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Expert Review of Precision Medicine and Drug Development
Personalized medicine in drug development and clinical practice
Volume 1, 2016 - Issue 5
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Review

The pharmacogenetic road to avoid adverse drug reactions and therapeutic failures in revolving door patients with psychiatric illnesses: focus on the CYP2D6 isoenzymes

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Pages 431-442 | Received 23 Mar 2016, Accepted 24 Aug 2016, Published online: 14 Sep 2016

References

  • Global Burden of Disease at the Institute for Health Metrics and Evaluation. [cited 2016 May 6]. Available from: http://www.healthdata.org/gbd
  • National Comorbidity Survey. [cited 2016 May 6]. Available from: http://www.hcp.med.harvard.edu/ncs/
  • Begley CE, Annegers JF, Swann AC, et al. The lifetime cost of bipolar disorder in the US: an estimate for new cases in 1998. Pharmacoeconomics. 2001;19:483–495.
  • Hakkaart-van Roijen L, Hoeijenbos MB, Regeer EJ, et al. The societal costs and quality of life of patients suffering from bipolar disorder in the Netherlands. Acta Psychiatr Scand. 2004;110(5):383–392.
  • Degli Esposti L, Sangiorgi D, Mencacci C, et al. Pharmaco-utilisation and related costs of drugs used to treatschizophrenia and bipolar disorder in Italy: the IBIS study. BMC Psychiatry. 2014;14(1):282.
  • Suppes T, Dennehy EB, Hirschfeld RM, et al. Texas consensus conference panel onmedication treatment of bipolar disorder. the Texas implementation of medication algorithms: update to the algorithms for treatment of bipolar I disorder. J Clin Psychiatry. 2005;66:870–886.
  • Perlis RH, Keck PE. The Texas implementation of medication algorithms update for treatment of bipolar I disorder. J Clin Psychiatry. 2005;66(7):818–820.
  • Yatham LN, Kennedy SH, Parikh SV, et al. Canadian networkfor mood and anxiety treatments (CANMAT) and international society for bipolar disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disord. 2013;15:1–44.
  • Thase ME. New approaches to managing difficult-to-treat depressions. J Clin Psychiatry. 2003;64(Suppl 1):3–4.
  • Bauer M, Pfennig A, Severus E, et al. World federation of societies of biological psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders. World J Biol Psychiatry. 2013;14:334–385.
  • Brandl EJ, Kennedy JL, Müller DJ. Pharmacogenetics of antipsychotics. Can J Psychiatry. 2014;59(2):76–88.
  • Kirchheiner J, Nickchen K, Bauer M, et al. Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry. 2004;9(5):442–473.
  • Stingl J, Viviani R. Polymorphism in CYP2D6 and CYP2C19, members of the cytochrome P450 mixed-function oxidase system, in the metabolism of psychotropic drugs. J Intern Med. 2015;277:167–177.
  • Murru A, Popovic D, Pacchiarotti I, et al. Management of adverse effects of mood stabilizers. Curr Psychiatry Rep. 2015;17(8):66.
  • Moore TR, Hill AM, Panguluri SK. Pharmacogenomics in psychiatry: implications for practice. Recent Pat Biotechnol. 2014;8(2):152–159.
  • Lewis T, Joyce P. The new revolving-door patients: results from a national cohort of first admissions. Acta Psychiatr Scand. 1990;82(2):130–135.
  • Marcum ZA, Pugh MJ, Amuan ME, et al. Prevalence of potentially preventable unplanned hospitalizations caused by therapeutic failures and adverse drug withdrawal events among older veterans. J Gerontol A BiolSci Med Sci. 2012;67(8):867–874.
  • Patel RS, Marcum ZA, Peron EP, et al. Prevalence of and factors associated with therapeutic failure-related hospitalizations in the elderly. Consult Pharm. 2014;29(6):376–386.
  • AHRQ - Agency for Healthcare Research and Quality, Advancing Excellence in Health Care. Reducing and Preventing Adverse Drug Events To Decrease Hospital Costs. Research in action. Issue. [cited 2016 Mar 22]. Available from: http://archive.ahrq.gov/research/findings/factsheets/errors-safety/aderia/ade.html
  • Franceschi M, Scarcelli C, Niro V, et al. Prevalence, clinical features and avoidability of adverse drug reactions as cause of admission to a geriatric unit: a prospective study of 1756 patients. Drug Saf. 2008;31(6):545–556.
