 746-755
  • 71 Pratt VM, Del Tredici AL, Hachad H. et al. Recommendations for clinical CYP2C19 genotyping allele selection: A report of the Association for Molecular Pathology. J Mol Diagn 2018; 20: 269-276
  • 72 Bousman CA, Zierhut H, Müller DJ. Navigating the labyrinth of pharmacogenetic testing: A guide to test selection. Clin Pharmacol Ther 2019; 106: 309-312
  • 73 Nofziger C, Paulmichl M. Accurately genotyping CYP2D6: not for the faint of heart. Pharmacogenomics 2018; 19: 999-1002
  • 74 Nofziger C, Turner AJ, Sangkuhl K. et al. PharmVar GeneFocus: CYP2D6. Clin Pharmacol Ther 2020; 107: 154-170
  • 75 Ingelman-Sundberg M, Mkrtchian S, Zhou Y. et al. Integrating rare genetic variants into pharmacogenetic drug response predictions. Hum Genomics 2018; 12: 26
  • 76 Haga SB, O‘Daniel JM, Tindall GM. et al. Survey of US public attitudes toward pharmacogenetic testing. Pharmacogenomics J 2012; 12: 197-204
  • 77 Walden LM, Brandl EJ, Tiwari AK. et al. Genetic testing for CYP2D6 and CYP2C19 suggests improved outcome for antidepressant and antipsychotic medication. Psychiatry Res 2019; 279: 111-115
  • 78 Walden LM, Brandl EJ, Changasi A. et al. Physicians’ opinions following pharmacogenetic testing for psychotropic medication. Psychiatry Res 2015; 229: 913-918
  • 79 Stanek EJ, Sanders CL, Taber KA. et al. Adoption of pharmacogenomic testing by US physicians: results of a nationwide survey. Clin Pharmacol Ther 2012; 91: 450-458
  • 80 Brown L, Eum S, Haga SB. et al. Clinical utilization of pharmacogenetics in psychiatry - perspectives of pharmacists, genetic counselors, implementation science, clinicians, and industry. Pharmacopsychiatry 2020; 53: 162-173
  • 81 McKillip RP, Borden BA, Galecki P. et al. Patient perceptions of care as influenced by a large institutional pharmacogenomic implementation program. Clin Pharmacol Ther 2017; 102: 106-114
  • 82 Haga SB. Challenges of development and implementation of point of care pharmacogenetic testing. Expert Rev Mol Diagn 2016; 16: 949-960
  • 83 Chan J, Soraya GV, Craig L. et al. Rapid detection of HLA-B*57:01-expressing cells using a label-free interdigitated electrode biosensor platform for prevention of abacavir Hypersensitivity in HIV treatment. Sensors (Basel) 2019; 19: 3543
  • 84 Paterson J. Pharmacogenetic testing a growing area as pilot projects, research get underway. benefitscanada.com. February 1 2018
  • 85 Bousman CA, Arandjelovic K, Mancuso SG. et al. Pharmacogenetic tests and depressive symptom remission: a meta-analysis of randomized controlled trials. Pharmacogenomics 2019; 20: 37-47
  • 86 Rosenblat JD, Lee Y, McIntyre RS. The effect of pharmacogenomic testing on response and remission rates in the acute treatment of major depressive disorder: a meta-analysis. J Affect Disord 2018; 241: 484-491
  • 87 Greden JF, Parikh SV, Rothschild AJ. et al. Impact of pharmacogenomics on clinical outcomes in major depressive disorder in the GUIDED trial: a large, patient- and rater-blinded, randomized, controlled study. J Psychiatr Res 2019; 111: 59-67
  • 88 Perlis RH, Dowd D, Fava M. et al. Randomized, controlled, participant- and rater-blind trial of pharmacogenomic test-guided treatment versus treatment as usual for major depressive disorder. Depress Anxiety 2020; 37: 834-841
  • 89 Zeier Z, Carpenter LL, Kalin NH. et al. Clinical implementation of pharmacogenetic decision support tools for antidepressant drug prescribing. Am J Psychiatry 2018; 175: 873-886
  • 90 Benitez J, Cool CL, Scotti DJ. Use of combinatorial pharmacogenomic guidance in treating psychiatric disorders. Per Med 2018; 15: 481-494
  • 91 Perlis RH, Mehta R, Edwards AM. et al. Pharmacogenetic testing among patients with mood and anxiety disorders is associated with decreased utilization and cost: a propensity-score matched study. Depress Anxiety 2018; 35: 946-952
