Effects of the Serotonin 1A, 2A, 2C, 3A, and 3B and Serotonin Transporter Gene Polymorphisms on the Occurrence of Paroxetine Discontinuation Syndrome
Effects of the Serotonin 1A, 2A, 2C, 3A, and 3B and Serotonin Transporter Gene Polymorphisms on the Occurrence of Paroxetine Discontinuation Syndrome
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DOI：
10.1097/jcp.0b013e3181c8ae80
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发表时间：
2010-02-01
影响因子：
2.9
通讯作者：
Mine, Kazunori
中科院分区：
文献类型：
--
作者：
Murata, Yusuke;Kobayashi, Daisuke;Mine, Kazunori
帕罗西汀停药症状有时可能严重到降低生活质量。然而，目前无法在开始或停止帕罗西汀治疗之前预测停药综合征的发生。在本研究中，我们研究了血清素 1A、2A、2C、3A 和 3B 受体、血清素转运蛋白和细胞色素 P450 2D6 (CYP2D6) 基因的遗传多态性对帕罗西汀停药综合征发生的影响。根据《精神疾病诊断与统计手册》第四版，连续对 56 名被诊断为重度抑郁症或焦虑症的日本患者进行了帕罗西汀治疗。通过直接访谈发现 35.7% 的患者存在帕罗西汀停药综合征。突然停止服用帕罗西汀的患者比逐渐减少药物剂量的患者更容易出现帕罗西汀停药综合征。具有 -1019C 等位基因的患者比具有 5-羟色胺 1A 受体基因 -1019G 纯合子（名义 P = 0.0423）的患者更频繁地经历帕罗西汀停药综合征。然而，经过 Bonferroni 校正进行多重比较后，这一结果不再显着。研究结果提示，突然停药是帕罗西汀停药综合征发生的主要危险因素，血清素1A受体基因C(-1019)G多态性可能与该综合征的发生有关。
Paroxetine discontinuation symptoms can at times be severe enough to reduce the quality of life. However, it is currently not possible to predict the occurrence of discontinuation syndrome before the initiation or discontinuation of paroxetine treatment. In this study, we investigated the effects of genetic polymorphisms in the serotonin 1A, 2A 2C, 3A, and 3B receptor, the serotonin transporter, and the cytochrome P450 2D6 (CYP2D6) genes on the occurrence of paroxetine discontinuation syndrome. A consecutive series of 56 Japanese patients who had a diagnosis of major depressive or anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were treated with paroxetine. Paroxetine discontinuation syndrome was found in 35.7% of the patients by direct interview. Patients who stopped taking paroxetine abruptly experienced paroxetine discontinuation syndrome significantly more often than patients who had a tapering off of the dosage of medication. Patients who had the -1019C allele experienced paroxetine discontinuation syndrome more frequently than patients who had the -1019G homozygote (nominal P = 0.0423) of the serotonin 1A receptor gene. However, this result did not remain significant after the Bonferroni correction for multiple comparisons. The findings suggest that the abrupt stoppage of medication is a major risk factor for the occurrence of paroxetine discontinuation syndrome and that C(-1019)G polymorphism of the serotonin 1A receptor gene may be related to the occurrence of the syndrome.