Influence of CYP2C1917 Genetic Polymorphism on the Steady-State Concentration of Escitalopram in Patients with Recurrent Depressive Disorder

• Published in: Psychopharmacology bulletin 2022-06, Vol.52 (3), p.8-19
• Main Authors: Zastrozhin, M S, Skryabin, VYu, Rwere, F, Petukhov, A E, Pankratenko, E P, Pozdniakov, S A, Ivanchenko, V A, Noskov, V V, Zaytsev, I A, Vinokurova, N V, Horyaev, D S, Vlasovskih, R V, Bryun, E A, Sychev, D A
• Format: Article
• Language: English
• Subjects: Citalopram - adverse effects; Cytochrome P-450 CYP2C19 - genetics; Depressive Disorder - drug therapy; Escitalopram; Humans; Original Research; Polymorphism, Genetic; Tandem Mass Spectrometry
• ISSN: 0048-5764; 2472-2448

Escitalopram is commonly prescribed to patients with recurrent depressive disorder. Some of them do not show adequate response to treatment with escitalopram, while many of them experience adverse drug reactions. The objective of our study was to evaluate the impact of -806C>T polymorphism of CYP2C19 (CYP2C19*17) on the concentration/dose ratio of escitalopram in patients with recurrent depressive disorder. Our study enrolled 267 patients with recurrent depressive disorder (average age -40.2 ± 16.4 years). Treatment regimen included escitalopram in an average daily dose of 12.5 ± 5.0 mg per day. The efficacy and safety rates of treatment were evaluated using the international psychometric scales. For genotyping, we performed the real-time polymerase chain reaction. Therapeutic drug monitoring has been performed using HPLC-MS/MS. Our findings revealed the statistically significant results in terms of both treatment efficacy evaluation (HAMD scores at the end of the treatment course): (CC) 9.0 [7.0; 11.0], (CT) 4.0 [2.0; 6.0] and (TT) 2.0 [1.0; 4.0], p < 0.001; and safety profile (the UKU scores): (CC) 7.0 [7.0; 8.0], (CT) 3.0 [3.0; 4.0] and (TT) 3.0 [2.0; 3.0], p < 0.001. We revealed no statistically significant results for the concentration/dose ratio of escitalopram in patients with different genotypes: (CC) 5.762 [3.939; 9.076], (CT) 5.714 [3.485; 8.533] and (TT) 7.388 [4.618; 10.167], p = 0.268). The CYP2C19*17 genetic variant significantly affected the efficacy and safety profiles of escitalopram in a group of 267 patients with recurrent depressive disorder but did not greatly affect its equilibrium plasma concentration.