Orexin is a neurotransmitter produced by a small group of hypothalamic neurons. Besides its well-known role in the regulation of the sleep-wake cycle, the orexin system was shown to be relevant in several physiological functions including cognition, mood and emotion modulation, and energy homeostasis. Indeed, the implication of orexin neurotransmission in neurological and psychiatric diseases has been hypothesized via a direct effect exerted by the projections of orexin neurons to several brain areas, and via an indirect effect through orexin-mediated modulation of sleep and wake. Along with the growing evidence concerning the use of dual orexin receptor antagonists (DORAs) in the treatment of insomnia, studies assessing their efficacy in insomnia comorbid with psychiatric and neurological diseases have been set in order to investigate the potential impact of DORAs on both sleep-related symptoms and disease-specific manifestations. This narrative review aimed at summarizing the current evidence on the use of DORAs in neurological and psychiatric conditions comorbid with insomnia, also discussing the possible implication of modulating the orexin system for improving the burden of symptoms and the pathological mechanisms of these disorders. Target searches were performed on PubMed/MEDLINE and Scopus databases and ongoing studies registered on Clinicaltrials.gov were reviewed. Despite some contradictory findings, preclinical studies seemingly support the possible beneficial role of orexin antagonism in the management of the most common neurological and psychiatric diseases with sleep-related comorbidities. However, clinical research is still limited and further studies are needed for corroborating these promising preliminary results.

食欲素是由一小群下丘脑神经元产生的神经递质。除了众所周知的调节睡眠-觉醒周期的作用外，食欲素系统还被证明与多种生理功能相关，包括认知、情绪和情绪调节以及能量稳态。事实上，食欲素神经传递在神经和精神疾病中的意义已经被假设为通过食欲素神经元投射到几个大脑区域所产生的直接作用，以及通过食欲素介导的睡眠和觉醒调节的间接作用。随着越来越多的证据表明使用双重食欲素受体拮抗剂（DORA）治疗失眠，评估其治疗伴有精神和神经系统疾病的失眠的疗效的研究已经开始，以调查 DORA 对睡眠和睡眠的潜在影响。相关症状和疾病特异性表现。这篇叙述性综述旨在总结目前使用 DORA 治疗伴有失眠的神经和精神疾病的证据，并讨论调节食欲素系统对改善症状负担和这些疾病的病理机制的可能意义。在 PubMed/MEDLINE 和 Scopus 数据库上进行目标搜索，并对在ClinicalTrials.gov上注册的正在进行的研究进行审查。尽管存在一些相互矛盾的发现，但临床前研究似乎支持食欲素拮抗剂在治疗具有睡眠相关合并症的最常见神经和精神疾病中可能发挥的有益作用。然而，临床研究仍然有限，需要进一步的研究来证实这些有希望的初步结果。