The impact of the CYP2D6-polymorphism on dose recommendations for current antidepressants

European Archives of Psychiatry and Clinical Neuroscience

Volumn 256, Issue 5, 2006, Pages 287-293

  Thuerauf, Norbert ^a   Lunkenheimer, Jens ^a  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

Antidepressant therapy; CYP2D6; Cytochrome P450; Polymorphism

Indexed keywords

AMFEBUTAMONE; AMITRIPTYLINE; ANTIDEPRESSANT AGENT; CITALOPRAM; CLOMIPRAMINE; CYTOCHROME P450 2D6; DESIPRAMINE; DOXEPIN; DRUG METABOLITE; DRUG METABOLIZING ENZYME; FLUOXETINE; IMIPRAMINE; MAPROTILINE; MIANSERIN; MIRTAZAPINE; MOCLOBEMIDE; NORTRIPTYLINE; PAROXETINE; REBOXETINE; SERTRALINE; TRAZODONE; TRIMIPRAMINE; VENLAFAXINE;

CONTROLLED STUDY; DEMETHYLATION; DRUG DOSE REGIMEN; DRUG METABOLISM; ENZYME ACTIVITY; GENETIC POLYMORPHISM; HUMAN; PRIORITY JOURNAL; REVIEW;

ANIMALS; ANTIDEPRESSIVE AGENTS; CYTOCHROME P-450 CYP2D6; DOSE-RESPONSE RELATIONSHIP, DRUG; GENOTYPE; HUMANS; MIXED FUNCTION OXYGENASES; PHARMACEUTICAL PREPARATIONS; POLYMORPHISM, GENETIC; SUBSTRATE SPECIFICITY;

EID: 33747822956     PISSN: 09401334     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00406-006-0663-5     Document Type: Review

References (82)

