{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T03:02:04Z","timestamp":1760151724336,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:00:00Z","timestamp":1650412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Delirium and psychomotor agitation are relevant clinical conditions that may develop during COVID-19 infection, especially in intensive care unit (ICU) settings. The psychopharmacological management of these conditions is receiving increasing interest in psychiatry, considering hyperkinetic delirium as one of the most common neuropsychiatries acute consequences in COVID-19 recovery patients. However, there are no actual internationally validated guidelines about this topic, due to the relatively newly introduced clinical condition; in addition, a standardized psychopharmacologic treatment of these cases is a complex goal to achieve due to the risk of both drug\u2013drug interactions and the vulnerable conditions of those patients. The aim of this systematic review and case series is to evaluate and gather the scientific evidence on pharmacologic handling during delirium in COVID-19 patients to provide practical recommendations on the optimal management of psychotropic medication in these kinds of patients. The electronic databases PubMed, Embase and Web of Science were reviewed to identify studies, in accordance with the PRISMA guidelines. At the end of the selection process, a total of 21 studies (n = 2063) were included. We also collected a case series of acute psychomotor agitation in COVID-19 patients hospitalized in ICU. Our results showed how the symptom-based choice of the psychotropic medication is crucial, and even most of the psychotropic drug classes showed good safety, one must not underestimate the possible drug interactions and also the possible decrease in vital functions which need to be strictly monitored especially during treatment with some kinds of molecules. We believe that the evidence-based recommendations highlighted in the present research will enhance the current knowledge and could provide better management of these patients.<\/jats:p>","DOI":"10.3390\/ijerph19094978","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T01:55:51Z","timestamp":1650506151000},"page":"4978","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacological Treatment of Acute Psychiatric Symptoms in COVID-19 Patients: A Systematic Review and a Case Series"],"prefix":"10.3390","volume":"19","author":[{"given":"Claudia","family":"Carmassi","sequence":"first","affiliation":[{"name":"Psychiatric Unit, Department of Clinical and Experimental Medicine, AOUP, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Pacciardi","sequence":"additional","affiliation":[{"name":"Psychiatric Unit, Department of Clinical and Experimental Medicine, AOUP, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Gravina","sequence":"additional","affiliation":[{"name":"Psychiatric Unit, Department of Clinical and Experimental Medicine, AOUP, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Fantasia","sequence":"additional","affiliation":[{"name":"Psychiatric Unit, Department of Clinical and Experimental Medicine, AOUP, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gennaro","family":"De Pascale","sequence":"additional","affiliation":[{"name":"Department of Emergency, Catholic University of the Sacred Heart, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8135-6284","authenticated-orcid":false,"given":"Salvatore Lucio","family":"Cutuli","sequence":"additional","affiliation":[{"name":"Department of Emergency, Catholic University of the Sacred Heart, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1752-0339","authenticated-orcid":false,"given":"Carlo Antonio","family":"Bertelloni","sequence":"additional","affiliation":[{"name":"Psychiatric Unit, Department of Clinical and Experimental Medicine, AOUP, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliana","family":"Dell\u2019Osso","sequence":"additional","affiliation":[{"name":"Psychiatric Unit, Department of Clinical and Experimental Medicine, AOUP, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S2215-0366(20)30203-0","article-title":"Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: A systematic review and meta-analysis with comparison to the COVID-19 pandemic","volume":"7","author":"Rogers","year":"2020","journal-title":"Lancet Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Desforges, M., Le Coupanec, A., Dubeau, P., Bourgouin, A., Lajoie, L., Dube, M., and Talbot, P.J. (2019). Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?. Viruses, 12.","DOI":"10.3390\/v12010014"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/PRA.0000000000000533","article-title":"Abrupt Late-onset Psychosis as a Presentation of Coronavirus 2019 Disease (COVID-19): A Longitudinal Case Report","volume":"27","author":"Parker","year":"2021","journal-title":"J. Psychiatr. Pract."},{"key":"ref_4","first-page":"e11993","article-title":"Persistent Hallucinations in a 46-Year-Old Woman After COVID-19 Infection: A Case Report","volume":"12","author":"Clouden","year":"2020","journal-title":"Cureus"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.bbi.2020.03.031","article-title":"Nervous system involvement after infection with COVID-19 and other coronaviruses","volume":"87","author":"Wu","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1007\/s11126-020-09868-6","article-title":"Psychiatric Clinical Profiles and Pharmacological Interactions in COVID-19 Inpatients Referred to a Consultation Liaison Psychiatry Unit: A Cross-Sectional Study","volume":"92","author":"Arbelo","year":"2021","journal-title":"Psychiatr. Q."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1021\/acschemneuro.0c00156","article-title":"Astragalin Exerted Antidepressant-like Action through SIRT1 Signaling Modulated NLRP3 Inflammasome Deactivation","volume":"11","author":"Tong","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Menculini, G., Tortorella, A., Albert, U., Carmassi, C., Carr\u00e0, G., Cirulli, F., Dell\u2019Osso, B., Luciano, M., Nanni, M.G., and Pompili, M. (2021). Access to Mental Health Care during the First Wave of the COVID-19 Pandemic in Italy: Results from the COMET Multicentric Study. Brain Sci., 11.","DOI":"10.3390\/brainsci11111413"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"580736","DOI":"10.3389\/fpsyt.2020.580736","article-title":"Tele-Psychiatry Assessment of Post-traumatic Stress Symptoms in 100 Patients With Bipolar Disorder During the COVID-19 Pandemic Social-Distancing Measures in Italy","volume":"11","author":"Carmassi","year":"2020","journal-title":"Front. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"113312","DOI":"10.1016\/j.psychres.2020.113312","article-title":"PTSD symptoms in healthcare workers facing the three coronavirus outbreaks: What can we expect after the COVID-19 pandemic","volume":"292","author":"Carmassi","year":"2020","journal-title":"Psychiatry Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1007\/s00134-020-05966-y","article-title":"China Critical Care Clinical Trials Group (CCCCTG) Intensive care during the coronavirus epidemic","volume":"46","author":"Qiu","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, DSM-5, American Psychiatric Press.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.1007\/s10072-021-05461-2","article-title":"Delirium in COVID-19 patients: A multicentric observational study in Italy","volume":"42","author":"Martinotti","year":"2021","journal-title":"Neurol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e050045","DOI":"10.1136\/bmjopen-2021-050045","article-title":"Delirium and neuropsychological outcomes in critically Ill patients with COVID-19: A cohort study","volume":"11","author":"Ragheb","year":"2021","journal-title":"BMJ Open"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1097\/CCM.0b013e3182a645bd","article-title":"Delirium in the ICU and Subsequent Long-Term Disability Among Survivors of Mechanical Ventilation","volume":"42","author":"Brummel","year":"2014","journal-title":"Crit. Care Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1001\/jama.291.14.1753","article-title":"Delirium as a Predictor of Mortality in Mechanically Ventilated Patients in the Intensive Care Unit","volume":"291","author":"Ely","year":"2004","journal-title":"JAMA"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ostuzzi, G., Papola, D., Gastaldon, C., Schoretsanitis, G., Bertolini, F., Amaddeo, F., Cuomo, A., Emsley, R., Fagiolini, A., and Imperadore, G. (2020). Safety of psychotropic medications in people with COVID-19: Evidence review and practical recommendations. BMC Med., 18.","DOI":"10.1186\/s12916-020-01685-9"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.psym.2020.05.013","article-title":"Neurocovid: Pharmacological Recommendations for Delirium Associated With COVID-19","volume":"61","author":"Baller","year":"2020","journal-title":"J. Psychosom. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2045125320942703","DOI":"10.1177\/2045125320942703","article-title":"Pharmacological treatment of hyperactive delirium in people with COVID-19: Rethinking conventional approaches","volume":"10","author":"Ostuzzi","year":"2020","journal-title":"Ther. Adv. Psychopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1016\/j.mayocp.2012.04.017","article-title":"Ten Common Questions (and Their Answers) About Off-label Drug Use","volume":"87","author":"Wittich","year":"2012","journal-title":"Mayo Clin. Proc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1001\/jama.2020.4742","article-title":"Treating COVID-19\u2014Off-Label Drug Use, Compassionate Use, and Randomized Clinical Trials During Pandemics","volume":"323","author":"Kalil","year":"2020","journal-title":"JAMA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1007\/s11064-014-1293-3","article-title":"On the Discovery and Development of Pimavanserin: A Novel Drug Candidate for Parkinson\u2019s Psychosis","volume":"39","author":"Hacksell","year":"2014","journal-title":"Neurochem. Res."},{"key":"ref_23","first-page":"105906","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1136\/bmjebm-2017-110853","article-title":"Methodological quality and synthesis of case series and case reports","volume":"23","author":"Murad","year":"2018","journal-title":"BMJ Evid. Based Med."},{"key":"ref_25","unstructured":"(2022, February 23). National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, Available online: https:\/\/www.nhlbi.nih.gov\/health-topics\/study-quality-assessment-tools."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1007\/s42399-021-00952-x","article-title":"Acute Psychosis in COVID-19: Is It Due to Favipiravir Treatment or Acute Viral Illness?","volume":"3","author":"Duyan","year":"2021","journal-title":"SN Compr. Clin. Med."},{"key":"ref_27","first-page":"e13428","article-title":"Neuroleptic Malignant Syndrome After Re-introduction of Atypical Antipsychotics in a COVID-19 Patient","volume":"13","author":"Espiridion","year":"2021","journal-title":"Cureus"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.ejpsy.2020.12.002","article-title":"Time for lessons from the first wave of SARS-CoV-2 epidemic. A case report of a patient with acute psychosis and COVID-19 and later virus reactivation","volume":"35","author":"Saje","year":"2021","journal-title":"Eur. J. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e01140","DOI":"10.1016\/j.idcr.2021.e01140","article-title":"Acute psychosis associated with recent SARS-CoV-2 infection: A case report","volume":"24","author":"Elfil","year":"2021","journal-title":"IDCases"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"102513","DOI":"10.1016\/j.ajp.2020.102513","article-title":"Delirium in a pregnant woman with SARS-CoV-2 infection in India","volume":"55","author":"Mahajan","year":"2021","journal-title":"Asian J. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.jad.2020.05.149","article-title":"COVID-19 inpatients with psychiatric disorders: Real-world clinical recommendations from an expert team in consultation-liaison psychiatry","volume":"274","author":"Anmella","year":"2020","journal-title":"J. Affect. Disord."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.psym.2020.05.007","article-title":"COVID-19\u2013Associated Hyperactive Intensive Care Unit Delirium With Proposed Pathophysiology and Treatment: A Case Report","volume":"61","author":"Sher","year":"2020","journal-title":"J. Psychosom. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.psym.2020.09.002","article-title":"A Case of Concurrent Delirium and Catatonia in a Woman With Coronavirus Disease 2019","volume":"62","author":"Amouri","year":"2021","journal-title":"J. Acad. Consult.-Liaison Psychiatry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e236123","DOI":"10.1136\/bcr-2020-236123","article-title":"Neurotropism of SARS-CoV-2: COVID-19 presenting with an acute manic episode","volume":"13","author":"Mawhinney","year":"2020","journal-title":"BMJ Case Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"114245","DOI":"10.1016\/j.psychres.2021.114245","article-title":"Delirium in hospitalized COVID-19 patients: A case series","volume":"305","year":"2021","journal-title":"Psychiatry Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1177\/0091217420985979","article-title":"Management challenges in patients with comorbid COVID-19 associated delirium and serious mental illness\u2014A case series","volume":"56","author":"Syed","year":"2021","journal-title":"Int. J. Psychiatry Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"726059","DOI":"10.3389\/fpsyt.2021.726059","article-title":"First-Time Psychotic Symptoms in a Patient After COVID-19 Infection\u2014A Case Report","volume":"12","author":"Kulikowska","year":"2021","journal-title":"Front. Psychiatry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e239191","DOI":"10.1136\/bcr-2020-239191","article-title":"Severe