Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2C19 and CYP2D6 and SSRIs

J.M.J.L. Brouwer; M. Nijenhuis; B. Soree; H.J. Guchelaar; J.J. Swen; R.H.N. van Schaik; J. van der Weide; G.A.P.J.M. Rongen; A.M. Buunk; N.J. De Boer-Veger; E.J.F. Houwink; R. van Westrhenen; B. Wilffert; V.H.M. Deneer; H. Mulder

doi:10.1038/s41431-021-01004-7

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2C19 and CYP2D6 and SSRIs

J.M.J.L. Brouwer, M. Nijenhuis^*, B. Soree, H.J. Guchelaar, J.J. Swen, R.H.N. van Schaik, J. van der Weide, G.A.P.J.M. Rongen, A.M. Buunk, N.J. De Boer-Veger, E.J.F. Houwink, R. van Westrhenen, B. Wilffert, V.H.M. Deneer, H. Mulder

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The Dutch Pharmacogenetics Working Group (DPWG) guideline presented here, presents the gene-drug interaction between the genes CYP2C19 and CYP2D6 and antidepressants of the selective serotonin reuptake inhibitor type (SSRIs). Both genes' genotypes are translated into predicted normal metabolizer (NM), intermediate metabolizer (IM), poor metabolizer (PM), or ultra-rapid metabolizer (UM). Evidence-based dose recommendations were obtained, based on a structured analysis of published literature. In CYP2C19 PM patients, escitalopram dose should not exceed 50% of the normal maximum dose. In CYP2C19 IM patients, this is 75% of the normal maximum dose. Escitalopram should be avoided in UM patients. In CYP2C19 PM patients, citalopram dose should not exceed 50% of the normal maximum dose. In CYP2C19 IM patients, this is 70% (65-75%) of the normal maximum dose. In contrast to escitalopram, no action is needed for CYP2C19 UM patients. In CYP2C19 PM patients, sertraline dose should not exceed 37.5% of the normal maximum dose. No action is needed for CYP2C19 IM and UM patients. In CYP2D6 UM patients, paroxetine should be avoided. No action is needed for CYP2D6 PM and IM patients. In addition, no action is needed for the other gene-drug combinations. Clinical effects (increase in adverse events or decrease in efficacy) were lacking for these other gene-drug combinations. DPWG classifies CYP2C19 genotyping before the start of escitalopram, citalopram, and sertraline, and CYP2D6 genotyping before the start of paroxetine as "potentially beneficial" for toxicity/effectivity predictions. This indicates that genotyping prior to treatment can be considered on an individual patient basis.

Original language	English
Pages (from-to)	1114-1120
Number of pages	7
Journal	European Journal of Human Genetics
Volume	30
Issue number	10
Early online date	16 Nov 2021
DOIs	https://doi.org/10.1038/s41431-021-01004-7
Publication status	Published - Oct 2022

Keywords

IMPLEMENTATION CONSORTIUM
CYP2C19-ASTERISK-17 ALLELE
GENOTYPE
INHIBITORS
FLUOXETINE
PAROXETINE
SERTRALINE
VARIANT
BENCH

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Cite this

Brouwer, J. M. J. L., Nijenhuis, M., Soree, B., Guchelaar, H. J., Swen, J. J., van Schaik, R. H. N., van der Weide, J., Rongen, G. A. P. J. M., Buunk, A. M., De Boer-Veger, N. J., Houwink, E. J. F., van Westrhenen, R., Wilffert, B., Deneer, V. H. M., & Mulder, H. (2022). Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2C19 and CYP2D6 and SSRIs. European Journal of Human Genetics, 30(10), 1114-1120. https://doi.org/10.1038/s41431-021-01004-7

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title = "Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2C19 and CYP2D6 and SSRIs",

abstract = "The Dutch Pharmacogenetics Working Group (DPWG) guideline presented here, presents the gene-drug interaction between the genes CYP2C19 and CYP2D6 and antidepressants of the selective serotonin reuptake inhibitor type (SSRIs). Both genes' genotypes are translated into predicted normal metabolizer (NM), intermediate metabolizer (IM), poor metabolizer (PM), or ultra-rapid metabolizer (UM). Evidence-based dose recommendations were obtained, based on a structured analysis of published literature. In CYP2C19 PM patients, escitalopram dose should not exceed 50% of the normal maximum dose. In CYP2C19 IM patients, this is 75% of the normal maximum dose. Escitalopram should be avoided in UM patients. In CYP2C19 PM patients, citalopram dose should not exceed 50% of the normal maximum dose. In CYP2C19 IM patients, this is 70% (65-75%) of the normal maximum dose. In contrast to escitalopram, no action is needed for CYP2C19 UM patients. In CYP2C19 PM patients, sertraline dose should not exceed 37.5% of the normal maximum dose. No action is needed for CYP2C19 IM and UM patients. In CYP2D6 UM patients, paroxetine should be avoided. No action is needed for CYP2D6 PM and IM patients. In addition, no action is needed for the other gene-drug combinations. Clinical effects (increase in adverse events or decrease in efficacy) were lacking for these other gene-drug combinations. DPWG classifies CYP2C19 genotyping before the start of escitalopram, citalopram, and sertraline, and CYP2D6 genotyping before the start of paroxetine as {"}potentially beneficial{"} for toxicity/effectivity predictions. This indicates that genotyping prior to treatment can be considered on an individual patient basis.",

keywords = "IMPLEMENTATION CONSORTIUM, CYP2C19-ASTERISK-17 ALLELE, GENOTYPE, INHIBITORS, FLUOXETINE, PAROXETINE, SERTRALINE, VARIANT, BENCH",

