Abstract
Background: Genetic polymorphisms significantly influence individual responses to antidepressant medications. Among these, variations in the cytochrome P450 enzyme CYP2C19, particularly the *2 allele, are known to affect drug metabolism, with implications for both efficacy and safety. South Indian populations exhibit a relatively high prevalence of this polymorphism, yet data specific to psychiatric cohorts remain limited. Purpose: This study aimed to determine the prevalence of the CYP2C19*2 polymorphism among South Indian psychiatric patients and to classify the corresponding metaboliser phenotypes to inform precision prescribing strategies for psychotropic medications. Methods: A cross-sectional observational study was conducted involving 140 psychiatric patients of South Indian ancestry across two tertiary psychiatric centres. Genomic DNA was extracted from peripheral blood samples and genotyped for the CYP2C19*2 (681G>A) variant using TaqMan-based real-time PCR. Participants were categorised into metaboliser phenotypes based on CPIC guidelines: normal (*1/*1), intermediate (*1/*2) and poor (*2/*2) metabolisers. Genotype frequencies were assessed for Hardy-Weinberg equilibrium (HWE) and descriptive statistics were used to summarise allele and phenotype distributions. Results: The CYP2C19*2 allele frequency was 27.5%. Genotype distribution was as follows: *1/*1 in 55.7%, *1/*2 in 33.6% and *2/*2 in 10.7% of participants. Accordingly, 44.3% of patients were classified as non-normal metabolisers (NMs) (intermediate or poor). The genotype distribution did not deviate significantly from HWE (p = .0614), indicating population stability. Conclusion: A substantial proportion of South Indian psychiatric patients exhibit reduced CYP2C19 enzyme activity due to the presence of the *2 allele. These findings highlight the clinical utility of pre-emptive pharmacogenetic testing to guide antidepressant selection and dosing in this population, supporting the implementation of precision psychiatry in routine mental health care.