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

From the Guidelines

The treatment of SIADH should prioritize the use of vasopressin receptor antagonists, such as tolvaptan, due to their effectiveness in improving serum sodium concentration and managing hypervolemic hyponatremia, as demonstrated in recent studies 1.

Key Considerations

• The goal of treatment is to normalize serum sodium levels while preventing neurological complications from either hyponatremia or overly rapid correction.
• For mild to moderate cases with minimal symptoms, fluid restriction of 800-1000 mL/day may be considered, but its efficacy is often limited 1.
• In more severe or symptomatic cases, vasopressin receptor antagonists such as tolvaptan (starting at 15 mg daily, maximum 60 mg) are a preferred option, requiring careful monitoring due to the risk of overcorrection 1.

Treatment Approach

• Tolvaptan has been shown to be effective in improving serum sodium concentration in patients with SIADH, heart failure, and liver cirrhosis, with a low risk of significant side effects 1.
• The treatment should be individualized based on symptom severity, chronicity, and underlying etiology, with close monitoring of serum sodium levels to avoid rapid correction.
• Other options, such as urea, demeclocycline, and loop diuretics, may be considered in specific cases, but their use should be guided by the patient's clinical presentation and response to treatment.

Monitoring and Safety

• Patients treated with vaptans should be closely monitored for signs of overcorrection, dehydration, and renal impairment, with regular assessments of serum sodium levels and urine output.
• The risk of osmotic demyelination syndrome should be carefully considered, and treatment should be started in a hospital setting with close clinical monitoring.

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)

Tolvaptan is used to treat SIADH. The usual starting dose for tolvaptan tablets is 15 mg administered once daily without regard to meals. Increase the dose 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.

• Key points:
  • Initiate and re-initiate in a hospital and monitor serum sodium.
  • Avoid too rapid correction of hyponatremia.
  • Do not administer tolvaptan tablets for more than 30 days to minimize the risk of liver injury.
  • During initiation and titration, frequently monitor for changes in serum electrolytes and volume.
  • Patients receiving tolvaptan tablets should be advised that they can continue ingestion of fluid in response to thirst. 2

From the Research

Treatment Options for SIADH

• The primary goal of treating SIADH is to alleviate symptoms, with treatment approaches including fluid restriction, hypertonic saline, urea, demeclocycline, and vasopressin receptor antagonists (vaptans) 3, 4.
• Vaptans have been shown to be effective in treating SIADH, with advantages including no need for fluid restriction and rapid correction of hyponatremia 3, 4.
• However, the use of vaptans is not without limitations, with potential side effects including thirst, polydipsia, and frequency of urination 3, 4.

Management of Hyponatremia in SIADH

• Correction of hyponatremia should be done slowly, with a daily increase in serum sodium of less than 8-10 mmol/liter to avoid osmotic demyelination 3, 4.
• In patients treated with vaptans, serum sodium levels should be closely monitored, particularly in the first 24 hours of treatment 3.
• Discontinuation of vaptan therapy should be done cautiously, with monitoring for potential hyponatremic relapse 3.

Alternative Treatment Approaches

• Intermittent lower-dose tolvaptan combined with fluid restriction may be an effective treatment option for patients with chronic SIADH, allowing for individualized dosing and minimizing side effects 5.
• Non-drug management, including fluid restriction, may be a viable alternative to pharmacological treatment for some patients with SIADH 6.

Limitations and Considerations

• The efficacy of tolvaptan in treating SIADH has not been fully established, with limited clinical trial data and potential methodological flaws 6.
• The use of vaptans in clinical practice is still relatively limited, and careful postmarketing surveillance is necessary to fully appreciate their risks and benefits 4.