{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:21:46Z","timestamp":1778631706564,"version":"3.51.4"},"reference-count":60,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacopsychiatry"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Since few therapeutic options are clinically accessible for coronavirus disease 2019 (COVID-19), effective, safe, and globally available pharmaceuticals need to be urgently developed to prevent severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and alleviate the severity of COVID-19. In this regard, the present paper is intended to provide an extensive review of the clinical and preclinical evidence on the psychotropics\u2019 anti-SARS-CoV-2 effects, giving an insight into their potential applications for patients with a proven or high likelihood of COVID-19 pneumonia. The results showed that psychotropic drugs such as melatonin, lithium carbonate, valproate, olanzapine, quetiapine, clozapine, fluoxetine, escitalopram, fluvoxamine, and cannabidiol could help lower the mortality due to SARS-CoV-2 infection. According to these medications\u2019 direct immunomodulatory actions against the destructive cytokine storm, as well as other direct\/indirect mechanisms (e.\u2009g., the endolysosomal pathway modulation, interactions with specific receptors, and membrane fusion), it was perceived that such drugs could effectively weaken the worsened immune response and avoid adult respiratory distress syndrome and acute lung injury. According to the author\u2019s analysis of the currently available evidence, there is significant support for psychotropics as complementary interventions during SARS-CoV-2 infection. However, further studies need to be carried out to assess the effects of the above psychotropic drugs in vitro and clinical settings.<\/jats:p>","DOI":"10.1055\/a-1551-3756","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T23:29:59Z","timestamp":1629156599000},"page":"16-23","source":"Crossref","is-referenced-by-count":23,"title":["Candidate Psychotropics against SARS\u2009\u2013\u2009CoV\u2009\u2013\u20092: A Narrative Review"],"prefix":"10.1055","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2970-6309","authenticated-orcid":false,"given":"Mohsen","family":"Khosravi","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Clinical Psychology, Zahedan University of Medical Sciences, Zahedan, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1001\/jama.2020.12839","article-title":"Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review","volume":"324","author":"W J Wiersinga","year":"2020","journal-title":"J Am Med Assoc"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1007\/s40265-020-01367-z","article-title":"Pharmaco-immunomodulatory therapy in COVID-19","volume":"80","author":"J G Rizk","year":"2020","journal-title":"Drugs"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"102569","DOI":"10.1016\/j.autrev.2020.102569","article-title":"Immunomodulatory therapy for the management of severe COVID-19. Beyond the antiviral therapy: a comprehensive review","volume":"19","author":"J Alijotas-Reig","year":"2020","journal-title":"Autoimmun Rev"},{"key":"ref4","first-page":"1","article-title":"Immune responses in COVID-19 and potential vaccines: lessons learned from SARS and MERS epidemic","volume":"38","author":"E Prompetchara","year":"2020","journal-title":"Asian Pac J Allergy Immunol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1172\/JCI137647","article-title":"SARS-CoV-2: a storm is raging","volume":"130","author":"S F Pedersen","year":"2020","journal-title":"J Clin Invest"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"677","DOI":"10.3389\/fcell.2020.00677","article-title":"Preventing mortality in COVID-19 patients: which cytokine to target in a raging storm?","volume":"8","author":"L Lu","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"113856","DOI":"10.1016\/j.psychres.2021.113856","article-title":"A meta-analysis: the mortality and severity of COVID-19 among patients with mental disorders","volume":"299","author":"A A Toubasi","year":"2021","journal-title":"Psychiatry Res"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.drudis.2020.06.022","article-title":"Prevention of COVID-19 by drug repurposing: rationale from drugs prescribed for mental disorders","volume":"25","author":"B O Villoutreix","year":"2020","journal-title":"Drug Discov Today"},{"key":"ref9","volume-title":"\u2018Clarity Bordering on Stupidity\u2019: Where\u2019s the Quality in Systematic Review?","author":"M MacLure","year":"2007"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"226","DOI":"10.3389\/fmed.2020.00226","article-title":"Therapeutic algorithm for use of melatonin in patients with COVID-19","volume":"7","author":"R J Reiter","year":"2020","journal-title":"Front Med"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"e2109","DOI":"10.1002\/rmv.2109","article-title":"Melatonin: roles in influenza, Covid-19, and other viral infections","volume":"30","author":"G Anderson","year":"2020","journal-title":"Rev Med Virol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"8229","DOI":"10.1007\/s11033-020-05830-8","article-title":"Role of melatonin in the treatment of COVID-19; as an adjuvant through cluster differentiation 147 (CD147)","volume":"47","author":"A O Sehirli","year":"2020","journal-title":"Mol Biol Rep"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"198108","DOI":"10.1016\/j.virusres.2020.198108","article-title":"Melatonin potentials against viral infections including COVID-19: current evidence and new findings","volume":"287","author":"K B Juybari","year":"2020","journal-title":"Virus Res"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"297","DOI":"10.32794\/mr11250063","article-title":"Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 PRO): a case series","volume":"3","author":"R R Castillo","year":"2020","journal-title":"Melatonin Research"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"4410","DOI":"10.3390\/molecules25194410","article-title":"Targeting host defense system and rescuing compromised mitochondria to increase tolerance against pathogens by melatonin may impact outcome of deadly virus infection pertinent to COVID-19","volume":"25","author":"D X Tan","year":"2020","journal-title":"Molecules"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1172\/JCI137244","article-title":"Clinical and immunological features of severe and moderate coronavirus disease 2019","volume":"130","author":"G Chen","year":"2020","journal-title":"J Clin Invest"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"100044","DOI":"10.1016\/j.medidd.2020.100044","article-title":"Melatonin inhibits COVID-19-induced cytokine storm by reversing aerobic glycolysis in immune cells: a mechanistic analysis","volume":"6","author":"R J Reiter","year":"2020","journal-title":"Med Drug Discov"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"380","DOI":"10.32794\/mr11250069","article-title":"The potential of melatonin in the prevention and attenuation of oxidative hemolysis and myocardial injury from cd147 SARS-CoV-2 spike protein receptor binding","volume":"3","author":"D Loh","year":"2020","journal-title":"Melatonin Research"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"e0240149","DOI":"10.1371\/journal.pone.0240149","article-title":"In-silico drug repurposing study predicts the combination of pirfenidone and melatonin as a promising candidate therapy to reduce SARS-CoV-2 infection progression and respiratory distress caused by cytokine storm","volume":"15","author":"L Artigas","year":"2020","journal-title":"PLoS One"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.7150\/ijms.48053","article-title":"COVID-19: Rational discovery of the therapeutic potential of Melatonin as a SARS-CoV-2 main Protease Inhibitor","volume":"17","author":"E L Feitosa","year":"2020","journal-title":"Int J Med Sci"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/j.cell.2020.05.015","article-title":"Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals","volume":"181","author":"A Grifoni","year":"2020","journal-title":"Cell"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1007\/s11481-020-09956-1","article-title":"Exogenous melatonin as potential adjuvant in anti-SarsCov2 vaccines","volume":"15","author":"G Maestroni","year":"2020","journal-title":"J Neuroimmune Pharmacol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1002\/ddr.21701","article-title":"Lithium as a candidate treatment for COVID-19: Promises and pitfalls","volume":"81","author":"R P Rajkumar","year":"2020","journal-title":"Drug Dev Res"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"557629","DOI":"10.3389\/fphar.2020.557629","article-title":"Does lithium deserve a place in the treatment against COVID-19? A preliminary observational study in six patients, case report","volume":"11","author":"C Spuch","year":"2020","journal-title":"Front Pharmacol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s40345-020-00191-4","article-title":"Lithium\u2019s antiviral effects: a potential drug for CoViD-19 disease?","volume":"8","author":"A Murru","year":"2020","journal-title":"Int J Bipolar Disord"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/bdi.12991","article-title":"Association between trace levels of lithium in drinking water and COVID-19\u2013associated mortality","volume":"23","author":"N Ishii","year":"2021","journal-title":"Bipolar Disord"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"109891","DOI":"10.1016\/j.mehy.2020.109891","article-title":"Immunopharmacological management of COVID-19: potential therapeutic role of valproic acid","volume":"143","author":"G Unal","year":"2020","journal-title":"Med Hypotheses"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1097\/ALN.0000000000000618","article-title":"Valproic acid attenuates