{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T11:29:11Z","timestamp":1787398151204,"version":"build-2736575974"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:00:00Z","timestamp":1696896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Serotonin syndrome has been recognized as a serious adverse reaction to antidepressants and is characterized by sudden or severe autonomic nerve dysfunction and neuromuscular symptoms. Without an accurate diagnosis and prompt treatment, serotonin syndrome progresses rapidly and can be life-threatening. It is usually related to the dose of 5-hydroxytryptamine drugs, and the dose is the basis for diagnosis. Therefore, serotonin syndrome induced by low-dose antidepressants rarely occurs, and clinicians are more likely to misdiagnose patients who take low-dose antidepressants with similar symptoms. Here, we present a case study of serotonin syndrome caused by a relatively low dose of escitalopram, which is not common in past references.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case summary<\/jats:title><jats:p>The patient was a 74-year-old Asian woman with a 42-year history of schizophrenia. After 6\u2009weeks of antidepressant treatment, our patient presented with characteristic myoclonus in the lower limbs and closed eyes with fluttering. Initially, she was misdiagnosed with neuroleptic malignant syndrome (NMS) due to antipsychotic medication and was treated accordingly, even with discontinuation of clozapine. However, her symptoms persisted, and then therapeutic drug monitoring was initiated with the involvement of a clinical pharmacist. Eventually, she was diagnosed with serotonin syndrome due to escitalopram levels reaching the warning level. Subsequently, the patient\u2019s treatment was modified, and her clinical outcome was satisfactory without any other serious adverse reactions. Gene detection was also performed, and a cytochrome P450 enzyme (CYP) 2C19-mediated interaction between low-dose escitalopram and clopidogrel seems to be a possible mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Data on this is extremely scarce, and to the best of our knowledge, serotonin syndrome caused by low-dose antidepressants has not yet been discussed to any great extent in the literature. Our case provides more clinical experience in the treatment of serotonin syndrome.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpsyt.2023.1257984","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:37:07Z","timestamp":1696984627000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Serotonin syndrome caused by a CYP2C19-mediated interaction between low-dose escitalopram and clopidogrel: a case report"],"prefix":"10.3389","volume":"14","author":[{"given":"Jianhong","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kankan","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunming","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1056\/NEJMra041867","article-title":"The serotonin syndrome","volume":"352","author":"Boyer","year":"2005","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"810","DOI":"10.3949\/ccjm.83a.15129","article-title":"Serotonin syndrome: preventing, recognizing, and treating it","volume":"83","author":"Wang","year":"2016","journal-title":"Cleve Clin J Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s12934-022-01745-0","article-title":"Construction of cell factory capable of efficiently converting L-tryptophan into 5-hydroxytryptamine","volume":"21","author":"Wang","year":"2022","journal-title":"Microb Cell Factories"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s10522-012-9406-3","article-title":"Serotonin: from top to bottom","volume":"14","author":"Fidalgo","year":"2013","journal-title":"Biogerontology"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.ejphar.2018.08.009","article-title":"L-tryptophan administration and increase in cerebral serotonin levels: systematic review","volume":"836","author":"Carneiro","year":"2018","journal-title":"Eur J Pharmacol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s13041-017-0306-y","article-title":"The role of 5-HT receptors in depression","volume":"10","author":"Yohn","year":"2017","journal-title":"Mol Brain"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.cell.2018.07.043","article-title":"Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems","volume":"175","author":"Ren","year":"2018","journal-title":"Cells"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.genhosppsych.2007.09.007","article-title":"Serotonin syndrome: a complex but easily avoidable condition","volume":"30","author":"Dvir","year":"2008","journal-title":"Gen Hosp Psychiatry"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"169","DOI":"10.4088\/JCP.13m08443","article-title":"National trends in long-term use of antidepressant medications: results from the U.S. National Health and nutrition examination survey","volume":"75","author":"Mojtabai","year":"2014","journal-title":"J Clin Psychiatry"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1007\/BF01250975","article-title":"Antidepressants and the serotonin syndrome in general practice","volume":"49","author":"Mackay","year":"1999","journal-title":"Br J Gen Pract"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1001\/jamaneurol.2017.5144","article-title":"Association of coprescription of triptan antimigraine drugs and selective serotonin reuptake inhibitor or selective norepinephrine reuptake inhibitor antidepressants with serotonin