title: Clinical validity of cytochrome P450 metabolism and serotonin gene variants in psychiatric pharmacotherapy.
abstract: Adverse events, response failures and medication non-compliance are common in patients receiving medications for the treatment of mental illnesses. A systematic literature review assessed whether pharmacokinetic (PK) or pharmacodynamic (PD) responses to 26 commonly prescribed antipsychotic and antidepressant medications, including efficacy or side effects, are associated with nucleotide polymorphisms in eight commonly studied genes in psychiatric pharmacotherapy: CYP2D6, CYP2C19, CYP2C9, CYP1A2, CYP3A4, HTR2C, HTR2A, and SLC6A4. Of the 294 publications included in this review, 168 (57%) showed significant associations between gene variants and PK or PD outcomes. Other studies that showed no association often had insufficient control for confounding variables, such as co-medication use, or analysis of medications not substrates of the target gene. The strongest gene-outcome associations were for the PK profiles of CYP2C19 and CYP2D6 (93% and 90%, respectively), for the PD associations between HTR2C and weight gain (57%), and for SLC6A4 and clinical response (54%), with stronger SLC6A4 response associations for specific drug classes (60-83%). The preponderance of evidence supports the validity of analyzing nucleotide polymorphisms in CYP and pharmacodynamic genes to predict the metabolism, safety, or therapeutic efficacy of psychotropic medications commonly used for the treatment of depression, schizophrenia, and bipolar illness.
authors.affiliation: AssureRx Health , Mason, Ohio.
authors.forename: C Anthony
authors.initials: CA
authors.lastname: Altar
authors.forename: John
authors.initials: J
authors.lastname: Hornberger
authors.forename: Ashwini
authors.initials: A
authors.lastname: Shewade
authors.forename: Victor
authors.initials: V
authors.lastname: Cruz
authors.forename: Jill
authors.initials: J
authors.lastname: Garrison
authors.forename: David
authors.initials: D
authors.lastname: Mrazek
mesh_terms: D000928:Antidepressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics*; D011985:Receptors, Serotonin / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D003577:Cytochrome P-450 Enzyme System