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Research Article

Clinical validity of cytochrome P450 metabolism and serotonin gene variants in psychiatric pharmacotherapy

, , , , &
Pages 509-533 | Received 29 Apr 2013, Accepted 10 Jul 2013, Published online: 23 Oct 2013

References

  • Reeves WC, Strine TW, Pratt LA, Thompson W, Ahluwalia I, Dhingra SS, … Safran MA. Mental illness surveillance among adults in the United States. Morbidity and Mortality Weekly Report: Surveillance Summaries 2011;3:1–29.
  • Insel TR. Assessing the economic costs of serious mental illness. American Journal of Psychiatry 2008;165:663–5.
  • Mrazek DA. Psychiatric Pharmacogenomics. Oxford University Press, 2010.
  • Laje G, Perlis RH, Rush AJ, McMahon FJ. Pharmacogenetics studies in STAR*D: Strengths, limitations, and results. Psychiatric Services 2009;60:1446–57.
  • Pickar D, Rubinow K. Pharmacogenomics of psychiatric disorders. Trends in Pharmacological Sciences 2001;22: 75–83.
  • Masellis M, Basile VS, Meltzer HY, Lieberman JA, Sevy S, Goldman DA, … Kennedy JL. Lack of association between the T–> C 267 serotonin 5-HT6 receptor gene (HTR6) polymorphism and prediction of response to clozapine in schizophrenia. Schizophrenia Research 2001;47:49–58.
  • de Leon J, Susce MT, Pan RM, Koch WH, Wedlund PJ. Polymorphic variations in GSTM1, GSTT1, PgP, CYP2D6, CYP3A5, and dopamine D2 and D3 receptors and their association with tardive dyskinesia in severe mental illness. Journal of Clinical Psychopharmacology 2005;25:448–56.
  • Arias B, Catalan R, Gasto C, Gutierrez B, Fananas L. Evidence for a combined genetic effect of the 5-HT(1A) receptor and serotonin transporter genes in the clinical outcome of major depressive patients treated with citalopram. Journal of Psychopharmacology 2005;19:166–72.
  • Kirchheiner J, Nickchen K, Bauer M, Wong ML, Licinio J, Roots I, Brockmoller J. Pharmacogenetics of antidepressants and antipsychotics: The contribution of allelic variations to the phenotype of drug response. Molecular Psychiatry 2004;9:442–73.
  • Taylor MJ, Sen S, Bhagwagar Z. Antidepressant response and the serotonin transporter gene-linked polymorphic region. Biological Psychiatry 2010;68:536–43.
  • Serretti A, Kato M, De Ronchi D, Kinoshita T. Meta- analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients. Molecular Psychiatry 2007;12:247–57.
  • Matchar DB, Thakur ME, Grossman I, McCrory DC, Orlando LA, Steffens DC, … Gray RN. Testing for cytochrome P450 polymorphisms in adults with non-psychotic depression treated with selective serotonin reuptake inhibitors (SSRIs). Evidence Report/Technology Assessment 2007;146:1–77.
  • Mrazek DA, Rush AJ, Biernacka JM, O’Kane DJ, Cunningham JM, Wieben ED, … Weinshilboum RM. SLC6A4 variation and citalopram response. American Journal of Medical Genetics Part B– Neuropsychiatric Genetics 2009;5:341–51.
  • Black JL, O’Kane DJ, Mrazek DA. The impact of CYP allelic variation on antidepressant metabolism: A review. Expert Opinion on Drug Metabolism and Toxicology 2007;3: 21–31.
  • Porcelli S, Drago A, Fabbri C, Gibiino S, Calati R, Serretti A. Pharmacogenetics of antidepressant response. Journal of Psychiatry and Neuroscience 2011;36:87–113.
  • Dong C, Wong ML, Licinio J. Sequence variations of ABCB1, SLC6A2, SLC6A3, SLC6A4, CREB1, CRHR1 and NTRK2: association with major depression and antidepressant response in Mexican-Americans. Molecular Psychiatry 2009;14:1105–18.
  • Malhotra AK, Correll CU, Chowdhury NI, Muller DJ, Gregersen PK, Lee AT, … Kennedy JL. Association between common variants near the melanocortin 4 receptor gene and severe antipsychotic drug-induced weight gain. Archives of General Psychiatry 2012;69:904–12.
  • de Leon J. Pharmacogenomics: The promise of personalized medicine for CNS disorders. Neuropsychopharmacology 2009;34:159–72.
  • Prows CA, Nick TG, Saldana SN, Pathak S, Liu C, Zhang K, … Glauser TA. Drug-metabolizing enzyme genotypes and aggressive behavior treatment response in hospitalized pediatric psychiatric patients. Journal of Child and Adolescent Psychopharmacology 2009;19:385–94.
  • Zandi PP, Judy JT. The promise and reality of pharmacogenetics in psychiatry. Clinics in Laboratory Medicine 2010; 30:931–74.
  • Recommendations from the EGAPP Working Group: Testing for cytochrome P450 polymorphisms in adults with nonpsychotic depression treated with selective serotonin reuptake inhibitors. Genetic Medicine 2007;9:819–25.
  • Zhang JP, Malhotra AK. Pharmacogenetics and antipsychotics: Therapeutic efficacy and side effects prediction. Expert Opinion on Drug Metabolism and Toxicology 2011;7:9–37.
  • Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, … Preissner R. SuperCYP: A comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Research 2010;38:24.
  • Oxford Center for Evidence-based Medicine – Levels of evidence. Available from URL: http://www.cebm.net/index.aspx?o=1025 (accessed November 2012).
  • Wang L, Yu L, Zhang AP, Fang C, Du J, Gu NF, … He L. Serum prolactin levels, plasma risperidone levels, polymorphism of cytochrome P450 2D6 and clinical response in patients with schizophrenia. Journal of Psychopharmacology 2007;21:837–42.
  • Bijl MJ, Visser LE, Hofman A, Vulto AG, van Gelder T, Stricker BH, van Schaik RH. Influence of the CYP2D6*4 polymorphism on dose, switching and discontinuation of antidepressants. British Journal of Clinical Pharmacology 2008;65:558–64.
  • de Vos A, Loovers HM, van der Weide J. Association between CYP2C19*17 and metabolism of amitriptyline, citalopram and clomipramine in Dutch hospitalized patients. Pharmacogenomics Journal 2011;11:359–67.
  • Dorado P, Penas LEM, de la Rubia A, A LL. Relevance of CYP2D6 –1584C> G polymorphism for thioridazine: mesoridazine plasma concentration ratio in psychiatric patients. Pharmacogenomics 2009;10:1083–9.
  • Feng Y, Pollock BG, Ferrell RE, Kimak MA, Reynolds CF, 3rd, Bies RR. Paroxetine: Population pharmacokinetic analysis in late-life depression using sparse concentration sampling. British Journal of Clinical Pharmacology 2006; 61:558–69.
  • Gex-Fabry M, Eap CB, Oneda B, Gervasoni N, Aubry JM, Bondolfi G, Bertschy G. CYP2D6 and ABCB1 genetic variability: Influence on paroxetine plasma level and therapeutic response. Therapeutic Drug Monitoring 2008;30: 474–82.
  • Grasmader K, Verwohlt PL, Kuhn KU, Dragicevic A, von Widdern O, Zobel A, … Rao ML. Population pharmacokinetic analysis of mirtazapine. European Journal of Clinical Pharmacology 2004;60:473–80.
  • Gunes A, Spina E, Dahl ML, Scordo MG. ABCB1 polymorphisms influence steady-state plasma levels of 9-hydroxyrisperidone and risperidone active moiety. Therapeutic Drug Monitoring 2008;30:628–33.
  • Halling J, Weihe P, Brosen K. The CYP2D6 polymorphism in relation to the metabolism of amitriptyline and nortriptyline in the Faroese population. British Journal of Clinical Pharmacology 2008;65:134–8.
  • Hendset M, Hermann M, Lunde H, Refsum H, Molden E. Impact of the CYP2D6 genotype on steady-state serum concentrations of aripiprazole and dehydroaripiprazole. European Journal of Clinical Pharmacology 2007;63: 1147–51.
  • Hendset M, Molden E, Refsum H, Hermann M. Impact of CYP2D6 genotype on steady-state serum concentrations of risperidone and 9-hydroxyrisperidone in patients using long-acting injectable risperidone. Journal of Clinical Psychopharmacology 2009;29:537–41.
  • Hermann M, Hendset M, Fosaas K, Hjerpset M, Refsum H. Serum concentrations of venlafaxine and its metabolites O-desmethylvenlafaxine and N-desmethylvenlafaxine in heterozygous carriers of the CYP2D6*3, *4 or *5 allele. European Journal of Clinical Pharmacology 2008; 64:483–7.