acute lung injury induced by ischemia-reperfusion in rats","volume":"122","author":"S Y Wu","year":"2015","journal-title":"Anesthesiology"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.4161\/epi.6.12.18396","article-title":"Protective effects of valproic acid against airway hyperresponsiveness and airway remodeling in a mouse model of allergic airways disease","volume":"6","author":"S G Royce","year":"2011","journal-title":"Epigenetics"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/S0006-8993(99)02439-7","article-title":"Sodium valproate inhibits production of TNF-\u03b1 and IL-6 and activation of NF-\u03baB","volume":"857","author":"T Ichiyama","year":"2000","journal-title":"Brain Res"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"173988","DOI":"10.1016\/j.ejphar.2021.173988","article-title":"Potential repurposing of the HDAC inhibitor valproic acid for patients with COVID-19","volume":"898","author":"B Pitt","year":"2021","journal-title":"Eur J Pharmacol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"65","DOI":"10.4103\/CRST.CRST_156_20","article-title":"Repurposing valproate to prevent acute respiratory distress syndrome\/acute lung injury in COVID-19: a review of immunomodulatory action","volume":"3","author":"P Bhargava","year":"2020","journal-title":"Cancer Res Stat Treat"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/s41586-020-2286-9","article-title":"A SARS-CoV-2 protein interaction map reveals targets for drug repurposing","volume":"583","author":"D E Gordon","year":"2020","journal-title":"Nature"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"e0247122","DOI":"10.1371\/journal.pone.0247122","article-title":"Observational study of haloperidol in hospitalized patients with COVID-19","volume":"16","author":"N Hoertel","year":"2021","journal-title":"PLoS One"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.4049\/jimmunol.166.6.4083","article-title":"Histamine induces exocytosis and IL-6 production from human lung macrophages through interaction with H1 receptors","volume":"166","author":"M Triggiani","year":"2001","journal-title":"J Immunol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0024-3205(00)00911-5","article-title":"Binding of antipsychotic drugs to human brain receptors: focus on newer generation compounds","volume":"68","author":"E Richelson","year":"2000","journal-title":"Life Sci"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.mehy.2005.01.036","article-title":"Using histamine (H1) antagonists, in particular atypical antipsychotics, to treat anemia of chronic disease via interleukin-6 suppression","volume":"65","author":"E L Altschuler","year":"2005","journal-title":"Med Hypotheses"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"109774","DOI":"10.1016\/j.mehy.2020.109774","article-title":"Dapsone, colchicine and olanzapine as treatment adjuncts to prevent COVID-19 associated adult respiratory distress syndrome (ARDS)","volume":"141","author":"E L Altschuler","year":"2020","journal-title":"Med Hypotheses"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"110350","DOI":"10.1016\/j.jpsychores.2020.110350","article-title":"A rapid review of the pathoetiology, presentation, and management of delirium in adults with COVID-19","volume":"141","author":"M Hawkins","year":"2021","journal-title":"J Psychosom Res"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"em301","DOI":"10.29333\/ejgm\/11010","article-title":"Quetiapine versus clozapine in treating psychiatric patients with Severe COVID-19: a netosis-based opinion","volume":"18","author":"M Khosravi","year":"2021","journal-title":"Electron J Gen Med"},{"key":"ref41","first-page":"110320","article-title":"COVID-19 Pandemic: what are the risks and challenges for schizophrenia?","volume":"14","author":"M Khosravi","year":"2020","journal-title":"Clin Schizophr Relat Psychoses"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"110140","DOI":"10.1016\/j.mehy.2020.110140","article-title":"The possible immunoregulatory and anti-inflammatory effects of selective serotonin reuptake inhibitors in coronavirus disease patients","volume":"144","author":"M G Hamed","year":"2020","journal-title":"Med Hypotheses"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1080\/22221751.2020.1829082","article-title":"Targeting the endolysosomal host-SARS-CoV-2 interface by clinically licensed functional inhibitors of acid sphingomyelinase (FIASMA) including the antidepressant fluoxetine","volume":"9","author":"S Schloer","year":"2020","journal-title":"Emerg Microbes Infect"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor","volume":"181","author":"M Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"5890","DOI":"10.1038\/s41598-021-85049-0","article-title":"The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2","volume":"11","author":"M Zimniak","year":"2021","journal-title":"Sci