Factors affecting interindividual differences in clozapine response: A review and case report

Human Psychopharmacology

Volumn 26, Issue 3, 2011, Pages 177-187

  Bersani, Francesco Saverio ^a   Capra, Enrico ^a   Minichino, Amedeo ^a   Pannese, Rossella ^a   Girardi, Nicoletta ^a   Marini, Isabella ^a   Chiaie, Roberto Delle ^a   Biondi, Massimo ^a  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

Clozapine metabolism; CYP450 polymorphisms; Drug drug interactions; Therapeutic drug monitoring

Indexed keywords

AMISULPRIDE; BENZODIAZEPINE; CAFFEINE; CARBAMAZEPINE; CLOZAPINE; CYTOCHROME P450; CYTOCHROME P450 1A2; CYTOCHROME P450 2C; CYTOCHROME P450 2C8; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; DIAZEPAM; DOPAMINE RECEPTOR; FLUVOXAMINE; HALOPERIDOL; MULTIDRUG RESISTANCE PROTEIN 1; NEUROTRANSMITTER RECEPTOR; NICOTINE; NORCLOZAPINE; ORAL CONTRACEPTIVE AGENT; PHENOBARBITAL; PHENYTOIN; RIFAMPICIN; RISPERIDONE; SEROTONIN RECEPTOR; SEROTONIN TRANSPORTER; VALPROIC ACID; WARFARIN;

ADULT; BINDING AFFINITY; CASE REPORT; DIZZINESS; DNA SEQUENCE; DROWSINESS; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG MECHANISM; DRUG METABOLISM; DRUG MONITORING; DRUG SUBSTITUTION; DRUG UTILIZATION; DRUG WITHDRAWAL; ENZYME INHIBITION; ETHNICITY; FOOD; GASTROINTESTINAL SYMPTOM; GENE FREQUENCY; GENETIC VARIABILITY; HEADACHE; HUMAN; HYPERMETABOLISM; LIVER TOXICITY; MALE; MENTAL DISEASE; NEUROLEPTIC MALIGNANT SYNDROME; NUCLEAR MAGNETIC RESONANCE IMAGING; ORTHOSTATIC HYPOTENSION; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; RISK FACTOR; SCHIZOPHRENIA; SEDATION; SEIZURE; SEX DIFFERENCE; SIDE EFFECT; SINGLE NUCLEOTIDE POLYMORPHISM; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY; SMOKING; SWEATING; TACHYCARDIA; TARDIVE DYSKINESIA; TREATMENT RESPONSE; VISUAL DISORDER; XEROSTOMIA;

CLOZAPINE; CYTOCHROME P-450 CYP1A2; HUMANS; INDIVIDUALITY; MALE; SCHIZOPHRENIA; TREATMENT OUTCOME; YOUNG ADULT;

EID: 80051796589     PISSN: 08856222     EISSN: 10991077     Source Type: Journal    
DOI: 10.1002/hup.1191     Document Type: Review

References (74)

