Efficacy of Prolonged-Release Melatonin 2 mg (PRM 2 mg) Prescribed for Insomnia in Hospitalized Patients for COVID-19: A Retrospective Observational Study
Carolina Bologna, Pasquale Madonna, Eduardo Pone
Journal of Clinical Medicine, doi:10.3390/jcm10245857
Background: we have observed the effect of insomnia treatment in clinical and prognostic differences of patients admitted for COVID-19 pneumonia in respiratory sub-intensive units that were administered a prolonged-release melatonin 2 mg (PRM 2 mg) therapy versus a group of patients out of therapy. Materials and Methods: We evaluated 40 patients on prolonged-release melatonin 2 mg (PRM 2 mg) therapy versus a control group of 40 patients out of therapy. Results: patients in the PRM 2 mg group had a shorter duration of therapy with non-invasive ventilation (5.2 ± 3.0 vs. 12.5 ± 4.2; p < 0.001), with a shorter stay in sub-intensive care (12.3 ± 3.2 vs. 20.1 ± 6.1; p < 0.001), and, therefore, a shorter overall duration of hospitalization (31.3 ± 6.8 vs. 34.3 ± 6.9 p = 0.03). In addition, a lower incidence of delirium was found (2.2 ± 1.1 vs. 3.3 ± 1.3; p < 0.001). Conclusions: A significant increase in sleep hours and a reduction in delirium episodes occurs in hospitalized insomniac patients treated with PRM 2 mg, compared to untreated patients. Based on these preliminary results, we can assume that there are benefits of prolonged-release melatonin 2 mg in COVID-19 therapy.
Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.
Conflicts of Interest: The authors declare no conflict of interest.
References
Anderson, Reiter, Melatonin: Roles in influenza, COVID-19, and other viral infections, R. J. Rev. Med. Virol
Arbon, Knurowska, Dijk, Randomised clinical trial of the effects of prolonged-release melatonin, temazepam and zolpidem on slow-wave activity during sleep in healthy people, J. Psychopharmacol,
doi:10.1177/0269881115581963Bahrampour, Juybari, Pourhanifeh, Hosseinzadeh, Hemati et al., Melatonin potentials against viral infections including COVID-19: Current evidence and new findings, Virus Res,
doi:10.1016/j.virusres.2020.198108Baller, Hogan, Fusunyan, Ivkovic, Luccarelli et al., Neurocovid: Pharmacological Recommendations for Delirium Associated With COVID-19, Psychosomatics,
doi:10.1016/j.psym.2020.05.013Cardinali, Brown, Pandi-Perumal, Can Melatonin Be a Potential "Silver Bullet" in Treating COVID-19 Patients, Diseases,
doi:10.3390/diseases8040044Cerezo, Leal, Álvarez-Fernández, Hornedo-Ortega, Troncoso et al., Quality control and determination of melatonin in food supplements, J. Food Compos. Anal,
doi:10.1016/j.jfca.2015.09.013Duggan, Van, Ely, Assessment in Critically Ill Older Adults: Considerations During the COVID-19 Pandemic, Crit. Care Clin,
doi:10.1016/j.ccc.2020.08.009Erland, Saxena, Melatonin Natural Health Products and Supplements: Presence of Serotonin and Significant Variability of Melatonin Content, J. Clin. Sleep Med,
doi:10.5664/jcsm.6462Lemoine, Laudon, Nir, Zisapel, Prolonged-release melatonin for insomnia-An open-label long-term study of efficacy, safety, and withdrawal, Ther. Clin. Risk Manag,
doi:10.2147/TCRM.S23036Luthringer, Muzet, Zisapel, Staner, The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia, Int. Clin. Psychopharmacol,
doi:10.1097/YIC.0b013e32832e9b08Martín Giménez, Inserra, Tajer, Mariani, Ferder et al., Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment, Life Sci,
doi:10.1016/j.lfs.2020.117808Missiry, El-Missiry, Othman, Melatonin is a potential adjuvant to improve clinical outcomes in individuals with obesity and diabetes with coexistence of COVID-19, J. Pharmacol,
