Common selective serotonin reuptake inhibitor side effects in older adults associated with genetic polymorphisms in the serotonin transporter and receptors: data from a randomized controlled trial.
Common selective serotonin reuptake inhibitor side effects in older adults associated with genetic polymorphisms in the serotonin transporter and receptors: data from a randomized controlled trial.
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老年人中常见的选择性血清素再摄取抑制剂副作用与血清素转运蛋白和受体的遗传多态性相关：来自随机对照试验的数据。
DOI：
10.1016/j.jagp.2013.07.003
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Lenze,EricJ
中科院分区：
文献类型：
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作者：
Garfield,LaurenD;Dixon,David;Nowotny,Petra;Lotrich,FrancisE;Pollock,BruceG;Kristjansson,SeanD;Doré,PeterM;Lenze,EricJ
目的抗抑郁药的副作用是一个重要的公共卫生问题，与依从性差，过早停止治疗和在罕见的情况下严重的伤害。这对老年人尤其重要，他们承担着最大和最严重的药物副作用负担。我们研究了在焦虑的老年人中，抗抑郁药副作用与5-羟色胺系统遗传变异之间的相关性，这些老年人参加了SSRI依他普仑的随机、安慰剂对照试验。方法将年龄≥ 60岁的成年人（n=177）随机接受活性药物治疗或安慰剂治疗12周。使用UKU副作用评定量表评估副作用。遗传多态性是5-羟色胺转运体和1A和2A受体（分别为5-HTTLPR（L/S + rs 25531）、HTR 1A rs6295、HTR 2A rs6311）启动子中的推定功能变体。结果发现四种药物与安慰剂的副作用差异，包括睡眠时间延长、口干、腹泻和性欲下降。使用假定的高与低转录基因型分组的分析揭示了6种药物遗传学效应：5-羟色胺转运蛋白的低表达和高表达基因型分别导致口干和性欲下降，1A受体的低转录基因型导致腹泻加重。性欲减退在高表达基因型和5-羟色胺转运体1A或2A受体的患者中明显更多。药物浓度和副作用之间没有显著关系，低表达和高表达基因型之间的药物浓度也没有平均差异。结论5-HT系统的遗传变异可以预测谁会出现常见的SSRI副作用及其原因。需要更多的工作来进一步表征这种遗传调节，并将研究结果转化为对更个性化的患者护理有用的策略。
Objective Antidepressant side-effects are a significant public health issue, associated with poor adherence, premature treatment discontinuation and in rare cases significant harm. This is especially relevant for older adults, who assume the largest and most serious burden of medication side-effects. We investigated the association between antidepressant side-effects and genetic variation in the serotonin system in anxious, older adults participating in a randomized, placebo-controlled trial of the SSRI escitalopram. Method Adults (n=177) aged ≥ 60 years were randomized to active treatment or placebo for 12-weeks. Side-effects were assessed using the UKU side effect rating scale. Genetic polymorphisms were putative functional variants in the promoters of the serotonin transporter and 1A and 2A receptors (5-HTTLPR (L/S + rs25531), HTR1A rs6295, HTR2A rs6311, respectively). Results Four significant drug-placebo side-effect differences were found, including increased duration of sleep, dry mouth, diarrhea and diminished sexual desire. Analyses using putative high- vs low-transcription genotype groupings revealed 6 pharmacogenetic effects: greater dry mouth and decreased sexual desire for the low- and high-expressing genotypes of the serotonin transporter, respectively, and greater diarrhea with the low-transcription genotype of the 1A receptor. Diminished sexual desire was experienced significantly more in those with high-expressing genotype and either the serotonin transporter, 1A or 2A receptors. There was not a significant relationship between drug concentration and side-effects nor a mean difference in drug concentration between low- and high-expressing genotypes. Conclusion Genetic variation in the 5HT system may predict who develops common SSRI side-effects and why. More work is needed to further characterize this genetic modulation and to translate research findings into strategies useful for more personalized patient care.