1. Adachi J, Mori Y, Matsui S, et al. 2001. Indirubin and indigo are potent aryl hydrocarbon receptor ligands present in human urine. J Biol Chem 276(34): 31475-31478.
2. Aklillu E, Carrillo JA, Makonnen E, et al. 2003. Genetic polymorphism of CYP1A2 in Ethiopians affecting induction and expression: characterization of novel haplotypes with single-nucleotide polymorphisms in intron 1. Mol Pharmacol 64: 659-669. (Pubitemid 37048569)
3. Arranz MJ, Collier DA, Sodhi M, et al. 1995. Association between clozapine response and allelic variation in the 5-HT2Areceptor gene. Lancet 346: 281-282.
4. Arranz MJ, Collier DA, Munro J, et al. 1996. Analysis of a structural polymorphism in the 5-HT2A receptor and clinical response to clozapine. Neurosci Lett 217: 177-178. (Pubitemid 26358831)
5. Arranz MJ, Munro J, Sham P, et al. 1998. Meta-analysis of studies on genetic variation in 5-HT2A receptors and clozapine response. Schizophr Res 32: 93-99. (Pubitemid 28364714)
6. Arranz MJ, Munro J, Birkett J, et al. 2000. Pharmacogenetic prediction of clozapine response. Lancet 355: 1615-1616. (Pubitemid 30240510)
7. Basile VS, Masellis M, Badri F, et al. 1999. Association of the Mscl polymorphismof the dopamine D3 receptor gene with tardive dyskinesia in schizophrenia. Neuropsychopharmacology 21: 17-27. (Pubitemid 29253832)
8. Bilgen T, Tosun O, Luleci G, Keser I. 2008. Frequencies of four genetic polymorphisms in the CYP1A2 gene in Turkish population. Genetika 44: 1133-1136.
9. Birkett JT, Arranz MJ, Munro J, et al. 2000. Association analysis of the 5-HT5A gene in depression, psychosis and antipsychotic response. NeuroReport 11(9): 2017-2020. (Pubitemid 30429155)
10. Bondolfi G, Morel F, Crettol S, Rachid F, Baumann P, Eap CB. 2005. Increased clozapine plasma concentrations and side effects induced by smoking cessation in 2 CYP1A2 genotyped patients. Ther Drug Monit 27(4): 539-543. (Pubitemid 41098833)
11. Carrillo JA, Herraiz AG, Ramos SI, Benitez J. 1998. Effect of caffeine withdrawal from the diet on the metabolism of clozapine in schizophrenic patients. J Clin Psychopharmacol 18: 311-316. (Pubitemid 28353874)
12. Chida M, Yokoi T, Fukui T, Kinoshita M, Yokota J, Kamataki T. 1999. Detection of three genetic polymorphisms in the 5′-flanking region and intron 1 of human CYP1A2 in the Japanese population. Jpn J Cancer Res 90: 899-902. (Pubitemid 29500425)
13. Consoli G, Lastella M, Ciapparelli A, et al. 2009. ABCB1 polymorphisms are associated with clozapine plasma levels in psychotic patients. Pharmacogenomics 10(8): 1267-1276.
14. Denison MS, Nagy SR. 2003. Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Annu Rev Pharmacol Toxicol 43: 309-334. (Pubitemid 37372644)
15. Dennis MJ, Massey RC, Cripps G, et al. 1991. Factors affecting the polycyclic aromatic hydrocarbon content of cereals, fats and other food products. Food Addit Contam 8(4): 517-530.
16. Dresser GK, Spence JD, Bailey DG. 2000. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet 38(1): 41-57. (Pubitemid 30055093)
17. Eap CB, Bender S, Jaquenoud Sirot E, et al. 2004. Nonresponse to clozapine and ultrarapid CYP1A2 activity: clinical data and analysis of CYP1A2 gene. J Clin Psychopharmacol 24: 214-219. (Pubitemid 38380846)
18. Eiermann B, Engel G, Johansson I, Zanger UM, Bertilsson L. 1997. The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. Br J Clin Pharmacol 44: 439-446. (Pubitemid 27485474)
19. Facciolà G, Avenoso A, Spina E, Perucca E. 1998. Inducing effects of phenobarbital on clozapine metabolism in patients with chronic schizophrenia. Ther Drug Monit 20: 628-630. (Pubitemid 28544291)
