Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update

J K Hicks; K Sangkuhl; J J Swen; V L Ellingrod; D J Müller; K Shimoda; J R Bishop; E D Kharasch; T C Skaar; A Gaedigk; H M Dunnenberger; T E Klein; K E Caudle; J C Stingl

doi:10.1002/cpt.597

Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update

Clin Pharmacol Ther. 2017 Jul;102(1):37-44. doi: 10.1002/cpt.597. Epub 2017 Feb 13.

Authors

J K Hicks¹, K Sangkuhl², J J Swen³, V L Ellingrod⁴, D J Müller⁵, K Shimoda⁶, J R Bishop⁷, E D Kharasch⁸, T C Skaar⁹, A Gaedigk¹⁰, H M Dunnenberger¹¹, T E Klein², K E Caudle¹², J C Stingl¹³

Affiliations

¹ DeBartolo Family Personalized Medicine Institute, Division of Population Science, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
² Department of Genetics, Stanford University, Stanford, California, USA.
³ Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Department of Clinical, Social and Administrative Sciences, College of Pharmacy, and Department of Psychiatry, School of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
⁵ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
⁶ Department of Psychiatry, Dokkyo Medical University, Japan.
⁷ Department of Experimental and Clinical Pharmacology, College of Pharmacy, and Department of Psychiatry, College of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
⁸ Division of Clinical and Translational Research, Department of Anesthesiology, Washington University in St, Louis, St, Louis, Missouri, USA.
⁹ Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹⁰ Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children's Mercy, Kansas City, Missouri and Department of Pediatrics, University of Missouri-Kansas City, Kansas City, Missouri, USA.
¹¹ Center for Molecular Medicine, NorthShore University HealthSystem, Evanston, Illinois, USA.
¹² Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
¹³ Division of Research, Federal Institute of Drugs and Medical Devices, Bonn, Germany.

PMID: 27997040
PMCID: PMC5478479
DOI: 10.1002/cpt.597

Abstract

CYP2D6 and CYP2C19 polymorphisms affect the exposure, efficacy and safety of tricyclic antidepressants (TCAs), with some drugs being affected by CYP2D6 only (e.g., nortriptyline and desipramine) and others by both polymorphic enzymes (e.g., amitriptyline, clomipramine, doxepin, imipramine, and trimipramine). Evidence is presented for CYP2D6 and CYP2C19 genotype-directed dosing of TCAs. This document is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants.

Publication types

Practice Guideline
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Antidepressive Agents, Tricyclic* / adverse effects
Antidepressive Agents, Tricyclic* / pharmacokinetics
Cytochrome P-450 CYP2C19 / genetics*
Cytochrome P-450 CYP2D6 / genetics*
Dose-Response Relationship, Drug
Genotyping Techniques / methods*
Humans
Medication Therapy Management / standards*
Pharmacogenomic Variants / genetics*
Polymorphism, Genetic
Treatment Outcome

Substances

Antidepressive Agents, Tricyclic
Cytochrome P-450 CYP2C19
Cytochrome P-450 CYP2D6

Abstract

Publication types

MeSH terms

Substances

Grants and funding