1. Alexanderson B, Bertilsson L, Borga O, Sjoqvist F (1971) Studies on the metabolism and pharamcokinetics of nortriptyline and desmethylimipramine in man. Chem Biol Interact 3:235-236
2. Amsterdam JD, Fawcett J, Quitkin FM, Reimherr FW, Rosenbaum JF, Michelson D, Hornig-Rohan M, Beasley CM (1997) Fluoxetine and norfluoxetine plasma concentrations in major depression: a multicenter study. Am J Psychiatry 154:963-969
3. Balant-Gorgia AE, Schulz P, Dayer P, Balant L, Kubli A, Gertsch C, Garrone G (1982) Role of oxidation polymorphism on blood and urine concentrations of amitriptyline and its metabolites in man. Arch Psychiatr Nervenkr 232:215-222
4. Barbhaiya RH, Buch AB, Greene DS (1996) Single and multiple dose pharmacokinetics of nefazodone in subjects classified as extensive and poor metabolizers of dextromethorphan. Br J Clin Pharmacol 42:573-581
5. Baumann P, Jonzier-Perey M, Koeb L, Kupfer A, Tinguely D, Schopf J (1986) Amitriptyline pharmacokinetics and clinical response: II. Metabolic polymorphism assessed by hydroxylation of debrisoquine and mephenytoin. Int Clin Psychopharmacol 1:102-112
6. Bertilsson L, Aberg-Wistedt A, Gustafsson LL, Nordin C (1985) Extremely rapid hydroxylation of debrisoquine: a case report with implication for treatment with nortriptyline and other tricyclic antidepressants. Ther Drug Monit 7:478-480
7. Bertilsson L, Dahl ML, Sjoqvist F, Aberg-Wistedt A, Humble M, Johansson I, Lundqvist E, Ingelman-Sundberg M (1993) Molecular basis for rational megaprescribing in ultrarapid hydroxylators of debrisoquine. Lancet 341:63
8. Bertilsson L, Mellstrom B, Sjoqvist F (1979) Pronounced inhibition of noradrenaline uptake by 10-hydroxymetabolites of nortriptyline. Life Sci 25:1285-1292
9. Bertschy G, Vandel S, Francois T, Bonin B, Bouquet S, Baumann P, Volmat R, Sechter D, Bizouard P (1992) Metabolic interaction between tricyclic antidepressant and fluvoxamine and fluoxetine, a pharmacogenetic approach. Clin Neuropharmacol 15 Suppl 1 Pt A:78A-79A
10. Bertschy G, Vandel S, Vandel B, Allers G, Volmat R (1991) Fluvoxamine-tricyclic antidepressant interaction. An accidental finding. Eur J Clin Pharmacol 40:119-120
11. Bolaji OO, Coutts RT, Baker GB (1993) Metabolism of trimipramine in vitro by human CYP2D6 isozyme. Res Commun Chem Pathol Pharmacol 82:111-120
12. Breyer-Pfaff U, Kroeker M, Winkler T, Kriemler P (1985) Isolation and identification of hydroxylated maprotiline metabolites. Xenobiotica 15:57-66
13. Breyer-Pfaff U, Pfandl B, Nill K, Nusser E, Monney C, Jonzier-Perey M, Baettig D, Baumann P (1992) Enantioselective amitriptyline metabolism in patients phenotyped for two cytochrome P450 isozymes. Clin Pharmacol Ther 52:350-358
14. Brosen K, Skjelbo E (1991) Fluoxetine and norfluoxetine are potent inhibitors of P450IID6 - the source of the sparteine/debrisoquine oxidation polymorphism. Br J Clin Pharmacol 32:136-137
15. Carrillo JA, Dahl ML, Svensson JO, Alm C, Rodriguez I, Bertilsson L (1996) Disposition of fluvoxamine in humans is determined by the polymorphic CYP2D6 and also by the CYP1A2 activity. Clin Pharmacol Ther 60:183-190
16. Dahl ML, Bertilsson L, Nordin C (1996) Steady-state plasma levels of nortriptyline and its 10-hydroxy metabolite: relationship to the CYP2D6 genotype. Psychopharmacology (Berl) 123:315-319
17. Dahl ML, Johansson I, Palmertz MP, Ingelman-Sundberg M, Sjoqvist F (1992) Analysis of the CYP2D6 gene in relation to debrisoquin and desipramine hydroxylation in a Swedish population. Clin Pharmacol Ther 51:12-17
18. Dahl ML, Tybring G, Elwin CE, Alm C, Andreasson K, Gyllenpalm M, Bertilsson L (1994) Stereoselective disposition of mianserin is related to debrisoquin hydroxylation polymorphism. Clin Pharmacol Ther 56:176-183
19. Dahl ML, Voortman G, Alm C, Elwin CE, Delbressine L, Vos R, Bogaards JJP, Bertilsson L (1997) In vitro and in vivo studies on the disposition of mirtazapine in humans. Clin Drug Invest 13:37-46
20. Dalen P, Dahl ML, Ruiz ML, Nordin J, Bertilsson L (1998) 10-Hydroxylation of nortriptyline in white persons with 0, 1, 2, 3, and 13 functional CYP2D6 genes. Clin Pharmacol Ther 63:444-452