author = "J.M.J.L. Brouwer and M. Nijenhuis and B. Soree and H.J. Guchelaar and J.J. Swen and {van Schaik}, R.H.N. and {van der Weide}, J. and G.A.P.J.M. Rongen and A.M. Buunk and {De Boer-Veger}, N.J. and E.J.F. Houwink and {van Westrhenen}, R. and B. Wilffert and V.H.M. Deneer and H. Mulder",

year = "2022",

month = oct,

doi = "10.1038/s41431-021-01004-7",

language = "English",

volume = "30",

pages = "1114--1120",

journal = "European Journal of Human Genetics",

issn = "1018-4813",

publisher = "Nature Publishing Group",

number = "10",

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Brouwer, JMJL, Nijenhuis, M, Soree, B, Guchelaar, HJ, Swen, JJ, van Schaik, RHN, van der Weide, J, Rongen, GAPJM, Buunk, AM, De Boer-Veger, NJ, Houwink, EJF, van Westrhenen, R, Wilffert, B, Deneer, VHM & Mulder, H 2022, 'Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2C19 and CYP2D6 and SSRIs', European Journal of Human Genetics, vol. 30, no. 10, pp. 1114-1120. https://doi.org/10.1038/s41431-021-01004-7

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AU - Brouwer, J.M.J.L.

AU - Nijenhuis, M.

AU - Soree, B.

AU - Guchelaar, H.J.

AU - Swen, J.J.

AU - van Schaik, R.H.N.

AU - van der Weide, J.

AU - Rongen, G.A.P.J.M.

AU - Buunk, A.M.

AU - De Boer-Veger, N.J.

AU - Houwink, E.J.F.

AU - van Westrhenen, R.

AU - Wilffert, B.

AU - Deneer, V.H.M.

AU - Mulder, H.

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N2 - The Dutch Pharmacogenetics Working Group (DPWG) guideline presented here, presents the gene-drug interaction between the genes CYP2C19 and CYP2D6 and antidepressants of the selective serotonin reuptake inhibitor type (SSRIs). Both genes' genotypes are translated into predicted normal metabolizer (NM), intermediate metabolizer (IM), poor metabolizer (PM), or ultra-rapid metabolizer (UM). Evidence-based dose recommendations were obtained, based on a structured analysis of published literature. In CYP2C19 PM patients, escitalopram dose should not exceed 50% of the normal maximum dose. In CYP2C19 IM patients, this is 75% of the normal maximum dose. Escitalopram should be avoided in UM patients. In CYP2C19 PM patients, citalopram dose should not exceed 50% of the normal maximum dose. In CYP2C19 IM patients, this is 70% (65-75%) of the normal maximum dose. In contrast to escitalopram, no action is needed for CYP2C19 UM patients. In CYP2C19 PM patients, sertraline dose should not exceed 37.5% of the normal maximum dose. No action is needed for CYP2C19 IM and UM patients. In CYP2D6 UM patients, paroxetine should be avoided. No action is needed for CYP2D6 PM and IM patients. In addition, no action is needed for the other gene-drug combinations. Clinical effects (increase in adverse events or decrease in efficacy) were lacking for these other gene-drug combinations. DPWG classifies CYP2C19 genotyping before the start of escitalopram, citalopram, and sertraline, and CYP2D6 genotyping before the start of paroxetine as "potentially beneficial" for toxicity/effectivity predictions. This indicates that genotyping prior to treatment can be considered on an individual patient basis.

AB - The Dutch Pharmacogenetics Working Group (DPWG) guideline presented here, presents the gene-drug interaction between the genes CYP2C19 and CYP2D6 and antidepressants of the selective serotonin reuptake inhibitor type (SSRIs). Both genes' genotypes are translated into predicted normal metabolizer (NM), intermediate metabolizer (IM), poor metabolizer (PM), or ultra-rapid metabolizer (UM). Evidence-based dose recommendations were obtained, based on a structured analysis of published literature. In CYP2C19 PM patients, escitalopram dose should not exceed 50% of the normal maximum dose. In CYP2C19 IM patients, this is 75% of the normal maximum dose. Escitalopram should be avoided in UM patients. In CYP2C19 PM patients, citalopram dose should not exceed 50% of the normal maximum dose. In CYP2C19 IM patients, this is 70% (65-75%) of the normal maximum dose. In contrast to escitalopram, no action is needed for CYP2C19 UM patients. In CYP2C19 PM patients, sertraline dose should not exceed 37.5% of the normal maximum dose. No action is needed for CYP2C19 IM and UM patients. In CYP2D6 UM patients, paroxetine should be avoided. No action is needed for CYP2D6 PM and IM patients. In addition, no action is needed for the other gene-drug combinations. Clinical effects (increase in adverse events or decrease in efficacy) were lacking for these other gene-drug combinations. DPWG classifies CYP2C19 genotyping before the start of escitalopram, citalopram, and sertraline, and CYP2D6 genotyping before the start of paroxetine as "potentially beneficial" for toxicity/effectivity predictions. This indicates that genotyping prior to treatment can be considered on an individual patient basis.

KW - IMPLEMENTATION CONSORTIUM

KW - CYP2C19-ASTERISK-17 ALLELE

KW - GENOTYPE

KW - INHIBITORS

KW - FLUOXETINE

KW - PAROXETINE

KW - SERTRALINE

KW - VARIANT

KW - BENCH

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DO - 10.1038/s41431-021-01004-7

M3 - Article

C2 - 34782755

SN - 1018-4813

VL - 30

SP - 1114

EP - 1120

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

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ER -