| 刘岩,刘传宏,刘艳霞,孙艳丽,张若男,张晓琳,黄带发.CYP2D6基因多态性对氟西汀治疗老年抑郁症患者效果的影响[J].中国临床保健杂志,2023,26(1):61-65. |
| CYP2D6基因多态性对氟西汀治疗老年抑郁症患者效果的影响 |
| Effect of CYP2D6 gene polymorphism on the efficacy of fluoxetine in elderly patients with depression |
| 投稿时间：2022-01-10 |
| DOI：10.3969/J.issn.1672-6790.2023.01.013 |
| 中文关键词: 抑郁症 多态现象,遗传 氟西汀 血药浓度 老年人 |
| 英文关键词: Depressive Disorder Polymorphism,genetic Fluoxetine Plasma concentration Aged 〖FL |
| 基金项目:军委后勤保障部技术标准项目(面上项目)(18BJZ17) |
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| 中文摘要: |
| 目的 探讨细胞色素P450-2D6(CYP2D6)基因多态性对老年抑郁症患者应用氟西汀的疗效及安全性的影响。方法 选取2016年1月至2019年12月在北部战区总医院就诊的年龄≥65岁的抑郁症患者200例,使用Taq Man基因分型技术测定CYP2D6*2、*3、*4、*5、*6、*9、*10和*41等位点多态性,按不同的代谢表型分为A组(超强代谢型,13例),B组(正常代谢型,148例),C组(中间代谢型和弱代谢型,39例),应用氟西汀20 mg,1次/d。用药12周后抽取清晨空腹静脉血,应用超高效液相色谱-串联质谱法(UPLC-MS/MS)检测氟西汀及其代谢产物去甲氟西汀浓度并计算比值,以研究氟西汀在不同基因携带者体内的代谢情况。通过汉密尔顿抑郁量表(HAMD)和药物不良反应量表(TESS)来明确氟西汀对不同CYP2D6基因携带者的治疗效果和安全性。结果 治疗12周后3组患者氟西汀及其代谢产物去甲氟西汀浓度比值分别为A组0.438±0.037,B组0.790±0.033,C组0.920±0.120,各组间差异均有统计学意义(P＜0.05)。3组患者治疗前后HAMD分数下降幅度分别为A组(3.31±1.38)分,B组(8.23±4.96)分,C组(10.62±5.42)分,各组间差异均有统计学意义(P＜0.05)。3组患者治疗有效率分别为A组38.46%,B组70.95%,C组87.18%,各组间差异均有统计学意义(P＜0.05)。3组不良反应发生率分别为A组15.38%,B组18.24%,C组47.06%,A组与B组差异无统计学意义(P＞0.05),都明显低于C组,差异有统计学意义(P＜0.05);3组均未见严重不良反应。结论 CYP2D6等位基因代谢型对于老年患者应用氟西汀的血药浓度有一定影响,CYP2D6基因正常代谢型老年患者应用小剂量氟西汀治疗抑郁症疗效较好,且不良反应较少。 |
| 英文摘要: |
| Objective To explore the effect of cytochrome p450-2D6 (CYP2D6) gene polymorphism on the efficacy and safety of fluoxetine in elderly patients with depression.Methods Two hundred patients (≥65 years old) with depression were selected from General Hospital of Northern Theatre Command between January 2016 to December 2019.The polymorphisms of CYP2D6*2,*3,*4,*5,*6,*9,*10 and *41 were determined by Taq Man genotyping.According to different metabolic phenotypes,they were divided into group A (super metabolic type,13 cases),group B (normal metabolic type,148 cases),and group C(intermediate metabolic type and weak metabolic type,39 cases).The patients oraled fluoxetine 20 mg once a day for 12 weeks.After 12 weeks of administration,morning fasting venous blood was extracted,and the concentrations of fluoxetine and its metabolite,demefluoxetine,were determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS),and the ratio was calculated to study the metabolism of fluoxetine in different gene carriers.HamiltonDepression Scale (HAMD) and adverse drug reaction scale (TESS) were used to determine the effect and safety of fluoxetine in different groups.Results After 12 weeks treatment,the concentration ratio of fluoxetine and demethylfluoxetine were 0.438±0.037 in group A,0.790±0.033 in group B and 0.920±0.120 in group C,respectively.The concentration ratios in group A were the lowest,while those in group C were the highest,with statistical significance among all groups (P＜0.05).The decline of the HAMD scores before and after treatment were 3.31±1.38 in group A,8.23±4.96 in group B and 10.62±5.42 in group C,respectively.The decreasing range of group A was the lowest,and that of group C was the highest,with statistical significance among all groups(P<0.05).The effective rates of the three groups were 38.46% in group A,70.95% in group B and 87.18% in group C,respectively.Statistical significance among all groups (P<0.05).The incidence of adverse reactions in three groups were 15.38% in group A,18.24% in group B and 47.06% in group C,respectively.The incidence of adverse reactions in group A has no significant difference with group B (P>0.05),which was significantly lower than that in group C (P<0.05).No serious adverse reactions were found in the three groups.Conclusions The metabolic type of CYP2D6 allele has a certain influence on the blood concentration of fluoxetine in elderly patients.The application of low dose fluoxetine in the treatment of depression in elderly patients with the normal metabolic type of CYP2D6 gene has better efficacy and less adverse reactions. |
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