Preventative effects of ramelteon against postoperative delirium after elective liver resection

Kongsaengdao

et al. 2022

Background: 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. Objectives: This study systematically reviewed the efficacy, acceptability, and tolerability of MRAs for delirium prevention. Materials and Methods: 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. Results: 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 of either Melatonin- or Ramelteon--the treated group 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 benzodiazepine-treated group. Conclusion: Based on this review, Melatonin, could prevent delirium with a small effect size. However, Ramelteon did not show efficacy in preventing delirium. Additionally, either Melatonin or Ramelteon individually, did not show effectiveness in preventing delirium in elderly patients. Therefore, using MRAs to prevent delirium in clinical practice should be cautious. However, future well-defined and large sample size studies could verify these findings.

Section: Resultsmentioning

confidence: 99%

Melatonin Receptor Agonists for the Prevention of Delirium: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

Kongsaengdao

et al. 2022

“…Risk factors for delirium development were calculated using adjusted odds ratios (aORs) via multivariate logistic regression analysis. Based on previous reports, 39,42 a post-hoc analysis of surgical cases in which ramelteon was used was performed, as the efficacy of ramelteon in preventing delirium may differ depending on the surgical setting and patient characteristics. All statistical analyses were conducted using JMP Pro 16 software (SAS Institute, Cary, NC).…”

Section: Discussionmentioning

confidence: 99%

“…35 Moreover, ramelteon has been reported to be effective in preventing delirium in older adults, 36,37 ICU patients, 38 and patients who have undergone hepatectomy according to a retrospective study. 39 However, meta-analyses have reported that ramelteon exhibits a limited effect on preventing delirium, 40,41 and no consistent findings have been obtained regarding its effectiveness in preventing delirium. There are two interesting reports on the prevention of postoperative delirium with ramelteon.…”

mentioning

confidence: 99%

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

Henmi,

Nakamura,

Mashimoto

et al. 2024

J Clin Psychopharmacol

Background New sleep-inducing drugs (eg, ramelteon, suvorexant, and lemborexant) have been shown to prevent delirium in high-risk groups. However, no single study has simultaneously evaluated the delirium-preventing effects of all novel sleep-inducing drugs in hospitalized patients. Therefore, this study aimed to clarify the relationship between sleep-inducing drugs and delirium prevention in patients hospitalized in general medical-surgical settings for nonpsychiatric conditions who underwent liaison interventions for insomnia. Methods This retrospective cohort study included patients treated in general medical-surgical settings for nonpsychiatric conditions with consultation-liaison psychiatry consult for insomnia. Delirium was diagnosed by fully certified psychiatrists using the Diagnostic and Statistical Manual of Mental Disorders 5th edition. The following items were retrospectively examined from medical records as factors related to delirium development: type of sleep-inducing drugs, age, sex, and delirium risk factors. The risk factors of delirium development were calculated using adjusted odds ratios (aORs) via multivariate logistic regression analysis. Results Among the 710 patients analyzed, 257 (36.2%) developed delirium. Suvorexant (aOR, 0.61; 95% confidence interval [CI], 0.40–0.94; P = 0.02) and lemborexant (aOR, 0.23; 95% CI, 0.14–0.39; P < 0.0001) significantly reduced the risk of developing delirium. Benzodiazepines (aOR, 1.90; 95% CI, 1.15–3.13; P = 0.01) significantly increased this risk. Ramelteon (aOR, 1.30; 95% CI, 0.84–2.01; P = 0.24) and Z-drugs (aOR, 1.27; 95% CI, 0.81–1.98; P = 0.30) were not significantly associated with delirium development. Conclusions The use of suvorexant and lemborexant may prevent delirium in patients with a wide range of medical conditions.

“…Based on previous data, it was estimated that 400 patients would be required to confirm these effects with an α of 5% and 80% power. Further assuming a 10% loss to follow up, 497 patients were enrolled [Hokuto 2020]. A research nurse entered all baseline and outcome data in the study database.…”

Section: Discussionmentioning

confidence: 99%

Effects of Melatonin for Delirium in Elderly Acute Heart Failure Patients: A Randomized, Single-Center, Double-Blind, and Placebo-Controlled Trial

Yin

Liu

et al. 2022

HSF

Background: Delirium is a common, life-threatening, typical clinical syndrome with the main clinical manifestations of temporary organic mental disorder without specific drug treatment. The aim of the study was to explore the benefits of melatonin for the treatment of delirium after acute heart failure in elderly patients. Methods: This was a randomized, double-blind, and placebo-controlled trial. This study enrolled patients aged more than 60 years after acute heart failure. A computer-generated randomization sequence (in a 1:1 ratio) was used to randomly assign patients to receive either melatonin (3 mg/day, 7 days) or placebos. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method during the first 7 days. Analyses were performed by intention-to-treat and safety populations. Results: Between October 2015 and October 2019, 584 patients were assessed. A total of 497 patients randomly were assigned to receive either placebo (N = 249) or melatonin (N = 248). The incidence of delirium was significantly lower in the melatonin group than in the placebo group (27.0% vs. 36.9%, P = 0.021). Regarding safety, the occurrence of rhabdomyolysis and abnormal hepatic function did not differ between the two groups. Conclusion: The current study (clinical trial registered number: CHWX-904-201511) suggests that acute melatonin treatment can reduce the incidence of delirium for elderly acute heart failure. It also can reduce the time of hospital stays and hospitalization costs. The therapy was safe and worth spreading.