Neuropsychiatric Decline in a Patient with Extensive Cerebral Metastases: An Overlooked Case of Antidepressant Discontinuation Syndrome

Abstract

Acute behavioural changes in patients with newly discovered cerebral metastases are often attributed to disease progression, corticosteroid-induced psychosis, or oncological treatment-related toxicity. However, withdrawal of psychotropics such as Trazodone can cause similar neuropsychiatric symptoms, complicating the diagnostic evaluation of behavioural changes in oncology patients. This case highlights the challenge of distinguishing antidepressant discontinuation syndrome (ADS) from neurological deterioration in a patient with extensive cerebral metastases.

A 56-Year-old man with stage IIIC scalp melanoma (BRAF V600E positive) presented with an acute headache, nausea, and left-sided facial weakness. An MRI head with contrast revealed 16 new cerebral and cerebellar metastases, with the largest lesion (7 cm) in the right parieto-temporal region causing vasogenic oedema and midline shift. This patient had a history of depression with suicidal ideation, well controlled with 6 months of Trazodone 100mg OD. During admission, Trazodone was discontinued due to polypharmacy concerns and Trazodone’s sedative nature masking neurological deficits. Within 48 hours, he exhibited irritability, blunted affect, and anhedonia, initially attributed to neurological decline and steroid-induced mood disturbance. Despite initiation of Encorafenib and Binimetinib, his neuropsychiatric symptoms persisted. Following liaison psychiatry consultation, Trazodone was reintroduced with slow-upward titration, resulting in clinical improvement of low mood within 5 days. ADS can mimic the clinical presentation of progressive cerebral metastases, though it is importantly reversible in aspects of depressive symptomology. Misattributing these symptoms can lead to unnecessary interventions and delayed psychiatric management, underscoring the need for careful medication reconciliation, gradual tapering, and multidisciplinary involvement.