Download PDF
Pharmacopsychiatry 2020; 53(04): 185-192
DOI: 10.1055/a-1096-1171
Original Paper

Pharmacogenetic Testing in Depressed Patients and Interdisciplinary Exchange between a Pharmacist and Psychiatrists Results in Reduced Hospitalization Times

Victor A. D. Bättig
1   Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
2   Department of Psychiatry, Vitos Klinik Eichberg, Eltville, Germany
,
Sibylle C. Roll
2   Department of Psychiatry, Vitos Klinik Eichberg, Eltville, Germany
,
Martina Hahn
2   Department of Psychiatry, Vitos Klinik Eichberg, Eltville, Germany
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Introduction Pharmacogenetics (PGx) is a well-researched tool to improve pharmacotherapy. So far, it has not been implemented into daily practice in Germany. In psychopharmacology, substantial benefit can be expected by using PGx due to the excessive CYP metabolism of the psychotropic drugs as well as already discovered target polymorphisms (e. g., serotonin receptor).

Methods An evaluation of a naturalistic pharmacist-led pilot implementation of PGx testing in a psychiatric hospital in patients undergoing inpatient treatment for major depressive disorder was conducted. Length of stay, number of antidepressant switches, and rehospitalization rates were analyzed. A PGx-tested intervention cohort of n=49 was retrospectively compared to a control cohort of n=94 patients.

Results The intervention cohort showed significantly shorter stays than the control, after correction of the length of hospital stay and the time to genotyping results (mean intervention: 36.3 d (SD: ±19.3 d); control: 46.6 d (±19.1 d); p=0.003). Antidepressant- naïve patients had the largest benefit from the PGx testing (intervention: 24.7 d (±13.5 d); control: 50.2 d (±22.5 d); p < 0.001. The number of antidepressant switches during the entire stay did not differ between the groups: 0.41 (0.64) vs. 0.21 (0.46); p=0.063 [95% CI −0.01–0.40]).

Discussion Depressed patients, especially treatment-naïve, seem to benefit from PGx testing prior to treatment. Although the results of this retrospective evaluation are promising, more systematic prospective studies are needed to assess the effect of PGx testing on the treatment of major depressive disorder.