psychiatric disturbance and attempted suicide in a patient with COVID-19 and no psychiatric history","volume":"13","author":"Gillett","year":"2020","journal-title":"BMJ Case Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1002\/ccr3.4015","article-title":"Managing a patient with bipolar disorder associated with COVID-19: A case report from Qatar","volume":"9","author":"Khatib","year":"2021","journal-title":"Clin. Case Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e243816","DOI":"10.1136\/bcr-2021-243816","article-title":"Delirious mania in a patient with COVID-19 pneumonia","volume":"14","author":"Haddad","year":"2021","journal-title":"BMJ Case Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.genhosppsych.2020.05.008","article-title":"Delirium in COVID-19: A case series and exploration of potential mechanisms for central nervous system involvement","volume":"65","author":"Beach","year":"2020","journal-title":"Gen. Hosp. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"586686","DOI":"10.3389\/fpsyt.2020.586686","article-title":"Delirium: Clinical Presentation and Outcomes in Older COVID-19 Patients","volume":"11","author":"Rozzini","year":"2020","journal-title":"Front. Psychiatry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.2165\/00003495-200565090-00003","article-title":"Pharmacological Management of Acute Agitation","volume":"65","author":"Battaglia","year":"2005","journal-title":"Drugs"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1177\/00912700122012896","article-title":"The Effect of Intravenous Haloperidol on QT Interval Dispersion in Critically Ill Patients: Comparison with QT Interval Prolongation for Assessment of Risk of Torsades de Pointes","volume":"41","author":"Tisdale","year":"2001","journal-title":"J. Clin. Pharmacol."},{"key":"ref_45","first-page":"543","article-title":"Torsade de pointes associated with the administration of intravenous haloperidol:a review of the literature and practical guidelines for use","volume":"2","author":"Hassaballa","year":"2003","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_46","first-page":"E8","article-title":"The FDA extended warning for intravenous haloperidol and torsades de pointes: How should institutions respond?","volume":"5","author":"Cheng","year":"2010","journal-title":"J. Hosp. Med."},{"key":"ref_47","first-page":"CD004990","article-title":"Trazodone for agitation in dementia","volume":"18","author":"Fioravanti","year":"2004","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1097\/00019442-199705010-00008","article-title":"A Double-Blind Comparison of Trazodone and Haloperidol for Treatment of Agitation in Patients With Dementia","volume":"5","author":"Sultzer","year":"1997","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.hrtlng.2018.08.007","article-title":"Evaluating the use of dexmedetomidine for the reduction of delirium: An integrative review","volume":"47","author":"Pavone","year":"2018","journal-title":"Heart Lung"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1097\/CCM.0000000000001622","article-title":"Dexmedetomidine for the Treatment of Hyperactive Delirium Refractory to Haloperidol in Nonintubated ICU Patients: A Nonrandomized Controlled Trial","volume":"44","author":"Carrasco","year":"2016","journal-title":"Crit. Care Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1097\/CNQ.0000000000000172","article-title":"Oral Agents for the Management of Agitation and Agitated Delirium in Critically Ill Patients","volume":"40","author":"Yeo","year":"2017","journal-title":"Crit. Care Nurs. Q."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"26","DOI":"10.5811\/westjem.2011.9.6866","article-title":"The psychopharmacology of agitation: Consensus statement of the American Association for Emergency Psychiatry Project BETA Psychopharmacology Workgroup","volume":"13","author":"Wilson","year":"2012","journal-title":"West. J. Emerg. Med."},{"key":"ref_53","first-page":"5","article-title":"The pathophysiology of agitation","volume":"61","author":"Lindenmayer","year":"2000","journal-title":"J. Clin. Psychiatry"}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/9\/4978\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:57:11Z","timestamp":1760137031000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/9\/4978"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,20]]},"references-count":53,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["ijerph19094978"],"URL":"https:\/\/doi.org\/10.3390\/ijerph19094978","relation":{},"ISSN":["1660-4601"],"issn-type":[{"type":"electronic","value":"1660-4601"}],"subject":[],"published":{"date-parts":[[2022,4,20]]}}}