Yu Chia-Ling, Carvalho Andre F, Thompson Trevor, Tsai Tzu-Cheng, Tseng Ping-Tao, Tu Yu-Kang, Yang Szu-Nian, Yang Fu-Chi, Chang Cheng-Ho, Hsu Chih-Wei, Hsu Tien-Wei, Liang Chih-Sung
Department of Pharmacy, Chang-Gung Memorial Hospital, Linkou, Taiwan.
IMPACT (Innovation in Mental and Physical Health and Clinical Treatment) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, Victoria, Australia.
J Pineal Res. 2023 Apr;74(3):e12857. doi: 10.1111/jpi.12857. Epub 2023 Feb 8.
Although ramelteon has been examined as a relatively new therapeutic option for delirium prevention, current evidence to evaluate its efficacy is limited. We conducted an updated meta-analysis and examine the reliability of existing evidence regarding the effect of ramelteon on delirium prevention in hospitalized patients. Seven major electronic databases were systematically searched to identify randomized controlled trials examining the efficacy of ramelteon in delirium prevention. Data were pooled using a frequentist-restricted maximum-likelihood random-effects model. A trial sequential analysis was performed using relative risk reduction thresholds of 50%. The primary outcome was the incidence of delirium (reported as odds ratio with 95% confidence intervals). The secondary outcomes were the days of delirium, all-cause mortality, and all-cause discontinuation. Of 187 potentially eligible studies identified, 8 placebo-controlled randomized controlled trials (n = 587) were included. This updated meta-analysis showed that ramelteon was associated with lower odds of delirium occurrence than placebo (0.50; 0.29-0.86; I = 17.48%). In trial sequential analysis, the effect of ramelteon across the superiority boundary when using a relative risk reduction threshold ranging from 40% to 60%. In subgroup analyses, ramelteon compared with placebo was associated with lower odds of delirium occurrence in the elderly group (k = 5; 0.28; 0.09-0.85; I = 27.93%) and multiple dosage group (k = 5; 0.34; 0.14-0.82; I = 44.24%) but not in the non-elderly and non-multiple dosage groups. When considering surgical patients and medical patients separately, ramelteon showed a trend in the treatment of delirium prevention in both groups, while these findings were not statistically significant. No significant between-group differences were found in the secondary outcomes. The current meta-analysis provides updated and reliable evidence that ramelteon, in comparison with placebo, reduces the risk of delirium among hospitalized patients.
尽管雷美替胺作为一种预防谵妄的相对较新的治疗选择已被研究，但目前评估其疗效的证据有限。我们进行了一项更新的荟萃分析，并检验了现有证据关于雷美替胺对住院患者预防谵妄效果的可靠性。系统检索了七个主要电子数据库，以识别检验雷美替胺预防谵妄疗效的随机对照试验。使用频率学派限制最大似然随机效应模型汇总数据。使用50%的相对风险降低阈值进行试验序贯分析。主要结局是谵妄的发生率（报告为比值比及95%置信区间）。次要结局是谵妄天数、全因死亡率和全因停药率。在识别出的187项潜在合格研究中，纳入了8项安慰剂对照随机对照试验（n = 587）。这项更新的荟萃分析表明，与安慰剂相比，雷美替胺发生谵妄的几率更低（0.50；0.29 - 0.86；I² = 17.48%）。在试验序贯分析中，当使用40%至60%的相对风险降低阈值时，雷美替胺的效应跨越了优效性边界。在亚组分析中，与安慰剂相比，雷美替胺在老年组（k = 5；0.28；0.09 - 0.85；I² = 27.93%）和多剂量组（k = 5；0.34；0.14 - 0.82；I² = 44.24%）中发生谵妄的几率更低，但在非老年组和非多剂量组中并非如此。当分别考虑外科患者和内科患者时，雷美替胺在两组预防谵妄的治疗中均显示出一种趋势，而这些发现无统计学意义。在次要结局方面未发现组间显著差异。当前的荟萃分析提供了更新且可靠的证据，表明与安慰剂相比，雷美替胺可降低住院患者发生谵妄的风险。
