Can Depakote (valproate) cause hyponatremia (low sodium levels)?

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 taking Depakote, patients and healthcare providers should be aware of potential symptoms of hyponatremia, which include headache, confusion, nausea, seizures, and in severe cases, coma. The mechanism behind Depakote-induced hyponatremia likely involves its effect on antidiuretic hormone (ADH) regulation, similar to other anticonvulsants that can cause syndrome of inappropriate antidiuretic hormone secretion (SIADH) 1.

Key Considerations

• This risk may be higher in elderly patients, those taking other medications that affect sodium levels, or patients with certain medical conditions.
• Regular monitoring of serum sodium levels is advisable, especially when initiating therapy or adjusting dosages.
• If hyponatremia develops, dose adjustment or discontinuation of Depakote may be necessary, depending on the severity of the condition and under medical supervision.
• The treatment of hyponatremia should focus on correcting the underlying cause, and in the case of Depakote-induced hyponatremia, this may involve adjusting the medication regimen 1.

Management of Hyponatremia

• The management of hyponatremia depends on the severity of the condition and the presence of symptoms.
• In patients with severe hyponatremia (serum sodium <125 mmol/L), fluid restriction to 1-1.5 L/day may be necessary, although this is rarely effective in improving serum sodium concentration 1.
• Hypertonic sodium chloride administration may be considered in severe cases, but its efficacy is partial and usually short-lived 1.
• Vaptans, such as tolvaptan, may be effective in improving serum sodium concentration in patients with hypervolemic hyponatremia, but their use should be carefully monitored to avoid complications such as hypernatremia and dehydration 1.

From the Research

Depakote and Hyponatremia

• Depakote, also known as valproic acid, has been associated with hyponatremia in several studies 2, 3, 4, 5.
• Hyponatremia is a condition where the sodium level in the blood is lower than normal, and it can be caused by various factors, including the use of certain medications like Depakote.
• The mechanism by which Depakote causes hyponatremia is not fully understood, but it is thought to be related to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) 3, 4, 5.
• SIADH is a condition where the body produces too much antidiuretic hormone, leading to an imbalance of fluids in the body and a decrease in sodium levels.

Case Reports and Studies

• A case report published in 1998 described a patient who developed hyponatremia while taking Depakote for epilepsy 2.
• Another case report published in 2015 described a patient who developed severe hyponatremia after taking an overdose of Depakote 3.
• A study published in 2001 reported a case of SIADH associated with the use of Depakote 4.
• A case/non-case analysis of the WHO's Vigibase database found a significant association between the use of Depakote and the development of hyponatremia or SIADH 5.

Importance of Monitoring

• The studies suggest that patients taking Depakote should be monitored for signs of hyponatremia, particularly if they are taking high doses of the medication 2, 3, 4, 5.
• Healthcare professionals should be aware of the potential risk of hyponatremia associated with Depakote use and take steps to prevent and treat it promptly.