Ramelteon for delirium prevention in hospitalized patients: An updated meta‐analysis and trial sequential analysis of randomized controlled trials

Abstract

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; I2 = 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; I2 = 27.93%) and multiple dosage group (k = 5; 0.34; 0.14−0.82; I2 = 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.

Preventive Effects of Ramelteon, Suvorexant, and Lemborexant on Delirium in Hospitalized Patients With Physical Disease

“…Based on Green's report, 47 the target sample size was set to 810. The 14 variables used in this study included 11 variables that increase the risk of developing delirium, 1,48–51 and 3 sleep-inducing drugs (ramelteon, suvorexant, and lemborexant) that may prevent delirium 26,32,44,52 . The 14 explanatory variables and delirium incidence are summarized in Table 1.…”

Melatonin or its analogs as premedication to prevent emergence agitation in children: a systematic review and meta-analysis

“…Studies have confirmed that ramelteon has a superior receptor affinity and longer half-life than melatonin [ 13 ]. Ramelteon has demonstrated efficacy in reducing delirium risk among hospitalized adult patients [ 14 ]. Furthermore, in pediatric surgical settings, a clinical trial has explored ramelteon as a premedication to assess its potential to mitigate EA [ 15 ].…”