Rep"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1001\/jama.2020.22760","article-title":"Fluvoxamine vs placebo and clinical deterioration in outpatients with symptomatic COVID-19: a randomized clinical trial","volume":"324","author":"E J Lenze","year":"2020","journal-title":"JAMA"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"106044","DOI":"10.1016\/j.ijantimicag.2020.106044","article-title":"Widely available lysosome targeting agents should be considered as potential therapy for COVID-19","volume":"56","author":"J Homolak","year":"2020","journal-title":"Int J Antimicrob Agents"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.virol.2019.05.002","article-title":"The ER stress sensor IRE1 and MAP kinase ERK modulate autophagy induction in cells infected with coronavirus infectious bronchitis virus","volume":"533","author":"T S Fung","year":"2019","journal-title":"Virology"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"149","DOI":"10.2165\/00129784-200303030-00001","article-title":"Effect of selective serotonin reuptake inhibitors on platelet activation","volume":"3","author":"R G Schlienger","year":"2003","journal-title":"Am J Cardiovasc Drugs"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1038\/s41598-021-81049-2","article-title":"Cannabis compounds exhibit anti-inflammatory activity in vitro in COVID-19-related inflammation in lung epithelial cells and proinflammatory activity in macrophages","volume":"11","author":"S M Anil","year":"2021","journal-title":"Sci Rep"},{"key":"ref52","first-page":"22425","article-title":"In search of preventive strategies: novel high-CBD Cannabis sativa extracts modulate ACE2 expression in COVID-19 gateway tissues","volume":"12","author":"B Wang","year":"2020","journal-title":"Aging"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/ddr.21752","article-title":"CB2 receptor-selective agonists as candidates for targeting infection, inflammation, and immunity in SARS-CoV-2 infections","volume":"82","author":"M F Nagoor Meeran","year":"2021","journal-title":"Drug Dev Res"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.imbio.2009.09.007","article-title":"Cannabinoid activation of peroxisome proliferator-activated receptors: potential for modulation of inflammatory disease","volume":"215","author":"S E O'Sullivan","year":"2010","journal-title":"Immunobiology"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"e0223430","DOI":"10.1371\/journal.pone.0223430","article-title":"Macrophage PPAR-\u03b3 suppresses long-term lung fibrotic sequelae following acute influenza infection","volume":"14","author":"S Huang","year":"2019","journal-title":"PLoS One"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"116","DOI":"10.4103\/0974-8490.199780","article-title":"Potential of cannabidiol for the treatment of viral hepatitis","volume":"9","author":"H I Lowe","year":"2017","journal-title":"Pharmacognosy Res"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"L891","DOI":"10.1152\/ajplung.00333.2007","article-title":"PPAR-\u03b3 agonists inhibit profibrotic phenotypes in human lung fibroblasts and bleomycin-induced pulmonary fibrosis","volume":"294","author":"J E Milam","year":"2008","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"4967","DOI":"10.1111\/bph.15157","article-title":"The potential of cannabidiol in the COVID-19 pandemic","volume":"177","author":"G Esposito","year":"2020","journal-title":"Br J Pharmacol"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"129","DOI":"10.14740\/jocmr4090","article-title":"Dosage, efficacy and safety of cannabidiol administration in adults: a systematic review of human trials","volume":"12","author":"C Larsen","year":"2020","journal-title":"J Clin Med Res"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1001\/jama.2020.8711","article-title":"Planning for a COVID-19 vaccination program","volume":"323","author":"S S DeRoo","year":"2020","journal-title":"JAMA"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"657316","DOI":"10.3389\/fpsyt.2021.657316","article-title":"Ursodeoxycholic Acid in Patients with Treatment-Resistant Schizophrenia Suffering From Coronavirus Disease 2019: A Hypothesis Letter","volume":"12","author":"M Khosravi","year":"2021","journal-title":"Front Psychiatry"}],"container-title":["Pharmacopsychiatry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1551-3756.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T02:39:58Z","timestamp":1643337598000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1551-3756"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,16]]},"references-count":60,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2022,1,25]]},"published-print":{"date-parts":[[2022,1]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1551-3756","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0176-3679","1439-0795"],"issn-type":[{"value":"0176-3679","type":"print"},{"value":"1439-0795","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,16]]}}}