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Pharmacogenomics of Antidepressant and Antipsychotic Treatment: How Far Have We Got and Where Are We Going?

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2020
Pharmacogenomics_of_Antidepressant_pub_2020.pdf (543.1Kb)
Authors
van Westrhenen, Roos
Aitchison, Katherine J.
Ingelman-Sundberg, Magnus
Jukić, Marin
Article (Published version)
Metadata
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Abstract
In recent decades, very few new psychiatric drugs have entered the market. Thus, improvement in the use of antidepressant and antipsychotic therapy has to focus mainly on enhanced and more personalized treatment with the currently available drugs. One important aspect of such individualization is emphasizing interindividual differences in genes relevant to treatment, an area that can be termed neuropsychopharmacogenomics. Here, we review previous efforts to identify such critical genetic variants and summarize the results obtained to date. We conclude that most clinically relevant genetic variation is connected to phase I drug metabolism, in particular to genetic polymorphism of CYP2C19 and CYP2D6. To further improve individualized pharmacotherapy, there is a need to take both common and rare relevant mutations into consideration; we discuss the present and future possibilities of using whole genome sequencing to identify patient-specific genetic variation relevant to treatment in psyc...hiatry. Translation of pharmacogenomic knowledge into clinical practice can be considered for specific drugs, but this requires education of clinicians, instructive guidelines, as well as full attention to polypharmacy and other clinically relevant factors. Recent large patient studies (n > 1,000) have replicated previous findings and produced robust evidence warranting the clinical utility of relevant genetic biomarkers. To further judge the clinical and financial benefits of preemptive genotyping in psychiatry, large prospective randomized trials are needed to quantify the value of genetic-based patient stratification in neuropsychopharmacotherapy and to demonstrate the cost-effectiveness of such interventions.

Keywords:
CYP2C19 / CYP2D6 / depression / genotyping / NGS / schizophrenia / CYP2C19 / CYP2D6 / depression / genotyping / NGS / schizophrenia
Source:
Frontiers in Psychiatry, 2020, 11
Publisher:
  • Frontiers Media S.A.

DOI: 10.3389/fpsyt.2020.00094

ISSN: 1664-0640

WoS: 000525597600001

Scopus: 2-s2.0-85082685220
[ Google Scholar ]
45
30
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/3575
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - van Westrhenen, Roos
AU  - Aitchison, Katherine J.
AU  - Ingelman-Sundberg, Magnus
AU  - Jukić, Marin
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3575
AB  - In recent decades, very few new psychiatric drugs have entered the market. Thus, improvement in the use of antidepressant and antipsychotic therapy has to focus mainly on enhanced and more personalized treatment with the currently available drugs. One important aspect of such individualization is emphasizing interindividual differences in genes relevant to treatment, an area that can be termed neuropsychopharmacogenomics. Here, we review previous efforts to identify such critical genetic variants and summarize the results obtained to date. We conclude that most clinically relevant genetic variation is connected to phase I drug metabolism, in particular to genetic polymorphism of CYP2C19 and CYP2D6. To further improve individualized pharmacotherapy, there is a need to take both common and rare relevant mutations into consideration; we discuss the present and future possibilities of using whole genome sequencing to identify patient-specific genetic variation relevant to treatment in psychiatry. Translation of pharmacogenomic knowledge into clinical practice can be considered for specific drugs, but this requires education of clinicians, instructive guidelines, as well as full attention to polypharmacy and other clinically relevant factors. Recent large patient studies (n > 1,000) have replicated previous findings and produced robust evidence warranting the clinical utility of relevant genetic biomarkers. To further judge the clinical and financial benefits of preemptive genotyping in psychiatry, large prospective randomized trials are needed to quantify the value of genetic-based patient stratification in neuropsychopharmacotherapy and to demonstrate the cost-effectiveness of such interventions.
PB  - Frontiers Media S.A.
T2  - Frontiers in Psychiatry
T1  - Pharmacogenomics of Antidepressant and Antipsychotic Treatment: How Far Have We Got and Where Are We Going?
VL  - 11
DO  - 10.3389/fpsyt.2020.00094
ER  - 
@article{
author = "van Westrhenen, Roos and Aitchison, Katherine J. and Ingelman-Sundberg, Magnus and Jukić, Marin",
year = "2020",
abstract = "In recent decades, very few new psychiatric drugs have entered the market. Thus, improvement in the use of antidepressant and antipsychotic therapy has to focus mainly on enhanced and more personalized treatment with the currently available drugs. One important aspect of such individualization is emphasizing interindividual differences in genes relevant to treatment, an area that can be termed neuropsychopharmacogenomics. Here, we review previous efforts to identify such critical genetic variants and summarize the results obtained to date. We conclude that most clinically relevant genetic variation is connected to phase I drug metabolism, in particular to genetic polymorphism of CYP2C19 and CYP2D6. To further improve individualized pharmacotherapy, there is a need to take both common and rare relevant mutations into consideration; we discuss the present and future possibilities of using whole genome sequencing to identify patient-specific genetic variation relevant to treatment in psychiatry. Translation of pharmacogenomic knowledge into clinical practice can be considered for specific drugs, but this requires education of clinicians, instructive guidelines, as well as full attention to polypharmacy and other clinically relevant factors. Recent large patient studies (n > 1,000) have replicated previous findings and produced robust evidence warranting the clinical utility of relevant genetic biomarkers. To further judge the clinical and financial benefits of preemptive genotyping in psychiatry, large prospective randomized trials are needed to quantify the value of genetic-based patient stratification in neuropsychopharmacotherapy and to demonstrate the cost-effectiveness of such interventions.",
publisher = "Frontiers Media S.A.",
journal = "Frontiers in Psychiatry",
title = "Pharmacogenomics of Antidepressant and Antipsychotic Treatment: How Far Have We Got and Where Are We Going?",
volume = "11",
doi = "10.3389/fpsyt.2020.00094"
}
van Westrhenen, R., Aitchison, K. J., Ingelman-Sundberg, M.,& Jukić, M.. (2020). Pharmacogenomics of Antidepressant and Antipsychotic Treatment: How Far Have We Got and Where Are We Going?. in Frontiers in Psychiatry
Frontiers Media S.A.., 11.
https://doi.org/10.3389/fpsyt.2020.00094
van Westrhenen R, Aitchison KJ, Ingelman-Sundberg M, Jukić M. Pharmacogenomics of Antidepressant and Antipsychotic Treatment: How Far Have We Got and Where Are We Going?. in Frontiers in Psychiatry. 2020;11.
doi:10.3389/fpsyt.2020.00094 .
van Westrhenen, Roos, Aitchison, Katherine J., Ingelman-Sundberg, Magnus, Jukić, Marin, "Pharmacogenomics of Antidepressant and Antipsychotic Treatment: How Far Have We Got and Where Are We Going?" in Frontiers in Psychiatry, 11 (2020),
https://doi.org/10.3389/fpsyt.2020.00094 . .

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