From the Research
Valproate can produce SIADH, and clinicians should be aware of this potential adverse effect, particularly in patients with risk factors for electrolyte disturbances or those taking other medications that might affect sodium balance. The mechanism likely involves valproate's effect on hypothalamic regulation of ADH secretion, disrupting the normal osmotic control of this hormone 1. Patients taking valproate who develop symptoms such as headache, confusion, lethargy, nausea, seizures, or muscle cramps should be evaluated for possible hyponatremia related to SIADH.
Some key points to consider in the management of valproate-induced SIADH include:
- Monitoring sodium levels in patients on valproate therapy, particularly those with risk factors for electrolyte disturbances or those taking other medications that might affect sodium balance 2, 3, 4
- If SIADH is suspected, sodium levels should be checked promptly, and management may involve fluid restriction, discontinuation of valproate if appropriate, or switching to an alternative antiepileptic or mood stabilizer depending on the indication for treatment 1
- The use of urea and vaptans can be effective in managing the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure, but have adverse effects 5
- Severely symptomatic hyponatremia (with signs of somnolence, obtundation, coma, seizures, or cardiorespiratory distress) is a medical emergency that requires prompt treatment with bolus hypertonic saline to reverse hyponatremic encephalopathy 5
It is essential to note that hyponatremia is a secondary cause of osteoporosis, and even mild hyponatremia is associated with increased hospital stay and mortality 5. Therefore, clinicians should prioritize the monitoring and management of sodium levels in patients on valproate therapy to prevent the development of SIADH and its associated morbidity and mortality.