CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: A first step towards subpopulation-specific dosages

Acta Psychiatrica Scandinavica

Volumn 104, Issue 3, 2001, Pages 173-192

  Kirchheiner, J ^a   Brosen K ^b   Dahl, M L ^d   Gram, L F ^b   Kasper, S ^e   Roots, I ^a   Sjoqvist F ^d   Spina, E ^c   Brockmoller J ^f,g  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^c UNIVERSITY OF MESSINA   (Italy)

^d KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^e UNIVERSITY OF VIENNA   (Austria)

^f UNIVERSITY OF GÖTTINGEN   (Germany)

^g UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

Author keywords

Antidepressant therapy; CYP2C19; CYP2D6; Cytochrome P 450; Pharmacogenetics; Polymorphism

Indexed keywords

AMFEBUTAMONE; AMITRIPTYLINE; ANTIDEPRESSANT AGENT; CITALOPRAM; CLOMIPRAMINE; CYTOCHROME P450 2C19; CYTOCHROME P450 2D6; DESIPRAMINE; FLUOXETINE; FLUVOXAMINE; IMIPRAMINE; MAPROTILINE; MIANSERIN; MIRTAZAPINE; MOCLOBEMIDE; NEFAZODONE; NORTRIPTYLINE; PAROXETINE; SEROTONIN UPTAKE INHIBITOR; SERTRALINE; TRAZODONE; TRIMIPRAMINE; VENLAFAXINE;

DOSE RESPONSE; DRUG METABOLISM; DRUG MONITORING; GENOTYPE; PHARMACOGENETICS; PHENOTYPE; PRIORITY JOURNAL; REVIEW;

ANTIDEPRESSIVE AGENTS; ARYL HYDROCARBON HYDROXYLASES; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 ENZYME SYSTEM; DEPRESSIVE DISORDER; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG MONITORING; FEMALE; GENOTYPE; HUMANS; MALE; MIXED FUNCTION OXYGENASES; PHENOTYPE; POLYMORPHISM, GENETIC;

EID: 0034894010     PISSN: 0001690X     EISSN: None     Source Type: Journal    
DOI: 10.1034/j.1600-0447.2001.00299.x     Document Type: Review

References (190)