doi:10.1016/j.ejphar.2020.173329Otmani, Demazieres, Staner, Jacob, Nir et al., Effects of prolonged-release melatonin, zolpidem, and their combination on psychomotor functions, memory recall, and driving skills in healthy middle aged and elderly volunteers, Hum. Psychopharmacol. Clin. Exp,
doi:10.1002/hup.980Otmani, Metzger, Guichard, Danjou, Nir et al., Effects of prolonged-release melatonin and zolpidem on postural stability in older adults, Hum. Psychopharmacol. Clin. Exp,
doi:10.1002/hup.2219Palagini, Manni, Aguglia, Amore, Brugnoli et al., Expert Opinions and Consensus Recommendations for the Evaluation and Management of Insomnia in Clinical Practice: Joint Statements of Five Italian Scientific Societies, Front. Psychiatry,
doi:10.3389/fpsyt.2020.00558Pinto, Ferri, Pengo, Lombardi, Pucci et al., The Italian Society of Hypertension. Diagnostic and Therapeutic Approach to Sleep Disorders, High Blood Pressure and Cardiovascular Diseases: A Consensus Document by the Italian Society of Hypertension (SIIA), High Blood Press Cardiovasc. Prev,
doi:10.1007/s40292-021-00436-yReiter, Abreu-Gonzalez, Marik, Dominguez-Rodriguez, Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19, Front. Med,
doi:10.3389/fmed.2020.00226Wade, Ford, Crawford, Mcmahon, Nir et al., Efficacy of prolonged release melatonin in insomnia patients aged 55-80 years: Quality of sleep and next-day alertness outcomes, Curr. Med. Res. Opin,
doi:10.1185/030079907X233098Wilson, Anderson, British Association for Psycopharmacology consensus statement on evidence based treatment of insomnia, parasomnias and citrcadian rhythm disorders: An update, J. Psychopharmacol,
doi:10.1177/0269881119855343Zisapel, New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation, Br. J. Pharmacol,
doi:10.1111/bph.14116Öztürk, Akbulut, Güney, Turk Melatonin, aging, and COVID-19: Could melatonin be beneficial for COVID-19 treatment in the elderly?, Med. Sci,
doi:10.3906/sag-2005-356{ 'indexed': { 'date-parts': [[2021, 12, 16]],
'date-time': '2021-12-16T06:47:30Z',
'timestamp': 1639637250710},
'reference-count': 25,
'publisher': 'MDPI AG',
'issue': '24',
'license': [ { 'start': { 'date-parts': [[2021, 12, 14]],
'date-time': '2021-12-14T00:00:00Z',
'timestamp': 1639440000000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by/4.0/'}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'short-container-title': ['JCM'],
'abstract': '<jats:p>Background: we have observed the effect of insomnia treatment in clinical and '
'prognostic differences of patients admitted for COVID-19 pneumonia in respiratory '
'sub-intensive units that were administered a prolonged-release melatonin 2 mg (PRM 2 mg) '
'therapy versus a group of patients out of therapy. Materials and Methods: We evaluated 40 '
'patients on prolonged-release melatonin 2 mg (PRM 2 mg) therapy versus a control group of 40 '
'patients out of therapy. Results: patients in the PRM 2 mg group had a shorter duration of '
'therapy with non-invasive ventilation (5.2 ± 3.0 vs. 12.5 ± 4.2; p < 0.001), with a '
'shorter stay in sub-intensive care (12.3 ± 3.2 vs. 20.1 ± 6.1; p < 0.001), and, therefore, '
'a shorter overall duration of hospitalization (31.3 ± 6.8 vs. 34.3 ± 6.9 p = 0.03). In '
'addition, a lower incidence of delirium was found (2.2 ± 1.1 vs. 3.3 ± 1.3; p < 0.001). '
'Conclusions: A significant increase in sleep hours and a reduction in delirium episodes '
'occurs in hospitalized insomniac patients treated with PRM 2 mg, compared to untreated '
'patients. Based on these preliminary results, we can assume that there are benefits of '
'prolonged-release melatonin 2 mg in COVID-19 therapy.</jats:p>',
'DOI': '10.3390/jcm10245857',
'type': 'journal-article',