  • Hinrichs JW, Loovers HM, Scholten B, van der Weide J. Semi-quantitative CYP2D6 gene doses in relation to metabolic ratios of psychotropics. European Journal of Clinical Pharmacology 2008;64:979–86.
  • Huezo-Diaz P, Perroud N, Spencer EP, Smith R, Sim S, Virding S, … Aitchison KJ. CYP2C19 genotype predicts steady state escitalopram concentration in GENDEP. Journal of Psychopharmacology 2012;26:398–407.
  • Jovanovic N, Bozina N, Lovric M, Medved V, Jakovljevic M, Peles AM. The role of CYP2D6 and ABCB1 pharmacogenetics in drug-naive patients with first-episode schizophrenia treated with risperidone. European Journal of Clinical Pharmacology 2010;66:1109–17.
  • Kang RH, Jung SM, Kim KA, Lee DK, Cho HK, Jung BJ, … Park JY. Effects of CYP2D6 and CYP3A5 genotypes on the plasma concentrations of risperidone and 9-hydroxyrisperidone in Korean schizophrenic patients. Journal of Clinical Psychopharmacology 2009;29:272–7.
  • Kim JR, Seo HB, Cho JY, Kang DH, Kim YK, Bahk WM, … Jang IJ. Population pharmacokinetic modelling of aripiprazole and its active metabolite, dehydroaripiprazole, in psychiatric patients. British Journal of Clinical Pharmacology 2008;66:802–10.
  • Lind AB, Reis M, Bengtsson F, Jonzier-Perey M, Powell Golay K, Ahlner J, … Dahl ML. Steady-state concentrations of mirtazapine, N-desmethylmirtazapine, 8-hydroxymirtazapine and their enantiomers in relation to cytochrome P450 2D6 genotype, age and smoking behaviour. Clinical Pharmacokinetics 2009;48:63–70.
  • Llerena A, Berecz R, Dorado P, de la Rubia A. QTc interval, CYP2D6 and CYP2C9 genotypes and risperidone plasma concentrations. Journal of Psychopharmacology 2004;18: 189–93.
  • Mas S, Gasso P, Alvarez S, Parellada E, Bernardo M, Lafuente A. Intuitive pharmacogenetics: Spontaneous risperidone dosage is related to CYP2D6, CYP3A5 and ABCB1 genotypes. Pharmacogenomics Journal 2012;12:255–9.
  • McAlpine DE, Biernacka JM, Mrazek DA, O’Kane DJ, Stevens SR, Langman LJ, … Moyer TP. Effect of cytochrome P450 enzyme polymorphisms on pharmacokinetics of venlafaxine. Therapeutic Drug Monitoring 2011;33:14–20.
  • McAlpine DE, O’Kane DJ, Black JL, Mrazek DA. Cytochrome P450 2D6 genotype variation and venlafaxine dosage. Mayo Clinic Proceedings 2007;82:1065–8.
  • Mulder H, Herder A, Wilmink FW, Tamminga WJ, Belitser SV, Egberts ACG. The impact of cytochrome P450-2D6 genotype on the use and interpretation of therapeutic drug monitoring in long-stay patients treated with antidepressant and antipsychotic drugs in daily psychiatric practice. Pharmacoepidemiology and Drug Safety 2006;15:107–14.
  • Panagiotidis G, Arthur HW, Lindh JD, Dahl ML, Sjoqvist F. Depot haloperidol treatment in outpatients with schizophrenia on monotherapy: Impact of CYP2D6 polymorphism on pharmacokinetics and treatment outcome. Therapeutic Drug Monitoring 2007;29:417–22.
  • Sawamura K, Suzuki Y, Someya T. Effects of dosage and CYP2D6-mutated allele on plasma concentration of paroxetine. European Journal of Clinical Pharmacology 2004;60: 553–7.
  • Schenk PW, van Fessem MA, Verploegh-Van Rij S, Mathot RA, van Gelder T, Vulto AG, … van Schaik RH. Association of graded allele-specific changes in CYP2D6 function with imipramine dose requirement in a large group of depressed patients. Molecular Psychiatry 2008;13:597–605.
  • Scordo MG, Spina E, Dahl ML, Gatti G, Perucca E. Influence of CYP2C9, 2C19 and 2D6 genetic polymorphisms on the steady-state plasma concentrations of the enantiomers of fluoxetine and norfluoxetine. Basic and Clinical Pharmacology and Toxicology 2005;97:296–301.
  • Shams ME, Arneth B, Hiemke C, Dragicevic A, Muller MJ, Kaiser R, … Hartter S. CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine. Journal of Clinical Pharmacy and Therapeutics 2006;31:493–502.
  • Steimer W, Zopf K, von Amelunxen S, Pfeiffer H, Bachofer J, Popp J, … Leucht S. Allele-specific change of concentration and functional gene dose for the prediction of steady-state serum concentrations of amitriptyline and nortriptyline in CYP2C19 and CYP2D6 extensive and intermediate metabolizers. Clinical Chemistry 2004;50: 1623–33.
  • Suzuki T, Mihara K, Nakamura A, Nagai G, Kagawa S, Nemoto K, … Kondo T. Effects of the CYP2D6*10 allele on the steady-state plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, in Japanese patients with schizophrenia. Therapeutic Drug Monitoring 2011;33:21–4.
  • Suzuki Y, Fukui N, Tsuneyama N, Watanabe J, Ono S, Sugai T, … Someya T. Effect of the cytochrome P450 2D6*10 allele on risperidone metabolism in Japanese psychiatric patients. Human Psychopharmacology 2012;27:43–6.
  • Thanacoody RH, Daly AK, Reilly JG, Ferrier IN, Thomas SH. Factors affecting drug concentrations and QT interval during thioridazine therapy. Clinical Pharmacology and Therapeutics 2007;82:555–65.
  • van der Weide J, van Baalen-Benedek EH, Kootstra-Ros JE. Metabolic ratios of psychotropics as indication of cytochrome P450 2D6/2C19 genotype. Therapeutic Drug Monitoring 2005;27:478–83.
  • Watanabe J, Suzuki Y, Fukui N, Sugai T, Ono S, Inoue Y, Someya T. Dose-dependent effect of the CYP2D6 genotype on the steady-state fluvoxamine concentration. Therapeutic Drug Monitoring 2008;30:705–8.
  • Whyte EM, Romkes M, Mulsant BH, Kirshne MA, Begley AE, Reynolds CF, III, Pollock BG. CYP2D6 genotype and venlafaxine-XR concentrations in depressed elderly. International Journal of Geriatric Psychiatry 2006; 21:542–9.
  • Yagihashi T, Mizuno M, Chino B, Sato Y, Sakuma K, Takebayashi T, … Kosaki K. Effects of the CYP2D6*10 alleles and co-medication with CYP2D6-dependent drugs on risperidone metabolism in patients with schizophrenia. Human Psychopharmacology 2009;24:301–8.
  • Yasui-Furukori N, Mihara K, Takahata T, Suzuki A, Nakagami T, De Vries R, … Kaneko S. Effects of various factors on steady-state plasma concentrations of risperidone and 9-hydroxyrisperidone: Lack of impact of MDR-1 genotypes. British Journal of Clinical Pharmacology 2004;57: 569–75.
  • de Leon J, Diaz FJ, Wedlund P, Josiassen RC, Cooper TB, Simpson GM. Haloperidol half-life after chronic dosing. Journal of Clinical Psychopharmacology 2004;24: 656–60.
  • Katoh Y, Uchida S, Kawai M, Takei N, Mori N, Kawakami J, … Hashimoto H. Effects of cigarette smoking and cytochrome P450 2D6 genotype on fluvoxamine concentration in plasma of Japanese patients. Biological and Pharmaceutical Bulletin 2010;33:285–8.
  • Nozawa M, Ohnuma T, Matsubara Y, Sakai Y, Hatano T, Hanzawa R, … Arai H. The relationship between the response of clinical symptoms and plasma olanzapine concentration, based on pharmacogenetics: Juntendo University Schizophrenia Projects (JUSP). Therapeutic Drug Monitoring 2008;30:35–40.
  • Riedel M, Schwarz MJ, Strassnig M, Spellmann I, Muller-Arends A, Weber K, … Moller HJ. Risperidone plasma levels, clinical response and side-effects. European Archives of Psychiatry and Clinical Neuroscience 2005;255:261–8.
  • Alenius M, Wadelius M, Dahl ML, Hartvig P, Lindstrom L, Hammarlund-Udenaes M. Gene polymorphism influencing treatment response in psychotic patients in a naturalistic setting. Journal of Psychiatric Research 2008;42:884–93.
