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      Efficacy, Safety, and Drug–Drug Interactions for Insomnia Therapy in COVID-19 Patients

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          Abstract

          Coronavirus disease-19 (COVID-19) is a systemic viral infection. COVID-19 patients show diverse clinical presentations ranging from asymptomatic, mild symptoms to severe symptoms characterized by severe respiratory distress. Sleep disorders or insomnia is one of the psychiatric problems that arise during the COVID-19 pandemic. The term used to define this particular insomnia is coronasomnia or COVID-19 insomnia. Data show that the prevalence of this problem is increasing, especially in the confirmed COVID-19 patient group. Anti-insomnia drugs such as hypnotics, sedatives, and anxiolytics are the easiest option. As with drugs generally, anti-insomnia drugs are associated with various safety issues, especially in people with COVID-19. Therefore, their use may be hazardous. The literature review aims to make health practitioners aware of the anti-insomnia drugs that have the best efficacy and safety issues that are clinically relevant from the use of anti-insomnia drugs and the interactions of anti-insomnia drugs with various drugs used in the treatment of COVID-19. The articles were explored on PubMed and Cochrane Library, whereas the drug–drug interactions between the anti-insomnia and COVID-19 drugs were searched on Drugs.com Interaction Checker and Lexiomp-interact. Overall anti-insomnia drugs have efficacy in improving sleep parameters. Orexin receptor antagonist drugs have good efficacy in increasing WASO, LPS, and SE with an acceptable safety profile. Meanwhile, the combination of zolpidem, lorazepam, and diphenhydramine improved TST parameters better than other drugs. Side effects such as drowsiness and dizziness were among the most commonly reported effects. Therefore, attention and monitoring of the use of anti-insomnia drugs in COVID-19 patients need to be carried out by considering the side effects and interactions that are very risky.

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          Most cited references42

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          Diagnostic and Statistical Manual of Mental Disorders

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            Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19)

            In hospitalized patients with coronavirus disease 2019 (COVID-19), what is the risk of corrected QT (QTc) prolongation when taking hydroxychloroquine with or without azithromycin? In a cohort study of 90 hospitalized patients with coronavirus disease 2019, use of hydroxychloroquine with or without azithromycin for treatment of COVID-19 was associated with frequent QTc prolongation, and those taking hydroxychloroquine and azithromycin had greater QT prolongation than those taking hydroxychloroquine alone. One patient developed torsades de pointes. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage. This cohort study examines the association of hydroxychloroquine or hydroxychloroquine and azithromycin with QT prolongation in adult patients hospitalized with coronavirus disease 2019. Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)–associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias. To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin. This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020. Change in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events. Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P  < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 [10-40] milliseconds) compared with those receiving hydroxychloroquine alone (5.5 [−15.5 to 34.25] milliseconds; P  = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (3%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 [95% CI, 1.03-11.08]) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 [95% CI, 1.75-28.87]). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes. In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.
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              Sleep problems during the COVID-19 pandemic by population: a systematic review and meta-analysis

              No systematic review or meta-analysis has yet been conducted to examine the impact of the pandemic on the prevalence of sleep problems among the general population, health care workers, or patients with COVID-19. Therefore, this systematic review was conducted to assess the impact and prevalence of sleep problems among those categories.
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                Author and article information

                Journal
                J Multidiscip Healthc
                J Multidiscip Healthc
                jmdh
                Journal of Multidisciplinary Healthcare
                Dove
                1178-2390
                21 January 2022
                2022
                : 15
                : 137-152
                Affiliations
                [1 ]Undergraduate Program of Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran , Sumedang, 45363, Indonesia
                [2 ]Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran , Sumedang, 45363, Indonesia
                [3 ]Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran , Sumedang, 45363, Indonesia
                Author notes
                Correspondence: Resmi Mustarichie Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran , Sumedang, 45363, Indonesia Tel +6222-84288888 Ext 3510 Email resmi.mustarichie@unpad.ac.id
                Author information
                http://orcid.org/0000-0002-4578-4174
                http://orcid.org/0000-0001-6453-0236
                Article
                337053
                10.2147/JMDH.S337053
                8789249
                35087274
                2ce5fe6e-706c-4f68-9524-0317e78250bf
                © 2022 Saputra et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 29 September 2021
                : 23 December 2021
                Page count
                Figures: 3, Tables: 7, References: 42, Pages: 16
                Categories
                Review

                Medicine
                insomnia,covid-19,polysomnography,efficacy,safety,interaction
                Medicine
                insomnia, covid-19, polysomnography, efficacy, safety, interaction

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