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Clinical impact of functional CYP2C19 and CYP2D6 gene variants on treatment outcomes in patients with depression: a Danish cohort study

Published online by Cambridge University Press:  01 September 2022

L. Thiele ,
K. Ishtiak-Ahmed ,
J. Thirstrup ,
C. Lunenburg ,
D. Müller  and
C. Gasse
L. Thiele*
Affiliation:
Aarhus University Hospital Psychiatry, Department Of Affective Disorders, Aarhus N, Denmark
K. Ishtiak-Ahmed
Affiliation:
Aarhus University Hospital Psychiatry, Department Of Affective Disorders, Aarhus N, Denmark Aarhus University, Department Of Clinical Medicine, Aarhus, Denmark
J. Thirstrup
Affiliation:
Aarhus University Hospital Psychiatry, Department Of Affective Disorders, Aarhus N, Denmark Aarhus University, Department Of Clinical Medicine, Aarhus N, Denmark
C. Lunenburg
Affiliation:
Aarhus University Hospital Psychiatry, Department Of Affective Disorders, Aarhus N, Denmark Aarhus University, Department Of Clinical Medicine, Aarhus, Denmark
D. Müller
Affiliation:
Institute of Medical Science, University of Toronto, Department Of Psychiatry, Toronto, Canada Centre for Addiction and Mental Health, Pharmacogenetics Research Clinic, Toronto, Canada
C. Gasse
Affiliation:
Aarhus University Hospital Psychiatry, Department Of Affective Disorders, Aarhus N, Denmark Aarhus University, Department Of Clinical Medicine, Aarhus, Denmark
*
*Corresponding author.

Abstract

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Introduction

Pharmacogenetic (PGx) targets to optimize drug therapy, but its implementation is rare.

Objectives

We evaluate the clinical utility of PGx testing in psychiatry by investigating the one-year risks of clinical outcomes in patients with depression taking sertraline, (es)citalopram or fluoxetine by their Cytochrome P450 (CYP) 2C19/2D6 phenotypes.

Methods

We investigated 17,297 individuals born between 1981-2005 with a depression diagnosis between 1996-2012 from the iPsych2012 case-cohort. Based on array-based single-nucleotide-polymorphism genotype data, individuals were phenotyped as CYP2C19/CYP2D6 normal (NM, reference group), ultra-rapid- (UM), rapid- (RM), intermediate- (IM), or poor-metabolizer (PM). Outcomes were treatment switching or discontinuation, psychiatric in-, out-, and emergency room contacts (ER), and suicide attempt/self-harm. Incidence rate ratios (IRR) by age groups were estimated using Poisson regression analysis with 95% confidence intervals, adjusted for potential confounders.

Results

Risks of switching (IRR=1.89[1.22-2.93]), ERs (1.69 [1.01-2.81]) and suicide attempt/self-harm (2.73 [1.49-5.01]) were higher in CYP2C19 PMs <19 years taking (es)citalopram. Fluoxetine users <19 years had a decreased risk of discontinuation in CYP2D6 PMs (0.5 [0.27-0.95]) and decreased risk of out-patient contacts in CYP2D6 PMs and IMs (IRRIM=0.83 [0.68-1.00] and IRRPM=0.59 [ 0.37-0.96]). We observed an increased risk for ERs in CYP2D6 PMs aged 19-25 years taking fluoxetine (4.53 [1.54-13.35]). In CYP2C19 UMs >25 years taking (es)citalopram the risk of suicide attempt/self-harm was more than three-fold increased (3.64 [ 1.01-13.19]). We found no significant results in users of sertraline.

Conclusions

PGx variability was associated with treatment outcomes in depression in patients with CYP2C19 PM or UM status taking (es)citalopram, or CYP2D6 PM or IM status taking fluoxetine.

Disclosure

No significant relationships.

Keywords

pharmacogeneticssertraline(es)citalopram and fluoxetineDepression
Type
Abstract
Information
European Psychiatry , Volume 65 , Special Issue S1: Abstracts of the 30th European Congress of Psychiatry , June 2022 , pp. S228
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of the European Psychiatric Association
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