Resolution of Selective Serotonin Reuptake Inhibitor-Associated Sexual Dysfunction After Switching From Fluvoxamine to Fluoxetine.
Resolution of Selective Serotonin Reuptake Inhibitor-Associated Sexual Dysfunction After Switching From Fluvoxamine to Fluoxetine.
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DOI：
10.1097/jcp.0000000000001636
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发表时间：
2023-01-01
影响因子：
2.9
通讯作者：
Javanbakht, Arash
中科院分区：
文献类型：
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作者：
Moses, Tabitha E. H.;Javanbakht, Arash
选择性5-羟色胺再摄取抑制剂（SSRIs）是一类药物，其主要作用机制是通过拮抗5-HT转运蛋白，从而抑制5-羟色胺再进入神经末梢并增加突触间隙中的5-羟色胺水平。虽然SSRIs最初用于治疗抑郁症，但它也显示出治疗一系列焦虑症和强迫症（OCD）的功效。2虽然SSRI药物类别的主要机制是5-羟色胺再摄取抑制，但基于5-羟色胺与去甲肾上腺素的选择性、消除半衰期、受体亲和力和对代谢的影响（例如，β-羟色胺抑制），药物类别内存在差异1，3; SSRI之间的这些微小机制差异有助于我们理解同一药物类别内药物的不同反应性。除了SSRIs之间的微小机制差异外，患者因素（如代谢、受体亚型和酶活性）存在个体差异，这可能导致不同的反应性和不良反应经历。4，5此外，SSRIs的影响不仅在行为和分子水平上因药物而异，而且这些影响也因药物给药时间的长短而异。性功能障碍是所有SSRIs的常见不良反应，这些药物相关的功能障碍甚至可能在停止治疗后继续存在。6性功能障碍主要有三种类型：性欲障碍（如性欲丧失）、性唤起障碍、性高潮和射精障碍。由于性方面的不良反应而停药被认为是治疗失败的主要因素，因此了解这些不良反应对于确保有效治疗至关重要。8估计表明，25%至73%的SSRI治疗的人将发展某种形式的性功能障碍;然而，一些SSRI可能更容易导致功能障碍。6，8，9一项多中心、前瞻性研究的结果发现，西酞普兰的性功能障碍发生率最高（72.7%），但其他SSRIs（包括氟伏沙明（62.3%）和氟西汀（57.7%））的发生率仍然很高，结果与类似研究一致。6，8，10，11虽然SSRIs和性功能障碍之间的关系背后的机制尚未完全理解，它被认为是，至少部分地，与5-HT结合到某些受体亚型的水平，6，9一个理论，这是由以下事实支持的SSRIs具有最高的5-HT选择性比率往往表现出较高的性功能障碍率。10
Selective serotonin reuptake inhibitors (SSRIs) are a class of medications whose primary mechanism of action is via antagonism of the 5-HT transporter, which results in the inhibition of serotonin reentry into nerve terminals and increased levels of serotonin in the synaptic cleft. 1 Although first used to treat depression, SSRIs have also shown efficacy in treating a range of anxiety disorders and obsessive-compulsive disorder (OCD). 2 Although the main mechanism of the SSRI drug class is serotonin reuptake inhibition, there are variations within the drug class based on selectivity for serotonin versus noradrenaline, elimination half-life, receptor affinity, and impact on metabolism (eg, CYP inhibition) 1, 3; these minor mechanistic differences across SSRIs contribute to our understanding of the differential responsiveness to medications within the same drug class. In addition to the minor mechanistic differences between the SSRIs, there are individual differences in patient factors such as metabolism, receptor subtypes, and enzymatic activity that can contribute to the differential responsiveness and experiences of adverse effects. 4, 5 Furthermore, not only does the impact of SSRIs vary between medications in the class at both the behavioral and molecular levels, but also these effects differ depending on length of medication administration.Sexual dysfunctions are a common adverse effect of all SSRIs, and these medication-associated dysfunctions may even continue after the cessation of treatment. 6 There are 3 main types of sexual dysfunction: disorders of sexual drive (eg, loss of libido), disorders of arousal, and disorders of orgasm and ejaculation. 7 Medication discontinuation due to sexual adverse effects is believed to be a major factor in treatment failure, so understanding these adverse effects is vital to ensuring effective treatment. 8 Estimates suggest that between 25% and 73% of people treated with an SSRI will develop some form of sexual dysfunction; however, some SSRIs may be more likely to cause dysfunction. 6, 8, 9 Results of a multicenter, prospective study found that incidence of sexual dysfunction was highest for citalopram (72.7%), but incidence was still high for other SSRIs including fluvoxamine (62.3%) and fluoxetine (57.7%), results that align with similar studies. 6, 8, 10, 11 Although the mechanism behind the relationship between SSRIs and sexual dysfunction is not yet fully understood, it is thought to be, at least in part, associated with the level of 5-HT binding to certain receptor subtypes, 6, 9 a theory that is supported by the fact that the SSRIs with the highest 5-HT selectivity ratios tend to demonstrate higher rates of sexual dysfunction. 10