Key words

pharmacogenetics - depression treatment - antidepressants - depression


Publication History

Received: 19 November 2018
Received: 26 November 2019

Accepted: 03 January 2020

Article published online:
11 February 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Wolf CR, Smith G, Smith RL. Science, medicine, and the future: Pharmacogenetics. BMJ 2000; 320: 987-990
    CrossrefPubMedGoogle Scholar
  • 2 Hammer W, Sjöqvist F. Plasma levels of monomethylated tricyclic antidepressants during treatment with imipramine-like compounds. Life Sci 1967; 6: 1895-1903
    CrossrefPubMedGoogle Scholar
  • 3 Whirl-Carrillo M, McDonagh EM, Hebert JM. et al. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther 2012; 92: 414-417
    CrossrefPubMedGoogle Scholar
  • 4 Van Der Weide J, Van Baalen-Benedek EH, Kootstra-Ros JE. Metabolic ratios of psychotropics as indication of cytochrome P450 2D6/2C19 genotype. Ther Drug Monit 2005; 27: 478-483
    CrossrefPubMedGoogle Scholar
  • 5 Steimer W, Zöpf K, von Amelunxen S. et al. Allele-specific change of concentration and functional gene dose for the prediction of steady-state serum concentrations of amitriptyline and nortriptyline in CYP2C19 and CYP2D6 extensive and intermediate metabolizers. Clin Chem 2004; 50: 1623-1633
    CrossrefPubMedGoogle Scholar
  • 6 Wang JH, Liu ZQ, Wang W. et al. Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19. Clin Pharmacol Ther 2001; 70: 42-47
    PubMedGoogle Scholar
  • 7 Grasmäder K, Verwohlt PL, Rietschel M. et al. Impact of polymorphisms of cytochrome-P450 isoenzymes 2C9, 2C19 and 2D6 on plasma concentrations and clinical effects of antidepressants in a naturalistic clinical setting. Eur J Clin Pharmacol 2004; 60: 329-336
    PubMedGoogle Scholar
  • 8 Hodgson K, Tansey K, Dernovšek MZ. et al. Genetic differences in cytochrome P450 enzymes and antidepressant treatment response. J Psychopharmacol 2014; 28: 133-141
    CrossrefPubMedGoogle Scholar
  • 9 Sirot EJ, Harenberg S, Vandel P. et al. Multicenter study on the clinical effectiveness, pharmacokinetics, and pharmacogenetics of mirtazapine in depression. J Clin Psychopharmacol 2012; 32: 622-629
    CrossrefPubMedGoogle Scholar
  • 10 McAlpine DE, O’Kane DJ, Black JL. et al. Cytochrome P450 2D6 genotype variation and venlafaxine dosage. Mayo Clin Proc 2007; 82: 1065-1068
    CrossrefPubMedGoogle Scholar
  • 11 Ring BJ, Gillespie JS, Eckstein JA. et al. Identification of the human cytochromes P450 responsible for atomoxetine metabolism. Drug Metab Dispos 2002; 30: 319-323
    CrossrefPubMedGoogle Scholar
  • 12 Kirchheiner J, Klein C, Meineke I. et al. Bupropion and 4-OH-bupropion pharmacokinetics in relation to genetic polymorphisms in CYP2B6. Pharmacogenetics 2003; 13: 619-626
    CrossrefPubMedGoogle Scholar
  • 13 Gram LF, Guentert TW, Grange S. et al. Moclobemide, a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6, and CYP1A2: A panel study. Clin Pharmacol Ther 1995; 57: 670-677
    CrossrefPubMedGoogle Scholar
  • 14 Swen JJ, Nijenhuis M, De Boer A. et al. Pharmacogenetics: From bench to byte an update of guidelines. Clin Pharmacol Ther 2011; 89: 662-673
    CrossrefPubMedGoogle Scholar
  • 15 Tansey KE, Guipponi M, Hu X. et al. Contribution of common genetic variants to antidepressant response. Biol Psychiatry 2013; 73: 679-682
    CrossrefPubMedGoogle Scholar
  • 16 Humatrix AG. https://www.stratipharm.de/aerzte/das-ist-stratipharm/prinzip website, last accessed November 18 2019
    PubMed
  • 17 Hahn M, Roll SC. A new approach to pharmaceutical care: Experiences with the “Eichberger” model in a psychiatric clinic in Germany. Drugs Ther Perspect 2012; 28: 24-26
    PubMedGoogle Scholar
  • 18 The World Health Organization ICD-10: The ICD-10 Classification of Mental and Behavioral Disorders: Clinical Descriptions and Diagnostic Guidelines. 1. AuflGeneva: The World Health Organization; 1992
  • 19 Hautzinger M, Keller F, Kühner C. Das Beck Depressionsinventar II. Deutsche Bearbeitung und Handbuch zum BDI-II. Pearson. 2006
    PubMed
  • 20 Jones SH, Thornicroft G, Coffey M. et al. A brief mental health outcome scale reliability and validity of the global assessment of functioning (gaf). Br J Psychiatry 1995; 166: 654-659
    CrossrefPubMedGoogle Scholar
  • 21 Boldrini M, Santiago AN, Hen R. et al. Hippocampal granule neuron number and dentate gyrus volume in antidepressant-treated and untreated major depression. Neuropsychopharmacology 2013; 38: 1068-1077
    CrossrefPubMedGoogle Scholar
  • 22 Rosenblat JD, Lee Y, McIntyre RS. The effect of pharmacogenomic testing on response and remission rates in the acute treatment of major depressive disorder: A meta-analysis. J Affect Disord 2018; 241: 484-491
    CrossrefPubMedGoogle Scholar
  • 23 Hall-Flavin DK, Winner JG, Allen JD. et al. Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting. Pharmacogenet Genomics 2013; 23: 535-548
    CrossrefPubMedGoogle Scholar
  • 24 Pérez V, Salavert A, Espadaler J. et al. Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: Results of a randomized, double-blind clinical trial. BMC Psychiatry 2017; 17: 250
    CrossrefPubMedGoogle Scholar
  • 25 Bradley P, Shiekh M, Mehra V. et al. Improved efficacy with targeted pharmacogenetic-guided treatment of patients with depression and anxiety: A randomized clinical trial demonstrating clinical utility. J Psychiatr Res 2018; 96: 100-107
    CrossrefPubMedGoogle Scholar