He Qianqian, Yuan Zhuo, Liu Yuanyuan, Zhang Jian, Yan Hong, Shen Li, Luo Xingguang, Zhang Yong
aTianjin Anding Hospital bTianjin Medical University cFirst Teaching Hospital of Tianjin University of Traditional Chinese Medicine dTianjin Chest Hospital, Tianjin, People's Republic of China eDepartment of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
Pharmacogenet Genomics. 2017 Aug;27(8):279-284. doi: 10.1097/FPC.0000000000000290.
Escitalopram (S-CT) is used widely to treat patients with panic disorder (PD) and the CYP2C19 enzyme is responsible for S-CT metabolism. We hypothesized that CYP2C19 polymorphisms were associated with S-CT treatment response in Chinese patients with PD.
Seventy-eight patients with PD completed the assessment by the Panic Disorder Severity Scale - Chinese Version (PDSS-CV) and the Hamilton Anxiety Scale (HAMA-14) during an 8-week period. All patients were administered a fixed dose of 10 mg/day S-CT. Three CYP2C19 metabolizer phenotypes were analyzed by PCR-genotyping microarray, including extensive metabolizer (EM), intermediate metabolizer, and poor metabolizer (PM).
This prospective, open-label and observational study showed that the proportion of EM (43.6%) was higher than that of PM (10.2%). There were higher response ratios of PDSS-CV in PM (the second to fourth week: 62.5-100%) than in EM (the second to fourth week: 23.5-55.9%) (Ps<0.05); also, there were higher response ratios of HAMA-14 in PM (the second to fourth week: 75.0-100%) than in EM (the second to fourth week: 17.7-52.9%) (Ps<0.05). Treatment response was based on the reduction of PDSS-CV and HAMA compared with the baseline. There was higher reduction of PDSS-CV in the patients with PM (68.78±9.04 for the fourth week and 84.30±9.81 for the eighth week) than EM (49.66±20.77 for the fourth week and 63.12±22.60 for the eighth week) (Ps<0.05); also, there was higher reduction of HAMA-14 in the patients with PM (70.11±8.98 for the fourth week and 81.32±8.25 for the eighth week) than EM (51.51±18.53 for the fourth week and 62.79±18.28 for the eighth week) (Ps<0.05).
The CYP2C19 genetic polymorphism is associated with S-CT treatment response in Chinese patients with PD. CYP2C19 PM could play a key role in early treatment response of S-CT.
艾司西酞普兰（S-CT）被广泛用于治疗惊恐障碍（PD）患者，细胞色素P450 2C19（CYP2C19）酶负责S-CT的代谢。我们假设CYP2C19基因多态性与中国PD患者的S-CT治疗反应相关。
78例PD患者在8周内完成了惊恐障碍严重程度量表中文版（PDSS-CV）和汉密尔顿焦虑量表（HAMA-14）评估。所有患者均接受固定剂量10mg/天的S-CT治疗。通过聚合酶链反应-基因分型微阵列分析三种CYP2C19代谢酶表型，包括广泛代谢型（EM）、中间代谢型和慢代谢型（PM）。
这项前瞻性、开放标签和观察性研究表明，EM的比例（43.6%）高于PM（10.2%）。PM组PDSS-CV的反应率（第二至第四周：62.5%-100%）高于EM组（第二至第四周：23.5%-55.9%）（P<0.05）；同样，PM组HAMA-14的反应率（第二至第四周：75.0%-100%）高于EM组（第二至第四周：17.7%-52.9%）（P<0.05）。治疗反应基于与基线相比PDSS-CV和HAMA的降低。PM组患者PDSS-CV的降低幅度（第四周为68.78±9.04，第八周为84.30±9.81）高于EM组（第四周为49.
