Association of Serotonin Transporter Gene 5HTTLPR rs25531 Polymorphism With Escitalopram Efficacy in Patients With Major Depressive Disorder.

BACKGROUND

Escitalopram is considered a cornerstone therapy for major depression, but inter-individual variations exist in its clinical efficacy. The current study aims to explore the possible association between serotonin transporter gene (SLC6A4) polymorphism 5HTTLPR-rs25531 and clinical efficacy of escitalopram in a Pakistani population suffering from major depressive disorder.

METHODOLOGY

This prospective observational analytical study was conducted from April 2023 to October 2024 in tertiary care hospitals. Four hundred and thirty depressive patients were recruited through non-probability purposive sampling. Patients were treated with escitalopram 10 mg once daily for 12 weeks. Patients were enrolled based on Hamilton Depression Rating Scale score of less than or equal to 20. Patients with a minimum 50% reduction in score at 12 weeks were designated as responders. Genotyping of 5-HTTLPR- rs25531 was performed by allele-specific polymerase chain reaction.

RESULTS

Responders and non-responders of escitalopram therapy were 217 (50.50%) and 213 (49.5%) patients, respectively. Frequencies of LL, LS, and SS genotypes of HTTLPR polymorphisms were 19%, 47%, and 34%, respectively, and frequencies of L and S alleles were 0.43 and 0.57, respectively. A higher percentage reduction in the Hamilton Depression Rating Scale was observed in patients carrying LL (60.05% ± 21.24%) and LS (53.63% ± 22.8%) genotypes compared to those having the SS genotype (32.22% ± 16.59%).

CONCLUSION

5HTTLPR and rs-25,531 polymorphisms significantly influenced escitalopram efficacy, and patients carrying LL genotypes with L_AL_A haplotype and 2 L functional group have better treatment response to escitalopram therapy compared to other groups.

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