  • Grasmader K, Verwohlt PL, Rietschel M, Dragicevic A, Muller M, Hiemke C, … Rao ML. Impact of polymorphisms of cytochrome-P450 isoenzymes 2C9, 2C19 and 2D6 on plasma concentrations and clinical effects of antidepressants in a naturalistic clinical setting. European Journal of Clinical Pharmacology 2004;60:329–36.
  • Jaquenoud Sirot E, Knezevic B, Morena GP, Harenberg S, Oneda B, Crettol S, … Eap CB. ABCB1 and cytochrome P450 polymorphisms: Clinical pharmacogenetics of clozapine. Journal of Clinical Psychopharmacology 2009;29: 319–26.
  • Jurgens G, Rasmussen HB, Werge T, Dalhoff K, Nordentoft M, Andersen SE. Does the medication pattern reflect the CYP2D6 genotype in patients with diagnoses within the schizophrenic spectrum?Journal of Clinical Psychopharmacology 2012;32:100–5.
  • Melkersson KI, Scordo MG, Gunes A, Dahl ML. Impact of CYP1A2 and CYP2D6 polymorphisms on drug metabolism and on insulin and lipid elevations and insulin resistance in clozapine-treated patients. Journal of Clinical Psychiatry 2007;68:697–704.
  • Sugahara H, Maebara C, Ohtani H, Handa M, Ando K, Mine K, … Sawada Y. Effect of smoking and CYP2D6 polymorphisms on the extent of fluvoxamine-alprazolam interaction in patients with psychosomatic disease. European Journal of Clinical Pharmacology 2009;65:699–704.
  • Vetti HH, Molven A, Eliassen AK, Steen VM. Is pharmacogenetic CYP2D6 testing useful?Journal of the Norweigian Medical Association 2010;130:2224–8.
  • Conrado DJ, Rogers HL, Zineh I, Pacanowski MA. Consistency of drug-drug and gene-drug interaction information in US FDA-approved drug labels. Pharmacogenomics 2013; 14:215–23.
  • Preskorn SH, Flockhart D. 2010 Guide to Psychiatric Drug Interactions. Primary Psychiatry 2009;16:45–74.
  • Kawanishi C, Lundgren S, Agren H, Bertilsson L. Increased incidence of CYP2D6 gene duplication in patients with persistent mood disorders: Ultrarapid metabolism of antidepressants as a cause of nonresponse. A pilot study. European Journal of Clinical Pharmacology 2004;59:803–7.
  • Laika B, Leucht S, Heres S, Steimer W. Intermediate metabolizer: Increased side effects in psychoactive drug therapy. The key to cost-effectiveness of pretreatment CYP2D6 screening? Pharmacogenomics Journal 2009;9: 395–403.
  • Plesnicar BK, Zalar B, Breskvar K, Dolzan V. The influence of the CYP2D6 polymorphism on psychopathological and extrapyramidal symptoms in the patients on long-term antipsychotic treatment. Journal of Psychopharmacology 2006;20:829–33.
  • Rau T, Wohlleben G, Wuttke H, Thuerauf N, Lunkenheimer J, Lanczik M, Eschenhagen T. CYP2D6 genotype: Impact on adverse effects and nonresponse during treatment with antidepressants – A pilot study. Clinical Pharmacology and Therapeutics 2004;75:386–93.
  • Tsai MH, Lin KM, Hsiao MC, Shen WW, Lu ML, Tang HS, … Liu YL. Genetic polymorphisms of cytochrome P450 enzymes influence metabolism of the antidepressant escitalopram and treatment response. Pharmacogenomics 2010;11:537–46.
  • Kakihara S, Yoshimura R, Shinkai K, Matsumoto C, Goto M, Kaji K, … Nakamura J. Prediction of response to risperidone treatment with respect to plasma concencentrations of risperidone, catecholamine metabolites, and polymorphism of cytochrome P450 2D6. International Clinical Psychopharmacology 2005;20:71–8.
  • Kohlrausch FB, Gama CS, Lobato MI, Belmonte-de-Abreu P, Callegari-Jacques SM, Gesteira A, … Hutz MH. Naturalistic pharmacogenetic study of treatment resistance to typical neuroleptics in European–Brazilian schizophrenics. Pharmacogenetics and Genomics 2008;18:599–609.
  • Peters EJ, Slager SL, Kraft JB, Jenkins GD, Reinalda MS, McGrath PJ, Hamilton SP. Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample. PLoS One 2008;3:e1872.
  • Serretti A, Calati R, Massat I, Linotte S, Kasper S, Lecrubier Y, … Souery D. Cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes are not associated with response and remission in a sample of depressive patients. International Clinical Psychopharmacology 2009; 24:250–6.
  • Thomas P, Srivastava V, Singh A, Mathur P, Nimgaonkar VL, Lerer B, … Deshpande SN. Correlates of response to Olanzapine in a North Indian Schizophrenia sample. Psychiatry Research 2008;161:275–83.
  • Zourkova A, Ceskova E, Hadasova E, Ravcukova B. Links among paroxetine-induced sexual dysfunctions, gender, and CYP2D6 activity. Journal of Sex and Marital Therapy 2007;33:343–55.
  • Mrazek DA, Biernacka JM, O’Kane DJ, Black JL, Cunningham JM, Drews MS, … Weinshilboum RM. CYP2C19 variation and citalopram response. Pharmacogenetics and Genomics 2011;21:1–9.
  • Parker G, Rowe M, Mehta F, Kumar S. Will a new genotyping test help the clinician predict response to antidepressant drugs?Australasian Psychiatry 2010;18:413–6.
  • Muller DJ, Brandl EJ, Hwang R, Tiwari AK, Sturgess JE, Zai CC, … Richter MA. The AmpliChip(R) CYP450 test and response to treatment in schizophrenia and obsessive compulsive disorder: A pilot study and focus on cases with abnormal CYP2D6 drug metabolism. Genetic Testing and Molecular Biomarkers 2012;16:897–903.
  • Brockmoller J, Meineke I, Kirchheiner J. Pharmacokinetics of mirtazapine: Enantioselective effects of the CYP2D6 ultra rapid metabolizer genotype and correlation with adverse effects. Clinical Pharmacology and Therapeutics 2007;81: 699–707.
  • Crescenti A, Mas S, Gasso P, Parellada E, Bernardo M, Lafuente A. Cyp2d6*3, *4, *5 and *6 polymorphisms and antipsychotic-induced extrapyramidal side-effects in patients receiving antipsychotic therapy. Clinical and Experimental Pharmacology and Physiology 2008;35:807–11.
  • Kobylecki CJ, Jakobsen KD, Hansen T, Jakobsen IV, Rasmussen HB, Werge T. CYP2D6 genotype predicts antipsychotic side effects in schizophrenia inpatients: A retrospective matched case-control study. Neuropsychobiology 2009;59:222–6.
  • Lane HY, Liu YC, Huang CL, Chang YC, Wu PL, Lu CT, Chang WH. Risperidone-related weight gain: Genetic and nongenetic predictors. Journal of Clinical Psychopharmacology 2006;26:128–34.
  • Liou YJ, Wang YC, Bai YM, Lin CC, Yu SC, Liao DL, … Lai IC. Cytochrome P-450 2D6*10 C188T polymorphism is associated with antipsychotic-induced persistent tardive dyskinesia in Chinese schizophrenic patients. Neuropsychobiology 2004;49:167–73.
  • Suzuki Y, Sawamura K, Someya T. Polymorphisms in the 5-hydroxytryptamine 2A receptor and CytochromeP4502D6 genes synergistically predict fluvoxamine-induced side effects in Japanese depressed patients. Neuropsychopharmacology 2006;31:825–31.
  • Steimer W, Zopf K, von Amelunxen S, Pfeiffer H, Bachofer J, Popp J, … Leucht S. Amitriptyline or not, that is the question: pharmacogenetic testing of CYP2D6 and CYP2C19 identifies patients with low or high risk for side effects in amitriptyline therapy. Clinical Chemistry 2005;51: 376–85.
  • Roberts RL, Mulder RT, Joyce PR, Luty SE, Kennedy MA. No evidence of increased adverse drug reactions in cytochrome P450 CYP2D6 poor metabolizers treated with fluoxetine or nortriptyline. Human Psychopharmacology 2004;19:17–23.
  • Sugai T, Suzuki Y, Sawamura K, Fukui N, Inoue Y, Someya T. The effect of 5-hydroxytryptamine 3A and 3B receptor genes on nausea induced by paroxetine. Pharmacogenomics Journal 2006;6:351–6.
  • Fu Y, Fan CH, Deng HH, Hu SH, Lv DP, Li LH, … Lu XQ. Association of CYP2D6 and CYP1A2 gene polymorphism with tardive dyskinesia in Chinese schizophrenic patients. Acta Pharmacologica Sinica 2006;27:328–32.
