Psychiatric pharmacogenomics: from genetic evidence to clinical integration - structural, educational, and ethical...

The role of pharmacogenomics (PGx) for identifying individualized therapeutic approaches in patients with psychiatric disorders is a topic of intense debate in the literature, from clinical, pharmacoeconomic, ethical, educational, and theoretical perspectives. The objectives of this narrative review were (1) to synthesise the genetic evidence base for psychiatric PGx, with particular attention to the hierarchy between pharmacokinetics, pharmacodynamics and emerging epigenetic or polygenic markers; (2) to evaluate the clinical integration of pharmacogenomics in psychiatry, focusing on PGx-guided versus treatment-as-usual randomized trials, meta-analyses, economic evaluations and real-world implementation projects; (3) to analyse structural, educational and ethical challenges that condition the translation of genetic evidence into practice. Based on the reviewed primary and secondary reports, relevant data were found regarding antidepressant PGx, and less for antipsychotics and mood stabilizers. Pharmacoenomic data and structural, economic, and implementation barriers have also been explored, as well as educational and ethical challenges in the field of PGx implementation in psychiatry. In conclusion, psychiatric pharmacogenomics is placed at the intersection between relatively strong but narrow pharmacokinetic evidence, weaker and heterogeneous pharmacodynamic findings, and substantial implementation and ethical constraints. The most clinically actionable data concern CYP2D6 and CYP2C19 variants for certain antidepressants and, to a lesser extent, antipsychotics, which reliably predict serum levels and adverse effects and show modest associations with treatment response and remission.