Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream enactment and the loss of muscle atonia during REM sleep, known as REM sleep without atonia (RSWA). RBD can result in significant injuries, prompting patients to seek medical attention. However, in others, it may present only as non-violent behaviors noted as an incidental finding during polysomnography (PSG). RBD typically occurs in the context of synuclein-based neurodegenerative disorders but can also be seen accompanying brain lesions and be exacerbated by medications, particularly antidepressants. There is also an increasing appreciation regarding isolated or idiopathic RBD (iRBD). Symptomatic treatment of RBD is a priority to prevent injurious complications, with usual choices being melatonin or clonazepam. The discovery that iRBD represents a prodromal stage of incurable synucleinopathies has galvanized the research community into delineating the pathophysiology of RBD and defining biomarkers of neurodegeneration that will facilitate future disease-modifying trials in iRBD. Despite many advances, there has been no progress in available symptomatic or neuroprotective therapies for RBD, with recent negative trials highlighting several challenges that need to be addressed to prepare for definitive therapeutic trials for patients with this disorder. These challenges relate to i) the diagnostic and screening strategies applied to RBD, ii) the limited evidence base for symptomatic therapies, (iii) the existence of possible subtypes of RBD, (iv) the relevance of triggering medications, (v) the absence of objective markers of severity, (vi) the optimal design of disease-modifying trials, and vii) the implications around disclosing the risk of future neurodegeneration in otherwise healthy individuals. Here, we review the current concepts in the therapeutics of RBD as it relates to the above challenges and identify pertinent research questions to be addressed by future work.

快速眼动 (REM) 睡眠行为障碍 (RBD) 的特点是在快速眼动睡眠期间做梦和肌张力丧失，称为无张力的快速眼动睡眠 (RSWA)。 RBD 可能会导致严重伤害，促使患者寻求医疗救助。然而，在其他情况下，它可能仅表现为非暴力行为，作为多导睡眠图 (PSG) 期间的偶然发现。 RBD 通常发生在基于突触核蛋白的神经退行性疾病中，但也可能伴随脑部病变出现，并因药物（尤其是抗抑郁药）而加剧。人们对孤立性或特发性RBD (iRBD) 的认识也日益提高。 RBD 的对症治疗是预防伤害性并发症的首要任务，通常选择褪黑激素或氯硝西泮。 iRBD 代表不可治愈的突触核蛋白病的前驱阶段这一发现激励研究界描述 RBD 的病理生理学并定义神经退行性变的生物标志物，这将有助于未来 iRBD 的疾病修饰试验。尽管取得了许多进展，但针对 RBD 的可用症状或神经保护疗法尚未取得进展，最近的阴性试验凸显了为为这种疾病患者进行明确的治疗试验做好准备需要解决的几个挑战。 这些挑战涉及 i) 适用于 RBD 的诊断和筛查策略，ii) 对症治疗的证据基础有限，(iii) RBD 可能亚型的存在，(iv) 触发药物的相关性，(v) 缺乏严重程度的客观标记，(vi) 疾病修饰试验的最佳设计，以及 vii) 披露健康个体未来神经退行性变风险的影响。在这里，我们回顾了 RBD 治疗学中与上述挑战相关的当前概念，并确定了未来工作需要解决的相关研究问题。