  • Matsumoto C, Shinkai T, De Luca V, Hori H, Hwang R, Ohmori O, … Nakamura J. Association study between functional polymorphisms in the cytochrome P450 1A2 and 2D6 genes and polydipsia in schizophrenia. Neuromolecular Medicine 2006;8:381–8.
  • Tiwari AK, Deshpande SN, Rao AR, Bhatia T, Mukit SR, Shriharsh V, … Thelma BK. Genetic susceptibility to tardive dyskinesia in chronic schizophrenia subjects: I. Association of CYP1A2 gene polymorphism.Pharmacogenomics Journal 2005;5:60–9.
  • Jin Y, Pollock BG, Frank E, Cassano GB, Rucci P, Muller DJ, … Bies RR. Effect of age, weight, and CYP2C19 genotype on escitalopram exposure. Journal of Clinical Pharmacology 2010;50:62–72.
  • Rudberg I, Hermann M, Refsum H, Molden E. Serum concentrations of sertraline and N-desmethyl sertraline in relation to CYP2C19 genotype in psychiatric patients. European Journal of Clinical Pharmacology 2008;64:1181–8.
  • Rudberg I, Mohebi B, Hermann M, Refsum H, Molden E. Impact of the ultrarapid CYP2C19*17 allele on serum concentration of escitalopram in psychiatric patients. Clinical Pharmacology and Therapeutics 2008;83:322–7.
  • Schenk PW, van Vliet M, Mathot RA, van Gelder T, Vulto AG, van Fessem MA, … van Schaik RH. The CYP2C19*17 genotype is associated with lower imipramine plasma concentrations in a large group of depressed patients. Pharmacogenomics Journal 2010;10:219–25.
  • Yin OQ, Wing YK, Cheung Y, Wang ZJ, Lam SL, Chiu HF, Chow MS. Phenotype-genotype relationship and clinical effects of citalopram in Chinese patients. Journal of Clinical Psychopharmacology 2006;26:367–72.
  • LLerena A, Dorado P, Berecz R, Gonzalez A, Penas L. Effect of CYP2D6 and CYP2C9 genotypes on fluoxetine and norfluoxetine plasma concentrations during steady-state conditions. European Journal of Clinical Pharmacology 2004;59:869–73.
  • LLerena A, de la Rubia A, Berecz R, Dorado P. Relationship between haloperidol plasma concentration, debrisoquine metabolic ratio, CYP2D6 and CYP2C9 genotypes in psychiatric patients. Pharmacopsychiatry 2004;37:69–73.
  • Matsumoto C, Ohmori O, Shinkai T, Hori H, Nakamura J. Genetic association analysis of functional polymorphisms in the cytochrome P450 1A2 (CYP1A2) gene with tardive dyskinesia in Japanese patients with schizophrenia. Psychiatric Genetics 2004;14:209–13.
  • Laika B, Leucht S, Heres S, Schneider H, Steimer W. Pharmacogenetics and olanzapine treatment: CYP1A2*1F and serotonergic polymorphisms influence therapeutic outcome. Pharmacogenomics Journal 2010;10:20–9.
  • Ghotbi R, Mannheimer B, Aklillu E, Suda A, Bertilsson L, Eliasson E, Osby U. Carriers of the UGT1A4 142T> G gene variant are predisposed to reduced olanzapine exposure – An impact similar to male gender or smoking in schizophrenic patients. European Journal of Clinical Pharmacology 2010;66:465–74.
  • Kootstra-Ros JE, Smallegoor W, van der Weide J. The cytochrome P450 CYP1A2 genetic polymorphisms *1F and *1D do not affect clozapine clearance in a group of schizophrenic patients. Annals of Clinical Biochemistry 2005;42: 216–9.
  • Lin KM, Tsou HH, Tsai IJ, Hsiao MC, Hsiao CF, Liu CY, … Liu YL. CYP1A2 genetic polymorphisms are associated with treatment response to the antidepressant paroxetine. Pharmacogenomics 2010;11:1535–43.
  • Lamba JK, Lin YS, Schuetz EG, Thummel KE. Genetic contribution to variable human CYP3A-mediated metabolism. Advanced Drug Delivery Reviews 2002;54:1271–94.
  • Elens L, van Schaik RH, Panin N, de Meyer M, Wallemacq P, Lison D, … Haufroid V. Effect of a new functional CYP3A4 polymorphism on calcineurin inhibitors’ dose requirements and trough blood levels in stable renal transplant patients. Pharmacogenomics 2011;12:1383–96.
  • Fang J, McKay G, Song J, Remillrd A, Li X, Midha K. In vitro characterization of the metabolism of haloperidol using recombinant cytochrome p450 enzymes and human liver microsomes. Drug Metabolism and Disposition 2001;29: 1638–43.
  • Hu YF, Tu JH, Tan ZR, Liu ZQ, Zhou G, He J, … Zhou HH. Association of CYP3A4*18B polymorphisms with the pharmacokinetics of cyclosporine in healthy subjects. Xenobiotica 2007;37:315–27.
  • Jin M, Gock SB, Jannetto PJ, Jentzen JM, Wong SH. Pharmacogenomics as molecular autopsy for forensic toxicology: Genotyping cytochrome P450 3A4*1B and 3A5*3 for 25 fentanyl cases. Journal of Analytical Toxicology 2005;29:590–8.
  • Lee SJ, Bell DA, Coulter SJ, Ghanayem B, Goldstein JA. Recombinant CYP3A4*17 is defective in metabolizing the hypertensive drug nifedipine, and the CYP3A4*17 allele may occur on the same chromosome as CYP3A5*3, representing a new putative defective CYP3A haplotype. Journal of Pharmacology and Experimental Therapeutics 2005;313: 302–9.
  • Murayama N, Nakamura T, Saeki M, Soyama A, Saito Y, Sai K, … Sawada J. CYP3A4 gene polymorphisms influence testosterone 6beta-hydroxylation. Drug Metababolism and Pharmacokinetics 2002;17:150–6.
  • Puranik YG, Birnbaum AK, Marino SE, Ahmed G, Cloyd JC, Remmel RP, … Lamba JK. Association of carbamazepine major metabolism and transport pathway gene polymorphisms and pharmacokinetics in patients with epilepsy. Pharmacogenomics 2013;14:35–45.
  • Yuan R, Zhang X, Deng Q, Wu Y, Xiang G. Impact of CYP3A4*1G polymorphism on metabolism of fentanyl in Chinese patients undergoing lower abdominal surgery. Clinical Chimica Acta 2011;412:755–60.
  • Dong ZL, Li H, Chen QX, Hu Y, Wu SJ, Tang LY, … Fang XM. Effect of CYP3A4*1G on the fentanyl consumption for intravenous patient-controlled analgesia after total abdominal hysterectomy in Chinese Han population. Journal of Clinical Pharmacy and Therapeutics 2012;37: 153–6.
  • Crettol S, Deglon JJ, Besson J, Croquette-Krokar M, Hammig R, Gothuey I, … Eap CB. ABCB1 and cytochrome P450 genotypes and phenotypes: Influence on methadone plasma levels and response to treatment. Clinical Pharmacology and Therapeutics 2006;80:668–81.
  • Dai D, Tang J, Rose R, Hodgson E, Bienstock RJ, Mohrenweiser HW, Goldstein JA. Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. Journal of Pharmacology and Experimental Therapeutics 2001;299:825–31.
  • Maekawa K, Harakawa N, Yoshimura T, Kim SR, Fujimura Y, Aohara F, … Saito Y. CYP3A4*16 and CYP3A4*18 alleles found in East Asians exhibit differential catalytic activities for seven CYP3A4 substrate drugs. Drug Metabolism and Disposition 2010;38:2100–4.
  • Miyazaki M, Nakamura K, Fujita Y, Guengerich FP, Horiuchi R, Yamamoto K. Defective activity of recombinant cytochromes P450 3A4.2 and 3A4.16 in oxidation of midazolam, nifedipine, and testosterone. Drug Metabolism and Disposition 2008;36:2287–91.
  • Wandel C, Witte JS, Hall JM, Stein CM, Wood AJ, Wilkinson GR. CYP3A activity in African American and European American men: Population differences and functional effect of the CYP3A4*1B5’-promoter region polymorphism. Clinical Pharmacology and Therapeutics 2000;68:82–91.
  • Oneda B, Crettol S, Jaquenoud Sirot E, Bochud M, Ansermot N, Eap CB. The P450 oxidoreductase genotype is associated with CYP3A activity in vivo as measured by the midazolam phenotyping test. Pharmacogenetics and Genomics 2009;19:877–83.
  • Robertson SM, Maldarelli F, Natarajan V, Formentini E, Alfaro RM, Penzak SR. Efavirenz induces CYP2B6- mediated hydroxylation of bupropion in healthy subjects. Journal of Acquired Immune Deficiency Syndromes 2008; 49:513–19.