  • Petrovic M, van der Cammen T, Onder G. Adverse drug reactions in older people: detection and prevention. Drugs Aging. 2012;29(6):453–462.
  • Moore TJ, Cohen MR, Furberg CD. Serious adverse drug events reported to the food and drug administration, 1998–2005. Arch Intern Med. 2007;167(16):1752–1759.
  • Miguel A, Azevedo LF, Araújo M, et al. Frequency of adverse drug reactions in hospitalized patients: a systematic review and meta-analysis. Pharmacoepidemiol Drug Saf. 2012;21(11):1139–1154.
  • Seripa D, Panza F, Daragjati J, et al. Measuring pharmacogenetics in special groups: geriatrics. Expert Opin Drug MetabToxicol. 2015;11(7):1073–1088.
  • Basile VS, Masellis M, Potkin SG, et al. Pharmacogenomics in schizophrenia: the quest for individualized therapy. Hum Mol Genet. 2002;11(20):2517–2530.
  • Jenike MA. Clinical practice. Obsessive-compulsive disorder. N Engl J Med. 2004;350(3):259–265.
  • Gonzalez FJ, Nebert DW. Evolution of the P450 gene superfamily: animal–plant ‘warfare’, molecular drive and human genetic differences in drug oxidation. Trends Genet. 1990;6(6):182–186.
  • Nelson DR. Metazoan cytochrome P450 evolution. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1998;121(1–3):15–22.
  • Ingelman-Sundberg M, Oscarson M, McLellan RA. Polymorphic human cytochrome P450 enzymes: an opportunity for individualized drug treatment. Trends Pharmacol Sci. 1999;20(8):342–349.
  • Pilotto A, Panza F, Seripa D. Pharmacogenetics in geriatric medicine: challenges and opportunities for clinical practice. Curr Drug Metab. 2011;12(7):621–634.
  • Seripa D, Paroni G, Urbano M, et al. Pharmacogenetics in older people: what we know and what we need to know. J Nephrol. 2012;25(Suppl 19):S38–S47.
  • Thomas JH. Rapid birth-death evolution specific to xenobiotic cytochrome P450 genes in vertebrates. PLoS Genet. 2007;3(5):e67.
  • Sim SC, Ingelman-Sundberg M. The human cytochrome P450 Allele nomenclature committee web site: submission criteria, procedures, and objectives. Methods Mol Biol. 2006;320:183–191.
  • The Human Cytochrome P450 (CYP) Allele Nomenclature Database. Allele nomenclature for Cytochrome P450 enzymes. [cited 2016 May 6]. Available from: http://www.cypalleles.ki.se/
  • Molecular basis of disease. Cytochrome P450s in humans. [cited 2016 May 6]. Available from: http://drnelson.uthsc.edu/P450.talks.html
  • Daly AK, Cholerton S, Gregory W, et al. Metabolic polymorphisms. Pharmacol Ther. 1993;57(2–3):129–160.
  • Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science. 1999;286:487–491.
  • Gardiner SJ, Begg EJ. Pharmacogenetics, drug-metabolizing enzymes, and clinical practice. Pharmacol Rev. 2006;58(3):521–590.
  • Gonzalez FJ, Vilbois F, Hardwick JP, et al. Human debrisoquine 4-hydroxylase (P450IID1). cDNA and deduced amino acid sequence and assignment of the CYP2D locus to chromosome 22. Genomics. 1988;2:174–179.
  • Kroemer HK, Eichelbaum M. “It’s the genes, stupid”. Molecular bases and clinical consequences of genetic cytochrome P450 2D6 polymorphism. Life Sci. 1995;56(26):2285–2298.
  • Preissner SC, Hoffmann MF, Preissner R, et al. Polymorphic cytochrome P450 enzymes (CYPs) and their role in personalized therapy. PLoS One. 2013;8(12):e82562.
  • Caraco Y. Genes and the response to drugs. N Engl J Med. 2004;351:2867–2869.
