Case Report: Corticosteroid-induced severe psychiatric manifestations in a patient with leptomeningeal metastases from lung adenocarcinoma

Background 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. Case presentation A 66-year-old male with EGFR-mutant lung adenocarcinoma and LM developed progressively worsening psychiatric manifestations after three short-course glucocorticoid exposures, despite >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. Conclusion 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 “basal vulnerability plus acute trigger” model and highlighting the pivotal role of clinical pharmacists in pharmacovigilance.