Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Food and Drug Vice Presidency, Mashhad University of Medical Sciences, Mashhad, Iran.
Adv Exp Med Biol. 2021;1286:115-124. doi: 10.1007/978-3-030-55035-6_8.
Depression is a mental disorder and a major public health concern affecting millions of people worldwide. It is a common disorder that has been associated with several medical comorbidities often linked with aging, such as dementia, type II diabetes, cardiovascular and cerebrovascular diseases, as well as metabolic syndrome. There are a variety of medications available for depression treatment. Selective serotonin reuptake inhibitors (SSRIs) are one of the antidepressant drug classes that are most widely used to treat depressive disorders and depressive symptoms in other diseases. Due to many contradictory findings on the adverse effects and toxicities of SSRIs (especially genotoxicities), we reviewed the genotoxic effects of these drugs. Based on the guidelines proposed in the PRISMA statement, we performed a systematic review by searching international electronic databases including PubMed, Scopus, Embase, and Web of Science to find the published documents on SSRIs and their genotoxic effects from January 1990 to November 2019. After the removal of 203 duplicate articles, 385 articles were screened and 167 articles met the inclusion criteria and qualified for evaluation of their full texts. After this, 26 articles were appropriate for final review. This revealed that the proportion of genotoxicities was highest for citalopram and fluoxetine, with a smaller proportion for sertraline. Limited documentations showed genotoxic and partial genotoxic effects for paroxetine and escitalopram, respectively. Although a number of studies have found genotoxic effects of SSRIs, there are also some factors including doses, duration of exposure, model of experiments, and the type of technique assay that may affect the results.
抑郁症是一种精神障碍，也是一个全球性的重大公共卫生问题，影响着全球数以百万计的人。它是一种常见的疾病，与许多与衰老相关的医学合并症有关，如痴呆、2 型糖尿病、心血管和脑血管疾病以及代谢综合征。有多种药物可用于治疗抑郁症。选择性 5-羟色胺再摄取抑制剂（SSRIs）是最广泛用于治疗抑郁症和其他疾病中抑郁症状的抗抑郁药类别之一。由于 SSRIs（尤其是遗传毒性）的不良反应和毒性存在许多相互矛盾的发现，我们回顾了这些药物的遗传毒性作用。根据 PRISMA 声明提出的指南，我们通过搜索国际电子数据库（包括 PubMed、Scopus、Embase 和 Web of Science），对从 1990 年 1 月至 2019 年 11 月发表的关于 SSRIs 及其遗传毒性作用的已发表文件进行了系统评价。在去除 203 篇重复文章后，筛选了 385 篇文章，其中 167 篇文章符合纳入标准，并符合评估其全文的标准。之后，有 26 篇文章适合最终审查。结果表明，西酞普兰和氟西汀的遗传毒性比例最高，舍曲林的比例较小。对于帕罗西汀和依地普仑，有限的文献分别显示出遗传毒性和部分遗传毒性作用。尽管许多研究发现了 SSRIs 的遗传毒性作用，但也存在一些因素，包括剂量、暴露持续时间、实验模型和技术测定类型，这些因素可能会影响结果。