  • Bradford LD. CYP2D6 allele frequency in European caucasians, Asians, Africans and their descendants. Pharmacogenomics. 2002;3(2):229–243.
  • de Leon J, Arranz MJ, Ruaño G. Pharmacogenetic testing in psychiatry: a review of features and clinical realities. Clin Lab Med. 2008;28(4):599–617.
  • Zanger UM, Raimundo S, Eichelbaum M. Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch Pharmacol. 2004;369(1):23–37.
  • Linder MW 1, Prough RA, Valdes R Jr. Pharmacogenetics: a laboratory tool for optimizing therapeutic efficiency. Clin Chem. 1997 Feb;43(2):254–266.
  • Meyer UA. Pharmacogenetics - five decades of therapeutic lessons from genetic diversity. Nat Rev Genet. 2004;5(9):669–676.
  • Al-Ghoul M, Valdes R Jr. Fundamentals of pharmacology and applications in pharmacogenetics. Clin Lab Med. 2008;28(4):485–497.
  • Gilham DE, Cairns W, Paine MJ, et al. Metabolism of MPTP by cytochrome P4502D6 and the demonstration of 2D6 mRNA in human foetal and adult brain by in situ hybridization. Xenobiotica. 1997;27:111–125.
  • LLerena A, Dorado P, Peñas-LLedó EM. Pharmacogenetics of debrisoquine and its use as a marker for CYP2D6 hydroxylation capacity. Pharmacogenomics. 2009;10(1):17–28.
  • LLerena A, Berecz R, de la Rubia A, et al. Effect of thioridazine dosage on the debrisoquine hydroxylation phenotype in psychiatric patients with different CYP2D6 genotypes. Ther Drug Monit. 2001;23(6):616–620.
  • Dorado P, Berecz R, Penas-LLedo EM, et al. Clinical implications of CYP2D6 genetic polymorphism during treatment with antipsychotic drugs. Curr Drug Targets. 2006;7:671–680.
  • Dorado P, Peñas-LLedó EM, LLerena A. CYP2D6 polymorphism: implications for antipsychotic drug response, schizophrenia and personality traits. Pharmacogenomics. 2007;8(11):1597–1608.
  • Fonne-Pfister R, Bargetzi MJ, Meyer UA. MPTP, the neurotoxin inducing Parkinson’s disease, is a potent competitive inhibitor of human and rat cytochrome P450 isozymes (P450bufI, P450db1) catalyzing debrisoquine 4-hydroxylation. Biochem Biophys Res Commun. 1987;148(3):1144–1150.
  • Miksys SL, Tyndale RF. Drug-metabolizing cytochrome P450s in the brain. J Psychiatry Neurosci. 2002;27:406–415.
  • McFadyen MC, Melvin WT, Murray GI. Cytochrome P450 in normal human brain and brain tumours. Biochem Soc Trans. 1997;25:S577.
  • Mann A, Miksys S, Lee A, et al. Induction of the drug metabolizing enzyme CYP2D in monkey brain by chronic nicotine treatment. Neuropharmacology. 2008;55(7):1147–1155.
  • Siegle I, Fritz P, Eckhardt K, et al. Cellular localization and regional distribution of CYP2D6 mRNA and protein expression in human brain. Pharmacogenetics. 2001;11:237–245.
  • Dutheil F, Dauchy S, Diry M, et al. Xenobiotic metabolizing enzymes and transporters in the normal human brain: regional and cellular mapping as a basis for putative roles in cerebral function. Drug Metab Dispos. 2009;37:1528–1538.
  • Hiroi T, Imaoka S, Funae Y. Dopamine formation from tyramine by CYP2D6. Biochem Biophys Res Commun. 1998;249:838–843.
  • Bromek E, Haduch A, Daniel WA. The ability of cytochrome P450 2D isoforms to synthesize dopamine in the brain: an in vitro study. Eur J Pharmacol. 2010 Jan 25;626(2–3):171–178.
  • Yu A-M, Idle JR, Byrd LG, et al. Regeneration of serotonin from 5-methoxytryptamine by polymorphic human CYP2D6. Pharmacogenetics. 2003;13(3):173–181.
  • Yu AM, Idle JR, Gonzalez FJ. Polymorphic cytochrome P450 2D6: humanized mouse model and endogenous substrates. Drug Metab Rev. 2004;36:243–277.
