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Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants

Clinical Pharmacology & Therapeutics · 2013 · Vol. 93(5) · pp. 402–408

J. Kevin Hicks(St. Jude Children's Research Hospital)Jesse J. Swen(Leiden University Medical Center)Caroline F. Thorn(Stanford University)Katrin Sangkuhl(Stanford University)E D Kharasch(Washington University in St. Louis)V L Ellingrod(University of Michigan–Ann Arbor)Todd C. Skaar(Indiana University – Purdue University Indianapolis)D Müller(Centre for Addiction and Mental Health)Andrea Gaedigk(Children's Mercy Hospital)Julia Stingl✉(Federal Institute for Drugs and Medical Devices)

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Abstract

Polymorphisms in CYP2D6 and CYP2C19 affect the efficacy and safety of tricyclics, with some drugs being affected by CYP2D6 only, and others by both polymorphic enzymes. Amitriptyline, clomipramine, doxepin, imipramine, and trimipramine are demethylated by CYP2C19 to pharmacologically active metabolites. These drugs and their metabolites, along with desipramine and nortriptyline, undergo hydroxylation by CYP2D6 to less active metabolites. Evidence from published literature is presented for CYP2D6 and CYP2C19 genotype-directed dosing of tricyclic antidepressants.

Pharmacogenetics and Drug Metabolism Cancer Treatment and Pharmacology Pharmacology and Obesity TreatmentDoxepinNortriptylineDesipramineTricyclicCYP2D6PharmacologyPharmacogeneticsClomipramineCYP2C19Dosing

MeSH terms

Antidepressive Agents, TricyclicAryl Hydrocarbon HydroxylasesMental DisordersDose-Response Relationship, DrugGenotypeHumansPharmacogeneticsPolymorphism, GeneticCytochrome P-450 CYP2D6Cytochrome P-450 CYP2C19