Department of Psychiatry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Division of Neurology, Department of Medicine, Rajavithi Hospital, Department of Medical Services, Ministry of Public Health, Bangkok, Thailand.
Curr Neuropharmacol. 2022;20(10):1956-1968. doi: 10.2174/1570159X20666220507024219.
Although a previous review illustrated the efficacy of melatonin receptor agonists (MRAs) in preventing delirium, some recent randomized controlled trials (RCTs) did not confirm these effects.
This study systematically reviewed the efficacy, acceptability, and tolerability of MRAs for delirium prevention.
We searched electronic databases, including Scopus, PubMed, CINAHL, and Controlled Trials Register, from their inception to February 20, 2022. The primary efficacy outcome was delirium incidence rate after MRA administration; relative risks (RRs), overall discontinuation, and discontinuation due to adverse events are also presented.
The overall pooled incidence rates of delirium in MRA-treated and placebo-treated groups were significantly different with RR (95% CI)=0.66(0.52, 0.84, ), I2=59%. Similarly, the incidence rate was significantly lower in the melatonin-treated group than in the placebo-treated group [RR (95% CI) =0.65 (0.49, 0.88), I2=65%]. Unfortunately, incidence rates were not significantly different between ramelteon-treated and placebo-treated groups [RR (95% CI) =0.67 (0.42, 1.08), I2=50%]. The pooled incidence rate of delirium in either melatonin or ramelteon-treated groups was not significantly different from the placebo-treated group in elderly patients. The pooled incidence rate of delirium was significantly lower in the melatonin-treated group than in the benzodiazepinetreated group.
Based on this review, melatonin could prevent delirium with a small effect size. However, ramelteon did not show efficacy in preventing delirium. Additionally, neither melatonin nor ramelteon individually showed effectiveness in preventing delirium in elderly patients. Therefore, using MRAs to prevent delirium in clinical practice should be cautious. However, future welldefined and large sample size studies could verify these findings.
尽管之前的一项综述表明褪黑素受体激动剂（MRAs）在预防谵妄方面有效，但最近的一些随机对照试验（RCTs）并未证实这些效果。
本研究系统评价了 MRA 预防谵妄的疗效、可接受性和耐受性。
我们检索了电子数据库，包括 Scopus、PubMed、CINAHL 和对照试验登记处，检索时间从建库至 2022 年 2 月 20 日。主要疗效结局为 MRA 给药后谵妄发生率；还报告了相对风险（RR）、总体停药率和因不良反应停药率。
MRA 治疗组和安慰剂治疗组的谵妄总发生率差异具有统计学意义，RR（95%CI）=0.66（0.52，0.84），I2=59%。同样，褪黑素治疗组的发生率也明显低于安慰剂治疗组[RR（95%CI）=0.65（0.49，0.88），I2=65%]。不幸的是，ramelteon 治疗组和安慰剂治疗组的发生率差异无统计学意义[RR（95%CI）=0.67（0.42，1.08），I2=50%]。在老年患者中，褪黑素或 ramelteon 治疗组的谵妄发生率与安慰剂治疗组无显著差异。褪黑素治疗组的谵妄发生率明显低于苯二氮䓬类药物治疗组。
基于本综述，褪黑素对预防谵妄有较小的效果。然而，ramelteon 并未显示出预防谵妄的疗效。此外，褪黑素和 ramelteon 单独使用均不能预防老年患者的谵妄。因此，在临床实践中使用 MRA 预防谵妄应谨慎。然而，未来定义明确且样本量大的研究可能会验证这些发现。