  • Ozdemir V, Bertilsson L, Miura J, et al. CYP2D6 genotype in relation to perphenazine concentration and pituitary pharmacodynamic tissue sensitivity in Asians: CYP2D6-serotonin-dopamine crosstalk revisited. Pharmacogenet Genomics. 2007;17:339–347.
  • Ozdemir V, Gunes A, Dahl ML, et al. Could endogenous substrates of drug-metabolizing enzymes influence constitutive physiology and drug target responsiveness? Pharmacogenomics. 2006;7:1199–1210.
  • Haduch A, Bromek E, Sadakierska-Chudy A, et al. The catalytic competence of cytochrome P450 in the synthesis of serotonin from 5-methoxytryptamine in the brain: an in vitro study. Pharmacol Res. 2013;67:53–59.
  • Haduch A, Bromek E, Kot M, et al. The cytochrome P450 2D-mediated formation of serotonin from 5-methoxytryptamine in the brain in vivo: a microdialysis study. J Neurochem. 2015;133:83–92.
  • Haduch A, Bromek E, Wójcikowski J, et al. Melatonin supports CYP2D-mediated serotonin synthesis in the brain. Drug Metab Dispos. 2016;44(3):445–452.
  • Kirchheiner J, Henckel HB, Franke L, et al. Impact of the CYP2D6 ultra-rapid metabolizer genotype on doxepin pharmacokinetics and serotonin in platelets. Pharmacogenet Genomics. 2005;15:579–587.
  • Bromek E, Haduch A, Gołembiowska K, et al. Cytochrome P450 mediates dopamine formation in the brain in vivo. J Neurochem. 2011 Sep;118(5):806–815.
  • Aklillu E, Kalow W, Endrenyi L, et al. CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007;17:989–993.
  • Bertilsson L. CYP2D6, serotonin, and suicide – a relationship? Clin Pharmacol Ther. 2010;88(3):304–305.
  • Snider NT, Sikora MJ, Sridar C, et al. The endocannabinoidanandamide is a substrate for the human polymorphic cytochrome P450 2D6. J Pharmacol Exp Ther. 2008;327:538–545.
  • Hiroi T, Kishimoto W, Chow T, et al. Progesterone oxidation by cytochrome P450 2D isoforms in the brain. Endocrinology. 2001;142(9):3901–3908.
  • Kishimoto W, Hiroi T, Shiraishi M, et al. Cytochrome P450 2D catalyze steroid 21-hydroxylation in the brain. Endocrinology. 2004;145(2):699–705.
  • Peñas-Lledó EM, Llerena A. CYP2D6 variation, behaviour and psychopathology: implicationsfor pharmacogenomics-guided clinical trials. Br J Clin Pharmacol. 2014;77(4):673–683.
  • Kootstra-Ros JE, Van Weelden MJ, Hinrichs JW, et al. Therapeutic drug monitoring of antidepressants and cytochrome p450 genotyping in general practice. J Clin Pharmacol. 2006;46:1320–1327.
  • Kirchheiner J, Brosen K, Dahl ML, et al. CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages. Acta Psychiatr Scand. 2001;104:173–192.
  • de Leon J, Armstrong SC, Cozza KL. Clinical guidelines for psychiatrists for the use of pharmacogenetic testing for CYP450 2D6 and CYP450 2C19. Psychosomatics. 2006;47:75–85.
  • Hodgson K, Tansey K, Dernovsek MZ, et al. Genetic differences in cytochrome P450 enzymes and antidepressant treatment response. J Psychopharmacol. 2014;28:133–141.
  • Serretti A, Calati R, Massat I, et al. Cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes are not associated with response and remission in a sample of depressive patients. Int Clin Psychopharmacol. 2009;24:250–256.
  • Gex-Fabry M, Eap CB, Oneda B, et al. CYP2D6 and ABCB1 genetic variability: influence on paroxetine plasma level and therapeutic response. Ther Drug Monit. 2008;30:474–482.
  • Peters EJ, Slager SL, Kraft JB, et al. Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample. PLoS One. 2008;3:e1872.
  • Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP working group: testing for cytochrome P450 polymorphisms in adults with nonpsychotic depression treated with selective serotonin reuptake inhibitors. Genet Med. 2007;9:819–825.
