{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T13:30:13Z","timestamp":1777987813815,"version":"3.51.4"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2010analysis 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\u2010restricted maximum\u2010likelihood random\u2010effects 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\u2010cause mortality, and all\u2010cause discontinuation. Of 187 potentially eligible studies identified, 8 placebo\u2010controlled randomized controlled trials (<jats:italic>n<\/jats:italic>\u2009=\u2009587) were included. This updated meta\u2010analysis showed that ramelteon was associated with lower odds of delirium occurrence than placebo (0.50; 0.29\u22120.86; <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u200917.48%). 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 (<jats:italic>k<\/jats:italic>\u2009=\u20095; 0.28; 0.09\u22120.85; <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u200927.93%) and multiple dosage group (<jats:italic>k<\/jats:italic>\u2009=\u20095; 0.34; 0.14\u22120.82; <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u200944.24%) but not in the non\u2010elderly and non\u2010multiple 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\u2010group differences were found in the secondary outcomes. The current meta\u2010analysis provides updated and reliable evidence that ramelteon, in comparison with placebo, reduces the risk of delirium among hospitalized patients.<\/jats:p>","DOI":"10.1111\/jpi.12857","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T04:54:00Z","timestamp":1675313640000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Ramelteon for delirium prevention in hospitalized patients: An updated meta\u2010analysis and trial sequential analysis of randomized controlled trials"],"prefix":"10.1111","volume":"74","author":[{"given":"Chia\u2010Ling","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Pharmacy Chang\u2010Gung Memorial Hospital Linkou Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre F.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"IMPACT (Innovation in Mental and Physical Health and Clinical Treatment) Strategic Research Centre, School of Medicine, Barwon Health Deakin University Geelong Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trevor","family":"Thompson","sequence":"additional","affiliation":[{"name":"Centre for Chronic Illness and Ageing University of Greenwich London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzu\u2010Cheng","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Chang\u2010Gung Memorial Hospital Linkou Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping\u2010Tao","family":"Tseng","sequence":"additional","affiliation":[{"name":"Prospect Clinic for Otorhinolaryngology &amp; Neurology Kaohsiung City Taiwan"},{"name":"Department of Psychology, College of Medical and Health Science Asia University Taichung Taiwan"},{"name":"Institute of Biomedical Sciences National Sun Yat\u2010sen University Kaohsiung 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Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fu\u2010Chi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology National Defense Medical Centre, Tri\u2010Service General Hospital Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng\u2010Ho","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Kaohsiung Veterans General Hospital Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih\u2010Wei","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4136-1251","authenticated-orcid":false,"given":"Tien\u2010Wei","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry 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