TY - JOUR
T1 - Pharmacogenetics of neurological and psychiatric diseases at older age
T2 - has the time come?
AU - Lozupone, Madia
AU - Panza, Francesco
AU - Stella, Eleonora
AU - La Montagna, Maddalena
AU - Bisceglia, Paola
AU - Miscio, Giuseppe
AU - Galizia, Ilaria
AU - Daniele, Antonio
AU - di Mauro, Lazzaro
AU - Bellomo, Antonello
AU - Logroscino, Giancarlo
AU - Greco, Antonio
AU - Seripa, Davide
PY - 2017/3/4
Y1 - 2017/3/4
N2 - Introduction: 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.
AB - Introduction: 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.
KW - 5-HTT
KW - 5-hydroxytriptamine transporter
KW - adverse drug reaction
KW - CYP2D6
KW - cytochrome P450
KW - DAT
KW - dopamine transporter
KW - pharmacogenetics
KW - psychiatric disorders
KW - Therapeutic failure
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U2 - 10.1080/17425255.2017.1246533
DO - 10.1080/17425255.2017.1246533
M3 - Review article
C2 - 27718745
AN - SCOPUS:85013276063
VL - 13
SP - 259
EP - 277
JO - Expert Opinion on Drug Metabolism and Toxicology
JF - Expert Opinion on Drug Metabolism and Toxicology
SN - 1742-5255
IS - 3
ER -