  • 92 Berm EJ, Looff M, Wilffert B. et al. Economic evaluations of pharmacogenetic and pharmacogenomic screening tests: A systematic review. Second update of the literature. PLoS One 2016; 11: e0146262
  • 93 Brown LC, Lorenz RA, Li J. et al. Economic utility: combinatorial pharmacogenomics and medication cost savings for mental health care in a primary care setting. Clin Ther 2017; 39: e591
  • 94 Chou WH, Yan FX, de Leon J. et al. Extension of a pilot study: Impact from the cytochrome P450 2D6 polymorphism on outcome and costs associated with severe mental illness. J Clin Psychopharmacol 2000; 20: 246-251
  • 95 Maciel A, Cullors A, Lukowiak AA. et al. Estimating cost savings of pharmacogenetic testing for depression in real-world clinical settings. Neuropsychiatr Dis Treat 2018; 14: 225-230
  • 96 Caudle KE, Sangkuhl K, Whirl-Carrillo M. et al. Standardizing CYP2D6 genotype to phenotype translation: consensus recommendations from the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group. Clin Transl Sci 2019; 13: 116-124
  • 97 Bousman CA, Eyre HA. “Black box” pharmacogenetic decision-support tools in psychiatry. Braz J Psychiatry 2020; 42: 113-115
  • 98 Bousman CA, Dunlop BW. Genotype, phenotype, and medication recommendation agreement among commercial pharmacogenetic-based decision support tools. Pharmacogenomics J 2018; 18: 613-622
  • 99 Tandy-Connor S, Guiltinan J, Krempely K. et al. False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care. Genet Med 2018; 20: 1515-1521
  • 100 Shiroma PR, Geda YE, Mrazek DA. Pharmacogenomic implications of variants of monoaminergic-related genes in geriatric psychiatry. Pharmacogenomics 2010; 11: 1305-1330
  • 101 Franconi F, Campesi I. Sex impact on biomarkers, pharmacokinetics and pharmacodynamics. Curr Med Chem 2017; 24: 2561-2575
  • 102 Sugarman EA, Cullors A, Centeno J. et al. Contribution of pharmacogenetic testing to modeled medication change recommendations in a long-term care population with polypharmacy. Drugs Aging 2016; 33: 929-936
  • 103 Kisor DF, Bodzin AS. Pharmacogenomics in liver transplantation: testing the recipient and the ex-vivo donor liver. Pharmacogenomics 2018; 19: 753-756
  • 104 Stanke-Labesque F, Gautier-Veyret E, Chhun S. et al. Inflammation is a major regulator of drug metabolizing enzymes and transporters: consequences for the personalization of drug treatment. Pharmacol Ther 2020; 215: 107627-107648
  • 105 Shah RR, Smith RL. Inflammation-induced phenoconversion of polymorphic drug metabolizing enzymes: hypothesis with implications for personalized medicine. Drug Metab Dispos 2015; 43: 400-410
  • 106 Smit C, De Hoogd S, Brüggemann RJM. et al. Obesity and drug pharmacology: a review of the influence of obesity on pharmacokinetic and pharmacodynamic parameters. Expert Opin Drug Metab Toxicol 2018; 14: 275-285
  • 107 Klomp SD, Manson ML, Guchelaar HJ. et al. Phenoconversion of cytochrome P450 metabolism: a systematic review. J Clin Med 2020; 9: E2890
  • 108 de Leon J. Personalizing dosing of risperidone, paliperidone and clozapine using therapeutic drug monitoring and pharmacogenetics. Neuropharmacology 2020; 168: 107656
  • 109 Brown JT, Bishop JR, Schneiderhan ME. Using pharmacogenomics and therapeutic drug monitoring to guide drug selection and dosing in outpatient mental health comprehensive medication management. Ment Health Clin 2020; 10: 254-258
  • 110 Gaedigk A, Sangkuhl K, Whirl-Carrillo M. et al. Prediction of CYP2D6 phenotype from genotype across world populations. Genet Med 2017; 19: 69-76
  • 111 PharmGKB. PGx gene-specific information tables www.pharmgkb.org/page/pgxGeneRef accessed September 15, 2020
  • 112 Botton MR, Whirl-Carrillo M, Del Tredici AL. et al. PharmVar GeneFocus: CYP2C19. Clin Pharmacol Ther DOI: 10.1002/cpt.1973.
  • 113 Blagec K, Koopmann R, Crommentuijn-van Rhenen M. et al. Implementing pharmacogenomics decision support across seven European countries: The Ubiquitous Pharmacogenomics (U-PGx) project. J Am Med Inform Assoc 2018; 25: 893-898