Depression, the most frequent psychiatric disorder following ischaemic stroke, negatively affects survivals' functional outcome, response to rehabilitation and quality of life. Approximately, one-third of them are affected by post-stroke depression (PSD), making it a serious social and public health problem and anti-depressant preventive and curative therapies worth investigating. However, a two-way association between depression and stroke has been also established: stroke increases the risk of PSD, but depression is an independent risk factor for stroke.

The pathophysiology of PSD is presumably multifactorial, involving a combination of various ischaemia-induced neurobiological dysfunctions in the context of psychosocial distress. The damage of frontal-basal ganglia brainstem pathway suggested alterations of monoaminergic neurotransmitter systems. Several lines of evidence point to a relationship between neuroinflammatory response to acute ischaemic stroke, stress activation of the hypothalamic-pituitary-adrenal (HPA) axis and the impairment of adaptive response (neurogenesis) within a background of altered energy metabolism (i.e. mitochondrial dysfunction).

The complexity of PSD mechanisms makes its biologically-based prevention and treatment a difficult task. So far, especially the selective serotonin (5-hydroxytriptamine, 5-HT) reuptake inhibitors (SSRIs) have mainly proved to be clinically active in preventing and treating PSD, although their effects have not been demonstrated unequivocally and they may cause bleeding and intracerebral haemorrhage. Besides the primary pharmacological activity of SSRIs (i.e. the inhibition of neuronal 5-HT reuptake) there is evidence supporting their pleiotropic mechanisms of action: anti-inflammatory and enhanced neurogenesis through the up-regulation of neurotrophins, conceivably supported by the stimulation of mitochondrial energy metabolism.

In the future, novel developments might point at anti-cytokine modulators which can improve symptoms of depression, especially in subjects affected by inflammation processes.

This review will address the various areas of epidemiology, pathophysiology, preventive and therapeutic strategies for PSD. The activity of SSRIs in clinical trials, as well as their pharmacology, pharmacokinetics, safety and mechanisms of action, will be examined in detail. A final section will deal with the effect of depression as risk factor for stroke. The literature on PubMed from 1990 to 2017 was reviewed.

抑郁症是缺血性中风后最常见的精神疾病，会对存活者的功能预后，对康复的反应和生活质量产生负面影响。大约有三分之一的人患有中风后抑郁症（PSD），这使其成为一个严重的社会和公共健康问题以及值得研究的抗抑郁药的预防和治疗方法。然而，抑郁症和中风之间也建立了双向关联：中风会增加PSD的风险，但是抑郁症是中风的独立危险因素。

PSD的病理生理学可能是多因素的，在社会心理困扰的情况下涉及各种缺血引起的神经生物学功能障碍。额-基底神经节脑干通路的损伤提示单胺能神经递质系统发生改变。有几条证据表明，在能量代谢改变（即线粒体功能障碍）的背景下，对急性缺血性中风的神经炎症反应，下丘脑-垂体-肾上腺（HPA）轴的应力激活与适应性反应（神经发生）的损害之间存在关联。。

PSD机制的复杂性使其基于生物学的预防和治疗成为一项艰巨的任务。迄今为止，尽管没有明确证实其作用，并且特别是选择性5-羟色胺（5-羟三甲胺，5-HT）再摄取抑制剂（SSRIs）在临床上已被证明在预防和治疗PSD方面具有临床活性，但它们可能会引起出血和脑出血。除了SSRIs的主要药理活性（即抑制神经元5-HT再摄取）外，有证据支持它们的多效性作用机制：通过上调神经营养蛋白（可能是通过刺激线粒体能量来支持）来消炎和增强神经发生。代谢。

将来，新的发展可能指向抗细胞因子调节剂，它可以改善抑郁症的症状，尤其是在受炎症过程影响的受试者中。

这篇综述将探讨PSD的流行病学，病理生理学，预防和治疗策略的各个领域。将详细检查SSRI在临床试验中的活性及其药理学，药代动力学，安全性和作用机理。最后一部分将探讨抑郁症作为中风危险因素的影响。回顾了1990年至2017年有关PubMed的文献。