21. Danish University Antidepressant Group (DUAG) (1999) Clomipramine dose-effect study in patients with depression: clinical end points and pharmacokinetics. Clin Pharmacol Ther 66:152-165
22. Dessain EC, Schatzberg AF, Woods BT, Cole JO (1986) Maprotiline treatment in depression. A perspective on seizures. Arch Gen Psychiatry 43:86-90
23. Eap CB, Bender S, Gastpar M, Fischer W, Haarmann C, Powell K, Jonzier-Perey M, Cochard N, Baumann P (2000) Steady state plasma levels of the enantiomers of trimipramine and of its metabolites in CYP2D6-, CYP. Ther Drug Monit 22:209-214
24. Eap CB, Koeb L, Holsboer-Trachsler E, Baumann P (1992) Plasma levels of trimipramine and metabolites in four patients: determination of the enantiomer concentrations of the hydroxy metabolites. Ther Drug Monit 14:380-385
25. Eap CB, Laurian S, Souche A, Koeb L, Reymond P, Buclin T, Baumann P (1992) Influence of quinidine on the pharmacokinetics of trimipramine and on its effect on the waking EEG of healthy volunteers. A pilot study on two subjects. Neuropsychobiology 25:214-220
26. Eap CB, Lima CA, Macciardi F, Woggon B, Powell K, Baumann P (1998) Steady state concentrations of the enantiomers of mianserin and desmethylmianserin in poor and in homozygous and heterozygous extensive metabolizers of debrisoquine. Ther Drug Monit 20:7-13
27. Firkusny L, Gleiter CH (1994) Maprotiline metabolism appears to co-segregate with the genetically-determined CYP2D6 polymorphic hydroxylation of debrisoquine. Br J Clin Pharmacol 37:383-388
28. Fjordside L, Jeppesen U, Eap CB, Powell K, Baumann P, Brosen K (1999) The stereoselective metabolism of fluoxetine in poor and extensive metabolizers of sparteine. Pharmacogenetics 9:55-60
29. Fukuda T, Yamamoto I, Nishida Y, Zhou Q, Ohno M, Takada K, Azuma J (1999) Effect of the CYP2D6*10 genotype on venlafaxine pharmacokinetics in healthy adult volunteers. Br J Clin Pharmacol 47:450-453
30. Fuller RW, Snoddy HD, Krushinski JH, Robertson DW (1992) Comparison of norfluoxetine enantiomers as serotonin uptake inhibitors in vivo. Neuropharmacology 31:997-1000
31. Haddock RE, Johnson AM, Langley PF, Nelson DR, Pope JA, Thomas DR, Woods FR (1989) Metabolic pathway of paroxetine in animals and man and the comparative pharmacological properties of its metabolites. Acta Psychiatr Scand Suppl 350:24-26
32. Hamelin BA, Turgeon J, Vallee F, Belanger PM, Paquet F, LeBel M (1996) The disposition of fluoxetine but not sertraline is altered in poor metabolizers of debrisoquin. Clin Pharmacol Ther 60:512-521
33. Haritos VS, Ghabrial H, Ahokas JT, Ching MS (2000) Role of cytochrome P450 2D6 (CYP2D6) in the stereospecific metabolism of E- and Z-doxepin. Pharmacogenetics 10:591-603
34. Hartter S, Wetzel H, Hammes E, Hiemke C (1993) Inhibition of antidepressant demethylation and hydroxylation by fluvoxamine in depressed patients. Psychopharmacology (Berl) 110:302-308
35. Hyttel J, Bogeso KP, Perregaard J, Sanchez C (1992) The pharmacological effect of citalopram residues in the (S)-(+)-enantiomer. J Neural Transm Gen Sect 88:157-160
36. Ishida M, Otani K, Kaneko S, Ohkubo T, Osanai T, Yasui N, Mihara K, Higuchi H, Sugawara K (1995) Effects of various factors on steady state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine. Int Clin Psychopharmacol 10:143-146
37. Jauch R, Griesser E, Oesterhelt G, Arnold W, Meister W, Ziegler WH, Guentert TW (1990) Biotransformation of moclobemide in humans. Acta Psychiatr Scand Suppl 360:87-90
38. Jauch R, Kopitar Z, Prox A, Zimmer A (1976) [Pharmacokinetics and metabolism of trazodone in man (author's transl)]. Arzneimittelforschung 26:2084-2089
39. Ketter TA, Flockhart DA, Post RM, Denicoff K, Pazzaglia PJ, Marangell LB, George MS, Callahan AM (1995) The emerging role of cytochrome P450 3A in psychopharmacology. J Clin Psychopharmacol 15:387-398
40. Ketter TA, Jenkins JB, Schroeder DH, Pazzaglia PJ, Marangell LB, George MS, Callahan AM, Hinton ML, Chao J, Post RM (1995) Carbamazepine but not valproate induces bupropion metabolism. J Clin Psychopharmacol 15:327-333