  • Du J, Zhang A, Wang L, Xuan J, Yu L, Che R, … He L. Relationship between response to risperidone, plasma concentrations of risperidone and CYP3A4 polymorphisms in schizophrenia patients. Journal of Psychopharmacology 2010;24:1115–20.
  • Ball SE, Scatina J, Kao J, Ferron GM, Fruncillo R, Mayer P, … Hall J. Population distribution and effects on drug metabolism of a genetic variant in the 5’ promoter region of CYP3A4. Clinical Pharmacology and Therapeutics 1999;66:288–94.
  • Elens L, Becker ML, Haufroid V, Hofman A, Visser LE, Uitterlinden AG, … van Schaik RH. Novel CYP3A4 intron 6 single nucleotide polymorphism is associated with simvastatin-mediated cholesterol reduction in the Rotterdam Study. Pharmacogenetics and Genomics 2011;21:861–6.
  • Gao Y, Zhang LR, Fu Q. CYP3A4*1G polymorphism is associated with lipid-lowering efficacy of atorvastatin but not of simvastatin. European Journal of Clinical Pharmacology 2008;64:877–82.
  • Wang D, Guo Y, Wrighton SA, Cooke GE, Sadee W. Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs. Pharmacogenomics Journal 2011; 11:274–86.
  • Chen CH, Wang SC, Tsou HH, Ho IK, Tian JN, Yu CJ, … Liu YL. Genetic polymorphisms in CYP3A4 are associated with withdrawal symptoms and adverse reactions in methadone maintenance patients. Pharmacogenomics 2011;12: 1397–406.
  • Zhang W, Chang YZ, Kan QC, Zhang LR, Li ZS, Lu H, … Zhang J. CYP3A4*1G genetic polymorphism influences CYP3A activity and response to fentanyl in Chinese gynecologic patients. European Journal of Clincial Pharmacology 2010;66:61–6.
  • Risselada A, Vehof J, Bruggeman R. Association between HTR2C gene polymorphisms and the metabolic syndrome in patients using antipsychotics: A replication study. Pharmacogenomics Journal 2012;12:62–7.
  • Bai YM, Chen TT, Liou YJ, Hong CJ, Tsai SJ. Association between HTR2C polymorphisms and metabolic syndrome in patients with schizophrenia treated with atypical antipsychotics. Schizophrenia Research 2011;125:179–86.
  • Gregoor JG, van der Weide J, Loovers HM, van Megen HJ, Egberts TC, Heerdink ER. Association between LEP and LEPR gene polymorphisms and dyslipidemia in patients using atypical antipsychotic medication. Psychiatric Genetics 2010;20:311–6.
  • Gunes A, Melkersson KI, Scordo MG, Dahl ML. Association between HTR2C and HTR2A polymorphisms and metabolic abnormalities in patients treated with olanzapine or clozapine. Journal of Clinical Psychopharmacology 2009;29:65–8.
  • Kuzman MR, Medved V, Bozina N, Grubisin J, Jovanovic N, Sertic J. Association study of MDR1 and 5-HT2C genetic polymorphisms and antipsychotic-induced metabolic disturbances in female patients with schizophrenia. Pharmacogenomics Journal 2011;11:35–44.
  • Mulder H, Cohen D, Scheffer H, Gispen-de Wied C, Arends J, Wilmink FW, … Egberts AC. HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia: A replication study. Journal of Clinical Psychopharmacology 2009;29:16–20.
  • Mulder H, Franke B, van der-Beek van der AA, Arends J, Wilmink FW, Scheffer H, Egberts AC. The association between HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia. Journal of Clinical Psychopharmacology 2007;27:338–43.
  • Yevtushenko OO, Cooper SJ, O’Neill R, Doherty JK, Woodside JV, Reynolds GP. Influence of 5-HT2C receptor and leptin gene polymorphisms, smoking and drug treatment on metabolic disturbances in patients with schizophrenia. British Journal of Psychiatry 2008;192:424–8.
  • Ellingrod VL, Perry PJ, Ringold JC, Lund BC, Bever-Stille K, Fleming F, … Miller D. Weight gain associated with the − 759C/T polymorphism of the 5HT2C receptor and olanzapine. American Journal of Medical Genetics Part B – Neuropsychiatric Genetics 2005;134B:76–8.
  • Godlewska BR, Olajossy-Hilkesberger L, Ciwoniuk M, Olajossy M, Marmurowska-Michalowska H, Limon J, Landowski J. Olanzapine-induced weight gain is associated with the − 759C/T and − 697G/C polymorphisms of the HTR2C gene. Pharmacogenomics Journal 2009;9:234–41.
  • Gregoor JG, Mulder H, Cohen D, van Megen HJ, Egberts TC, Heerdink ER, van der Weide J. Combined HTR2C-LEP genotype as a determinant of obesity in patients using antipsychotic medication. Journal of Clinical Psychopharmacology 2010;30:702–5.
  • Gregoor JG, van der Weide J, Loovers HM, van Megen HJ, Egberts TC, Heerdink ER. Polymorphisms of the LEP, LEPR and HTR2C gene: obesity and BMI change in patients using antipsychotic medication in a naturalistic setting. Pharmacogenomics 2011;12:919–23.
  • Miller DD, Ellingrod VL, Holman TL, Buckley PF, Arndt S. Clozapine-induced weight gain associated with the 5HT2C receptor − 759C/T polymorphism. American Journal of Medical Genetics Part B– Neuropsychiatric Genetics 2005;133B:97–100.
  • Opgen-Rhein C, Brandl EJ, Muller DJ, Neuhaus AH, Tiwari AK, Sander T, Dettling M. Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. Pharmacogenomics 2010; 11:773–80.
  • Ryu S, Cho EY, Park T, Oh S, Jang WS, Kim SK, … Hong KS. − 759 C/T polymorphism of 5-HT2C receptor gene and early phase weight gain associated with antipsychotic drug treatment.Progress in Neuro-Psychopharmacology and Biological Psychiatry 2007;31:673–7.
  • Sicard MN, Zai CC, Tiwari AK, Souza RP, Meltzer HY, Lieberman JA, … Muller DJ. Polymorphisms of the HTR2C gene and antipsychotic-induced weight gain: An update and meta-analysis. Pharmacogenomics 2010;11:1561–71.
  • Templeman LA, Reynolds GP, Arranz B, San L. Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis. Pharmacogenetics and Genomics 2005;15:195–200.
  • Kang SH, Lee JI, Chang AK, Joo YH, Kim CY, Kim SY. Genetic polymorphisms in the HTR2C and peroxisome proliferator–activated receptors are not associated with metabolic syndrome in patients with schizophrenia taking clozapine. Psychiatry Investigation 2011;8:262–8.
  • Mulder H, Franke B, van der-Beek van der AA, Arends J, Wilmink FW, Egberts AC, Scheffer H. The association between HTR2C polymorphisms and obesity in psychiatric patients using antipsychotics: A cross-sectional study. Pharmacogenomics Journal 2007;7:318–24.
  • Park YM, Cho JH, Kang SG, Choi JE, Lee SH, Kim L, Lee HJ. Lack of association between the − 759C/T polymorphism of the 5-HT2C receptor gene and olanzapine-induced weight gain among Korean schizophrenic patients. Journal of Clinical Pharmacy and Therapeutics 2008;33: 55–60.
  • Popp J, Leucht S, Heres S, Steimer W. DRD4 48 bp VNTR but not 5-HT 2C Cys23Ser receptor polymorphism is related to antipsychotic-induced weight gain. Pharmacogenomics Journal 2009;9:71–7.
  • Secher A, Bukh J, Bock C, Koefoed P, Rasmussen HB, Werge T, … Mellerup E. Antidepressive-drug-induced bodyweight gain is associated with polymorphisms in genes coding for COMT and TPH1. International Clinical Psychopharmacology 2009;24:199–203.
  • Theisen FM, Hinney A, Bromel T, Heinzel-Gutenbrunner M, Martin M, Krieg JC, … Hebebrand J. Lack of association between the − 759C/T polymorphism of the 5-HT2C receptor gene and clozapine-induced weight gain among German schizophrenic individuals. Psychiatric Genetics 2004;14: 139–42.
  • Ujike H, Nomura A, Morita Y, Morio A, Okahisa Y, Kotaka T, … Kuroda S. Multiple genetic factors in olanzapine-induced weight gain in schizophrenia patients: A cohort study. Journal of Clinical Psychiatry 2008;69:1416–22.
  • De Luca V, Muller DJ, Hwang R, Lieberman JA, Volavka J, Meltzer HY, Kennedy JL. HTR2C haplotypes and antipsychotics-induced weight gain: X-linked multimarker analysis. Human Psychopharmacology 2007;22:463–7.