1. Plasma levels of monomethylated tricyclic antidepressants during treatment with trimipramine-like compounds
2. Steady state plasma levels of nortriptyline in twins: Influence of genetic factors and drug therapy
3. Polymorphic hydroxylation of Debrisoquine in man
4. Pharmacogenetics of mephenytoin: A new drug hydroxylation polymorphism in man
5. Interethnic factors affecting drug response
6. Geographical/interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19
7. Pharmacogenetics of antidepressants: Clinical aspects
8. Polymorphic cytochromes P450 and drugs used in psychiatry
9. Antidepressants and drug-metabolizing enzymes - Expert group report
10. Metabolism of monoamine oxidase inhibitors
11. Clinical significance of the sparteine/debrisoquine oxidation polymorphism
12. The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans
13. Genotyping of poor metabolisers of debrisoquine by allele-specific PCR amplification
14. Cytochrome P450 2D6 variants in a Caucasian population: Allele frequencies and phenotypic consequences
15. Pharmacogenetic methods as a complement to therapeutic monitoring of antidepressants and neuroleptics
16. Genetically variable metabolism of antidepressants and neuroleptic drugs in man
17. The cytochrome P450 2D6 (CYP2D6) enzyme polymorphism: Screening costs and influence on clinical outcomes in psychiatry
18. Pilot study of the cytochrome P450-2D6 genotype in a psychiatric state hospital
19. Assessment of the predictive power of genotypes for the in-vivo catalytic function of CYP2D6 in a German population
20. Elucidation of the genetic basis of the common 'intermediate metabolizer' phenotype for drug oxidation by CYP2D6
21. A multifamily study on the relationship between CYP2C19 genotype and s-mephenytoin oxidation phenotype
22. CYP2CI9 genotype and phenotype determined with omeprazole in patients with acid-related disorders with and without Helicobacter pylori infection
23. CYP2C19 genotype and phenotype determined by omeprazole in a Korean population
24. Genotyping of S-mephenytion 4′-hydroxylation in an extended Japanese population
25. Use of omeprazole as a probe drug for CYP2CI9 phenotype in Swedish Caucasians: Comparison with S-mephenytoin hydroxylation phenotype and CYP2C19 genotype
26. Comparison of the effects of anti-depressants and their metabolites on reuptake of biogenic amines and on receptor binding
27. Metabolism of some second and fourth-generation anti-depressants: Iprindole, viloxazine, bupropion, mianserin, maprotiline, trazodone, nefazodone, and venlafaxine
28. Active hydroxymetabolites of anti-depressants. Emphasis on E-10-hydroxy-nortriptyline
29. Clinically relevant pharmacology of selective serotonin reuptake inhibitors: An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism
30. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions
31. Newer antidepressants and the cytochrome P450 system
32. The pharmacogenetics of the selective serotonin reuptake inhibitors
33. Drug-drug interactions involving antidepressants: Focus on venlafaxine
34. New antidepressants and the cytochrome P450 system: Focus on venlafaxine, nefazodone, and mirtazapine
35. Metabolism of the newer antidepressants. An overview of the pharmacological and pharmacokinetic implications
36. Differences in interactions of SSRIs
37. Pharmacokinetic interactions of antidepressants
38. Fluoxetine
39. Is there a right dose of psychotropic drugs? A discussion of the methodological problems in clinical dose-effect studies
40. Imipramine treatment of painful diabetic neuropathy
41. Plasma level monitoring of tricyclic antidepressant therapy
42. Tricyclic anti-depressants-blood level measurements and clinical outcome: An APA Task Force report
43. Pharmacokinetics of antidepressants: Why and how they are relevant to treatment
44. Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine
45. Effect of the CYP2D-6*10 genotype on venlafaxine pharmacokinetics in healthy adult volunteers
46. The CYP2D6 genotype and plasma concentrations of mianserin enantiomers in relation to therapeutic response to mianserin in depressed Japanese patients
47. Pharmacokinetics of nortriptyline and its 10-hydroxy metabolite in Chinese subjects of different CYP2D6 genotypes
48. Role of oxidation polymorphism on blood and urine concentrations of amitriptyline and its metabolites in man
49. Amitriptyline metabolism: Relationship to polymorphic debrisoquine hydroxylation
50. Amitriptyline pharmacokinetics and clinical response: II. Metabolic polymorphism assessed by hydroxylation of debrisoquine and mephenytoin
51. Amitriptyline metabolism: Association with debrisoquin hydroxylation in nonsmokers
