Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors

J K Hicks; J R Bishop; K Sangkuhl; D J Müller; Y Ji; S G Leckband; J S Leeder; R L Graham; D L Chiulli; A LLerena; T C Skaar; S A Scott; J C Stingl; T E Klein; K E Caudle; A Gaedigk; Clinical Pharmacogenetics Implementation Consortium

doi:10.1002/cpt.147

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors

Clin Pharmacol Ther. 2015 Aug;98(2):127-34. doi: 10.1002/cpt.147. Epub 2015 Jun 29.

Authors

J K Hicks¹, J R Bishop², K Sangkuhl³, D J Müller⁴, Y Ji⁵, S G Leckband⁶, J S Leeder⁷, R L Graham⁸, D L Chiulli⁹, A LLerena¹⁰, T C Skaar¹¹, S A Scott¹², J C Stingl¹³, T E Klein³, K E Caudle¹⁴, A Gaedigk⁷; Clinical Pharmacogenetics Implementation Consortium

Affiliations

¹ Department of Pharmacy, Cleveland Clinic, Cleveland, Ohio, USA; Genomic Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA; and Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.
² University of Minnesota College of Pharmacy, Department of Experimental and Clinical Pharmacology, Minneapolis, Minnesota, USA.
³ Department of Genetics, Stanford University, Stanford, California, USA.
⁴ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
⁵ Department of Laboratory Medicine and Pathology, Division of Laboratory Genetics, Mayo Clinic, Rochester, Minnesota, USA.
⁶ Veterans Affairs San Diego Healthcare System, Mental Health Care Line, University of California, San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences and Department of Psychiatry, San Diego, California, USA.
⁷ Division of Clinical Pharmacology, Toxicology & Innovative Therapeutics, Children's Mercy Hospital, Kansas City, Missouri and Department of Pediatrics, University of Missouri-Kansas City, Kansas City, Missouri, USA.
⁸ Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.
⁹ Veterans Affairs Palo Alto Health Care System, San Jose Division, San Jose, California, USA.
¹⁰ CICAB Clinical Research Center, Extremadura University Hospital and Medical School, Badajoz, Spain.
¹¹ Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹² Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹³ Federal Institute of Drugs and Medical Devices, Bonn, Germany.
¹⁴ Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

PMID: 25974703
PMCID: PMC4512908
DOI: 10.1002/cpt.147

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are primary treatment options for major depressive and anxiety disorders. CYP2D6 and CYP2C19 polymorphisms can influence the metabolism of SSRIs, thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide dosing recommendations for fluvoxamine, paroxetine, citalopram, escitalopram, and sertraline based on CYP2D6 and/or CYP2C19 genotype (updates at www.pharmgkb.org).

Publication types

Practice Guideline
Research Support, N.I.H., Extramural
Review

MeSH terms

Biotransformation
Cytochrome P-450 CYP2C19 / genetics*
Cytochrome P-450 CYP2C19 / metabolism
Cytochrome P-450 CYP2D6 / genetics*
Cytochrome P-450 CYP2D6 / metabolism
Drug Dosage Calculations*
Genotype
Humans
Patient Safety
Pharmacogenetics / standards*
Phenotype
Polymorphism, Genetic*
Risk Assessment
Risk Factors
Selective Serotonin Reuptake Inhibitors / administration & dosage*
Selective Serotonin Reuptake Inhibitors / adverse effects
Selective Serotonin Reuptake Inhibitors / pharmacokinetics

Substances

Serotonin Uptake Inhibitors
CYP2C19 protein, human
Cytochrome P-450 CYP2C19
Cytochrome P-450 CYP2D6

Abstract

Publication types

MeSH terms

Substances

Grants and funding