  • Preissner S, Kroll K, Dunkel M, et al. SuperCYP: a comprehensive database on cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010;38(Databaseissue):D237–D243.
  • SuperCYP – Cytochrome P450 database. [cited 2016 May 6]. Available from: http://bioinformatics.charite.de/supercyp/index.php
  • Lobello KW, Preskorn SH, Guico-Pabia CJ, et al. Cytochrome P450 2D6 phenotype predicts antidepressant efficacy of venlafaxine: a secondary analysis of 4 studies in major depressive disorder. J Clin Psychiatry. 2010;71:1482–1487.
  • Lessard E, Yessine MA, Hamelin BA, et al. Influence of CYP2D6 activity on the disposition and cardiovascular toxicity of the antidepressant agent venlafaxine in humans. Pharmacogenetics. 1999;9:435–443.
  • Bertilsson L, Dahl ML, Dalen P, et al. Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br J Clin Pharmacol. 2002;53:111–122.
  • Tsai MH, Lin KM, Hsiao MC, et al. Genetic polymorphisms of cytochrome P450 enzymes influence metabolism of the antidepressant escitalopram and treatment response. Pharmacogenomics. 2010;11:537–546.
  • Kawanishi C, Lundgren S, Agren H, et al. Increased incidence of CYP2D6 gene duplication in patients with persistent mood disorders: ultrarapid metabolism of antidepressants as a cause of nonresponse. A pilot study. Eur J Clin Pharmacol. 2004;59:803–807.
  • Penas-Lledo EM, Trejo HD, Dorado P, et al. CYP2D6 ultrarapid metabolism and early dropout from fluoxetine or amitriptyline monotherapy treatment in major depressive patients. Mol Psychiatry. 2013;18:8–9.
  • Penas-Lledo EM, Dorado P, Aguera Z, et al. High risk of lifetime history of suicide attempts among CYP2D6 ultrarapid metabolizers with eating disorders. Mol Psychiatry. 2011;16:691–692.
  • Stingl JC, Viviani R. CYP2D6 in the brain: impact on suicidality. Clin Pharmacol Ther. 2011;89:352–353.
  • Zackrisson AL, Lindblom B, Ahlner J. High frequency of occurrence of CYP2D6 gene duplication/multiduplication indicating ultrarapid metabolism among suicide cases. Clin Pharmacol Ther. 2010;88:354–359.
  • Sallee FR, DeVane CL, Ferrell RE. Fluoxetine-related death in a child with cytochrome P-450 2D6 genetic deficiency. J Child Adolesc Psychopharmacol. 2000;10(1):27–34.
  • Baumann P, Barbe R, Vabre-Bogdalova A, et al. Epileptiform seizure after sertraline treatment in an adolescent experiencing obsessive-compulsive disorder and presenting a rare pharmacogenetic status. J Clin Psychopharmacol. 2006;26:679–681.
  • Sánchez-Iglesias S, García-Solaesa V, García-Berrocal B, et al. Role of pharmacogenetics in improving the safety of psychiatric care by predicting the potential risks of mania in CYP2D6 poor metabolizers diagnosed with bipolar disorder. Medicine (Baltimore). 2016;95:e2473.
  • Dahl ML. Cytochrome p450 phenotyping/genotyping in patients receiving antipsychotics: useful aid to prescribing? Clin Pharmacokinet. 2002;41:453–470.
  • Brockmoller J, Kirchheiner J, Schmider J, et al. The impact of the CYP2D6 polymorphism on haloperidol pharmacokinetics and on the outcome of haloperidol treatment. Clin Pharmacol Ther. 2002;72:438–452.
  • Yoshii K, Kobayashi K, Tsumuji M, et al. Identification of human cytochrome P450 isoforms involved in the 7-hydroxylation of chlorpromazine by human liver microsomes. Life Sci. 2000;67:175–184.
  • Rau T, Wohlleben G, Wuttke H, et al. CYP2D6 genotype: impact on adverse effects and nonresponse during treatment with antidepressants-a pilot study. Clin Pharmacol Ther. 2004;75:386–393.
