Zastrozhin M S, Skryabin V Yu, Petukhov A E, Torrado M V, Pankratenko E P, Zastrozhina A K, Grishina E A, Ryzhikova K A, Shipitsyn V V, Bryun E A, Sychev D A
Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russian Federation.
Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation.
Pharmacogenomics J. 2021 Aug;21(4):435-439. doi: 10.1038/s41397-021-00219-7. Epub 2021 Feb 19.
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.
西酞普兰常用于治疗重度抑郁症患者。其中一些患者对西酞普兰治疗反应欠佳，还有许多患者会出现A型药物不良反应。目前的研究表明，CYP2C19同工酶参与西酞普兰的生物转化。我们研究的目的是调查CYP2C19基因681G>A多态性对西酞普兰疗效、安全性及浓度/剂量指标的影响。我们的研究纳入了130例患有重度抑郁症合并酒精使用障碍的患者（平均年龄38.7±14.1岁）。治疗方案包括每周平均每日剂量为31.1±14.4毫克的西酞普兰。使用国际心理测量量表评估治疗效果和安全性。对于基因分型，我们进行了实时聚合酶链反应。我们的研究结果显示，在治疗效果评估方面（治疗疗程结束时的汉密尔顿抑郁量表评分）有统计学显著差异：（GG）8.0[8.0；9.0]和（GA）10.0[9.0；11.0]，p<0.001。在安全性方面（UKU评分），也有统计学显著差异：（GG）3.0[3.0；4.0]和（GA）5.0[4.0；5.0]，p<0.001。我们发现不同基因型患者的西酞普兰浓度/剂量指标存在统计学显著差异：（GG）2.543[1.659；4.239]和（GA）4.196[2.643；5.753]，p<0.001）。在一组130例重度抑郁症患者中，证实了CYP2C19基因多态性对西酞普兰疗效和安全性方面的影响。
