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A Poor Metabolizer for Cytochromes P450 2D6 and 2C19: A Case Report on Antidepressant Treatment

Published online by Cambridge University Press:  07 November 2014

Maria Johnson ,
Courtney Markham-Abedi ,
Margaret T. Susce ,
Elaina Murray-Carmichael ,
Stuart McCollum  and
Jose de Leon
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Abstract

Scientific literature has never described a poor metabolizer for both the cytochrome P450 (CYP) 2D6 and the CYP 2C19. They are expected to be rare (<1% in different ethnic groups) and prone to adverse drug reactions with many antidepressants. In an ongoing pharmacogenetic study, after genotyping 1,576 subjects in three Kentucky state hospitals we have found one poor metabolizer for both CYP 2D6 and CYP 2C19, which corresponds to a prevalence of 0.06% (95% Cl 0.01 to 0.36).The naturalistic antidepressant treatment of this poor metabolizer for both enzymes is described in this article. As genotyping reaches clinical practice, it will be interesting to prospectively establish whether mirtazapine is a reasonable choice as an antidepressant for these patients, as the data and this case suggest.

Type
Case Report
Information
CNS Spectrums , Volume 11 , Issue 10 , October 2006 , pp. 757 - 760
Copyright
Copyright © Cambridge University Press 2006

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References

REFERENCES

1. Ingelman-Sundberg, M. Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms. Naunyan-Schmiedberg's Arch Pharmacol. 2004;369:89–104.Google Scholar
2. Rogers, JF, Nafziger, AN, Bertino, JS. Pharmacogenetics affects dosing, efficacy, and toxicity of cytochrome P450-metabol ized drugs. Am J Med. 2002;113:746–750.Google Scholar
3. de Leon, J, Armstrong, SC, Cozza, KL. The dosing of atypical antipsychotics. Psychosomatics. 2005;46:262–273.Google Scholar
4. Brosen, K. Some aspects of genetic polymorphism in the biotransformation of antidepressants. Therapie. 2004;59:5–12.Google Scholar
5. Spina, E, Scordo, MG, D'Arrigo, C. Metabolic drug interactions with new psychotropic agents. Fundamental Clin Pharmacol. 2003;17:517–538.Google Scholar
6. Kirchheiner, J, Nickchen, K, Bauer, M, et al. Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry. 2004;9:442–473.Google Scholar
7. de Leon, J, Armstrong, SC, Cozza, KL. Clinical guidelines for using pharmacogenetic testing of CYP450 2D6 and CYP450 2C19 in psychiatry. Psychosomatics. 2006;47:75–85.Google Scholar
8. Mrazek, DA, Smoller, JW, de Leon, J. Incorporating pharmacogenetics into clinical practice: reality of a new tool in psychiatry. CNS Spectr. 2006;11(suppl 3):1–13.Google Scholar
9. de Leon, J. The AmpliChip CYP450 Test: personalized medicine has arrived in psychiatry. Exp Rev Mol Diagn. 2006;6:277–286.Google Scholar
10. Timmer, CJ, Sitsen, JM, Delbressine, LP. Clinical pharmacokinetics of mirtazapine. Clin Pharmacokinet. 2000;38:661–674.Google Scholar
11. Steimer, W, Zopf, K, von Amelunxen, S, et al. 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. Clin Chemistry. 2005;51:376–385.Google Scholar
12. Reis, M, Lundmark, J, Bjork, H, Bengtsson, F. Therapeutic drug monitoring of racemic venlafaxine and its main metabolites in an everyday clinical setting. Ther Drug Monit. 2002;24:545–553.Google Scholar
13. Rudberg, I, Hendset, M, Uthus, LH, Molden, E, Refsum, H. Heterozygous mutation in CYP2C19 significantly increases the concentration/dose ratio of racemic citalopram and escitalopram (S-citalopram). Ther Drug Monit. 2006;28:102–105.Google Scholar
14. von Moltke, LL, Greenblatt, DJ, Giancarlo, GM, Granda, BW, Harmatz, JS, Shader, RI. Escitalopram (S-citalopram) and its metabolites in vitro: cytochromes mediating biotransformation, inhibitory effects, and comparison to R-citalopram. Drug Metab Dispos. 2001;29:1102–1109.Google Scholar
15. Kirchheiner, J, Henckel, HB, Meineke, I, Roots, I, Brockmoller, J. Impact of the CYP2D6 ultrarapid metabolizer genotype on mirtazapine pharmacokinetics and adverse events in healthy volunteers. J Clin Psychopharmacol. 2004;24:647–652.Google Scholar
16. de Leon, J, Susce, MT, Pan, RM, Fairchild, M, Koch, W, Wedlund, PJ. The CYP2D6 poor metabolizer phenotype may be associated with risperidone adverse drug reactions and discontinuation. J Clin Psychiatry. 2005;66:15–27.Google Scholar