20. Fang J, Coutts RT, McKenna KF, Baker GB, 1998. Elucidation of individual cytochrome P450 enzymes involved in the metabolism of clozapine. Naunyn Schmiedebergs Arch Pharmacol 358: 592-599. (Pubitemid 28518324)
21. Fuhr, U, Rost, KL , Engelhardt R, et al. 1996. Evaluation of caffeine as a test drug for CYP1A2, NAT2 and CYP2E1 phenotyping in man by in vivo versus in vitro correlations. Pharmacogenetics 6(2): 159-176. (Pubitemid 26153359)
22. Gabbay V, O'Dowd MA, Mamamtavrishvili M, Asnis GM. 2002. Clozapine and oral contraceptives: a possible drug interaction. J Clin Psychopharmacol 22: 621-622. (Pubitemid 35416789)
23. Gossen, D, de Suray JM, Vandenhende F, Onkelinx C, Gangji D. 2002. Influence of fluoxetine on olanzapine pharmacokinetics. AAPS PharmSci 4(2): E11.
24. Hagg S, Spigset O, Mjorndal T, Dahlqvist R. 2000. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 49: 59-63. (Pubitemid 30050487)
25. Hamdy SI, Hiratsuka M, Narahara K, et al. 2003. Genotyping of four genetic polymorphisms in the CYP1A2 gene in the Egyptian population. Br J Clin Pharmacol 55: 321-324. (Pubitemid 36390765)
26. Hasegawa M, Guiterrez R, Way L, Meltzer HI. 1993. Relationship between clinical efficacy and clozapine concentration in plasma in schizophrenia: effect of smoking. J Clin Psychopharmacol 13: 383-390. (Pubitemid 24026099)
27. Hwang R, Shinkai T, De Luca V, et al. 2007. Association study of four dopamine D1 receptor gene polymorphisms and clozapine treatment response. J Psychopharmacol 21(7):718-727. (Pubitemid 47439830)
28. Ishiguro H, Okuyama Y, Toru M, Aranami T. 2000. Mutation and association analysis of the 5′ region of the dopamine D3 receptor gene in schizophrenia patients: identification of the Ala38Thr polymorphism and suggested association between DRD3 haplotypes and schizophrenia. Mol Psychiatry 5(4): 433-438. (Pubitemid 30455958)
29. Jerling M, Lindström L, Bondesson U, Bertilsson L. 1994. Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: evidence from a therapeutic drug monitoring service. Ther Drug Monit 16(4): 368-374. (Pubitemid 24222520)
30. Kapur S. A new framework for investigating antipsychotic action in humans: lessons from PET imaging. 1998. Mol Psychiatry 3: 135-140. (Pubitemid 28149554)
31. Kinon BJ, Lieberman JA. 1996. Mechanisms of action of atypical antipsychotic drugs: a critical analysis. Psychopharmacology 124: 2-34. (Pubitemid 26111436)
32. Lane HY, Chang YC, Chang WH, Lin SK, Tseng YT, Jann MW. 1999. Effects of gender and age on plasma levels of clozapine and its metabolites: analyzed by critical statistics. J Clin Psychiatry 60: 36-40. (Pubitemid 29069884)
33. Li Z, Huang M, Ichikawa J, Dai J, Meltzer HY. 2005.N- desmethylclozapine, a major metabolite of clozapine, increases cortical acetylcholine and dopamine release in vivo via stimulation of M(1) muscarinic receptors. Neuropsychopharmacology 30: 1986-1995. (Pubitemid 43093499)
34. Lieberman J, Safferman AZ, Pollack S, et al. 1994. Clinical effects of clozapine in chronic schizophrenia-response to treatment and predictors of outcome. Am J Psychiatry 151(12): 1744-1745.
35. Linnet K, Olesen OV. 1997. Metabolism of clozapine by cDNA- expressed human cytochrome P450 enzymes. Drug Metab Dispos 25: 1379-1382. (Pubitemid 28010923)
36. Malhotra AK, Goldman D, Ozaki N, Breier A, Buchanan R, Pickar D. 1996. Lack of association between polymorphisms in the 5-HT2A receptor gene and the antipsychotic response to clozapine. Am J Psychiatry 153(8): 1092-1094. (Pubitemid 26264713)
