The interplay between serotonin syndrome and syndrome of inappropriate antidiuresis: a fatal case of acute hyponatremia during treatment with duloxetine, chlorphenamine, amitriptyline, and L-tryptophan.

Abstract

Serotonin syndrome (SS) and hyponatremia are severe, potentially life-threatening adverse reactions to serotonergic medications. Their concurrent manifestation is rare but clinically significant due to overlapping pathophysiological mechanisms. This report describes the fatal outcome of a 30-year-old female who presented to the Emergency Department with agitation following self-administration of duloxetine 60 mg, in addition to ongoing amitriptyline therapy and possible L-tryptophan supplementation. During hospitalization, she was treated with intravenous chlorphenamine for a suspected allergic reaction. Subsequently, she developed severe neurological deterioration, malignant arrhythmia, and profound acute hyponatremia (serum sodium 114 mmol/L), culminating in brain death within 48 h. The synergistic pharmacodynamic and pharmacokinetic interactions between duloxetine, amitriptyline, and chlorphenamine-three agents with serotonin reuptake inhibition properties-were implicated in precipitating SS and syndrome of inappropriate antidiuresis (SIAD)-induced hyponatremia. This combination resulted in extensive cerebral edema and cardiopulmonary arrest. The case highlights the diagnostic challenge posed by overlapping SS and hyponatremia manifestations, particularly when compounded by incomplete pharmacological histories and inappropriate drug administration. Clinicians should maintain high vigilance for SS and hyponatremia in patients receiving serotonergic agents, especially when multiple such drugs are co-administered. Comprehensive medication anamnesis, prompt electrolyte monitoring, and avoidance of pharmacodynamic duplication are essential to prevent similar outcomes.