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Corresponding author: Kotaro HattaDepartment of Psychiatry, Juntendo University Nerima Hospital3-1-10 Takanodai, Nerima-ku, Tokyo 177-8521, JapanTEL: +81-3-5923-3111　E-mail: khatta@juntendo.ac.jp354th Triannual Meeting of the Juntendo Medical Society “Recent topics in Psychiatry” 〔Held on sep. 9, 2021〕〔Received　Nov. 3, 2021〕〔Accepted　Nov. 10, 2021〕J-STAGE Advance published date: Feb. 4, 2022Copyright © 2022 The Juntendo Medical Society. This is an open access article distributed under the terms of Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original source is properly credited. doi: 10.14789/jmj.JMJ21-0035-R　The fundamental conception of delirium is altered arousal. In addition, sleep-wake cycle disturbances including insomnia, excessive daytime napping, and disintegration of the expected circadian patterns have been described as a characteristic component of delirium for decades, and demonstrated to be a core symptom domain of delirium. Although non-pharmacological interventions are successful to some extent, they have limitations due to various biological etiologies for delirium. Among pharmacological interventions, antipsychotics seem to be effective, but they are not suitable for preventive use because of relatively frequent side-effects such as extrapyramidal symptoms. Recently, new type of drugs for insomnia have been focused with respect to delirium prevention. Recent meta-analyses show effectiveness of melatonin receptor agonists and orexin receptor antagonists for delirium prevention, and real-world data support them.12Juntendo Medical Journal2022. 68(1), 12-16Special ReviewsPrevention of Delirium Via Melatonin and Orexin Neurotransmission1. IntroductionThe fundamental conception of delirium is altered arousal1). In addition, sleep-wake cycle disturbances including insomnia, excessive daytime napping, and disintegration of the expected circa-dian patterns have been described as a character-istic component of delirium for decades, and demon-strated to be a core symptom domain of delirium2). Although non-pharmacological interventions are successful to some extent3), they have limitations due to various biological etiologies for delirium. Among pharmacological interventions, antipsy-chotics seem to be effective, but they are not suit-able for preventive use because of relatively frequent side-effects such as extrapyramidal symp-toms. Recently, new type of drugs for insomnia have been focused with respect to delirium preven-tion.Key words: delirium, melatonin, orexin, prevention, sleep-wake cycle disturbanceDepartment of Psychiatry, Juntendo University Nerima Hospital, Tokyo, JapanMelatonin, a pineal gland hormone, regulates the sleep-wake cycle, and there is some emerging liter-ature suggesting that melatonin prophylaxis may reduce delirium incidence or a long-lasting episode of delirium4-6). Sultan reported that after medica-tions were given orally 90 min before operative time and at sleep time at night of operation, the melatonin group showed a statistically significant decrease in the percentage of postoperative delirium to 9.43% (5/53 patients), compared with the control group (32.65% [16/49], relative risk 0.29, P = .0062)4). Al-Aama et al. reported that melatonin (0.5 mg every night for 14 days or until discharge) was associated with a lower risk of delirium (12.0% vs. 31.0% [placebo], P = .014), with an odds ratio (OR), adjusted for dementia and co-morbidities of 0.195). de Jonghe et al. reported Kotaro HATTA2. Melatonin receptor agonists for delirium prevention