37. Malhotra AK, Buchanan RW, Kim S, et al. 1999. Allelic variation in the promoter region of the dopamine D2 receptor gene and clozapine response. Schizophr Res 36(1-3): 92-93.
38. Mancama D, Arranz MJ, Munro J, et al. 2000. The histamine 1 and histamine 2 receptor genes-candidates for schizophrenia and clozapine response. GeneScreen 1: 29-34.
39. Mancama D, Arranz MJ, Kerwin RW. 2002. Genetic predictors of therapeutic response to clozapine current status of research. CNS Drugs 16(5): 317-324. (Pubitemid 34548199)
40. Masellis M, Basile V, Meltzer HY, et al. 1998. Serotonin subtype 2 receptor genes and clinical response to clozapine in schizophrenia patients. Neuropsychopharmacology 19(2): 123-132. (Pubitemid 28288438)
41. Masellis M, Basile VS, Meltzer HY, et al. 2001. Lack of association between the T-C267 serotonin 5-HT6 receptor gene (HTR6) polymorphism and prediction of response to clozapine in schizophrenia. Schizophr Res 47: 49-58. (Pubitemid 32121770)
42. McCarthy R. 1994. Seizure following smoking cessation in a clozapine responder. Pharmacopsychiatry 27: 210-211. (Pubitemid 24291953)
43. McEvoy JP, Lieberman JA, Scott Stroup T, et al. 2006. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 163: 600-610. (Pubitemid 44464569)
44. Melkersson KI, Scordo MG, Gunes A, Dahl ML. 2007. Impact of CYP1A2 and CYP2D6 polymorphisms on drug metabolism and on insulin and lipid elevations and insulin resistance in clozapine treated patients. J Clin Psychiatry 68: 697-704. (Pubitemid 46841852)
45. Meltzer HY, Nash FJ. 1991. Effects of antipsychotic drugs on serotonin receptors. Pharmacol Rev 43: 587-604.
46. Meyer JM. 2001. Individual changes in clozapine levels after smoking cessation: results and a predictive model. J Clin Psychopharmacol 21: 569-574. (Pubitemid 33116655)
47. Miller RJ, Hiley CR. 1974. Anti-muscarinic properties of neuroleptics and drug-induced Parkinsonism. Nature 248: 596-597.
48. Naheed M, Green B. 2001. Focus on clozapine. Curr Med Res Opin 17(3): 223-229. (Pubitemid 34003125)
49. Nakajima M, Yokoi T, Mizutani M, Kinoshita M, Funayama M, Kamataki T. 1999. Genetic polymorphism in the 5′-flanking region of human CYP1A2 gene: effect on the CYP1A2 inducibility in humans. J Biochem 125: 803-808. (Pubitemid 29192503)
50. Nordstrom AL, Farde L, Nyberg S, Karlsson P, Halldin C, Sedvall G. 1995. D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentrations: a PET study of schizophrenia patients. Am J Psychiatry 152: 1444-1449.
51. Nothen MM, Rietschel M, Erdmann J, et al. 1995. Genetic variation of the 5-HT2A receptor and response to clozapine. Lancet 346: 908-909.
52. Ozdemir V, Masellis M, Basile V, et al. 1999. Variability in response to clozapine: potential role of cytochrome P4501A2 and the dopamineD4 receptor gene. CNS Spectr 4(6): 30-56. (Pubitemid 29284398)
53. Pai MP, Graci DM, Amsden GW. 2000. Macrolide drug interactions: an update. Ann Pharmacother 34: 495-513. (Pubitemid 30193784)
54. Pirmohamed M, Williams D, Madden S, Templeton E, Park BK. 1995. Metabolism and bioactivation of clozapine by human liver in vitro. J Pharmacol Exp Ther 272: 984-990.
55. Raedler TJ, Hinkelmann K, Wiedemann K. 2008. Variability of the in vivo metabolism of clozapine. Clin Neuropharmacol 31(6): 347-352.
56. Rasmussen BB, Brix TH, Kyvik KO, Brosen K. 2002. The interindividual differences in the 3-demethylation of caffeine alias CYP1A2 is determined by both genetic and environmental factors. Pharmacogenetics 12: 473-478. (Pubitemid 34913530)
