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Effects of CYP2C19 genetic polymorphism on the steady-state concentration of citalopram in patients with major depressive disorder

Abstract

Citalopram is commonly prescribed to patients suffering from major depressive disorder. Some of them do not respond adequately to therapy with citalopram, while many of them experience type A adverse drug reactions. Current research revealed that CYP2C19 isoenzyme is involved in the biotransformation of citalopram. The objective of our study was to investigate the impact of 681G>A polymorphism of the CYP2C19 gene on the efficacy, safety and the concentration/dose indicator of citalopram. Our study enrolled 130 patients with major depressive disorder and comorbid alcohol use disorder (average age–38.7 ± 14.1 years). Therapy regimen included citalopram in an average daily dose of 31.1 ± 14.4 mg per week. Therapy efficacy and safety were evaluated using the international psychometric scales. For genotyping, we performed the real-time polymerase chain reaction. Our findings revealed the statistically significant results in terms of the treatment efficacy evaluation (HAMD scores at the end of the treatment course): (GG) 8.0 [8.0; 9.0] and (GA) 10.0 [9.0; 11.0], p < 0.001. In the safety profile (the UKU scores), the statistical significance was also obtained: (GG) 3.0 [3.0; 4.0] and (GA) 5.0 [4.0; 5.0], p < 0.001. We revealed a statistical significance for concentration/dose indicator of citalopram in patients with different genotypes: (GG) 2.543 [1.659; 4.239] and (GA) 4.196 [2.643; 5.753], p < 0.001). The effect of CYP2C19 genetic polymorphism on the efficacy and safety profiles of citalopram was demonstrated in a group of 130 patients with major depressive disorder.

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Fig. 1: Dynamics of changes in the HAMD and UKU scales scores across patients with different genotypes by the polymorphic marker 681G>A of the CYP2C19 gene (rs4244285).
Fig. 2: Differences in the value citalopram concentration/dose in patients with different genotypes by the polymorphic marker 681G>A of the CYP2C19 gene (rs4244285).

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Funding

This work was financially supported by the project 16-15-00227 entitled “Fundamental research and exploratory research in priority areas of research” of the Russian Science Foundation. This work was supported by the grant of the Russian Science Foundation (project No. 18-75-10073).

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Correspondence to M. S. Zastrozhin.

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Zastrozhin, M.S., Skryabin, V.Y., Petukhov, A.E. et al. Effects of CYP2C19 genetic polymorphism on the steady-state concentration of citalopram in patients with major depressive disorder. Pharmacogenomics J (2021). https://doi.org/10.1038/s41397-021-00219-7

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