41. Kirchheiner J, Brosen K, Dahl ML, Gram LF, Kasper S, Roots I, Sjoqvist F, Spina E, Brockmoller J (2001) CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages. Acta Psychiatr Scand 104:173-192
42. Kobayashi K, Ishizuka T, Shimada N, Yoshimura Y, Kamijima K, Chiba K (1999) Sertraline N-demethylation is catalysed by multiple isoforms of human cytochrome P-450 in vitro. Drug Metab Dispos 27:763-766
43. Kuss HJ, Jungkunz G (1986) Nonlinear pharmacokinetics of chlorimipramine after infusion and oral administration in patients. Prog Neuropsychopharmacol Biol Psychiatry 10:739-748
44. Lessard E, Yessine MA, Hamelin BA, O'Hara G, LeBlanc J, Turgeon J (1999) Influence of CYP2D6 activity on the disposition and cardiovascular toxicity of the antidepressant agent venlafaxine in humans. Pharmacogenetics 9:435-443
45. Liu J, Stewart JT (1997) Quantitation of trimipramine enantiomers in human serum by enantioselective high-performance liquid chromatography and mixed-mode disc solid-phase extraction. J Chromatogr B Biomed Sci Appl 700:175-182
46. Madsen H, Hansen TS, Brosen K (1996) Imipramine metabolism in relation to the sparteine oxidation polymorphism - a family study. Pharmacogenetics 6:513-519
47. Mellstrom B, Bertilsson L, Lou YC, Sawe J, Sjoqvist F (1983) Amitriptyline metabolism: relationship to polymorphic debrisoquine hydroxylation. Clin Pharmacol Ther 34:516-520
48. Mellstrom B, Sawe J, Bertilsson L, Sjoqvist F (1986) Amitriptyline metabolism: association with debrisoquin hydroxylation in nonsmokers. Clin Pharmacol Ther 39:369-371
49. Meyer JW, Woggon B, Kupfer A (1988) Importance of oxidative polymorphism on clinical efficacy and side-effects of imipramine - a retrospective study. Pharmacopsychiatry 21:365-366
50. Meyer UA, Amrein R, Balant LP, Bertilsson L, Eichelbaum M, Guentert TW, Henauer S, Jackson P, Laux G, Mikkelsen H, Peck C, Pollock BG, Priest R, Sjoqvist F, Delini-Stula A (1996) Antidepressants and drug-metabolizing enzymes-expert group report. Acta Psychiatr Scand 93:71-79
51. Mihara K, Otani K, Suzuki A, Yasui N, Nakano H, Meng X, Ohkubo T, Nagasaki T, Kaneko S, Tsuchida S, Sugawara K, Gonzalez FJ (1997) Relationship between the CYP2D6 genotype and the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine. Psychopharmacology (Berl) 133:95-98
52. Mihara K, Otani K, Tybring G, Dahl ML, Bertilsson L, Kaneko S (1997) The CYP2D6 genotype and plasma concentrations of mianserin enantiomers in relation to therapeutic response to mianserin in depressed Japanese patients. J Clin Psychopharmacol 17:467-471
53. Muth EA, Moyer JAHJT, Andree TH, Husbands GEM (1991) Biochemical, neurophysiological, and behavioral effects of Wy-45,233 and other identified metabolites of the antidepressant venlafaxine. l. Drug Dev Res 23:191-199
54. Nielsen KK, Brosen K, Gram LF (1992) Steady-state plasma levels of clomipramine and its metabolites: impact of the sparteine/debrisoquine oxidation polymorphism. Danish University Antidepressant Group. Eur J Clin Pharmacol 43:405-411
55. Nielsen KK, Brosen K, Hansen MG, Gram LF (1994) Single-dose kinetics of clomipramine: relationship to the sparteine and S-mephenytoin oxidation polymorphisms. Clin Pharmacol Ther 55:518-527
56. Nordin C, Siwers B, Benitez J, Bertilsson L (1985) Plasma concentrations of nortriptyline and its 10-hydroxy metabolite in depressed patients - relationship to the debrisoquine hydroxylation metabolic ratio. Br J Clin Pharmacol 19:832-835
57. Olesen OV, Linnet K (1999) Studies on the stereoselective metabolism of citalopram by human liver microsomes and cDNA-expressed cytochrome P450 enzymes. Pharmacology 59:298-309
58. Otani K, Yasui N, Kaneko S, Ishida M, Ohkubo T, Osanai T, Sugawara K, Fukushima Y (1995) Trazodone treatment increases plasma prolactin concentrations in depressed patients. Int Clin Psychopharmacol 10:115-117
59. Otton SV, Ball SE, Cheung SW, Inaba T, Rudolph RL, Sellers EM (1996) Venlafaxine oxidation in vitro is catalysed by CYP2D6. Br J Clin Pharmacol 41:149-156
60. Pollock BG, Sweet RA, Kirshner M, Reynolds CF, III (1996) Bupropion plasma levels and CYP2D6 phenotype. Ther Drug Monit 18:581-585
