Title:Targeting Drug Metabolism in Psychiatry: Pharmacogenetic Insights into CYP2D6 and CYP2C19
Volume: 23
Author(s): Darshan Gowda Bharathi Srinivasa, Prashant Tiwari and Sunil Kumar Kadiri*
Affiliation:
- Department of Pharmacology, College of Pharmaceutical Sciences, Dayananda Sagar University, Devarakaggalahalli, Kanakapura Road, Bengaluru South, Karnataka, 562112, India
Keywords:
Pharmacogenetics, psychiatry, precision medicine, CYP2D6, CYP2C19, genetic testing, personalized treatment, pharmacogenomics, antidepressants, antipsychotics, CPIC guidelines.
Abstract:
Introduction: Pharmacogenetics is revolutionising psychiatric care by providing
insights into how genetic variants, particularly in CYP2D6 and CYP2C19, affect drug metabolism,
efficacy, and side effects. These insights help clinicians tailor treatment for drugs
such as SSRIs, tricyclic antidepressants, and antipsychotics, reducing trial-and-error prescribing
and improving patient outcomes. This study aims to investigate the influence of genetic
variations, particularly in CYP2D6 and CYP2C19, on drug metabolism, therapeutic effectiveness,
and adverse effects in psychiatric treatment.
Methods: This systematic review integrates information from PharmGKB and the Clinical
Pharmacogenetics Implementation Consortium (CPIC) guidelines, as well as data from
PubMed, Medline, Scopus, Web of Science, Google Scholar, and reputable health organisations
using keywords related to the study topic. Inclusion criteria encompassed peerreviewed
articles, studies in English, and research published within the last 10 years. Exclusion
criteria included non-relevant or duplicate studies. The selection process followed
PRISMA guidelines, with data extraction focusing on study design, outcomes, and reliability
to ensure transparency and credibility. The review also examines new findings, such as
polygenic risk scores and expanded multigene testing platforms, and highlights clinically
relevant gene–drug interactions, including the effect of CYP2D6 polymorphisms on risperidone
metabolism.
Results: This study emphasises the significant role of pharmacogenetics in psychiatric
treatment, specifically regarding genetic variants in CYP2D6 and CYP2C19. These genetic
factors influence treatment with SSRIs, tricyclic antidepressants, and antipsychotics by altering
medication metabolism, effectiveness, and adverse effects. The study examines key
gene–drug interactions and emerging technologies such as polygenic risk scores, utilising
data from PharmGKB, CPIC recommendations, and major medical databases.
Discussion: Despite its promise, widespread implementation faces challenges such as cost,
accessibility, and the need for clinician education. Addressing these obstacles through improved
insurance coverage and integration of electronic health records can advance precision
medicine, thereby enhancing patient outcomes and reducing adverse effects. The gap
can be narrowed by employing strategies such as increasing insurance coverage for testing
and incorporating genetic decision-support tools into electronic health records.
Conclusion: Integrating pharmacogenetics into psychiatric care can improve treatment safety
and precision. For broad adoption, challenges such as cost, test accessibility, and physician education
must be addressed. This review supports a future in which pharmacogenetic insights
guide psychiatric care to improve treatment outcomes and reduce adverse drug reactions.
