Is valproic acid (an anticonvulsant and mood stabilizer) used to treat hypernatremia?

Valproic Acid Is Not Used to Treat Hypernatremia and May Actually Cause Hyponatremia

Valproic acid should not be used to treat hypernatremia and is contraindicated in this condition as it can actually cause hyponatremia through a syndrome of inappropriate antidiuretic hormone secretion (SIADH)-like mechanism. 1, 2

Relationship Between Valproic Acid and Sodium Levels

Valproic acid (VPA) is an anticonvulsant and mood stabilizer that has no therapeutic role in treating hypernatremia. In fact, the evidence demonstrates the opposite effect:

• VPA has been documented to cause significant hyponatremia through an SIADH-like mechanism 2
• Case reports have shown VPA causing profound hyponatremia with serum sodium levels as low as 99 mEq/L 1
• The hyponatremic effect appears to be dose-dependent, with higher doses of VPA leading to greater impairment in water excretion 2

Appropriate Management of Hypernatremia

For hypernatremia management, the following approaches are recommended instead:

1. Identify and treat the underlying cause (water deficit, diabetes insipidus, excessive sodium intake)
2. Provide appropriate fluid replacement based on the calculated water deficit
3. Consider vasopressin antagonists for specific situations:
   • In patients with heart failure and persistent severe hypervolemic hyponatremia, vasopressin antagonists (tolvaptan or conivaptan) may be considered to improve serum sodium concentration 3

Seizure Management Considerations

If a patient has both hypernatremia and seizures requiring treatment:

• Levetiracetam is preferred over valproic acid for seizure management in patients with electrolyte disturbances 3, 4
• Valproic acid should be avoided due to its potential to worsen sodium imbalance 1, 2
• For status epilepticus, while valproic acid is generally effective (88% success rate), it should be avoided in patients with hypernatremia 3, 4

Adverse Effects of Valproic Acid Related to Electrolytes

Valproic acid has several documented adverse effects related to electrolyte disturbances:

• Hyponatremia through SIADH-like mechanism 1, 2, 5
• Rarely, hypernatremia has been reported when switching from lithium to valproic acid, but this was attributed to underlying lithium-induced diabetes insipidus rather than a direct effect of valproic acid 6
• Other serious adverse effects include pancreatitis, thrombocytopenia, and hepatotoxicity 3, 7

Clinical Monitoring

For patients on valproic acid therapy:

• Regular monitoring of serum sodium levels is recommended, especially with high doses 2
• Patients presenting with confusion, lethargy, or seizures while on valproic acid should have electrolytes checked to rule out hyponatremia 1, 5
• Discontinuation of valproic acid should be considered if significant hyponatremia develops 1

Conclusion

Valproic acid has no role in treating hypernatremia and should be avoided in this condition due to its potential to cause hyponatremia. For patients requiring both hypernatremia management and seizure control, alternative anticonvulsants such as levetiracetam are more appropriate choices.