61. Rau T, Heide R, Bergmann K, Wuttke H, Werner U, Feifel N, Eschenhagen T (2002) Effect of the CYP2D6 genotype on metoprolol metabolism persists during long-term treatment. Pharmacogenetics 12:465-472
62. Rau T, Wohlleben G, Wuttke H, Thuerauf N, Lunkenheimer J, Lanczik M, Eschenhagen T (2004) CYP2D6 genotype: impact on adverse effects and nonresponse during treatment with antidepressants-a pilot study. Clin Pharmacol Ther 75:386-393
63. Rocchetti M, Pellizzoni C, Poggesi L (1995) Genetic polymorphism and reboxetine metabolism. Therapie 50:80
64. Rudorfer MV, Golden RN, Potter WZ (1984) Second-generation antidepressants. Psychiatr Clin North Am 7:519-534
65. Sanchez C, Hyttel J (1999) Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding. Cell Mol Neurobiol 19:467-489
66. Sindrup SH, Brosen K, Gram LF, Hallas J, Skjelbo E, Allen A, Allen GD, Cooper SM, Mellows G, Tasker TC (1992) The relationship between paroxetine and the sparteine oxidation polymorphism. Clin Pharmacol Ther 51:278-287
67. Sindrup SH, Brosen K, Hansen MG, Aaes-Jorgensen T, Overo KF, Gram LF (1993) Pharmacokinetics of citalopram in relation to the sparteine and the mephenytoin oxidation polymorphisms. Ther Drug Monit 15:11-17
68. Sjoqvist F, Bertilsson L, Asberg M (1980) Monitoring tricyclic antidepressants. Ther Drug Monit 2:85-93
69. Spigset O, Granberg K, Hagg S, Norstrom A, Dahlqvist R (1997) Relationship between fluvoxamine pharmacokinetics and CYP2D6/CYP2C19 phenotype polymorphisms. Eur J Clin Pharmacol 52:129-133
70. Spigset O, Granberg K, Hagg S, Soderstrom E, Dahlqvist R (1998) Non-linear fluvoxamine disposition. Br J Clin Pharmacol 45:257-263
71. Spina E, Gitto C, Avenoso A, Campo GM, Caputi AP, Perucca E (1997) Relationship between plasma desipramine levels, CYP2D6 phenotype and clinical response to desipramine: a prospective study. Eur J Clin Pharmacol 51:395-398
72. Sprouse J, Clarke T, Reynolds L, Heym J, Rollema H (1996) Comparison of the effects of sertraline and its metabolite desmethylsertraline on blockade of central 5-HT reuptake in vivo. Neuropsychopharmacology 14:225-231
73. Stimmel GL, Dopheide JA, Stahl SM (1997) Mirtazapine: an antidepressant with noradrenergic and specific serotonergic effects. Pharmacotherapy 17:10-21
74. Suckow RF, Cooper TB (1984) Determination of trimipramine and metabolites in plasma by liquid chromatography with electrochemical detection. J Pharm Sci 73:1745-1748
75. Tasker TC, Kaye CM, Zussman BD, Link CG (1989) Paroxetine plasma levels: lack of correlation with efficacy or adverse events. Acta Psychiatr Scand Suppl 350:152-155
76. Traskman L, Asberg M, Bertilsson L, Cronholm B, Mellstrom B, Neckers LM, Sjoqvist F, Thoren P, Tybring G (1979) Plasma levels of chlorimipramine and its demethyl metabolite during treatment of depression. Clin Pharmacol Ther 26:600-610
77. Vormfelde SV, Bitsch A, Meineke I, Gundert-Remy UM, Gleiter CH (1997) Non-response to maprotiline caused by ultra-rapid metabolism that is different from CYP2D6? Eur J Clin Pharmacol 52:387-390
78. Wienkers LC, Allievi C, Hauer MJ, Wynalda MA (1999) Cytochrome P-450-mediated metabolism of the individual enantiomers of the antidepressant agent reboxetine in human liver microsomes. Drug Metab Dispos 27:1334-1340
79. Wong DT, Bymaster FP, Reid LR, Mayle DA, Krushinski JH, Robertson DW (1993) Norfluoxetine enantiomers as inhibitors of serotonin uptake in rat brain. Neuropsychopharmacology 8:337-344
80. Yasui N, Otani K, Kaneko S, Ohkubo T, Osanai T, Ishida M, Mihara K, Kondo T, Sugawara K, Fukushima Y (1995) Inhibition of trazodone metabolism by thioridazine in humans. Ther Drug Monit 17:333-335
81. Yue QY, Zhong ZH, Tybring G, Dalen P, Dahl ML, Bertilsson L, Sjoqvist F (1998) Pharmacokinetics of nortriptyline and its 10-hydroxy metabolite in Chinese subjects of different CYP2D6 genotypes. Clin Pharmacol Ther 64:384-390
82. Zanger UM, Fischer J, Raimundo S, Stuven T, Evert BO, Schwab M, Eichelbaum M (2001) Comprehensive analysis of the genetic factors determining expression and function of hepatic CYP2D6. Pharmacogenetics 11:573-585