Adverse Drug Reactions Following Nonresponse in a Depressed Patient with CYP2D6 Deficiency and Low CYP 3A4/5 Activity

P. L. Stephan; E. Jaquenoud Sirot; B. Mueller; C. B. Eap; P. Baumann

doi:10.1055/s-2006-946705

Pharmacopsychiatry, Table of Contents

Pharmacopsychiatry 2006; 39(4): 150-152
DOI: 10.1055/s-2006-946705

Letter

Adverse Drug Reactions Following Nonresponse in a Depressed Patient with CYP2D6 Deficiency and Low CYP 3A4/5 Activity

A Pharmacovigilance Case ReportP. L. Stephan¹ , E. Jaquenoud Sirot¹ , B. Mueller¹ , C. B. Eap² , P. Baumann²

¹Psychiatrische Dienste Aargau AG, Klinik Königsfelden, Brugg, Switzerland
²Unité de Biochimie et Psychopharmacologie Clinique, Centre de Neurosciences Psychiatriques, Département de Psychiatrie, CHUV, Prilly-Lausanne, Switzerland

Abstract

A 47-year-old male taxi driver experienced multiple adverse drug reactions during therapy with clomipramine (CMI) and quetiapine for major depressive disorder, after having been unsuccessfully treated with adequate doses of mirtazapine and venlafaxine. Drug serum concentrations of CMI and quetiapine were significantly increased and pharmacogenetic testing showed a poor metabolizer status for CYP2D6, low CYP3A4/5 activity and normal CYP2C19 genotype. After reduction of the CMI dose and discontinuation of quetiapine, all ADR subsided except for the increase in liver enzymes. The latter improved but did not normalize completely, even months later, possibly due to concomitant cholelithiasis.

Full Text

References

1 Alván G, Bechtel P, Iselius L, Gundert-Remy U. Hydroxylation polymorphisms of debrisoquine and mephenytoin in European populations. Eur J Clin Pharmacol. 1990; 39 533-537
2 Baumann P, Hiemke C, Ulrich S, Eckermann G, Gaertner I, Gerlach M. et al . The AGNP-TDM expert group concensus guidelines: therapeutic drug monitoring in psychiatry. Pharmacopsychiatry. 2004; 37 1-23
3 Bowden C L. Atypical antipsychotic augmentation of mood stabilizer therapy in bipolar disorder. J Clin Psychiatry. 2005; 66 (Suppl 3) 12-19
4 DeVane C L, Nemeroff C B. Clinical pharmacokinetics of quetiapine - An atypical antipsychotic. Clin Pharmacokinet. 2001; 40 509-522
5 Eap C B, Buclin T, Cucchia G, Zullino D, Hustert E, Bleiber G. et al . Oral administration of a low dose of midazolam (75 micrograms) as an in vivo probe for CYP3A activity. Eur J Clin Pharmacol. 2004; 60 237-246
6 Eap C B, Buclin T, Hustert E, Bleiber G, Powell Golay K, Aubert A C. et al . Pharmacokinetics of midazolam in CYP3A4 and CYP3A5 genotyped subjects. Eur J Clin Pharmacol. 2004; 60 231-236
7 Glue P, Andersen K O, Hansen M A, Stage K B, Hansen H, Norrie B. et al . Clomipramine dose-effect study in patients with depression: Clinical end points and pharmacokinetics. Clin Pharmacol Ther. 1999; 66 152-165
8 Grohmann R, Engel R R, Ruther E, Hippius H. The AMSP drug safety program: methods and global results. Pharmacopsychiatry. 2004; 37 (Suppl 1) S4-S11
9 Haller-Gloor F, Eap C B, Turgeon J, Baumann P. High-dose venlafaxine treatment in a depressed patient with a genetic CYP2D6 deficiency. Int J Psych Clin Pract. 2004; 8 191-195
10 Hasselstrom J, Linnet K. Quetiapine serum concentrations in psychiatric patients: the influence of comedication. Ther Drug Monit. 2004; 26 486-491
11 Kirchheiner J, Bertilsson L, Bruus H, Wolff A, Roots I, Bauer M. Individualized medicine - implementation of pharmacogenetic diagnostics in antidepressant drug treatment of major depressive disorders. Pharmacopsychiatry. 2003; 36 (Suppl 3) S235-243
12 Lee S J, Goldstein J A. Functionally defective or altered CYP3A4 and CYP3A5 single nucleotide polymorphisms and their detection with genotyping tests. Pharmacogenomics. 2005; 6 357-371
13 Nielsen K K, Brøsen K, Hansen M GJ, Gram L F. Single-dose kinetics of clomipramine : relationship to the sparteine and S-mephenytoin oxidation poly morphisms. Clin Pharmacol Ther. 1994; 55 518-527
14 Nielsen K K, Flinois J P, Beaune P, Brosen K. The biotransformation of clomipramine in vitro, identification of the cytochrome P450 s responsible for the separate metabolic pathways. J Pharmacol Exp Ther. 1996; 277 1659-1664
15 Sachse C, Haertter S, Mueller M J, Dragicevic A, Hiemke C. Therapeutisches Drug Monitoring von Quetiapin. Psychopharmakotherapie. 2003; 10 19-22
16 Shimoda K, Jerling M, Böttiger Y, Yasuda S, Morita S, Bertilsson L. Pronounced differences in the disposition of clomipramine between Japanese and Swedish patients. J Clin Psychopharmacol. 1999; 19 393-400
17 Yokono A, Morita S, Someya T, Hirokane G, Okawa M, Shimoda K. The effect of CYP2C19 and CYP2D6 genotypes on the metabolism of clomipramine in Japanese psychiatric patients. J Clin Psychopharmacol. 2001; 21 549-555

E. Jaquenoud Sirot

Psychiatrische Dienste Aargau AG

Klinik Königsfelden

Postfach 432

5201 Brugg

Switzerland

Phone: +41 56 462 26 65

Fax: +41 56 462 27 66

Email: eveline.jaquenoudsirot@pdag.ch