{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T07:02:58Z","timestamp":1774940578960,"version":"3.50.1"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"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:p>\n                    Serotonin syndrome (SS) is a potentially life-threatening condition resulting from excessive serotonergic activity in the central nervous system. We present a fatal case of SS complicated by multiple organ failure in a 72-year\u2212old patient with Parkinson\u2019s disease following the sequential administration of two selective serotonin reuptake inhibitors (sertraline and escitalopram) while on a stable regimen of the monoamine oxidase-B inhibitor rasagiline. Pharmacogenomic testing revealed a homozygous\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    *10\/*10 genotype, conferring an intermediate metabolizer phenotype, which is postulated to have contributed to serotonergic drug accumulation and resultant toxicity in combination with other significant pharmacodynamic and pharmacokinetic interactions. This case was distinguished by three key features: first, the sequential serotonergic challenge from two different SSRIs in combination with rasagiline; second, the unprecedented severity of clinical manifestations, including rhabdomyolysis, acute hepatic and renal injury, and a disseminated intravascular coagulation-like state; and finally, the pharmacogenetic findings that provide a partial mechanistic explanation for the extreme drug sensitivity. This report underscores the critical importance of pre-emptive pharmacogenomic screening in patients receiving complex polypharmacy, particularly when combining drugs with serotonergic properties. It also serves as a critical warning that even selective MAO-B inhibitors can precipitate life-threatening interactions with SSRIs in genetically susceptible individuals, thereby informing more stringent personalized therapeutic strategies.\n                  <\/jats:p>","DOI":"10.3389\/fpsyt.2026.1750596","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:32:05Z","timestamp":1774935125000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Pharmacogenetically-triggered fatal serotonin syndrome following sequential serotonergic therapy in Parkinson\u2019s disease: a case highlighting the role of CYP2D6*10\/*10 genotype and multifactorial drug interactions"],"prefix":"10.3389","volume":"17","author":[{"given":"Dong-Yang","family":"Liu","sequence":"first","affiliation":[{"name":"The Eighth People\u2019s Hospital of Longgang District","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Hui","family":"Yi","sequence":"additional","affiliation":[{"name":"The Eighth People\u2019s Hospital of Longgang District","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"The Eighth People\u2019s Hospital of Longgang District","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang-Ming","family":"Luo","sequence":"additional","affiliation":[{"name":"The Eighth People\u2019s Hospital of Longgang District","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Jing","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13912","article-title":"Serotonin syndrome\u2014A focused review","volume":"133","author":"Mikkelsen","year":"2023","journal-title":"Basic Clin Pharmacol Toxicology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1136\/dtb.2021.000032","article-title":"Serotonin syndrome","volume":"60","author":"Maitland","year":"2022","journal-title":"Drug Ther bulletin"},{"key":"B3","doi-asserted-by":"publisher","first-page":"196","DOI":"10.4212\/cjhp.v71i3.2586","article-title":"Interaction between monoamine oxidase b inhibitors and selective serotonin reuptake inhibitors","volume":"71","author":"Aboukarr","year":"2018","journal-title":"Can J Hosp Pharmacy"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1500","article-title":"Serotonin toxicity association with concomitant antidepressants and rasagiline treatment: Retrospective study (STACCATO)","volume":"34","author":"Panisset","year":"2014","journal-title":"Pharmacotherapy"},{"key":"B5","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1002\/cpt.2903","article-title":"Clinical pharmacogenetics implementation consortium (CPIC) guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A genotypes and serotonin reuptake inhibitor antidepressants","volume":"114","author":"Bousman","year":"2023","journal-title":"Clin Pharmacol Ther"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.104.002428","article-title":"Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study","volume":"33","author":"Obach","year":"2005","journal-title":"Drug Metab disposition"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200746040-00002","article-title":"The clinical pharmacokinetics of escitalopram","volume":"46","author":"Rao","year":"2007","journal-title":"Clin pharmacokinetics"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2013.47","article-title":"Serotonin toxicity from antidepressant overdose and its association with the T102C polymorphism of the 5-HT 2A receptor","volume":"14","author":"Cooper","year":"2014","journal-title":"Pharmacogenomics J"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1186\/s12877-024-05371-w","article-title":"Serotonin syndrome caused by escitalopram in Parkinson\u2019s disease psychosis: a case report","volume":"24","author":"Wang","year":"2024","journal-title":"BMC Geriatrics"},{"key":"B10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1080\/17512433.2023.2295428","article-title":"Insights into the population pharmacokinetics and pharmacodynamics of quetiapine: a systematic review","volume":"17","author":"Han","year":"2024","journal-title":"Expert Rev Clin Pharmacol"}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2026.1750596\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:32:12Z","timestamp":1774935132000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2026.1750596\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,31]]},"references-count":10,"alternative-id":["10.3389\/fpsyt.2026.1750596"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2026.1750596","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,31]]},"article-number":"1750596"}}