syndrome","volume":"75","author":"Orlova","year":"2018","journal-title":"JAMA Neurol"},{"key":"ref12","first-page":"720","article-title":"Demystifying serotonin syndrome (or serotonin toxicity)","volume":"64","author":"Foong","year":"2018","journal-title":"Can Fam Physician"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e2247426","DOI":"10.1001\/jamanetworkopen.2022.47426","article-title":"Association of linezolid with risk of serotonin syndrome in patients receiving antidepressants","volume":"5","author":"Bai","year":"2022","journal-title":"JAMA Netw Open"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1192\/bjp.148.1.47","article-title":"Neuroleptic malignant syndrome","volume":"148","author":"Abbott","year":"1986","journal-title":"Br J Psychiatry"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/0301-0082(91)90018-V","article-title":"The neuroleptic malignant syndrome","volume":"36","author":"Dickey","year":"1991","journal-title":"Prog Neurobiol"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-022-01621-0","article-title":"Turned to stone: a history of the neuroleptic malignant syndrome","author":"Wijdicks","year":"2022","journal-title":"Neurocrit Care"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1007\/978-1-4614-8948-1_49","article-title":"Serotonin syndrome","volume":"13","author":"Volpi-Abadie","year":"2013","journal-title":"Ochsner J"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"252","DOI":"10.4088\/JCP.v58n0603","article-title":"Clozapine withdrawal resulting in delirium with psychosis: a report of three cases","volume":"58","author":"Stanilla","year":"1997","journal-title":"J Clin Psychiatry"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1001\/jamaneurol.2013.95","article-title":"Serotonin syndrome associated with clozapine withdrawal","volume":"70","author":"Stevenson","year":"2013","journal-title":"JAMA Neurol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1093\/qjmed\/hcg109","article-title":"The hunter serotonin toxicity criteria: simple and accurate diagnostic decision rules for serotonin toxicity","volume":"96","author":"Dunkley","year":"2003","journal-title":"QJM"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"361","DOI":"10.5694\/j.1326-5377.2007.tb01282.x","article-title":"Serotonin toxicity: a practical approach to diagnosis and treatment","volume":"187","author":"Isbister","year":"2007","journal-title":"Med J Aust"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"117864691987392","DOI":"10.1177\/1178646919873925","article-title":"Serotonin syndrome: pathophysiology, clinical features, management, and potential future directions","volume":"12","author":"Scotton","year":"2019","journal-title":"Int J Tryptophan Res"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1176\/ajp.148.6.705","article-title":"The serotonin syndrome","volume":"148","author":"Sternbach","year":"1991","journal-title":"Am J Psychiatry"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1093\/jac\/dki368","article-title":"Linezolid-associated serotonin syndrome: what we can learn from cases reported so far","volume":"56","author":"Morales-Molina","year":"2005","journal-title":"J Antimicrob Chemother"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1007\/s40262-014-0162-1","article-title":"Impact of cytochrome P450 2C19 polymorphisms on citalopram\/escitalopram exposure: a systematic review and meta-analysis","volume":"53","author":"Chang","year":"2014","journal-title":"Clin Pharmacokinet"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.thromres.2011.04.010","article-title":"Pharmacogenomics of clopidogrel: evidence and perspectives","volume":"128","author":"Yin","year":"2011","journal-title":"Thromb Res"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.jad.2011.08.013","article-title":"Decreased serotonin content and reduced agonist-induced aggregation in platelets of patients chronically medicated with SSRI drugs","volume":"136","author":"Bismuth-Evenzal","year":"2012","journal-title":"J Affect Disord"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1192\/bjp.173.3.236","article-title":"5-HT2A receptor blockade in patients with schizophrenia treated with risperidone or clozapine. A SPET study using the novel 5-HT2A ligand 123I-5-I-R-91150","volume":"173","author":"Travis","year":"1998","journal-title":"Br J Psychiatry"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1016\/j.neuro.2007.05.004","article-title":"First time, low dose citalopram use-related serotonin syndrome","volume":"28","author":"Turedi","year":"2007","journal-title":"Neurotoxicology"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1177\/106002800303700209","article-title":"Serotonin syndrome induced by low-dose venlafaxine","volume":"37","author":"Pan","year":"2003","journal-title":"Ann Pharmacother"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.4065\/79.11.1444","article-title":"Life-threatening serotonin syndrome in a patient with chronic heart failure and CYP2D6*1\/*5","volume":"79","author":"Sato","year":"2004","journal-title":"Mayo Clin Proc"}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2023.1257984\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:37:10Z","timestamp":1696984630000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2023.1257984\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,10]]},"references-count":31,"alternative-id":["10.3389\/fpsyt.2023.1257984"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2023.1257984","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,10]]},"article-number":"1257984"}}