'created': { 'date-parts': [[2021, 12, 14]],
'date-time': '2021-12-14T16:11:35Z',
'timestamp': 1639498295000},
'page': '5857',
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': [ 'Efficacy of Prolonged-Release Melatonin 2 mg (PRM 2 mg) Prescribed for Insomnia in '
'Hospitalized Patients for COVID-19: A Retrospective Observational Study'],
'prefix': '10.3390',
'volume': '10',
'author': [ { 'ORCID': 'http://orcid.org/0000-0002-2007-3835',
'authenticated-orcid': False,
'given': 'Carolina',
'family': 'Bologna',
'sequence': 'first',
'affiliation': []},
{'given': 'Pasquale', 'family': 'Madonna', 'sequence': 'additional', 'affiliation': []},
{'given': 'Eduardo', 'family': 'Pone', 'sequence': 'additional', 'affiliation': []}],
'member': '1968',
'published-online': {'date-parts': [[2021, 12, 14]]},
'reference': [ {'key': 'ref1', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.lfs.2020.117583'},
{'key': 'ref2', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/rmv.2109'},
{'key': 'ref3', 'doi-asserted-by': 'publisher', 'DOI': '10.1080/08830185.2020.1756284'},
{'key': 'ref4', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/diseases8040044'},
{'key': 'ref5', 'doi-asserted-by': 'publisher', 'DOI': '10.5664/jcsm.7172'},
{'key': 'ref6', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jfca.2015.09.013'},
{'key': 'ref7', 'doi-asserted-by': 'publisher', 'DOI': '10.5664/jcsm.6462'},
{'key': 'ref8', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fpsyt.2020.00558'},
{'key': 'ref9', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/bph.14116'},
{'key': 'ref10', 'doi-asserted-by': 'publisher', 'DOI': '10.1185/030079907X233098'},
{'key': 'ref11', 'doi-asserted-by': 'publisher', 'DOI': '10.1097/YIC.0b013e32832e9b08'},
{'key': 'ref12', 'doi-asserted-by': 'publisher', 'DOI': '10.2147/TCRM.S23036'},
{'key': 'ref13', 'doi-asserted-by': 'publisher', 'DOI': '10.1177/0269881115581963'},
{'key': 'ref14', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/hup.980'},
{'key': 'ref15', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/hup.2219'},
{'key': 'ref16', 'doi-asserted-by': 'publisher', 'DOI': '10.1177/0269881119855343'},
{'key': 'ref17', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s40292-021-00436-y'},
{'key': 'ref18', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.psym.2020.05.013'},
{'key': 'ref19', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ccc.2020.08.009'},
{'key': 'ref20', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.lfs.2020.117808'},
{'key': 'ref21', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.virusres.2020.198108'},
{'key': 'ref22', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.sleep.2020.05.028'},
{'key': 'ref23', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ejphar.2020.173329'},
{'key': 'ref24', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fmed.2020.00226'},
{'key': 'ref25', 'doi-asserted-by': 'publisher', 'DOI': '10.3906/sag-2005-356'}],
'container-title': ['Journal of Clinical Medicine'],
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://www.mdpi.com/2077-0383/10/24/5857/pdf',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2021, 12, 15]],
'date-time': '2021-12-15T03:16:05Z',
'timestamp': 1639538165000},
'score': 1,
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2021, 12, 14]]},
'references-count': 25,
'journal-issue': {'issue': '24', 'published-online': {'date-parts': [[2021, 12]]}},
'alternative-id': ['jcm10245857'],
'URL': 'http://dx.doi.org/10.3390/jcm10245857',
'relation': {},
'ISSN': ['2077-0383'],
'issn-type': [{'value': '2077-0383', 'type': 'electronic'}],
'subject': ['General Medicine'],
'published': {'date-parts': [[2021, 12, 14]]}}
