{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:32:26Z","timestamp":1787614346525,"version":"build-2736575974"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005892","name":"China Academy of Chinese Medical Sciences","doi-asserted-by":"publisher","award":["CI2022C004-02"],"award-info":[{"award-number":["CI2022C004-02"]}],"id":[{"id":"10.13039\/501100005892","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005892","name":"China Academy of Chinese Medical Sciences","doi-asserted-by":"publisher","award":["HLCMHPP2023090"],"award-info":[{"award-number":["HLCMHPP2023090"]}],"id":[{"id":"10.13039\/501100005892","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005892","name":"China Academy of Chinese Medical Sciences","doi-asserted-by":"publisher","award":["CI2022C005"],"award-info":[{"award-number":["CI2022C005"]}],"id":[{"id":"10.13039\/501100005892","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Escitalopram is widely regarded as a well-tolerated selective serotonin reuptake inhibitor (SSRI) with a favorable safety profile. However, severe adverse events can occur even at therapeutic doses in susceptible individuals. Here, we report a rare case of simultaneous life-threatening Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) and cardiac toxicity induced by standard-dose escitalopram. A 51-year-old female (weight 50\u00a0kg) presented with severe fatigue and anorexia. Initial laboratory results revealed profound hyponatremia (116.1\u00a0mmol\/L). Following sodium supplementation, serum sodium paradoxically decreased to 114.7\u00a0mmol\/L (\u201cdesalination phenomenon\u201d), while urinary sodium excretion was markedly elevated (220 mmol\/24\u00a0h) alongside significant hypouricemia (76\u00a0\u03bcmol\/L), confirming the diagnosis of SIADH. Concurrently, the patient manifested significant cardiac toxicity, including sinus bradycardia (41\u201355 bpm) and marked QTc prolongation (570\u00a0ms). Pharmacogenetic analysis identified the CYP2C19 *1\/*2 genotype (Intermediate Metabolizer). Despite the therapeutic dosage (10\u00a0mg\/day) and a non-toxic serum concentration (5\u00a0ng\/mL measured 72\u00a0h post-discontinuation), the patient exhibited severe toxicity, likely driven by \u201cphenoconversion\u201d due to low muscle mass and physiological vulnerability, exacerbated by a pharmacodynamic synergism with low-dose quetiapine. Discontinuation of medications and strict fluid management resulted in complete resolution of both hyponatremia and arrhythmia. The causality was assessed as \u201cprobable\u201d for both drugs using the Naranjo Algorithm, and the drug-drug interaction was rated as \u201cprobable\u201d using the Drug Interaction Probability Scale (DIPS). This case highlights that genotype-phenotype mismatch, combined with pharmacodynamic synergism (escitalopram-quetiapine interaction), can precipitate severe neuro-cardiac toxicity even at therapeutic levels. It underscores that severe neuro-cardiac toxicity can occur even at therapeutic levels due to individual vulnerability. Therefore, routine monitoring of electrolytes and electrocardiograms (ECG) remains indispensable for patient safety, as pharmacogenetic screening and therapeutic drug monitoring may not predict such idiosyncratic reactions in resource-constrained settings.<\/jats:p>","DOI":"10.3389\/fphar.2026.1776959","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T06:41:47Z","timestamp":1769755307000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Severe SIADH and QTc prolongation induced by escitalopram-quetiapine interaction in a CYP2C19 intermediate metabolizer at therapeutic doses"],"prefix":"10.3389","volume":"17","author":[{"given":"Zongchen","family":"Jiang","sequence":"first","affiliation":[{"name":"Guang\u2019anmen Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Qu","sequence":"additional","affiliation":[{"name":"Guang\u2019anmen Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zimin","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Emergency, Guang\u2019anmen Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungang","family":"Fang","sequence":"additional","affiliation":[{"name":"Guang\u2019anmen Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Lan","sequence":"additional","affiliation":[{"name":"Guang\u2019anmen Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Emergency, Guang\u2019anmen Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wensheng","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Emergency, Guang\u2019anmen Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/s0165-0327(99)00092-0","article-title":"Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability","volume":"58","author":"Anderson","year":"2000","journal-title":"J. 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