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Background and Importance Serotonin syndrome (SS) is an uncommon potentially life-threatening adverse drug reaction caused by excessive serotonergic activity, usually related to drug interactions or high-dose antidepressant therapy. In older adults, diagnosis is particularly challenging due to atypical presentations, multiple comorbidities, and polypharmacy. Pharmacists play a key role in identifying drug-related risks and supporting early recognition.Aim and Objectives To describe the case of an 81-year-old man admitted after traumatic brain injury associated with hypotension, with a history of atrial fibrillation on rivaroxaban and bisoprolol, hypertension, prior ischaemic stroke without sequelae, and depression treated with clomipramine 150 mg/day and venlafaxine 300 mg/day. Relevant comorbidities included benign prostatic hyperplasia and orthostatic hypotension.Material and Methods During hospitalisation, the patient developed fever >39 °C, progressive somnolence, generalised tremor, and rigidity. Laboratory tests showed CK 9100 U/L, AST 883 U/L, ALT 391 U/L, creatinine 1.87 mg/dL, and hypernatraemia. EEG excluded seizures. Considering his medication history, SS was suspected. Neuroleptic malignant syndrome was considered less likely due to the absence of antipsychotics, though CK elevation and rigidity raised diagnostic uncertainty. Empirical therapy with oral cyproheptadine (12 mg initial dose followed by 2 mg every 2 h, maximum 32 mg/day) was started together with supportive measures. Bromocriptine was later added to cover potential diagnostic overlap.Results Over the following days, the patient showed progressive clinical improvement: fever resolved, myoclonus decreased, consciousness and orientation improved, and CK values declined. After psychiatric consultation, antidepressant therapy was switched to desvenlafaxine due to its lower risk of orthostatic hypotension and serotonergic toxicity. Beta-blocker therapy was also adjusted to minimise hypotensive episodes. The patient continued recovery in a rehabilitation unit.Conclusion and Relevance This case highlights the diagnostic complexity of SS in geriatric patients under polypharmacy, particularly when dual antidepressant therapy is involved. Clinical overlap with other syndromes, such as neuroleptic malignant syndrome, can delay recognition. Pharmacist involvement in medication review was crucial to identify the causative agents and propose safer alternatives. Early detection and tailored pharmacological management are essential to reduce morbidity in this vulnerable population.Conflict of Interest No conflict of interest