52. Dextromethorphan and mephenytoin phenotyping of patients treated with thioridazine or amitriptyline
53. Bupropion plasma levels and CYP2D6 phenotype
54. Pharmacokinetics of citalopram in relation to the sparteine and the mephenytoin oxidation polymorphisms
55. Steady state plasma levels of clomipramine and its metabolites: Impact of the sparteine/debrisoquine oxidation polymorphism
56. Single-dose kinetics of clomipramine: Relationship to the sparteine and S-mephenytoin oxidation polymorphisms
57. Clomipramine dose-effect study in patients with depression: Clinical end points and pharmacokinetics
58. Phenotypic consistency in hydroxylation of desmethylimipramine and debrisoquine in healthy subjects and in human liver microsomes
59. Imipramine demethylation and hydroxylation: Impact of the sparteine oxidation phenotype
60. Steady-state concentrations of imipramine and its metabolites in relation to the sparteine/debrisoquine polymorphism
61. Hydroxylation of desmethylimipramine: Dependence on the debrisoquine hydroxylation phenotype
62. Differences in the inhibitory effect of cimetidine on desipramine metabolism between rapid and slow debrisoquin hydroxylators
63. Inhibition of desipramine 2-hydroxylation by quinidine and quinine
64. Analysis of the CYP2D6 gene in relation to debrisoquin and desipramine hydroxylation in a Swedish population
65. Polymorphic 2-hydroxylation of desipramine. A population and family study
66. Imipramine metabolism in relation to the sparteine and mephenytoin oxidation polymorphisms - A population study
67. Relationship between plasma desipramine levels, CYP2D6 phenotype and clinical response to desipramine: A prospective study
68. Duplication of CYP2D6 predicts high clearance of desipramine but high clearance does not predict duplication of CYP2D6
69. Metabolism of desipramine in Japanese psychiatric patients: The impact of CYP2D6 genotype on the hydroxylation of desipramine
70. The disposition of fluoxetine but not sertraline is altered in poor metabolizers of debrisoquin
71. The stereoselective metabolism of fluoxetine in poor and extensive metabolizers of sparteine
72. Disposition of fluvoxamine in humans is determined by the polymorphic CYP2D6 and also by the CYPIA2 activity
73. Relationship between fluvoxamine pharmacokinetics and CYP2D6/CYP2C19 phenotype polymorphisms
74. Non-linear fluvoxamine disposition
75. The mephenytoin oxidation polymorphism is partially responsible for the N-demethylation of imipramine
76. Imipramine demethylation in vivo: Impact of CYP1A2, CYP2C19, and CYP3A4
77. Inhibitors of imipramine metabolism by human liver microsomes
78. The N-demethylation of imipramine correlates with the oxidation of S-mephenytoin (S/R-ratio). A population study
79. Reappraisal of human CYPisoforms involved in imipramine N- demethylation and 2-hydroxylation: A study using microsomes obtained from putative extensive and poor metabolizers of S- mephenytoin and eleven recombinant human CYPs
80. Effects of genetic defects in the CYP2CI9 gene on the N-demethylation of imipramine, and clinical outcome of imipramine therapy
81. N-methylation of maprotiline in debrisoquine/mephenytoin-phenotyped depressive patients
82. Maprotiline metabolism appears to co-segregate with the genetically-determined CYP2D6 polymorphic hydroxylation of debrisoquine
83. Stereoselective disposition of mianserin is related to debrisoquine hydroxylation polymorphism
84. Steady state concentrations of the enantiomers of mianserin and desmethylmianserin in poor and in homozygous and heterozygous extensive metabolizers of debrisoquine
85. In vitro and in vivo studies on the disposition of mirtazapine in humans
86. Comparison of the pharmacokinetics of moclobemide in poor and efficient metabolizers of debrisoquine
87. The role of cytochrome P450 2D6 in the metabolism of moclobemide
88. Moclobemide, a substrate of CYP2CI9 and an inhibitor of CYP2C19, CYP2D6, and CYPIA2: A panel study
89. Single and multiple-dose pharmacokinetics of nefazodone in subjects classified as extensive and poor metabolizers of dextromethorphan
90. Nortriptyline and antipyrine clearance in relation to debrisoquine hydroxylation in man
91. Demethylation and hydroxylation of amitriptyline, nortriptyline, and 10-hydroxyamitriptyline in human liver microsomes
92. Steady-state plasma levels of nortriptyline and its 10-hydroxy metabolite: Relationship to the CYP2D6 genotype
93. 10-Hydroxylation of nortriptyline in white persons with 0, 1, 2, 3, and 13 functional CYP2D6 genes
94. The relationship between paroxetine and the sparteine oxidation polymorphism
95. Review of the pharmacokinetics and metabolism of reboxetine, a selective noradrenaline reuptake inhibitor