  • Thompson A, Lavedan C, Volpi S. Absence of weight gain association with the HTR2C − 759C/T polymorphism in patients with schizophrenia treated with iloperidone. Psychiatry Research 2010;175:271–3.
  • Risselada AJ, Mulder H, Heerdink ER, Egberts TC. Pharmacogenetic testing to predict antipsychotic-induced weight gain: A systematic review. Pharmacogenomics 2011;12:1213–27.
  • Chen SF, Shen YC, Chen CH. HTR2A A-1438G/T102C polymorphisms predict negative symptoms performance upon aripiprazole treatment in schizophrenic patients. Psychopharmacology 2009;205:285–92.
  • Choi MJ, Kang RH, Ham BJ, Jeong HY, Lee MS. Serotonin receptor 2A gene polymorphism (− 1438A/G) and short-term treatment response to citalopram. Neuropsychobiology 2005;52:155–62.
  • Gunes A, Scordo MG, Jaanson P, Dahl ML. Serotonin and dopamine receptor gene polymorphisms and the risk of extrapyramidal side effects in perphenazine-treated schizophrenic patients. Psychopharmacology 2007;190:479–84.
  • Kato M, Fukuda T, Wakeno M, Fukuda K, Okugawa G, Ikenaga Y, … Kinoshita T. Effects of the serotonin type 2A, 3A and 3B receptor and the serotonin transporter genes on paroxetine and fluvoxamine efficacy and adverse drug reactions in depressed Japanese patients. Neuropsychobiology 2006;53:186–95.
  • Kato M, Zanardi R, Rossini D, De Ronchi D, Okugawa G, Kinoshita T, … Serretti A. 5-HT2A gene variants influence specific and different aspects of antidepressant response in Japanese and Italian mood disorder patients. Psychiatry Research 2009;167:97–105.
  • Kim B, Choi EY, Kim CY, Song K, Joo YH. Could HTR2A T102C and DRD3 Ser9Gly predict clinical improvement in patients with acutely exacerbated schizophrenia?Results from treatment responses to risperidone in a naturalistic setting. Human Psychopharmacology 2008;23:61–7.
  • McMahon FJ, Buervenich S, Charney D, Lipsky R, Rush AJ, Wilson AF, … Manji H. Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment. American Journal of Human Genetics 2006;78:804–14.
  • Hong CJ, Chen TJ, Yu YW, Tsai SJ. Response to fluoxetine and serotonin 1A receptor (C-1019G) polymorphism in Taiwan Chinese major depressive disorder. Pharmacogenomics Journal 2006;6:27–33.
  • Ikeda M, Yamanouchi Y, Kinoshita Y, Kitajima T, Yoshimura R, Hashimoto S, … Iwata N. Variants of dopamine and serotonin candidate genes as predictors of response to risperidone treatment in first-episode schizophrenia. Pharmacogenomics 2008;9:1437–43.
  • Illi A, Setala-Soikkeli E, Viikki M, Poutanen O, Huhtala H, Mononen N, … Kampman O. 5-HTR1A, 5-HTR2A, 5-HTR6, TPH1 and TPH2 polymorphisms and major depression. Neuroreport 2009;20:1125–8.
  • Kang RH, Choi MJ, Paik JW, Hahn SW, Lee MS. Effect of serotonin receptor 2A gene polymorphism on mirtazapine response in major depression. International Journal of Psychiatry in Medicine 2007;37:315–29.
  • Lin E, Chen PS, Chang HH, Gean PW, Tsai HC, Yang YK, Lu RB. Interaction of serotonin-related genes affects short-term antidepressant response in major depressive disorder. Progress in Neuro-psychopharmacology and Biological Psychiatry 2009;33:1167–72.
  • Pae CU, Artioli P, Serretti A, Kim TS, Kim JJ, Lee CU, … Paik IH. No evidence for interaction between 5-HT2A receptor and serotonin transporter genes in schizophrenia. Neuroscience Research 2005;52:195–9.
  • Peters EJ, Slager SL, McGrath PJ, Knowles JA, Hamilton SP. Investigation of serotonin-related genes in antidepressant response. Molecular Psychiatry 2004;9: 879–89.
  • Wilkie MJ, Smith G, Day RK, Matthews K, Smith D, Blackwood D, … Wolf CR. Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy. Pharmacogenomics Journal 2009;9: 61–70.
  • Penas-Lledo EM, Dorado P, Caceres MC, de la Rubia A, Llerena A. Association between T102C and A-1438G polymorphisms in the serotonin receptor 2A (5-HT2A) gene and schizophrenia: Relevance for treatment with antipsychotic drugs. Clinical Chemistry and Laboratory Medicine 2007; 45:835–8.
  • Horstmann S, Lucae S, Menke A, Hennings JM, Ising M, Roeske D, … Binder EB. Polymorphisms in GRIK4, HTR2A, and FKBP5 show interactive effects in predicting remission to antidepressant treatment. Neuropsychopharmacology 2010;35:727–40.
  • Liu W, Downing AC, Munsie LM, Chen P, Reed MR, Ruble CL, … Nisenbaum LK. Pharmacogenetic analysis of the mGlu2/3 agonist LY2140023 monohydrate in the treatment of schizophrenia. Pharmacogenomics Journal 2012;12: 246–54.
  • Lucae S, Ising M, Horstmann S, Baune BT, Arolt V, Muller-Myhsok B, … Domschke K. HTR2A gene variation is involved in antidepressant treatment response. European Neuropsychopharmacology 2010;20:65–8.
  • Manchia M, Congiu D, Squassina A, Lampus S, Ardau R, Chillotti C, … Del Zompo M. No association between lithium full responders and the DRD1, DRD2, DRD3, DAT1, 5-HTTLPR and HTR2A genes in a Sardinian sample. Psychiatry Research 2009;169:164–6.
  • Noro M, Antonijevic I, Forray C, Kasper S, Kocabas NA, Lecrubier Y, … Massat I. 5HT1A and 5HT2A receptor genes in treatment response phenotypes in major depressive disorder. International Clinical Psychopharmacology 2010;25:228–31.
  • Perlis RH, Fijal B, Adams DH, Sutton VK, Trivedi MH, Houston JP. Variation in catechol-O-methyltransferase is associated with duloxetine response in a clinical trial for major depressive disorder. Biological Psychiatry 2009;65: 785–91.
  • Peters EJ, Slager SL, Jenkins GD, Reinalda MS, Garriock HA, Shyn SI, … Hamilton SP. Resequencing of serotonin-related genes and association of tagging SNPs to citalopram response. Pharmacogenetics and Genomics 2009;19:1–10.
  • Uher R, Huezo-Diaz P, Perroud N, Smith R, Rietschel M, Mors O, … Craig I. Genetic predictors of response to antidepressants in the GENDEP project. Pharmacogenomics Journal 2009;9:225–33.
  • Kishi T, Yoshimura R, Kitajima T, Okochi T, Okumura T, Tsunoka T, … Iwata N. HTR2A is associated with SSRI response in major depressive disorder in a Japanese cohort. Neuromolecular Medicine 2010;12:237–42.
  • Altar CA, Wasley AM, Liebman J, Gerhardt S, Kim H, Welch JJ, Wood PL. CGS 10746B: An atypical antipsychotic candidate that selectively decreases dopamine release at behaviorally effective doses. Life Sciences 1986;39: 699–705.
  • Al Hadithy AF, Ivanova SA, Pechlivanoglou P, Semke A, Fedorenko O, Kornetova E, … Loonen AJ. Tardive dyskinesia and DRD3, HTR2A and HTR2C gene polymorphisms in Russian psychiatric inpatients from Siberia. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2009;33:475–81.
  • Al Hadithy AF, Wilffert B, Stewart RE, Looman NM, Bruggeman R, Brouwers JR, … van Harten PN. Pharmacogenetics of Parkinsonism, rigidity, rest tremor, and bradykinesia in African-Caribbean inpatients: Differences in association with dopamine and serotonin receptors. American Journal of Medical Genetics Part B – Neuropsychiatric Genetics 2008;147B:890–7.
  • Guzey C, Scordo MG, Spina E, Landsem VM, Spigset O. Antipsychotic-induced extrapyramidal symptoms in patients with schizophrenia: Associations with dopamine and serotonin receptor and transporter polymorphisms. European Journal of Clinical Pharmacology 2007;63:233–41.
  • Wilffert B, Al Hadithy AF, Sing VJ, Matroos G, Hoek HW, van Os J, … van Harten PN. The role of dopamine D3, 5-HT2A and 5-HT2C receptor variants as pharmacogenetic determinants in tardive dyskinesia in African-Caribbean patients under chronic antipsychotic treatment: Curacao extrapyramidal syndromes study IX. Journal of Psychopharmacology 2009;23:652–9.
