title: Pharmacogenetics of neurological and psychiatric diseases at older age: has the time come?
abstract: In recent years, a number of pharmacological approaches for treating neuropsychiatric conditions at older age have proven to be inadequate. The resulting increased prevalence of therapeutic failures (TF) and a worsening of clinical symptoms often linked to adverse reactions (ADRs), are perhaps among the major causes of the increasing rate of hospitalizations and institutionalizations observed in these patients. Areas covered: This review underlines the importance of pharmacogenetic data to fingerprint the pharmacological treatment of neuropsychiatric late-life conditions throughout the analysis of metabolizing enzymes and transporters of psychotropic drugs, mainly those of the cytochrome P450 (CYP) family. Pharmacodynamic response measures as treatment effects mediated through targets (i.e., receptors in the brain) may also contribute to this image. Expert opinion: CYP genetics is the basis of a continuum on which environmental and physiological factors act, modeling the phenotype observed in clinical practice with advancing age. Furthermore, other specific polymorphic genes influence drug response through differential effects of their functional genetic variants. The known genotypes associated with an altered metabolizer status and drug transporters may help clinical decision-making to avoid concomitant treatments, reduce therapeutic attempts and increase drug safety in neuropsychiatric conditions in older age, after controlling for other clinical variables.
authors.affiliation: a Unit of Neurodegenerative Disease, Department of Basic Medicine Sciences, Neuroscience, and Sense Organs , University of Bari 'Aldo Moro,' , Bari , Italy.
authors.forename: Madia
authors.initials: M
authors.lastname: Lozupone
authors.affiliation: a Unit of Neurodegenerative Disease, Department of Basic Medicine Sciences, Neuroscience, and Sense Organs , University of Bari 'Aldo Moro,' , Bari , Italy.|b Unit of Neurodegenerative Disease, Department of Clinical Research in Neurology , University of Bari 'Aldo Moro' at 'Pia Fondazione Card. G. Panico,' , Tricase , Lecce , Italy.|c Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences , IRCCS Casa Sollievo della Sofferenza , San Giovanni Rotondo , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Panza
authors.affiliation: d Psychiatric Unit, Department of Clinical and Experimental Medicine , University of Foggia , Foggia , Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Stella
authors.affiliation: d Psychiatric Unit, Department of Clinical and Experimental Medicine , University of Foggia , Foggia , Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: La Montagna
authors.affiliation: c Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences , IRCCS Casa Sollievo della Sofferenza , San Giovanni Rotondo , Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bisceglia
authors.affiliation: e Laboratory of Clinical Chemistry, Department of Clinical Pathology , IRCCS Casa Sollievo della Sofferenza , San Giovanni Rotondo , Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Miscio
authors.affiliation: d Psychiatric Unit, Department of Clinical and Experimental Medicine , University of Foggia , Foggia , Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Galizia
authors.affiliation: f Institute of Neurology , Catholic University of Sacred Heart , Rome , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Daniele
authors.affiliation: e Laboratory of Clinical Chemistry, Department of Clinical Pathology , IRCCS Casa Sollievo della Sofferenza , San Giovanni Rotondo , Italy.
authors.forename: Lazzaro
authors.initials: L
authors.lastname: di Mauro
authors.affiliation: d Psychiatric Unit, Department of Clinical and Experimental Medicine , University of Foggia , Foggia , Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Bellomo
authors.affiliation: a Unit of Neurodegenerative Disease, Department of Basic Medicine Sciences, Neuroscience, and Sense Organs , University of Bari 'Aldo Moro,' , Bari , Italy.|b Unit of Neurodegenerative Disease, Department of Clinical Research in Neurology , University of Bari 'Aldo Moro' at 'Pia Fondazione Card. G. Panico,' , Tricase , Lecce , Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Logroscino
authors.affiliation: c Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences , IRCCS Casa Sollievo della Sofferenza , San Giovanni Rotondo , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Greco
authors.affiliation: c Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences , IRCCS Casa Sollievo della Sofferenza , San Giovanni Rotondo , Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Seripa
mesh_terms: D000368:Aged; D001921:Brain / Q000503:physiopathology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D014644:Genetic Variation; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011619:Psychotropic Drugs / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D011619:Psychotropic Drugs; D003577:Cytochrome P-450 Enzyme System
keywords: 5-HTT; 5-hydroxytriptamine transporter; CYP2D6; DAT; Therapeutic failure; adverse drug reaction; cytochrome P450; dopamine transporter; pharmacogenetics; psychiatric disorders