96. Metabolic activation of the new tricyclic antidepressant tianeptine by human liver cytochrome P450
97. Relationship between the CYP2D6 genotype and the steady-state plasma concentrations of trazodone and its active metabolite m-chloro-phenylpiperazine
98. 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
99. Steady state plasma levels of the enantiomers of trimipramine and of its metabolites in CYP2D6-, CYP2C19- and CYP3A4/5-phenotyped patients
100. Influence of CYP2D6 activity on the disposition and cardiovascular toxicity of the antidepressant agent venlafaxine in humans
101. Venlafaxine serum levels and CYP2D6 genotype
102. Five distinct human cytochromes mediate amitriptyline N-demethylation in vitro: Dominance of CYP 2C19 and 3A4
103. Urinary desipramine hydroxylation index and steady-state plasma concentrations of imipramine and desipramine
104. Steady-state plasma concentrations of imipramine and desipraminc in relation to S-mephenytoin 4′-hydroxylation status in Japanese depressive patients
105. E- and Z-10-hydroxylation of nortriptyline: Relationship to polymorphic debrisoquine hydroxylation
106. Role of genetic polymorphism in psychopharmacology
107. Low frequency of defective alleles of cytochrome P450 enzymes 2C19 and 2D6 in the Turkish population
108. Debrisoquine/sparteine hydroxylation genotype and phenotype: Analysis of common mutations and alleles of CYP2D6 in a European population
109. Cytochrome P4502C9: An enzyme of major importance in human drug metabolism
110. Carbamazepine but not valproate induces bupropion metabolism
111. Clinical pharmacokinetics of nefazodone
112. The emerging role of cytochrome P450 3A in psychopharmacology
113. Effects of carbamazepine coadministration on plasma concentrations of trazodone and its active metabolite, m-chlorophenylpiperazine
114. Pronounced inhibition of noradrenaline uptake by 10-hydroxymetabolites of nortriptyline
115. Enantioselective amitriptyline metabolism in patients phenotyped for two cytochrome P450 isozymes
116. Plasma concentrations of nortriptyline and its 10-hydroxy metabolite in depressed patients - Relationship to the debrisoquine hydroxylation metabolic ratio
117. Antidepressant activity of 2-hydroxydesipramine
118. Three-dimensional quantitative structure activity relationship analyses of substrates for CYP2B6
119. The pharmacological effect of citalopram residues in the (S)-(+)-enantiomer
120. Determination of the enantiomers of citalopram, its demethylated and propionic acid metabolites in human plasma by chiral HPLC
121. Studies on the stereoselective metabolism of citalopram by human liver microsomes and cDNA-expressed cytochrome P450 enzymes
122. Identification of three cytochrome P450 isozymes involved in N-demethylation of citalopram enantiomers in human liver microsomes
123. Plasma levels of chlorimipramine and its demethyl metabolite during treatment of depression
124. Importance of oxidative polymorphism and levomepromazine treatment on the steady-state blood concentrations of clomipramine and its major metabolites
125. Metabolic interaction between tricyclic antidepressant and fluvoxamine and fluoxetine, a pharmacogenetic approach
126. Fluvoxamine-tricyclic antidepressant interaction. An accidental finding
127. Inhibition of antidepressant demethylation and hydroxylation by fluvoxamine in depressed patients
128. Nonlinear pharmacokinetics of chlorimipramine after infusion and oral administration in patients
129. The debrisoquine hydroxylation test predicts steady-state plasma levels of desipramine
130. First-pass metabolism of imipramine and desipramine: Impact of the sparteine oxidation phenotype
131. Quinidine inhibits the 2-hydroxylation of imipramine and desipramine but not the demethylation of imipramine
132. Inhibition of desipramine 2-hydroxylation by quinidine and quinine in rapid and slow debrisoquine hydroxylators
133. Imipramine metabolism in relation to the sparteine oxidation polymorphism - A family study
134. Active metabolites of imipramine and desipramine in man
135. Role of cytochrome P450 2D6 (CYP2D6) in the stereospecific metabolism of E- and Z-doxepin
136. Interaction of the enantiomers of fluoxetine and norfluoxetine with human liver cytochromes P450
137. Fluoxetine and norfluoxetine plasma concentrations in major depression: A multicenter study
138. Comparison of norfluoxetine enantiomers as serotonin uptake inhibitors in vivo
139. Fluoxetine and its two enantiomers as selective serotonin uptake inhibitors
140. Norfluoxetine enantiomers as inhibitors of serotonin uptake in rat brain
141. Pharmacological characterization of selective serotonin reuptake inhibitors (SSRIs)
142. Fluoxetine and norfluoxetine are potent inhibitors of P450IID6 - The source of the sparteine/debrisoquine oxidation polymorphism
