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Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 , CYP2C19 , CYP2B6 , SLC6A4 , and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants
Open accessAbstract
Serotonin reuptake inhibitor antidepressants, including selective serotonin reuptake inhibitors (SSRIs; i.e., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), serotonin and norepinephrine reuptake inhibitors (i.e., desvenlafaxine, duloxetine, levomilnacipran, milnacipran, and venlafaxine), and serotonin modulators with SSRI‐like properties (i.e., vilazodone and vortioxetine) are primary pharmacologic treatments for major depressive and anxiety disorders. Genetic variation in CYP2D6 , CYP2C19 , and CYP2B6 influences the metabolism of many of these antidepressants, which may potentially affect dosing, efficacy, and tolerability. In addition, the pharmacodynamic genes SLC6A4 (serotonin transporter) and HTR2A (serotonin‐2A receptor) have been examined in relation to efficacy and side effect profiles of these drugs. This guideline updates and expands the 2015 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and SSRI dosing and summarizes the impact of CYP2D6 , CYP2C19 , CYP2B6 , SLC6A4 , and HTR2A genotypes on antidepressant dosing, efficacy, and tolerability. We provide recommendations for using CYP2D6 , CYP2C19 , and CYP2B6 genotype results to help inform prescribing these antidepressants and describe the existing data for SLC6A4 and HTR2A , which do not support their clinical use in antidepressant prescribing.
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Metadata
- Authors
- Bousman, C. A., Stevenson, J. M., Ramsey, L. B., Sangkuhl, K., Hicks, J. K., Strawn, J. R., Singh, A. B., Ruaño, G., Mueller, D. J., Tsermpini, E. E., Brown, J. T., Bell, G. C., Leeder, J. S., Gaedigk, A., Scott, S. A., Klein, T. E., Caudle, K. E., & Bishop, J. R.
- Affiliations
- University of Calgary (CA)
- Johns Hopkins University (US)
- Cincinnati Children's Hospital Medical Center (US)
- Stanford University (US)
- Moffitt Cancer Center (US)
- Deakin University (AU)
- Hartford Hospital (US)
- Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health Toronto Ontario Canada
- University of Ljubljana (SI)
- University of Minnesota (US)
- Genome Medical South San Francisco California USA
- Children’s Mercy Research Institute (US)
- Stanford Medicine (US)
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Bishop, Jeffrey R.
- ORCID
- Venue
- Clinical Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2023-05-30
- Volume
- 114
- Issue
- 1
- Pages
- 51-68
- ISSN
- 0009-9236 (ISSN-L)
- 1532-6535
- PMC
- PMC10564324
- OpenAlex
- W4362735831
- Cited by
- 521
- References
- 1
- Citations by year
- 2026: 208 · 2025: 144 · 2024: 125 · 2023: 42
- FWCI
- 81.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health (UL1TR001425, U24HG010135, R24GM115264)
- National Institute of Child Health and Human Development (R01HD098757, R01HD099775)
- Patient-Centered Outcomes Research Institute
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- CYP2D6, CYP2C19, CYP2B6, serotonin transporter, HTR2A, pharmacogenetics, antidepressant dosing, drug metabolism, 5-HT2A receptor, major depressive disorder, anxiety disorders, prescribing recommendations, drug efficacy and tolerability
- MeSH terms
- Antidepressive Agents, Major Depressive Disorder, Genotype, Humans, Pharmacogenetics, Serotonin, Citalopram, Selective Serotonin Reuptake Inhibitors, Cytochrome P-450 CYP2D6, Serotonin Plasma Membrane Transport Proteins, Cytochrome P-450 CYP2B6, Cytochrome P-450 CYP2C19
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