CYP2C19 多态性对双相情感障碍患者抗抑郁药处方模式和治疗后出现的躁狂症的影响

IF 2.9 3区 医学 Q2 GENETICS & HEREDITY Pharmacogenomics Journal Pub Date : 2022-11-04 DOI:10.1038/s41397-022-00294-4
Erik Joas, Lina Jonsson, Alexander Viktorin, Erik Smedler, Erik Pålsson, Guy M. Goodwin, Mikael Landén
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引用次数: 0

摘要

尽管疗效不确定,抗抑郁药物仍被广泛用于治疗双相抑郁症。细胞色素 P450(CYP)2C19 酶可代谢多种抗抑郁药物,而相应基因 CYP2C19 的多态性会影响血浆浓度,进而影响重度抑郁症的治疗效果。在此,我们研究了 CYP2C19 多态性是否与双相情感障碍患者使用抗抑郁药时的抗抑郁治疗模式和躁狂症风险有关。我们利用两个单核苷酸多态性(rs4244285 和 rs12248560)将 5019 名双相情感障碍患者分为 CYP2C19 代谢表型,从代谢差到超快速代谢者不等。我们利用 2005-2017 年瑞典全国配药和住院治疗登记数据,估算了接受西酞普兰、艾司西酞普兰、舍曲林、阿米替林和氯米帕明治疗的患者在开始治疗后 3 个月内出现早期持续治疗、中断治疗、更换新的抗抑郁药物和躁狂症的风险。根据配药模式,CYP2C19的代谢表型与所调查的治疗结果并无明显关联。对于舍曲林(危险比[HR] = 1.3,95% CI = 1.04-1.62,p = 0.02)以及三环类抗抑郁药阿米替林和氯米帕明(HR = 1.46,95% CI = 1.05-2.02,p = 0.024),代谢较慢与治疗突发躁狂症的风险增加有关。在一项关于CYP2C19代谢表型对双相抑郁症抗抑郁治疗影响的大型研究中,我们发现CYP2C19代谢较慢与治疗后出现躁狂症的风险较高之间存在关联,这是向个性化风险评估迈出的一步。然而,这与早期治疗的持续性、治疗的中断以及转用新的抗抑郁药之间没有明显的关联。
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Effect of CYP2C19 polymorphisms on antidepressant prescription patterns and treatment emergent mania in bipolar disorder
Antidepressant medication is used extensively to treat bipolar depression despite uncertain efficacy. The cytochrome P450 (CYP) 2C19 enzyme metabolize several antidepressants, and polymorphisms in the corresponding gene CYP2C19 influence plasma concentration and hence treatment outcomes in major depressive disorder. Here, we investigate if CYP2C19 polymorphisms are associated with antidepressant treatment patterns and the risk of mania when antidepressants are used in bipolar disorder. Two single nucleotide polymorphisms (rs4244285 and rs12248560) were used to classify 5019 bipolar disorder patients into CYP2C19 metabolic phenotypes ranging from poor to ultra-rapid metabolizers. We used Swedish national registry data 2005–2017 on dispensed medications and inpatient care to estimate risks for early-treatment persistence, treatment discontinuation, switching to a new antidepressant medication, and mania within 3 months of treatment initiation in patients treated with citalopram, escitalopram, sertraline, amitriptyline, and clomipramine. Metabolic phenotypes of CYP2C19 were not robustly associated with the investigated treatment outcomes based on dispense patterns. Slower metabolism was associated with an increased risk of treatment emergent mania for sertraline (hazard ratio [HR] = 1.3, 95% CI = 1.04–1.62, p = 0.02) and the tricyclic antidepressants amitriptyline and clomipramine (HR = 1.46, 95% CI = 1.05–2.02, p = 0.024). In a large study of the impact of CYP2C19 metabolic phenotypes on antidepressant treatment of bipolar depression, we found an association between slower CYP2C19 metabolism and higher risk of treatment emergent mania, which is a step towards personalized risk assessments. There were, however, no clear associations with early treatment persistence, treatment discontinuation, and switching to a new antidepressant.
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来源期刊
Pharmacogenomics Journal
Pharmacogenomics Journal 医学-药学
CiteScore
7.20
自引率
0.00%
发文量
35
审稿时长
6-12 weeks
期刊介绍: The Pharmacogenomics Journal is a print and electronic journal, which is dedicated to the rapid publication of original research on pharmacogenomics and its clinical applications. Key areas of coverage include: Personalized medicine Effects of genetic variability on drug toxicity and efficacy Identification and functional characterization of polymorphisms relevant to drug action Pharmacodynamic and pharmacokinetic variations and drug efficacy Integration of new developments in the genome project and proteomics into clinical medicine, pharmacology, and therapeutics Clinical applications of genomic science Identification of novel genomic targets for drug development Potential benefits of pharmacogenomics.
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