143. Effect of cigarette smoking on fluvoxamine pharmacokinetics in humans
144. Lack of correlation between fluvoxamine clearance and CYP1A2 activity as measured by systemic caffeine clearance
145. Role of P450IID6, the target of the sparteine-debrisoquin oxidation polymorphism, in the metabolism of imipramine
146. Interethnic dissociation between debrisoquine and desipramine hydroxylation
147. Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver
148. Importance of oxidative polymorphism on clinical efficacy and side-effects of imipramine - A retrospective study
149. Isolation and identification of hydroxylated maprotiline metabolites
150. Non-response to maprotiline caused by ultra-rapid metabolism that is different from CYP2D6?
151. Seizures associated with high maprotiline serum concentrations
152. Maprotiline treatment in depression. A perspective on seizures
153. Second-generation antidepressants
154. Identification of human cytochrome P450 isoforms involved in the stereo-selective metabolism of mianserin enantiomers
155. Is there a therapeutic window for plasma concentration of mianserin plus desmethylmianserin?
156. Relationship between mianserin plasma levels and antidepressant effect in a double-blind trial comparing a single night-time and divided daily dose regimens
157. Mirtazapine: An antidepressant with noradrenergic and specific serotonergic effects
158. Clinical Pharmacokinetics of mirtazapine
159. Biotransformation of moclobemide in humans
160. Inhibition of cytochrome P450 by nefazodone in vitro: Studies of dextromethorphan O- and N-demethylation
161. Studies on the metabolism and pharmacokinetics of nortriptyline and desmethylimipramine in man
162. Disposition of single oral doses of E-10-hydroxynortriptyline in healthy subjects, with some observations on pharmacodynamic effects
163. Treatment of depression with E-10-hydroxynortriptyline - A pilot study on biochemical effects and pharmacokinetics
164. Molecular basis for rational megaprescribing in ultrarapid hydroxylators of debrisoquine
165. Monitoring tricyclic antidepressants
166. Extremely rapid hydroxylation of debrisoquine: A case report with implication for treatment with nortriptyline and other tricyclic antidepressants
167. Metabolic pathway of paroxetine in animals and man and the comparative pharmacological properties of its metabolites
168. Paroxetine plasma levels: Lack of correlation with efficacy or adverse events
169. Cytochrome P-450-mediated metabolism of the individual enantiomers of the antidepressant agent reboxetine in human liver microsomes
170. Genetic polymorphism and reboxetine metabolism
171. Comparison of the effects of sertraline and its metabolite desmethylsertraline on blockade of central 5-HT reuptake in vivo
172. Sertraline N-demethylation is catalyzed by multiple isoforms of human cytochrome P-450 in vitro
173. Effects of various factors on steady state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine
174. Pharmacokinetics and metabolism of trazodone in man
175. Trazodone treatment increases plasma prolactin concentrations in depressed patients
176. Inhibition of trazodone metabolism by thioridazine in humans
177. Plasma levels of trimipramine and metabolites in four patients: Determination of the enantiomer concentrations of the hydroxy metabolites
178. Quantitation of trimipramine enantiomers in human serum by enantioselective high-performance liquid chromatography and mixed-mode disc solid-phase extraction
179. Determination of trimipramine and metabolites in plasma by liquid chromatography with electrochemical detection
180. Metabolism of trimipramine in vitro by human CYP2D6 isozyme
181. Biochemical, neurophysiological, and behavioral effects of Wy-45,233 and other identified metabolites of the antidepressant venlafaxine
182. Venlafaxine oxidation in vitro is catalysed by CYP2D6
183. O- and N-demethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: Effect of metabolic inhibitors and SSRI antidepressants
184. The impact of the CYP2D6 and CYP2C19 genotypes on venlafaxine pharmacokinetics in a Japanese population
185. Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies
186. Ultrarapid metabolism of clomipramine in a therapy-resistant depressive patient, as confirmed by CYP2 D6 genotyping
187. Extremely slow metabolism of amitriptyline but normal metabolism of imipramine and desipramine in an extensive metabolizer of sparteine, debrisoquine, and mephenytoin
188. Seizures and myoclonus associated with antidepressant treatment: Assessment of potential risk factors, including CYP2D6 and CYP2C19 polymorphisms, and treatment with CYP2D6 inhibitors