CYP2D6*10 alleles do not determine plasma fluvoxamine concentration/dose ratio in Japanese subjects

Ohara, Koichi; Tanabu, Shigeru; Ishibashi, Kazuhisa; Ikemoto, Keiko; Yoshida, Kimiko; Shibuya, Haruo

doi:10.1007/s00228-002-0529-3

Cited by 25 publications

(20 citation statements)

References 15 publications

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“…For example, a lower antidepressant response or remission is reported for UMg and PMg (Kawanishi et al 2004;Tsai et al 2010;Rau et al 2004). However, several studies failed to report such an association: with fluvoxamine (Gerstenberg et al 2003;Ohara et al 2003); with citalopram (Peters et al 2008;Mrazek et al 2011);with paroxetine (Gex-Fabry et al 2008); with paroxetine and mirtazapine (Murphy et al 2003); with fluoxetine and nortriptyline (Roberts et al 2004); with escitalopram and nortriptyline (Hodgson et al 2014); with several antidepressants (Grasmader et al 2004;Serretti et al 2009). …”

Section: Introductionmentioning

confidence: 91%

Response to CYP2D6 substrate antidepressants is predicted by a CYP2D6 composite phenotype based on genotype and comedications with CYP2D6 inhibitors

Gressier¹,

Verstuyft

Hardy³

et al. 2014

J Neural Transm

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The cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of most antidepressants. Comedication with a potent CYP2D6 inhibitor can convert patients with extensive metabolizer (EM) or ultra-rapid metabolizer (UM) genotypes into poor metabolizer (PM) phenotypes. Since comedication is frequent in depressed patients treated with antidepressants, we investigated the effect of the CYP2D6 composite phenotype on antidepressant efficacy, taking into account both the CYP2D6 genotype and comedication with CYP2D6 inhibitors. 87 Caucasian in patients with a major depressive episode were prospectively treated with flexible doses of antidepressant monotherapy as well as comedications and genotyped for the major CYP2D6 alleles (CYP2D6*3 rs35742686, *4 rs3892097, *5 del, *6 rs5030655, and *2xN). They were classified for CYP2D6 composite phenotype and assessed for antidepressant response after 4 weeks. In terms of genotypes (g), 6 subjects were UMg, 6 PMg, and 75 EMg. Ten patients were coprescribed a CYP2D6 inhibitor, resulting in the following composite phenotypes (cp): 5 UMcp, 16 PMcp, and 66 EMcp. Whereas none of the CYP2D6 genotypes were significantly associated with antidepressant response, UMcp had a lower antidepressant response than PMcp or EMcp (respectively: 39.0 ± 17.9, 50.0 ± 26.0, and 61.6 ± 23.4, p = 0.02). Despite small sample size, this study suggests that a CYP2D6 composite phenotype, taking into account both genotype and comedications with CYP2D6 inhibitors, could predict CYP2D6 substrate antidepressants response. Thus, to optimize antidepressant response, CYP2D6 genotype could be performed and comedications with CYP2D6 inhibitors should be avoided, when prescribing CYP2D6 substrate antidepressants.

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Section: Introductionmentioning

confidence: 91%

Response to CYP2D6 substrate antidepressants is predicted by a CYP2D6 composite phenotype based on genotype and comedications with CYP2D6 inhibitors

Gressier¹,

Verstuyft

Hardy³

et al. 2014

J Neural Transm

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“…In parallel, certain mutations of the CYP2D6 (i.e. *5, *10) have been associated with decreased fluvoxamine (Gerstenberg et al, 2003a), paroxetine (Yoon et al, 2000) and fluoxetine metabolism (Yu et al, 2002b;Llerena et al, 2004), although not all studies support this finding (Ohara et al, 2003). However, the CYP2D6 genotype does not appear to influence the likelihood of responding or developing side-effects to fluoxetine in MDD (Gerstenberg et al, 2003b;Roberts et al, 2004).…”

