The pharmacogenetic road to avoid adverse drug reactions and therapeutic failures in revolving door patients with psychiatric illnesses: focus on the CYP2D6 isoenzymes

ABSTRACT

Introduction: A periodical hospital readmission caused by therapeutic failures (TFs) and a worsening of clinical symptoms most often linked to adverse drug reactions (ADRs) are probably the major causes for the so-called revolving door condition in psychiatric illnesses. This review underlined the importance that pharmacogenetic data on cytochrome P450 (CYP), particularly CYP2D6 polymorphisms, may offer for the finger printing of the pharmacological treatment of psychiatric illnesses, given the relevance of this enzyme in metabolizing psychotropic drugs.

Areas covered: We searched in the medical literature until July 2016 to review the role of functional variants in the CYP2D6 gene on observed ADRs and TFs in revolving door psychiatric patients.

Expert commentary: CYP2D6 gene variants could in part explain the revolving door condition in patients attending a psychiatric setting. The preemptive known CYP genotypes associated to a reduced metabolizer status may help clinical decision-making to avoid concomitant treatments, increasing drug safety, so reducing therapeutic attempts, hospital admission, and the overall costs for the national health services. However, CYP2D6 gene is only a part of a complex mechanism in which genetic and non-genetic factors may take part. A possible role of the intrinsic variability of pharmacodynamics and imponderable environmental factors influencing the revolving door condition cannot be excluded.

KEYWORDS:

• Therapeutic failure
• adverse drug reaction
• psychiatric disorders
• revolving door patients
• pharmacogenetics
• CYP2D6

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This study was completely supported by “Ministero della Salute”, IRCCS Research Program, RicercaCorrente 2015-2017, Linea n. 2 “Malattie complesse e terapie innovative” and by the “5 x 1000” voluntary contribution to the IRCCS “Casa Sollievo della Sofferenza”.