What is the treatment for Syndrome of Inappropriate Antidiuretic Hormone (SIADH)?

From the Guidelines

The treatment of SIADH should prioritize correcting hyponatremia while addressing the underlying cause, with first-line treatment involving fluid restriction and consideration of vasopressin receptor antagonists like tolvaptan for more severe cases, as supported by recent guidelines 1. The goal of treatment is to improve serum sodium levels, reduce water retention, and manage symptoms.

• Fluid restriction to less than 1 L/day is often recommended as a first-line approach to reduce water retention and increase serum sodium levels.
• For mild to moderate cases, increasing sodium intake through salt tablets or high-salt diets may be beneficial.
• Pharmacological options include vasopressin receptor antagonists such as tolvaptan, starting at 15 mg daily, which can be effective in correcting hyponatremia, especially in severe or resistant cases 1.
• Loop diuretics like furosemide can be used in combination with salt supplementation to enhance free water excretion.
• Urea, given at 30 g daily dissolved in water, is another option that increases solute excretion.
• In cases of severe symptomatic hyponatremia (sodium <120 mEq/L with neurological symptoms), hypertonic saline (3% NaCl) may be administered intravenously with close monitoring to avoid rapid sodium correction, which should not exceed 8-10 mEq/L in 24 hours to prevent osmotic demyelination syndrome 1. Treatment duration and approach depend on the underlying cause and whether it is transient or chronic, with regular monitoring of serum sodium, fluid status, and symptoms being essential throughout treatment. Given the potential for significant morbidity and mortality associated with untreated or inadequately treated SIADH, prioritizing the correction of hyponatremia and addressing the underlying cause is crucial for improving patient outcomes.

From the FDA Drug Label

Tolvaptan tablets are indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

The treatment for Syndrome of Inappropriate Antidiuretic Hormone (SIADH) is tolvaptan, which is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia, including patients with SIADH.

• The usual starting dose for tolvaptan tablets is 15 mg administered once daily without regard to meals.
• The dose can be increased to 30 mg once daily, after at least 24 hours, to a maximum of 60 mg once daily, as needed to achieve the desired level of serum sodium.
• Patients should be in a hospital for initiation and re-initiation of therapy to evaluate the therapeutic response and because too rapid correction of hyponatremia can cause osmotic demyelination resulting in serious neurologic sequelae 2.

From the Research

Treatment Options for SIADH

The treatment for Syndrome of Inappropriate Antidiuretic Hormone (SIADH) includes:

• Fluid restriction, which is often used for chronic hyponatremia in SIADH 3, 4
• Hypertonic saline, which remains the gold standard in the initial treatment of symptomatic SIADH with severe neurological deficits 3, 4
• Demeclocycline, which has been used to treat chronic hyponatremia in SIADH, but has safety concerns and lacks broad availability 3, 4
• Vasopressin receptor antagonists, such as vaptans, which have been shown to be efficacious in treating SIADH with an acceptable safety profile 3, 4, 5, 6
• Tolvaptan, a specific vasopressin receptor antagonist, which may be an attractive treatment option for correction of hyponatremia due to SIADH, especially in pediatric patients 5, 7
• Conivaptan, an intravenous vasopressin-receptor antagonist, which has been used to treat refractory SIADH in pediatric patients 6

Considerations for Treatment

When treating SIADH, it is essential to:

• Limit the daily increase of serum sodium to less than 8-10 mmol/liter to avoid osmotic demyelination 4
• Monitor serum sodium levels closely, especially during the first 24 hours of treatment with vaptans 4
• Be aware of the potential side effects of vaptans, such as thirst, polydipsia, and frequency of urination 4
• Consider the risks and benefits of using vaptans in SIADH, as clinical experience with these drugs is still limited 3, 4