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孕妇使用选择性5-羟色胺再摄取抑制剂;药物遗传学、药物相互作用及不良反应

Selective serotonin reuptake inhibitor use in pregnant women; pharmacogenetics, drug-drug interactions and adverse effects.

作者信息

Ornoy Asher, Koren Gideon

机构信息

a Laboratory of Teratology, Department of Medical Neurobiology , Hebrew University Hadassah Medical School , Jerusalem , Israel.

b Morris Kahn- Maccabi Institute of Research and Innovation, and Tel Aviv University , TEl - AVIV , Israel.

出版信息

Expert Opin Drug Metab Toxicol. 2018 Mar;14(3):247-259. doi: 10.1080/17425255.2018.1430139. Epub 2018 Jan 24.

Abstract

Possible negative effects of selective serotonin reuptake inhibitors (SSRIs) in pregnancy relate to congenital anomalies, negative perinatal events and neurodevelopmental outcome. Many studies are confounded by the underlying maternal disease and by pharmacogenetic and pharmacokinetic differences of these drugs. Areas covered: The possible interactions of SSRIs and serotonin and norepinephrine reuptake inhibitors with other drugs and the known effects of SSRIs on congenital anomalies, perinatal and neurodevelopmental outcome. Expert opinion: SSRIs should be given with caution when combined with other drugs that are metabolized by cytochrome P450 enzymes. SSRIs apparently increase the rate of severe cardiac malformations, induce neonatal adaptation problems in up to 30% of the offspring, increase the rate of persistent pulmonary hypertension of the newborn and possibly slightly increase the rate of prematurity and low birth weight. Most neurodevelopmental follow up studies did not find significant cognitive impairments except some transient gross motor delay, slight impairment of language abilities and possibly behavioral changes. The literature on the possible association of SSRIs with autism spectrum disorder is inconsistent; if an association exists, it is apparently throughout pregnancy. The risk associated with treatment discontinuation seems to outweigh the risk of treatment, as severe maternal depression may negatively affect the child's development. If needed, treatment should continue in pregnancy with the minimal effective dose.

摘要

选择性5-羟色胺再摄取抑制剂(SSRI)在孕期可能产生的负面影响与先天性异常、围产期不良事件及神经发育结局有关。许多研究因潜在的母体疾病以及这些药物的药物遗传学和药代动力学差异而受到干扰。涵盖领域:SSRI以及5-羟色胺和去甲肾上腺素再摄取抑制剂与其他药物之间可能的相互作用,以及SSRI对先天性异常、围产期和神经发育结局的已知影响。专家观点:当与细胞色素P450酶代谢的其他药物联用时,应谨慎使用SSRI。SSRI明显增加严重心脏畸形的发生率,在高达30%的后代中诱发新生儿适应问题,增加新生儿持续性肺动脉高压的发生率,并可能略微增加早产和低出生体重的发生率。除了一些短暂的大运动发育迟缓、语言能力轻度受损以及可能的行为改变外,大多数神经发育随访研究未发现明显的认知障碍。关于SSRI与自闭症谱系障碍可能关联的文献并不一致;如果存在关联,显然贯穿整个孕期。与停药相关的风险似乎超过治疗风险,因为严重的母体抑郁可能对儿童发育产生负面影响。如有必要,孕期应继续使用最低有效剂量进行治疗。

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