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

From the Guidelines

The treatment for Syndrome of Inappropriate Antidiuretic Hormone (SIADH) should prioritize addressing the underlying cause while managing hyponatremia, with first-line treatment including fluid restriction to less than 1 L/day, as recommended by expert opinion 1.

Key Considerations

• The goal of treatment is to correct hyponatremia while preventing rapid correction to avoid osmotic demyelination syndrome.
• For acute, severe, or symptomatic hyponatremia (sodium <120 mEq/L with neurological symptoms), hypertonic saline (3% NaCl) may be administered intravenously with close monitoring, as suggested by guidelines for managing hyponatremia in various conditions 1.
• Pharmacological options include vasopressin receptor antagonists (vaptans) such as tolvaptan, which has been approved for the management of severe hypervolemic hyponatremia, including SIADH, and can be started at 15 mg daily with titration as needed 1.

Management Strategies

• Fluid restriction is a cornerstone of SIADH management, aiming to reduce free water intake and correct sodium levels.
• Hypertonic saline is used in severe cases to rapidly correct sodium levels, but its use requires careful monitoring to avoid too rapid correction.
• Vaptans, by blocking ADH action at the kidney, enhance free water excretion and are effective in managing chronic SIADH, with tolvaptan being a commonly used option.
• Regular monitoring of serum sodium, fluid status, and neurological symptoms is crucial throughout treatment to adjust management strategies as needed and prevent complications.

Underlying Cause Treatment

• Treating the underlying cause of SIADH, whether it be malignancy, medications, CNS disorders, or pulmonary disease, is essential for long-term management and prevention of recurrence.
• The choice of treatment should be guided by the severity of hyponatremia, the presence of symptoms, and the underlying cause of SIADH, with consideration of the most recent and highest quality evidence available 1.

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 of tolvaptan can be increased to 30 mg once daily, then to 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 of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) primarily focuses on correcting hyponatremia, which is the most frequent electrolyte disorder associated with this condition 3. The therapeutic modalities include:

• Nonspecific measures such as fluid restriction, hypertonic saline, urea, and demeclocycline
• Vasopressin receptor antagonists, known as vaptans, which offer a specific and direct therapy for SIADH 3, 4

Fluid Restriction and Hypertonic Saline

Fluid restriction is a common treatment approach for SIADH, especially in patients with mild to moderate symptoms 5. Hypertonic saline is used in severely symptomatic patients to rapidly correct serum sodium levels 5. However, the use of hypertonic saline should be cautious to avoid overly rapid correction of hyponatremia, which can lead to osmotic demyelination 3.

Vasopressin Receptor Antagonists (Vaptans)

Vaptans have been introduced as a specific and direct therapy for SIADH, offering advantages such as no need for fluid restriction and rapid correction of hyponatremia 3, 6. Tolvaptan, a type of vaptan, has been shown to be effective in raising serum sodium levels in patients with SIADH, with few side effects 6. However, the high cost of therapy limits its use to the treatment of moderate symptomatic hyponatremia in SIADH 6.

Other Treatment Options

Other treatment options, such as furosemide, oral sodium chloride, and fluid restriction, have been investigated in a randomized controlled study 7. The study found that furosemide with or without sodium chloride supplementation did not show benefits in correction of serum sodium levels compared with treatment with fluid restriction alone 7. Additionally, the use of furosemide was associated with increased incidences of acute kidney injury and hypokalemia 7.

Monitoring and Prevention of Osmotic Demyelination

In any therapy for chronic SIADH, it is essential to limit the daily increase of serum sodium to less than 8-10 mmol/liter to prevent osmotic demyelination 3. Regular monitoring of serum sodium levels is crucial, especially during the first 24 hours of treatment with vaptans, to prevent overly rapid correction of hyponatremia 3.