Amantadine and syndrome of inappropriate antidiuretic hormone secretion: Clinical vignettes and lessons learned

Drug-induced hyponatremia secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a potentially reversible yet often overlooked cause of neurological deterioration. Individuals with parkinsonian syndromes represent a vulnerable population because of advanced age, comorbidities, and polypharmacy. We describe a case series of three elderly men who developed hyponatremia fulfilling the diagnostic criteria for SIADH in the setting of amantadine exposure. All individuals demonstrated euvolemic hyponatremia with inappropriately elevated urine osmolality and urinary sodium levels. Baseline sodium levels before presentation were unavailable. A structured evaluation excluding renal, endocrine, infectious, structural, and malignant causes did not identify an alternative etiology. The latency to onset ranged from two weeks to one year after initiation of amantadine. Hyponatremia showed limited response to standard corrective measures but improved consistently following drug withdrawal, accompanied by parallel clinical recovery. Although concurrent corrective interventions preclude definitive causal attribution, the temporal relationship and exclusion of alternative causes suggest a possible contributory association. These findings suggest a possible association between amantadine and SIADH and highlight the importance of meticulous medication review and electrolyte monitoring in individuals with parkinsonism presenting with unexplained neurological worsening.