  • Boke O, Gunes S, Kara N, Aker S, Sahin AR, Basar Y, Bagci H. Association of serotonin 2A receptor and lack of association of CYP1A2 gene polymorphism with tardive dyskinesia in a Turkish population. DNA and Cell Biology 2007;26:527–31.
  • Praschak-Rieder N, Kennedy J, Wilson AA, Hussey D, Boovariwala A, Willeit M, … Meyer JH. Novel 5-HTTLPR allele associates with higher serotonin transporter binding in putamen: A [(11)C] DASB positron emission tomography study. Biol Psychiatry 2007;62:327–31.
  • Baffa A, Hohoff C, Baune BT, Muller-Tidow C, Tidow N, Freitag C, … Domschke K. Norepinephrine and serotonin transporter genes: impact on treatment response in depression. Neuropsychobiology 2010;62:121–31.
  • Bozina N, Medved V, Kuzman MR, Sain I, Sertic J. Association study of olanzapine-induced weight gain and therapeutic response with SERT gene polymorphisms in female schizophrenic patients. Journal of Psychopharmacology 2007;21:728–34.
  • Bozina N, Peles AM, Sagud M, Bilusic H, Jakovljevic M. Association study of paroxetine therapeutic response with SERT gene polymorphisms in patients with major depressive disorder. World Journal of Biological Psychiatry 2008;9: 190–7.
  • Dolzan V, Serretti A, Mandelli L, Koprivsek J, Kastelic M, Plesnicar BK. Acute antipyschotic efficacy and side effects in schizophrenia: Association with serotonin transporter promoter genotypes. Progress in Neuro-psychopharmacology and Biological Psychiatry 2008;32:1562–6.
  • Durham LK, Webb SM, Milos PM, Clary CM, Seymour AB. The serotonin transporter polymorphism, 5HTTLPR, is associated with a faster response time to sertraline in an elderly population with major depressive disorder. Psychopharmacology 2004;174:525–9.
  • Gressier F, Bouaziz E, Verstuyft C, Hardy P, Becquemont L, Corruble E. 5-HTTLPR modulates antidepressant efficacy in depressed women. Psychiatric Genetics 2009;19:195–200.
  • Huezo-Diaz P, Uher R, Smith R, Rietschel M, Henigsberg N, Marusic A, … McGuffin P. Moderation of antidepressant response by the serotonin transporter gene. British Journal of Psychiatry 2009;195:30–8.
  • Illi A, Poutanen O, Setala-Soikkeli E, Kampman O, Viikki M, Huhtala H, … Lehtimaki T. Is 5-HTTLPR linked to the response of selective serotonin reuptake inhibitors in MDD?European Archives of Psychiatry and Clinical Neuroscience 2011;261:95–102.
  • Kato M, Ikenaga Y, Wakeno M, Okugawa G, Nobuhara K, Fukuda T, … Kinoshita T. Controlled clinical comparison of paroxetine and fluvoxamine considering the serotonin transporter promoter polymorphism. International Clinical Psychopharmacology 2005;20:151–6.
  • Keers R, Uher R, Huezo-Diaz P, Smith R, Jaffee S, Rietschel M, … Aitchison KJ. Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project. Pharmacogenomics Journal 2011;11:138–45.
  • Kohlrausch FB, Salatino-Oliveira A, Gama CS, Lobato MI, Belmonte-de-Abreu P, Hutz MH. Influence of serotonin transporter gene polymorphisms on clozapine response in Brazilian schizophrenics. Journal of Psychiatric Research 2010;44:1158–62.
  • Lee HY, Kim YK. Catechol-O-methyltransferase Val158Met polymorphism affects therapeutic response to mood stabilizer in symptomatic manic patients. Psychiatry Research 2010;175:63–6.
  • Lee MS, Lee HY, Lee HJ, Ryu SH. Serotonin transporter promoter gene polymorphism and long-term outcome of antidepressant treatment. Psychiatric Genetics 2004;14: 111–5.
  • Lenze EJ, Goate AM, Nowotny P, Dixon D, Shi P, Bies RR, … Pollock BG. Relation of serotonin transporter genetic variation to efficacy of escitalopram for generalized anxiety disorder in older adults. Journal of Clinical Psychopharmacology 2010;30:672–7.
  • Lotrich FE, Pollock BG, Kirshner M, Ferrell RF, Reynolds CF III. Serotonin transporter genotype interacts with paroxetine plasma levels to influence depression treatment response in geriatric patients. Journal of Psychiatry and Neuroscience 2008;33:123–30.
  • Min W, Li T, Ma X, Li Z, Yu T, Gao D, … Sun X. Monoamine transporter gene polymorphisms affect susceptibility to depression and predict antidepressant response. Psychopharmacology 2009;205:409–17.
  • Muhonen LH, Lahti J, Alho H, Lonnqvist J, Haukka J, Saarikoski ST. Serotonin transporter polymorphism as a predictor for escitalopram treatment of major depressive disorder comorbid with alcohol dependence. Psychiatry Research 2011;186:53–7.
  • Murphy GM, Jr., Hollander SB, Rodrigues HE, Kremer C, Schatzberg AF. Effects of the serotonin transporter gene promoter polymorphism on mirtazapine and paroxetine efficacy and adverse events in geriatric major depression. Archives of General Psychiatry 2004;61:1163–9.
  • Perna G, Favaron E, Di Bella D, Bussi R, Bellodi L. Antipanic efficacy of paroxetine and polymorphism within the promoter of the serotonin transporter gene. Neuropsychopharmacology 2005;30:2230–5.
  • Rybakowski JK, Suwalska A, Czerski PM, Dmitrzak-Weglarz M, Leszczynska-Rodziewicz A, Hauser J. Prophylactic effect of lithium in bipolar affective illness may be related to serotonin transporter genotype. Pharmacological Reports 2005; 57:124–7.
  • Rybakowski JK, Suwalska A, Skibinska M, Dmitrzak-Weglarz M, Leszczynska-Rodziewicz A, Hauser J. Response to lithium prophylaxis: interaction between serotonin transporter and BDNF genes. American Journal of Medical Genetics Part B – Neuropsychiatric Genetics 2007; 144B:820–3.
  • Serretti A, Cusin C, Rossini D, Artioli P, Dotoli D, Zanardi R. Further evidence of a combined effect of SERTPR and TPH on SSRIs response in mood disorders. American Journal of Medical Genetics Part B – Neuropsychiatric Genetics 2004;129B:36–40.
  • Smeraldi E, Serretti A, Artioli P, Lorenzi C, Catalano M. Serotonin transporter gene-linked polymorphic region: Possible pharmacogenetic implications of rare variants. Psychiatric Genetics 2006;16:153–8.
  • Stein MB, Seedat S, Gelernter J. Serotonin transporter gene promoter polymorphism predicts SSRI response in generalized social anxiety disorder. Psychopharmacology 2006;187:68–72.
  • Wang L, Yu L, He G, Zhang J, Zhang AP, Du J, … He L. Response of risperidone treatment may be associated with polymorphisms of HTT gene in Chinese schizophrenia patients. Neuroscience Letters 2007;414:1–4.
  • Dogan O, Yuksel N, Ergun MA, Yilmaz A, Ilhan MN, Karslioglu HE, … Menevse A. Serotonin transporter gene polymorphisms and sertraline response in major depression patients. Genetic Testing 2008;12:225–31.
  • Gudayol-Ferre E, Herrera-Guzman I, Camarena B, Cortes-Penagos C, Herrera-Abarca JE, Martinez-Medina P, … Guardia-Olmos J. The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder. Journal of Affective Disorders 2010;127:343–51.
  • Kirchheiner J, Nickchen K, Sasse J, Bauer M, Roots I, Brockmoller J. A 40-basepair VNTR polymorphism in the dopamine transporter (DAT1) gene and the rapid response to antidepressant treatment. Pharmacogenomics Journal 2007;7:48–55.
  • Kraft JB, Peters EJ, Slager SL, Jenkins GD, Reinalda MS, McGrath PJ, Hamilton SP. Analysis of association between the serotonin transporter and antidepressant response in a large clinical sample. Biological Psychiatry 2007;61: 734–42.
  • Lavretsky H, Siddarth P, Kumar A, Reynolds CF, 3rd. The effects of the dopamine and serotonin transporter polymorphisms on clinical features and treatment response in geriatric depression: A pilot study. International Journal of Geriatric Psychiatry 2008;23:55–9.
  • Lee HY, Kim DJ, Lee HJ, Choi JE, Kim YK. No association of serotonin transporter polymorphism (5-HTTVNTR and 5-HTTLPR) with characteristics and treatment response to atypical antipsychotic agents in schizophrenic patients. Progress in Neuro-psychopharmacology and Biological Psychiatry 2009;33:276–80.
