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      Effect of Suvorexant on Nocturnal Delirium in Elderly Patients with Alzheimer’s Disease: A Case-series Study

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          Abstract

          Suvorexant, an orexin receptor antagonist used for insomnia, has been shown to have a preventive effect on delirium in a randomized placebo-controlled trial. However, its effectiveness in the management of nocturnal delirium has not yet been determined. Here we report four cases in which elderly patients with moderate to severe Alzheimer’s disease who developed nocturnal delirium were treated with suvorexant. In case 1, 15 mg suvorexant was initiated to manage nocturnal delirium refractory to antipsychotics, antidepressants, and a Japanese herbal medicine, resulting in immediate sleep improvement. However, treatment discontinuation led to recurrence of symptoms, which were reversed by recommencing suvorexant. In case 2, as antipsychotics used for the treatment of nocturnal delirium were ineffective, 15 mg suvorexant was administered. The patient achieved rapid improvement in sleep. In case 3, the use of atypical antipsychotics for the treatment of nocturnal delirium was contraindicated, as the patient had diabetes. Therefore, 15 mg suvorexant was administered following good outcomes in cases 1 and 2, resulting in immediate sleep improvement. Finally, in case 4, 15 mg suvorexant was used as an initial medication for nocturnal delirium, and the patient showed sleep improvement immediately. Elevated orexin levels in the cerebrospinal fluid are reportedly linked to sleep deterioration in patients with moderate to severe Alzheimer’s disease. The immediate and reproducible action and effectiveness of suvorexant observed in our patients suggest that enhanced cerebral orexin activity might be associated with sleep-wake cycle disturbances due to delirium in elderly patients with Alzheimer’s disease.

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          Delirium in older persons.

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            Preventive effects of ramelteon on delirium: a randomized placebo-controlled trial.

            No highly effective interventions to prevent delirium have been identified. To examine whether ramelteon, a melatonin agonist, is effective for the prevention of delirium. A multicenter, rater-blinded, randomized placebo-controlled trial was performed in intensive care units and regular acute wards of 4 university hospitals and 1 general hospital. Eligible patients were 65 to 89 years old, newly admitted due to serious medical problems, and able to take medicine orally. Patients were excluded from the study if they had an expected stay or life expectancy of less than 48 hours. Sixty-seven patients were randomly assigned using the sealed envelope method to receive ramelteon (8 mg/d; 33 patients) or placebo (34 patients) every night for 7 days. Incidence of delirium, as defined by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). Ramelteon was associated with a lower risk of delirium (3% vs 32%; P = .003), with a relative risk of 0.09 (95% CI, 0.01-0.69). Even after risk factors were controlled for, ramelteon was still associated with a lower incidence of delirium (P = .01; odds ratio, 0.07 [95% CI, 0.008-0.54]). The Kaplan-Meier estimates of time to development of delirium were 6.94 (95% CI, 6.82-7.06) days for ramelteon and 5.74 (5.05-6.42) days for placebo. Comparison by log-rank test showed that the frequency of delirium was significantly lower in patients taking ramelteon than in those taking placebo (χ(2) = 9.83; P = .002). Ramelteon administered nightly to elderly patients admitted for acute care may provide protection against delirium. This finding supports a possible pathogenic role of melatonin neurotransmission in delirium. University Hospital Medical Information Network Clinical Trials Registry Identifier: UMIN000005591.
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              Delirium superimposed on dementia is associated with prolonged length of stay and poor outcomes in hospitalized older adults.

              Current literature does not identify the significance of underlying cognitive impairment and delirium in older adults during and 30 days following acute care hospitalization. Describe the incidence, risk factors, and outcomes associated with incident delirium superimposed on dementia. A 24-month prospective cohort study. Community hospital. A total of 139 older adults (>65 years) with dementia. This prospective study followed patients daily during hospitalization and 1 month posthospital. Main measures included dementia (Modified Blessed Dementia Rating score, Informant Questionnaire on Cognitive Decline in the Elderly), daily mental status change, dementia stage/severity (Clinical Dementia Rating, Global Deterioration Scale), delirium (Confusion Assessment Method), and delirium severity (Delirium Rating Scale-Revised-98). All statistical analysis was performed using SAS 9.3, and significance was an α level of 0.05. Logistic regression, analysis of covariance, or linear regression was performed controlling for age, gender, and dementia stage. The overall incidence of new delirium was 32% (44/139). Those with delirium had a 25% short-term mortality rate, increased length of stay, and poorer function at discharge. At 1 month follow-up, subjects with delirium had greater functional decline. Males were more likely to develop delirium, and for every 1 unit increase in dementia severity (Global Deterioration Scale), subjects were 1.5 times more likely to develop delirium. Delirium prolongs hospitalization for persons with dementia. Thus, interventions to increase early detection of delirium have the potential to decrease the severity and duration of delirium and to prevent unnecessary suffering and costs from the complications of delirium and unnecessary readmissions to the hospital. Copyright © 2013 Society of Hospital Medicine.
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                Author and article information

                Journal
                Clin Psychopharmacol Neurosci
                Clin Psychopharmacol Neurosci
                Clinical Psychopharmacology and Neuroscience
                Korean College of Neuropsychopharmacology
                1738-1088
                2093-4327
                November 2019
                30 November 2019
                : 17
                : 4
                : 547-550
                Affiliations
                [1 ]Emergency Medical Center and Poison Center, Saitama Medical University Hospital, Saitama, Japan
                [2 ]Department of General Medicine, Fujimi Hospital, Tokyo, Japan
                Author notes
                Address for correspondence: Tomoki Hanazawa, Emergency Medical Center and Poison Center, Saitama Medical University Hospital, 38 Morohongo, Moroyama, Iruma-gun, Saitama 350-0495, Japan, E-mail: tomokihanazawa34@ 123456yahoo.co.jp , ORCID: https://orcid.org/0000-0002-2738-3297
                Author information
                https://orcid.org/0000-0002-2738-3297
                https://orcid.org/0000-0003-0326-6165
                Article
                cpn-17-547
                10.9758/cpn.2019.17.4.547
                6852677
                31671494
                ebcfdbbe-5c1c-4827-b2f7-b2d7a54e027e
                Copyright © 2019, Korean College of Neuropsychopharmacology

                This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 April 2018
                : 08 May 2018
                : 15 May 2018
                Categories
                Case Report

                suvorexant,orexins,delirium,alzheimer disease
                suvorexant, orexins, delirium, alzheimer disease

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