  • de Leon J, Susce MT, Pan RM, et al. The CYP2D6 poor metabolizer phenotype may be associated with risperidone adverse drug reactions and discontinuation. J Clin Psychiatry. 2005;66(1):15–27.
  • Tamminga WJ, Wemer J, Oosterhuis B, et al. Polymorphic drug metabolism (CYP2D6) and utilisation of psychotropic drugs in hospitalized psychiatric patients: a retrospective study. Eur J Clin Pharmacol. 2003;59:57–64.
  • Dubovsky SL. The usefulness of genotyping cytochrome P450 enzymes in the treatment of depression. Expert Opin Drug Metab Toxicol. 2015;11(3):369–379.
  • Bakken GV, Molden E, Hermann M. Impact of genetic variability in CYP2D6, CYP3A5, and ABCB1 on serum concentrations of quetiapine and N-desalkylquetiapine in psychiatric patients. Ther Drug Monit. 2015;37:256–261.
  • Hodgson K, Tansey KE, Uher R, et al. Exploring the role of drug-metabolising enzymes in antidepressant side effects. Psychopharmacology (Berl). 2015;232(14):2609–2617.
  • van der Weide K, van der Weide J. The influence of the CYP3A4*22 Polymorphism and CYP2D6 polymorphisms on serum concentrations of aripiprazole, haloperidol, pimozide, and risperidone in psychiatric patients. J Clin Psychopharmacol. 2015;35(3):228–236.
  • Frick U, Frick H, Langguth B, et al. The revolving door phenomenon revisited: time to readmission in 17ʹ145 [corrected] patients with 37ʹ697 hospitalisations at a German psychiatric hospital. PLoS One. 2013;8(10):e75612.
  • Kastrup M. The use of a psychiatric register in predicting the outcome “revolving door patient”. A nation-wide cohort of first time admitted psychiatric patients. Acta Psychiatr Scand. 1987;76(5):552–560.
  • Mortensen P, Eaton W. Predictors for readmission risk in schizophrenia. Psychol Med. 1994;24(01):223–232.
  • Kessing L, Andersen P. Predictive effects of previous episodes on the riskof recurrence in depressive and bipolar disorders. Curr Psychiatry Rep. 2005;7(6):413–420.
  • Kastrup M. Who became revolving door patients: findings from a nation-wide cohort of first-time admitted patients. Acta Psychiatr Scand. 1987;76(1):80–88.
  • Meyer UA. Pharmacogenetics and adverse drug reactions. Lancet. 2000;356:1667–1671.
  • Pirmohamed M, Park BK. Genetic susceptibility to adverse drug reactions. Trends Pharmacol Sci. 2001;22(6):298–305.
  • Güzey C, Spigset O. Genotyping as a tool to predict adverse drug reactions. Curr Top Med Chem. 2004;4(13):1411–1421.
  • Wilke RA, Lin DW, Roden DM, et al. Identifying genetic risk factors for serious adverse drug reactions: current progress and challenges. Nat Rev Drug Discov. 2007;6(11):904–916.
  • Ingelman-Sundberg M. Pharmacogenomic biomarkers for prediction of severe adverse drug reactions. N Engl J Med. 2008;358(6):637–639.
  • Motulsky AG. Drug reactions, enzymes, and biochemical genetics. J Am Med Assoc. 1957;165(7):835–837.
  • Vogel F. Moderne problemeder humangenetik. Ergeb Inn Med Kinderheilkd. 1959;12:52–125.
  • Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician. 2007;76(3):391–396.
  • Seripa D, Pilotto A, Panza F, et al. Pharmacogenetics of cytochrome P450 (CYP) in the elderly. Ageing Res Rev. 2010;9(4):457–474.
  • Johansson I, Ingelman-Sundberg M. Genetic polymorphism and toxicology - with emphasis on cytochrome p450. Toxicol Sci. 2011;120(1):1–13.
  • de Leon J, Barnhill J, Rogers T, et al. Pilot study of the cytochrome P450-2D6 genotype in a psychiatric state hospital. Am J Psychiatry. 1998;155(9):1278–1280.
  • Dawson E, Powell JF, Nothen MM, et al. An association study of debrisoquine hydroxylase (CYP2D6) polymorphism in schizophrenia. Psychiatr Genet. 1994;4(4):215–218.
