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

From the Guidelines

The treatment for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) should focus on 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. The goal of treatment is to correct sodium levels and prevent complications such as seizures, coma, and death.

• For asymptomatic mild SIADH, fluid restriction is the primary treatment.
• For acute, severe, or symptomatic hyponatremia (sodium <120 mEq/L or neurological symptoms), hypertonic (3%) saline may be administered intravenously at 1-2 mL/kg/hour with careful monitoring to avoid rapid correction 1.
• Pharmacological options include demeclocycline, lithium, and vasopressin 2 receptor antagonists (conivaptan, lixivaptan, tolvaptan, and satavaptan) to correct hyponatremia 1.
• Vasopressin receptor antagonists (vaptans) such as tolvaptan have been shown to be effective in improving serum sodium concentration in conditions associated with high vasopressin levels, such as SIADH 1.
• Sodium correction should not exceed 8-10 mEq/L in 24 hours to prevent osmotic demyelination syndrome.
• Treating the underlying cause—whether malignancy, medications, pulmonary disease, or CNS disorders—is essential for long-term management.
• Regular monitoring of serum sodium, fluid status, and neurological symptoms is necessary throughout treatment. It is essential to note that there are no evidence-based guidelines for managing SIADH, and recommended management is based on expert opinion 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)

El tratamiento para el Síndrome de Secreción Inapropiada de Hormona Antidiurética (SIADH) es tolvaptan, que se administra por vía oral.

• La dosis inicial recomendada es de 15 mg una vez al día.
• La dosis puede aumentarse a 30 mg una vez al día, después de al menos 24 horas, hasta un máximo de 60 mg una vez al día, según sea necesario para alcanzar el nivel deseado de sodio sérico.
• Es importante iniciar y reiniciar el tratamiento en un hospital, donde se pueda monitorear estrechamente el sodio sérico, para evitar una corrección demasiado rápida de la hiponatremia, que puede causar secuelas neurológicas graves 2.

From the Research

Treatment Options for SIADH

The treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) aims to correct hyponatremia and alleviate symptoms. The following options are available:

• Fluid restriction: This is a common initial treatment for SIADH, but it may have limitations and be insufficient in some cases 3.
• Hypertonic saline: This can be used to rapidly correct severe hyponatremia, but it requires careful monitoring to avoid overcorrection 4.
• Urea and demeclocycline: These are nonspecific measures that can be used to treat SIADH, but they may have side effects and are not always effective 4.
• Vasopressin receptor antagonists (vaptans): These are specific and direct therapies for SIADH, which can effectively correct hyponatremia without the need for fluid restriction 4, 5, 6, 7.

Vaptans in SIADH Treatment

Vaptans, such as tolvaptan, have been shown to be effective and safe in the treatment of SIADH. They work by antagonizing the action of vasopressin, which helps to correct hyponatremia. The use of vaptans has several benefits, including:

• Rapid correction of hyponatremia: Vaptans can correct hyponatremia quickly and comfortably, without the need for fluid restriction 4.
• Low risk of overcorrection: Vaptans have a low risk of overcorrection, which can help to prevent osmotic demyelination syndrome 6, 7.
• Few side effects: Vaptans have few side effects, which are typically mild and include thirst, polydipsia, and frequency of urination 4, 6.

Dosage and Monitoring of Vaptans

The dosage of vaptans, such as tolvaptan, is important to ensure effective and safe treatment of SIADH. The following guidelines are recommended:

• Starting dose: The starting dose of tolvaptan can be lower than the licensed dose of 15mg, with some studies suggesting a starting dose of 7.5mg or 3.75mg 6, 7.
• Monitoring: Close monitoring of serum sodium levels is essential to avoid overcorrection and ensure effective treatment 4, 6, 7.
• Adjustment of dose: The dose of tolvaptan may need to be adjusted based on the patient's response to treatment and serum sodium levels 6, 7.