From the Guidelines
Yes, Depakote (valproic acid/divalproex sodium) can cause hyponatremia, though it is not among its most common side effects. Hyponatremia is a condition characterized by abnormally low sodium levels in the blood (typically below 135 mEq/L). When Depakote causes this condition, it typically develops gradually and may be more common in patients who are elderly, taking other medications that affect sodium levels, or have underlying conditions like heart failure, liver disease, or kidney problems. The mechanism appears to be related to valproic acid's effect on antidiuretic hormone (ADH) regulation, potentially causing syndrome of inappropriate antidiuretic hormone secretion (SIADH) 1.
Key Points to Consider
- Patients taking Depakote should be monitored for symptoms of hyponatremia, which include headache, confusion, lethargy, nausea, muscle cramps, seizures, and in severe cases, coma.
- Regular blood tests to check sodium levels are important for patients on long-term Depakote therapy, especially when starting the medication or adjusting the dose.
- If hyponatremia develops, treatment may involve fluid restriction, sodium supplementation, or in some cases, discontinuation of Depakote under medical supervision.
- According to the most recent guidelines, the management of hyponatremia should focus on correcting the underlying cause, and in cases of hypervolemic hyponatremia, inducing a negative water balance to normalize total body water and improve serum sodium concentration 1.
- Vaptans, such as tolvaptan, have been shown to be effective in improving serum sodium concentration in patients with hypervolemic hyponatremia, including those with cirrhosis and heart failure 1.
Recommendations for Management
- Monitor patients on Depakote for signs and symptoms of hyponatremia and regularly check sodium levels.
- Manage hyponatremia by addressing the underlying cause, which may include adjusting or discontinuing Depakote, fluid restriction, or the use of vaptans in appropriate cases.
- Consider the use of vaptans, such as tolvaptan, for the treatment of severe hypervolemic hyponatremia, especially in patients with cirrhosis or heart failure, under close medical supervision 1.
From the Research
Depakote and Hyponatremia
- Depakote, also known as valproic acid, has been associated with hyponatremia in several studies 2, 3.
- A case study published in the Annals of Neurology in 1998 reported a patient with hyponatremia who was taking sodium valproate, and the condition was resolved after the medication was discontinued 2.
- Another study published in Drug Safety in 2010 described four cases of severe symptomatic hyponatremia or syndrome of inappropriate antidiuretic hormone secretion (SIADH) associated with valproic acid use, and a case/non-case analysis of the WHO's Vigibase database supported the association between valproic acid and hyponatremia 3.
- The exact mechanism by which valproic acid causes hyponatremia is not fully understood, but it may be related to the drug's effect on the hypothalamic osmoreceptors or tubular cell function 3.
- Other studies have discussed the pharmacokinetics and potential side effects of valproic acid, but they do not provide direct evidence for the association between Depakote and hyponatremia 4, 5, 6.