  • Maier W, Zobel A. Contribution of allelic variations to the phenotype of response to antidepressants and antipsychotics. Eur Arch Psychiatry Clin Neurosci. 2008;258(Suppl 1):12–20.
  • Ravyn D, Ravyn V, Lowney R, et al. CYP450 pharmacogenetic treatment strategies for antipsychotics: a review of the evidence. Schizophr Res. 2013;149(1–3):1–14.
  • Peñas-Lledó EM, Llerena A. CYP2D6 genetic polymorphism and psychiatry patients’ hospitalization period. Biomark Med. 2013;7(6):915–916.
  • Spina E, de Leon J. Clinical applications of CYP genotyping in psychiatry. J Neural Transm (Vienna). 2015;122(1):5–28.
  • Hicks JK, Bishop JR, Sangkuhl K, et al. Pharmacogenetics implementation consortium (2015) clinical pharmacogenetics implementation consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther. 2015;98(2):127–134.
  • Ivanova SA, Filipenko ML, Vyalova NM, et al. CYP1A2 and CYP2D6 gene polymorphisms in schizophrenic patients with neuroleptic drug-induced side effects. Bull Exp Biol Med. 2016;160(5):687–690.
  • Plesnicar BK, Zalar B, Breskvar K, et al. The influence of the CYP2D6 polymorphism on psychopathological and extrapyramidal symptoms in the patients on long-term antipsychotic treatment. J Psychopharmacol. 2006;20(6):829–833.
  • Kirchheiner J, Rodriguez-Antona C. Cytochrome P450 2D6 genotyping: potential role in improving treatment outcomes in psychiatric disorders. CNS Drugs. 2009;23(3):181–191.
  • Kobylecki CJ, Jakobsen KD, Hansen T, et al. CYP2D6 genotype predicts antipsychotic side effects in schizophrenia inpatients: a retrospective matched case-control study. Neuropsychobiology. 2009;59(4):222–226.
  • Kemp DE. Managing the side effects associated with commonly used treatments for bipolar depression. J Affect Disord. 2014;169:S34–S44.
  • Gaynes B. Assessing the risk factors for difficult-to-treat depression and treatment-resistant depression. J Clin Psychiatry. 2016;77:S4–S8.
  • Givens CJ. Adverse drug reactions associated with antipsychotics, antidepressants, mood stabilizers, and stimulants. Nurs Clin North Am. 2016;51(2):309–321.
  • Ames D, Carr-Lopez SM, Gutierrez MA, et al. Detecting and managing adverse effects of antipsychotic medications: current state of play. Psychiatr Clin North Am. 2016;39(2):275–311.
  • Grasmader K, Vewohlt PL, Rietschel M, et al. Impact of polymorphisms of cytochrome-P450 isoenzymes2C9, 2C19 and 2D6 on plasma concentrations and clinical effectsof antidepressants in a naturalistic clinical setting. Eur J Clin Pharmacol. 2004;60(5):329–336.
  • NICE Guidelines CG185. Bipolar disorder: the assessment and management of bipolar disorder in adults, children and young people in primary and secondary care. [cited 2016 Mar 22]. Available from: https://www.nice.org.uk/guidance/cg185
  • de Leon J, Susce MT, Murray-Carmichael E. The AmpliChip CYP450 genotyping test: integrating a new clinical tool. Mol Diagn Ther. 2006;10(3):135–151.
  • de Leon J. AmpliChip CYP450 test: personalized medicine has arrived in psychiatry. Expert Rev Mol Diagn. 2006;6(3):277–286.
  • Haywood TW, Kravitz HM, Grossman LS, et al. Predicting the “revolving door” phenomenon among patients with schizophrenic, schizoaffective, and affective disorders. Am J Psychiatry. 1995;152:856–861.
  • Drozda K, Muller DJ, Bishop JR. Pharmacogenomic testing for neuropsychiatric drugs: current status of drug labeling, guidelines for using genetic information, and test options. Pharmacotherapy. 2014;34(2):166–184.
  • Panza F, Lozupone M, Stella E, et al. Psychiatry meets pharmacogenetics for the treatment of revolving door patients with psychiatric disorders. Expert Rev Neurother. 2016;11:1–13.

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