  • Lewis G, Mulligan J, Wiles N, Cowen P, Craddock N, Ikeda M, … Peters TJ. Polymorphism of the 5-HT transporter and response to antidepressants: Randomised controlled trial. British Journal of Psychiatry 2011;198:464–71.
  • Lin C, Tang W, Hu J, Gao L, Huang K, Xu Y, … Shi Y. Haplotype analysis confirms association of the serotonin transporter (5-HTT) gene with schizophrenia in the Han Chinese population. Neuroscience Letters 2009;453: 210–13.
  • Maron E, Tammiste A, Kallassalu K, Eller T, Vasar V, Nutt DJ, Metspalu A. Serotonin transporter promoter region polymorphisms do not influence treatment response to escitalopram in patients with major depression. European Neuropsychopharmacology 2009;19:451–6.
  • Masoliver E, Menoyo A, Perez V, Volpini V, Rio ED, Perez J, … Baiget M. Serotonin transporter linked promoter (polymorphism) in the serotonin transporter gene may be associated with antidepressant-induced mania in bipolar disorder. Psychiatric Genetics 2006;16:25–9.
  • Michelon L, Meira-Lima I, Cordeiro Q, Miguita K, Breen G, Collier D, Vallada H. Association study of the INPP1, 5HTT, BDNF, AP-2beta and GSK-3beta GENE variants and restrospectively scored response to lithium prophylaxis in bipolar disorder. Neuroscience Letters 2006; 403:288–93.
  • Ng CH, Easteal S, Tan S, Schweitzer I, Ho BK, Aziz S. Serotonin transporter polymorphisms and clinical response to sertraline across ethnicities. Progress in Neuro-psychopharmacology and Biological Psychiatry 2006;30: 953–7.
  • Pae CU, Serretti A, Artioli P, Kim TS, Kim JJ, Lee CU, … Lee C. Interaction analysis between 5-HTTLPR and TNFA − 238/− 308 polymorphisms in schizophrenia. Journal of Neural Transmission 2006;113:887–97.
  • Perlis RH, Fijal B, Dharia S, Heinloth AN, Houston JP. Failure to replicate genetic associations with antidepressant treatment response in duloxetine-treated patients. Biological Psychiatry 2010;67:1110–13.
  • Reimherr F, Amsterdam J, Dunner D, Adler L, Zhang S, Williams D, … Feldman P. Genetic polymorphisms in the treatment of depression: speculations from an augmentation study using atomoxetine. Psychiatry Research 2010;175: 67–73.
  • Serretti A, Malitas PN, Mandelli L, Lorenzi C, Ploia C, Alevizos B, … Smeraldi E. Further evidence for a possible association between serotonin transporter gene and lithium prophylaxis in mood disorders. Pharmacogenomics Journal 2004;4:267–73.
  • Vazquez-Bourgon J, Arranz MJ, Mata I, Pelayo-Teran JM, Perez-Iglesias R, Medina-Gonzalez L, … Crespo-Facorro B. Serotonin transporter polymorphisms and early response to antipsychotic treatment in first episode of psychosis. Psychiatry Research 2010;175:189–94.
  • Yevtushenko OO, Oros MM, Reynolds GP. Early response to selective serotonin reuptake inhibitors in panic disorder is associated with a functional 5-HT1A receptor gene polymorphism. Journal of Affective Disorders 2010;123:308–11.
  • Yoshimura R, Umene-Nakano W, Suzuki A, Ueda N, Miyamoto K, Ikenouchi-Sugita A, … Nakamura J. Rapid response to paroxetine is associated with plasma paroxetine levels at 4 but not 8 weeks of treatment, and is independent of serotonin transporter promoter polymorphism in Japanese depressed patients. Human Psychopharmacology 2009;24:489–94.
  • Kim H, Lim SW, Kim S, Kim JW, Chang YH, Carroll BJ, Kim DK. Monoamine transporter gene polymorphisms and antidepressant response in koreans with late-life depression. Journal of the American Medical Association 2006;296: 1609–18.
  • Saeki Y, Watanabe T, Ueda M, Saito A, Akiyama K, Inoue Y, … Shimoda K. Genetic and pharmacokinetic factors affecting the initial pharmacotherapeutic effect of paroxetine in Japanese patients with panic disorder. European Journal of Clinical Pharmacology 2009;65:685–91.
  • Stamm TJ, Adli M, Kirchheiner J, Smolka MN, Kaiser R, Tremblay PB, Bauer M. Serotonin transporter gene and response to lithium augmentation in depression. Psychiatric Genetics 2008;18:92–7.
  • Umene-Nakano W, Yoshimura R, Ueda N, Suzuki A, Ikenouchi-Sugita A, Hori H, … Nakamura J. Predictive factors for responding to sertraline treatment: Views from plasma catecholamine metabolites and serotonin transporter polymorphism. Journal of Psychopharmacology 2010;24: 1764–71.
  • Kraft JB, Slager SL, McGrath PJ, Hamilton SP. Sequence analysis of the serotonin transporter and associations with antidepressant response. Biological Psychiatry 2005;58: 374–81.
  • Ruhe HG, Ooteman W, Booij J, Michel MC, Moeton M, Baas F, Schene AH. Serotonin transporter gene promoter polymorphisms modify the association between paroxetine serotonin transporter occupancy and clinical response in major depressive disorder. Pharmacogenetics and Genomics 2009;19:67–76.
  • Smits KM, Smits LJ, Schouten JS, Peeters FP, Prins MH. Does pretreatment testing for serotonin transporter polymorphisms lead to earlier effects of drug treatment in patients with major depression?A decision-analytic model. Clinical Therapeutics 2007;29:691–702.
  • Ferreira Ade A, Neves FS, da Rocha FF, Silva GS, Romano-Silva MA, Miranda DM, … Correa H. The role of 5-HTTLPR polymorphism in antidepressant-associated mania in bipolar disorder. Journal of Affective Disorders 2009;112:267–72.
  • Hu XZ, Rush AJ, Charney D, Wilson AF, Sorant AJ, Papanicolaou GJ, … Lipsky RH. Association between a functional serotonin transporter promoter polymorphism and citalopram treatment in adult outpatients with major depression. Archives of General Psychiatry 2007;64:783–92.
  • Lee SH, Choi TK, Lee E, Seok JH, Lee HS, Kim SJ. Serotonin transporter gene polymorphism associated with short-term treatment response to venlafaxine. Neuropsychobiology 2010;62:198–206.
  • Smits K, Smits L, Peeters F, Schouten J, Janssen R, Smeets H, … Prins M. Serotonin transporter polymorphisms and the occurrence of adverse events during treatment with selective serotonin reuptake inhibitors. International Clinical Psychopharmacology 2007;22:137–43.
  • Serretti A, Artioli P, Zanardi R, Lorenzi C, Rossini D, Cusin C, … Catalano M. Genetic features of antidepressant induced mania and hypo-mania in bipolar disorder. Psychopharmacology 2004;174:504–11.
  • Myrand SP, Sekiguchi K, Man MZ, Lin X, Tzeng RY, Teng CH, … Wilner KD. Pharmacokinetics/genotype associations for major cytochrome P450 enzymes in native and first- and third-generation Japanese populations: Comparison with Korean, Chinese, and Caucasian populations. Clinical Pharmacology and Therapeutics 2008;84:347–61.
  • Zhou SF, Liu JP, Chowbay B. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metabolism Reviews 2009;41:89–295.
  • Relling MV, Klein TE. CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network. Clinical Pharmacology and Therapeutics 2011;89:464–7.
  • Lohoff FW, Narasimhan S, Rickels K. Interaction between polymorphisms in serotonin transporter (SLC6A4) and serotonin receptor 2A (HTR2A) genes predict treatment response to venlafaxine XR in generalized anxiety disorder. Pharmacogenomics Journal 2012;21:33.
  • Hall-Flavin DK, Winner JG, Allen JD, Jordan JJ, Nesheim RS, Snyder KA, … Mrazek DA. Using a pharmacogenomic algorithm to guide the treatment of depression. Translational Psychiatry 2012;16:99.
  • Altar CA, Winner JG, Allen JD, Mrazek DA, Hall-Flavin . Improved clinical outcomes with a pharmacogenomic treatment support product in a depressed population. Paper presented at the Society of Biological Psychiatry, Philadelphia, PA, 3–5 May 2012.
  • Hall-Flavin DK, Winner JG, Allen JD, Carhart JM, Proctor B, Snyder KA, … Mrazek DA. Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting. Pharmacogenetics and Genomics 2013;23:535–48.
  • Winner J, Allen J, Altar CA, Mihajlovic A. Genotype predicts health resource utilization of outpatients with anxiety and depression in a staff model health maintenance organization. Translational Psychiatry 2013;19:2.

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