Case Report: Neuropsychiatric and cognitive phenomena in a highly complex patient affected by psychiatric and oncological diseases.

Background: The introduction of innovative oncological therapies, such as immune checkpoint inhibitors (ICIs) and multikinase inhibitors (TKIs), has improved the prognosis of many malignancies but has introduced complex neuropsychiatric adverse events. This case report describes the management of a complex psycho-organic syndrome occurring in a patient treated with the combination of pembrolizumab and lenvatinib. Case presentation: A 69-year-old woman, with a history of anxious-depressive disorder and recurrent endometrial carcinoma, was admitted for the onset of a sub-confusional state, severe psychomotor retardation, akathisia, and tremors. These symptoms appeared in temporal relationship with the initiation of combined pembrolizumab-lenvatinib therapy. Diagnostic investigations (CT, MRI, FDG-PET, and CSF analysis) excluded brain metastases or primary neuroinflammatory processes, revealing diffuse cortical hypometabolism consistent with metabolic-iatrogenic encephalopathy. Management: The therapeutic strategy involved a multidisciplinary approach based on the precautionary suspension of oncological drugs and a structured pharmacological washout. Flumazenil was administered with diagnostic-therapeutic success to correct GABAergic redundancy, and pramipexole was introduced to treat extrapyramidal manifestations and akathisia. Conclusions: This case highlights how overlapping immunological, vascular, and neuropharmacological effects can generate reversible encephalopathic patterns in complex oncological patients. Symptom resolution through psychopharmacological modulation and suspension of targeted treatment alone underscores the critical importance of active neuropsychiatric surveillance and close interdisciplinary collaboration between oncologists and psychopharmacologists.