Pharmacogenetics of neurological and psychiatric diseases at older age: has the time come?

Madia Lozupone, Francesco Panza, Eleonora Stella, Maddalena La Montagna, Paola Bisceglia, Giuseppe Miscio, Ilaria Galizia, Antonio Daniele, Lazzaro di Mauro, Antonello Bellomo, Giancarlo Logroscino, Antonio Greco, Davide Seripa

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish
Pages (from-to)259-277
Number of pages19
JournalExpert Opinion on Drug Metabolism and Toxicology
Volume13
Issue number3
DOIs
Publication statusPublished - Mar 4 2017

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Keywords

  • 5-HTT
  • 5-hydroxytriptamine transporter
  • adverse drug reaction
  • CYP2D6
  • cytochrome P450
  • DAT
  • dopamine transporter
  • pharmacogenetics
  • psychiatric disorders
  • Therapeutic failure

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Lozupone, M., Panza, F., Stella, E., La Montagna, M., Bisceglia, P., Miscio, G., Galizia, I., Daniele, A., di Mauro, L., Bellomo, A., Logroscino, G., Greco, A., & Seripa, D. (2017). Pharmacogenetics of neurological and psychiatric diseases at older age: has the time come? Expert Opinion on Drug Metabolism and Toxicology, 13(3), 259-277. https://doi.org/10.1080/17425255.2017.1246533