Section: Dosagementioning

confidence: 61%

Monoaminergic‐based Pharmacotherapy for Depression

Papakostas¹,

Fava²

2005

Biology of Depression

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Although recent advances in neuropharmacology, neuroendocrinology, molecular biology, and pharmacogenetics have been instrumental in bringing about potential treatments for depression which are fundamentally unrelated to their predecessors, including substance P antagonists, glutaminergic agents, and corticotropinreleasing factor (CRF) antagonists, nevertheless it was agents that influenced the function of monoamine receptors and transporters that were discovered initially by serendipity and then developed as treatments for depression. The development of such compounds also served as a framework for the understanding of depression as a medical illness affecting brain functioning. As a result of these efforts, our field has gained further understanding of the role of monoamines in depression. In previous chapters, the relevance of monoamines in the underlying pathophysiology of depression was reviewed. In the following chapter we will focus on describing the contemporary role of monoaminergic agents in the treatment of depression. 6.

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“…Sixteen studies met inclusion criteria, of which five looked at metabolism of a single bolus of SSRI in healthy adults [32][33][34][35] or after a limited number of doses, 36 and 11 investigated the effects of CYP450 genotypes on the blood levels of specific SSRIs in patients at steady state doses. [37][38][39][40][41][42][43][44][45][46][47] • As expected based on the genotype, three single bolus studies of SSRI (sertraline, fluoxetine, or citalopram) metabolism in healthy adults showed that, compared with EMs, CYP2C19 PMs had significantly reduced metabolic function and significantly lower plasma concentrations of drug metabolites. In PMs, the parent drug had longer halflife and reduced clearance, compared with EMs.…”

Section: Recommendations From the Egapp Working Groupmentioning

confidence: 88%

Recommendations from the EGAPP Working Group: testing for cytochrome P450 polymorphisms in adults with nonpsychotic depression treated with selective serotonin reuptake inhibitors

Berg

Piper

Armstrong

et al. 2007

Genetics in Medicine

135

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This statement summarizes the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group recommendations regarding CYP450 genetic testing in adult patients beginning treatment with selective serotonin reuptake inhibitors (SSRIs), and the supporting scientific evidence. EGAPP is a project developed by the National Office of Public Health Genomics at the Centers for Disease Control and Prevention to support a rigorous, evidence-based process for evaluating genetic tests and other genomic applications that are in transition from research to clinical and public health practice in the United States. A key goal of the EGAPP Working Group is to develop conclusions and recommendations regarding clinical genomic applications and to establish clear linkage to the supporting scientific evidence. The Working Group members are nonfederal experts in genetics, laboratory medicine, and clinical epidemiology convened to establish methods and processes; set priorities for review topics; participate in technical expert panels for commissioned evidence reviews; publish recommendations; and provide guidance and feedback on other project activities. Summary of RecommendationThe EGAPP Working Group found insufficient evidence to support a recommendation for or against use of CYP450 testing in adults beginning SSRI treatment for non-psychotic depression. In the absence of supporting evidence, and with consideration of other contextual issues, EGAPP discourages use of CYP450 testing for patients beginning SSRI treatment until further clinical trials are completed.

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CYP2D6*10 alleles do not determine plasma fluvoxamine concentration/dose ratio in Japanese subjects

Abstract: Our results indicate that CYP2D6*10 genotypes do not exert significant effects on FV C/D ratio. As CYP2D6 genotypes differ with ethnic background, further studies should be conducted in different populations.

Cited by 25 publications

References 15 publications

Response to CYP2D6 substrate antidepressants is predicted by a CYP2D6 composite phenotype based on genotype and comedications with CYP2D6 inhibitors

Response to CYP2D6 substrate antidepressants is predicted by a CYP2D6 composite phenotype based on genotype and comedications with CYP2D6 inhibitors

Monoaminergic‐based Pharmacotherapy for Depression

Recommendations from the EGAPP Working Group: testing for cytochrome P450 polymorphisms in adults with nonpsychotic depression treated with selective serotonin reuptake inhibitors

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