{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:15:08Z","timestamp":1792800908524,"version":"4.5.0"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glucocorticoids are widely used in leptomeningeal metastases (LM) to reduce peritumoral edema, yet their psychiatric adverse effects remain underrecognized, particularly progressive sensitization following long-term tolerance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>A 66-year-old male with EGFR-mutant lung adenocarcinoma and LM developed progressively worsening psychiatric manifestations after three short-course glucocorticoid exposures, despite &amp;gt;9 months of prior tolerance to intrathecal dexamethasone. Symptoms escalated from manic-like agitation to homicidal ideation to persecutory delusions with complete treatment refusal. A Naranjo score of 10 confirmed definite causality. Symptoms resolved after discontinuation and psychiatric hospitalization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case demonstrates cumulative sensitization with paradoxical dose-independent worsening of corticosteroid-induced psychiatric toxicity following long-term tolerance, whereby repeated glucocorticoid exposures produced progressively severe psychiatric reactions despite fluctuating and overall decreasing cumulative doses, supporting a \u201cbasal vulnerability plus acute trigger\u201d model and highlighting the pivotal role of clinical pharmacists in pharmacovigilance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1939579","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:10:28Z","timestamp":1789510228000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Corticosteroid-induced severe psychiatric manifestations in a patient with leptomeningeal metastases from lung adenocarcinoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Fan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Medicine-Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangwen","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Medical University","place":["Dongguan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"B1","volume-title":"Diagnostic and Statistical Manual of Mental Disorders","year":"2022"},{"key":"B2","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.psym.2011.12.007","article-title":"The neuropsychiatric complications of glucocorticoid use: steroid psychosis revisited","volume":"53","author":"Dubovsky","year":"2012","journal-title":"Psychosomatics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1628765","DOI":"10.3389\/fphar.2025.1628765","article-title":"Corticosteroid-induced manic And\/or psychotic symptoms: a systematic review","volume":"16","author":"Gostoli","year":"2025","journal-title":"Front. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"3216","DOI":"10.21037\/tlcr-2025-163","article-title":"Advances in the research of leptomeningeal metastases in non-small cell lung cancer: a narrative review","volume":"14","author":"Hong","year":"2025","journal-title":"Transl. Lung Cancer Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e1442","DOI":"10.1210\/clinem\/dgad701","article-title":"Neuropsychiatric adverse effects of synthetic glucocorticoids: a systematic review and meta-analysis","volume":"109","author":"Koning","year":"2024","journal-title":"J. Clin. Endocrinol. and Metabolism"},{"key":"B6","doi-asserted-by":"publisher","first-page":"101624","DOI":"10.1016\/j.esmoop.2023.101624","article-title":"Leptomeningeal metastasis from solid tumours: EANO-ESMO clinical practice guideline for diagnosis, treatment and follow-up","volume":"8","author":"Le Rhun","year":"2023","journal-title":"ESMO Open"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e70088","DOI":"10.1111\/1759-7714.70088","article-title":"Chinese expert consensus on leptomeningeal metastases of lung cancer","volume":"16","author":"Lin","year":"2025","journal-title":"Thorac. Cancer"},{"key":"B8","doi-asserted-by":"publisher","first-page":"151","DOI":"10.4103\/aip.aip_56_25","article-title":"Psychiatric adverse effects of synthetic corticosteroids: a prospective observational study","volume":"10","author":"Mukherjee","year":"2026","journal-title":"Ann. Indian Psychiatry"},{"key":"B9","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/clpt.1981.154","article-title":"A method for estimating the probability of adverse drug reactions","volume":"30","author":"Naranjo","year":"1981","journal-title":"Clin. Pharmacol. Ther."},{"key":"B10","doi-asserted-by":"publisher","first-page":"300","DOI":"10.3390\/diseases12120300","article-title":"Corticosteroid-induced psychiatric disorders: mechanisms, outcomes, and clinical implications","volume":"12","author":"Nasereddin","year":"2024","journal-title":"Diseases"},{"key":"B11","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s11060-009-0057-4","article-title":"The role of steroids in the management of brain metastases: a systematic review and evidence-based clinical practice guideline","volume":"96","author":"Ryken","year":"2010","journal-title":"J. Neurooncol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"21cr03086","DOI":"10.4088\/PCC.21cr03086","article-title":"Clonazepam to the rescue? post-steroid mania and a paradoxical response to an atypical antipsychotic","volume":"24","author":"Schoenfeld","year":"2022","journal-title":"Prim. Care Companion CNS Disord."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.3390\/biomedicines12092131","article-title":"Molecular, pathophysiological, and clinical aspects of corticosteroid-induced neuropsychiatric effects: from bench to bedside","volume":"12","author":"Sofia-Avendano-Lopez","year":"2024","journal-title":"Biomedicines"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.4065\/81.10.1361","article-title":"Psychiatric adverse effects of corticosteroids","volume":"81","author":"Warrington","year":"2006","journal-title":"Mayo Clin. Proc."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1939579\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:10:35Z","timestamp":1789510235000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1939579\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":14,"alternative-id":["10.3389\/fphar.2026.1939579"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1939579","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]},"article-number":"1939579"}}