Treatment Response to Sertraline in the Pakistani Population and its Association with Cytochrome P450 2C19 Genotypes

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are metabolized differently depending on variations in the CYP2C19 gene. Clinical practitioners are using pharmacogenetic information based on the impact of CYP2C19 polymorphisms more frequently. Yet, the fundamental tenets connecting distinct metabolism to efficacy or adverse drug reactions are still poorly understood. This research was conducted in the hopes of establishing a link between genetic variants of the CYP2C19 gene and the therapeutic effect and adverse effects of the antidepressant Sertraline. The objective of this study was to determine the CYP2C19*2, *3, and *17 allele and genotype frequencies among the treatment-responsive and resistant patients and their correlation with the response and to determine the association of CYP2C19 allele to adverse effects of sertraline in major depressive disorder (MDD) patients. The study was conducted at the Institute of Pharmaceutical Sciences, Khyber Medical University. Fifty patients of MDD were recruited from a psychiatric clinic to take part in this study. Three scales, Hamilton Depression Rating Scale (HDRS or HAMD-17), General Medication Adherence Scale (GMAS),  and Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) were used to assess depression severity, adherence to drug therapy, and adverse effects respectively at baseline and then at weeks 2, 4, 6 and finally at 6 months. 3ml blood was also taken from patients for genotyping polymorphic variants of CYP2C19. We found that the risk factors for depression as indicated by our study are females (58%) OR 1.18 as compared to males OR 0.75, married individuals (74%), and poor socioeconomic status (40%). A high response rate to sertraline was recorded with 82% responders and only 18% non-responders. Response rate of males was slightly higher than females at 92% and 90% respectively. HAMD 1^st follow-up was significantly correlated to baseline score at p-value 0.01. GMAS was negatively correlated to HAMD with an R-value of -0.042. We found no significant association between CYP2C19 genotypes and sertraline therapeutic response or adverse effects. However, the study showed that adherence to drug therapy leads to better treatment response.