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首页> 外文期刊>European Journal of Pharmacology: An International Journal >Treatment of cognitive dysfunction in major depressive disorder-a review of the preclinical evidence for efficacy of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors and the multimodal-acting antidepressant vortioxetine
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Treatment of cognitive dysfunction in major depressive disorder-a review of the preclinical evidence for efficacy of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors and the multimodal-acting antidepressant vortioxetine

机译：重型抑郁症认知功能障碍的治疗-选择性5-羟色胺再摄取抑制剂，5-羟色胺-去甲肾上腺素再摄取抑制剂和多模式作用的抗抑郁药vortioxetine疗效的临床前证据综述

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Although major depressive disorder is primarily considered a mood disorder, depressed patients commonly present with clinically significant cognitive dysfunction that may add to their functional disability. This review paper summarizes the available preclinical data on the effects of antidepressants, including monoamine reuptake inhibitors and the multimodal antidepressant vortioxetine, in behavioral tests of cognition such as cognitive flexibility, attention, and memory, or in potentially cognition-relevant mechanistic assays such as electroencephalography, in vivo microdialysis, in vivo or in vitro electrophysiology, and molecular assays related to neurogenesis or synaptic sprouting. The available data are discussed in context with clinically relevant doses and their relationship to target occupancy levels, in order to evaluate the translational relevance of preclinical doses used during testing. We conclude that there is preclinical evidence suggesting that traditional treatment with monoamine reuptake inhibitors can induce improved cognitive function, for example in cognitive flexibility and memory, and that the multimodal-acting antidepressant vortioxetine may have some advantages by comparison to these treatments. However, the translational value of the reviewed preclinical data can be questioned at times, due to the use of doses outside the therapeutically-relevant range, the lack of data on target engagement or exposure, the tendency to investigate acute rather than long term antidepressant administration, and the trend towards using normal rodents rather than models with translational relevance for depression. Finally, several suggestions are made for advancing this field, including expanded use of target occupancy assessments in preclinical and clinical experiments, and the use of translationally valuable techniques such as electroencephalography. (C) 2014 The Authors. Published by Elsevier B.V.
机译：尽管主要的抑郁症主要被认为是一种情绪障碍，但抑郁症患者通常表现出具有临床意义的认知功能障碍，可能会加重其功能障碍。这篇综述总结了抗抑郁药（包括单胺再摄取抑制剂和多峰抗抑郁药vortioxetine）在认知行为测试（例如认知灵活性，注意力和记忆力）中或在与认知相关的机制分析（如脑电图）中可获得的临床前数据。 ，体内微透析，体内或体外电生理学以及与神经发生或突触发芽有关的分子测定。为了评估测试期间使用的临床前剂量的翻译相关性，将在临床上相关剂量及其与目标占用水平的关系的背景下讨论可用数据。我们得出的结论是，有临床前证据表明，传统的单胺再摄取抑制剂治疗可以诱导改善的认知功能，例如在认知柔韧性和记忆力方面，与这些治疗相比，多模式抗抑郁药伏替西汀具有某些优势。但是，由于使用了治疗相关范围之外的剂量，缺乏有关靶点参与或暴露的数据，倾向于研究急性而非长期服用抗抑郁药的趋势，有时可能会质疑所审查的临床前数据的翻译价值。 ，以及使用正常啮齿动物而不是使用具有平移相关性的模型来治疗抑郁症的趋势。最后，提出了一些促进该领域发展的建议，包括在临床前和临床实验中扩大目标占用率评估的使用，以及使用诸如脑电图等具有翻译价值的技术。 （C）2014作者。由Elsevier B.V.发布

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