Oldham Mark A, Lander Heather L, Choi Joy J, Gloff Marjorie S, Knight Peter A, Nadler Jacob W
Department of Psychiatry, University of Rochester Medical Center, Rochester, NY.
Department of Anesthesiology and Perioperative Medicine, University of Rochester Medical Center, Rochester, NY.
J Acad Consult Liaison Psychiatry. 2025 May 13. doi: 10.1016/j.jaclp.2025.05.003.
No medication is currently approved either for the prevention or treatment of delirium despite its tremendous clinical impact. Sleep-wake disturbances offer a promising target for delirium therapeutics, with a growing body of literature suggesting a potential role of dual orexin receptor antagonists (DORAs).
This report provides a scoping review of the literature on DORAs for delirium and the results of a feasibility trial of daridorexant to prevent delirium after heart surgery.
We conducted a scoping review according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) for Scoping Reviews guidelines for peer-reviewed reports of DORAs for delirium. Next, we report sample characteristics and results for the feasibility aims from our single-site, double-blind, randomized placebo-controlled feasibility trial of daridorexant 50 mg given the first three nights after heart surgery to prevent delirium.
Our scoping review includes 30 reports: 4 case reports/series, 1 clinical effectiveness project, 22 retrospective cohort studies, and 3 clinical trials. This literature is authored almost exclusively by teams from Japan. Most publications are on suvorexant. Although published data suggest a potential role for DORAs to prevent delirium, they remain inconclusive. We demonstrate the feasibility of our study (n = 11). In this preliminary trial, daridorexant-arm subjects had a numerically lower mean delirium symptom burden on postoperative days 1-3.
The evidence in support of DORAs for delirium calls for adequately powered efficacy trials. We also emphasize the importance of considering the pharmacokinetics of DORAs for delirium to maximize potential benefit and minimize the risk of next-morning sedation.
尽管谵妄具有巨大的临床影响，但目前尚无药物被批准用于预防或治疗谵妄。睡眠-觉醒障碍为谵妄治疗提供了一个有前景的靶点，越来越多的文献表明双重食欲素受体拮抗剂（DORAs）可能发挥作用。
本报告对关于DORAs用于谵妄的文献进行了范围综述，并报告了一项关于达利度胺预防心脏手术后谵妄的可行性试验结果。
我们根据系统评价和Meta分析的首选报告项目（PRISMA）针对范围综述的指南，对关于DORAs用于谵妄的同行评审报告进行了范围综述。接下来，我们报告了我们单中心、双盲、随机安慰剂对照的可行性试验的样本特征和可行性目标结果，该试验在心脏手术后的前三个晚上给予50mg达利度胺以预防谵妄。
我们的范围综述包括30篇报告：4篇病例报告/系列、1项临床有效性项目、22项回顾性队列研究和3项临床试验。这些文献几乎全部由日本的团队撰写。大多数出版物是关于苏沃雷生的。尽管已发表的数据表明DORAs在预防谵妄方面可能发挥作用，但仍无定论。我们证明了我们研究（n = 11）的可行性。在这项初步试验中，达利度胺组受试者在术后第1 - 3天的谵妄症状负担在数值上较低。
支持DORAs用于谵妄的证据需要有足够效力的疗效试验。我们还强调了考虑DORAs用于谵妄的药代动力学以最大化潜在益处并最小化次晨镇静风险的重要性。
