Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants by Hicks J K, Swen J J, Thorn C F, Sangkuhl K, Kharasch E D, Ellingrod V L, Skaar T C, Müller D J, Gaedigk A, Stingl J C in Clinical pharmacology and therapeutics (2013).

[PMID: 23486447] PubMed


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.Clinical Pharmacology & Therapeutics (2013); advance online publication 13 March 2013. doi:10.1038/clpt.2013.2.

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CPIC Guideline for amitriptyline and CYP2C19,CYP2D6
CPIC Guideline for clomipramine and CYP2C19,CYP2D6
CPIC Guideline for desipramine and CYP2D6
CPIC Guideline for doxepin and CYP2C19,CYP2D6
CPIC Guideline for imipramine and CYP2C19,CYP2D6
CPIC Guideline for nortriptyline and CYP2D6
CPIC Guideline for trimipramine and CYP2C19,CYP2D6