title: Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants.
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.
authors.affiliation: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Hicks
authors.forename: J J
authors.initials: JJ
authors.lastname: Swen
authors.forename: C F
authors.initials: CF
authors.lastname: Thorn
authors.forename: K
authors.initials: K
authors.lastname: Sangkuhl
authors.forename: E D
authors.initials: ED
authors.lastname: Kharasch
authors.forename: V L
authors.initials: VL
authors.lastname: Ellingrod
authors.forename: T C
authors.initials: TC
authors.lastname: Skaar
authors.forename: D J
authors.initials: DJ
authors.lastname: Müller
authors.forename: A
authors.initials: A
authors.lastname: Gaedigk
authors.forename: J C
authors.initials: JC
authors.lastname: Stingl
mesh_terms: D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy / Q000503:physiopathology; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
chemical_list: D000929:Antidepressive Agents, Tricyclic; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6