title: Do we need pharmacogenetics to personalize antidepressant therapy?
abstract: This review examines the role of drug metabolism and drug target polymorphism in determining the clinical response to antidepressants. Even though antidepressants are the most effective available treatment for depressive disorders, there is still substantial need for improvement due to the slow onset of appreciable clinical improvement and the association with side effects. Moreover, a substantial group of patients receiving antidepressant therapy does not achieve remission or fails to respond entirely. Even if the large variation in antidepressant treatment outcome across individuals remains poorly understood, one possible source of this variation in treatment outcome are genetic differences. The review focuses on a few polymorphisms which have been extensively studied, while reporting a more comprehensive reference to the existing literature in table format. It is relatively easy to predict the effect of polymorphisms in drug metabolizing enzymes, such as cytochromes P450 2D6 (CYP2D6) and cytochrome P450 2C19 (CYP2C19), which may be determined in the clinical context in order to explain or prevent serious adverse effects. The role of target polymorphism, however, is much more difficult to establish and may be more relevant for disease susceptibility and presentation rather than for response to therapy.
authors.affiliation: Department of Drug Sciences (Pharmacology Section), Center of Excellence in Applied Biology, University of Pavia, IUSS-Pavia (Istituto Universitario di Studi Superiori-Pavia), Viale Taramelli 14, 27100, Pavia, Italy. cristina.lanni@unipv.it
authors.forename: Cristina
authors.initials: C
authors.lastname: Lanni
authors.forename: Marco
authors.initials: M
authors.lastname: Racchi
authors.forename: Stefano
authors.initials: S
authors.lastname: Govoni
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D003863:Depression / Q000188:drug therapy* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D014365:Tryptophan Hydroxylase / Q000235:genetics; D000092864:Suicide Prevention
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000928:Antidepressive Agents; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D014365:Tryptophan Hydroxylase