57. Sachse C, Bhambra U, Smith G, et al. 2003. Polymorphisms in the cytochrome P450 CYP1A2 gene (CYP1A2) in colorectal cancer patients and controls: allele frequencies, linkage disequilibrium and influence on caffeine metabolism. Br J Clin Pharmacol 55: 68-76. (Pubitemid 36110841)
58. Sanyal S, Van Tol HHM. 1997. Review of the role of dopamine D4 receptors in schizophrenia and antipsychotic action. J Psychiatr Res 31 (2): 219-232. (Pubitemid 27317570)
59. Scharfetter J, Chaudhry HR, Hornik K, et al. 1998. Dopamine D3 receptor gene polymorphism and response to clozapine in schizophrenic Pakistani patients. Eur Neuropsychopharmacol 10(1): 17-20.
60. Shaikh S, Collier D, Arranz M, Ball D, Gill M, Kerwin R. 1994. DRD2 Ser311/Cys311 polymorphism in schizophrenia. Lancet 343(8904): 1045-1046.
61. Shimizu T, Tateishi T, Hatano M, Fujii-Kuriyama Y. 1991. Probing the role of lysines and arginines in the catalytic function of cytochrome P450d by site-directed mutagenesis. Interaction with NADPH cytochrome P450 reductase. J Biol Chem 266(6): 3372-3375. (Pubitemid 21909220)
62. Skarke C, Kirchhof A, Geisslinger G, Lotsch J. 2005. Rapid genotyping for relevant CYP1A2 alleles by pyrosequencing. Eur J Clin Pharmacol 61: 887-892. (Pubitemid 41803698)
63. Sodhi M, Arranz MJ, Curtis D, et al. 1995. Association between clozapine response and allelic variation in the 5-HT2C receptor gene. Neuroreport 7: 169-172. (Pubitemid 26077220)
64. Spina E, de Leon J. 2007. Metabolic drug interactions with newer antipsychotics: a comparative review . Basic Clin Pharmacol Toxicol 100: 4-22. (Pubitemid 46051438)
65. Toda, T, Ohi K, et al. 2009. Ciprofloxacin suppresses Cyp3a in mouse liver by reducing lithocholic acid-producing intestinal flora. Drug Metab Pharmacokinet 24(3): 201-208.
66. Tugnait M, Hawes EM, McKay G, Eichelbaum M, Midha KK. 1999. Characterization of the human hepatic cytochromes P450 involved in the in vitro oxidation of clozapine. Chem Biol Interact 118: 171-189. (Pubitemid 29179541)
67. Uges DRA, Boom K, Wientjes GD, Versteege J. 2000. Therapeutic drug monitoring of clozapine: an unexpected outcome. Ther Drug Monit 22: 323-324. (Pubitemid 30346450)
68. Vainer JL, Chouinard G. 1994. Interaction between caffeine and clozapine. J Clin Psychopharmacol 14: 284-285.
69. Vandel S, Netillard C, Perault M, Bel AM. 2000. Plasma levels of clozapine and desmethylclozapine are unaffected by concomitant ingestion of grapefruit juice. Eur J Clin Pharmacol 56: 347-348. (Pubitemid 30462934)
70. Warren Jr. JT, Peacock ML, Rodriguez LC, Fink JK. 1993. An MspI polymorphism in the human serotonin receptor gene (HTR2): detection by DGGE and RFLP analysis. Hum Mol Genet 2: 338. (Pubitemid 23129111)
71. Wen X, Wang JS, Neuvonen PJ, Backman JT. 2002. Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes. Eur J Clin Pharmacol 57(11): 799-804. (Pubitemid 34143338)
72. Wong AHC, Buckle CE, Van Tol HHM. 2000. Polymorphisms in dopamine receptors: what do they tell us? Eur J Pharmacol 410: 183-203. (Pubitemid 32008143)
73. Yu YW, Tsai SJ, Lin CH, Hsu CP, Yang KH, Hong CJ. 1999. Serotonin-6 receptor variant (C267T) and clinical response to clozapine. Neuroreport 10(6): 1231-1233. (Pubitemid 29403700)
74. Zhou Shu-Feng, Yang Li-Ping, Zhou Zhi-Wei, Liu Ya-He, Chan Eli. 2009. Insights into the substrate specificity, inhibitors, regulation, and polymorphisms and the clinical impact of human cytochrome P450 1A2. AAPS J 11(3): 481-494.