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

Treatment of Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

The first-line treatment for SIADH is fluid restriction, with vasopressin receptor antagonists (vaptans) recommended for refractory cases, particularly when serum sodium is below 125 mmol/L. 1

Initial Assessment and Treatment Algorithm

Step 1: Confirm SIADH Diagnosis

• Verify euvolemic hyponatremia
• Rule out other causes (hypovolemic, hypervolemic)
• Check for underlying causes (malignancy, pulmonary disease, CNS disorders, medications)

Step 2: Determine Severity and Treatment Approach

1. Mild to Moderate Hyponatremia (Na 125-135 mmol/L)

   • Fluid restriction (1-1.5 L/day) 1
   • Continue monitoring serum sodium levels
   • No water restriction if asymptomatic with Na >126 mmol/L 1

2. Severe Hyponatremia (Na <125 mmol/L) or Symptomatic

   • Initiate treatment in hospital setting with close monitoring 2
   • For severe neurological symptoms:
     • Hypertonic (3%) saline solution in small boluses
     • Target correction rate <8-10 mmol/L in 24 hours to prevent osmotic demyelination 1, 2

3. Refractory Cases

   • Vasopressin receptor antagonists (vaptans) 1
   • Demeclocycline as alternative 1

Specific Treatments

Fluid Restriction

• Initial approach for most SIADH cases
• Restrict to 500-1500 mL/day based on severity 1, 3
• Often difficult for patients due to increased thirst 1
• May be ineffective in up to 50% of cases 3

Pharmacologic Options

Vasopressin Receptor Antagonists (Vaptans)

• Tolvaptan:

  • Starting dose: 15 mg once daily
  • May increase to 30 mg after 24 hours, maximum 60 mg daily
  • Must be initiated in hospital setting with close monitoring
  • Limit treatment to 30 days to minimize liver injury risk 2
  • Monitor serum sodium at 0,6,24, and 48 hours after initiation 4

• Conivaptan:

  • Intravenous administration for short-term use (2-4 days)
  • Effective for euvolemic or hypervolemic hyponatremia 1

Other Medications

• Demeclocycline: Alternative when vaptans unavailable 1
• Urea: Considered effective and safe second-line therapy 3

Important Cautions

• Avoid overcorrection: Limit sodium increase to <8-10 mmol/L/24 hours to prevent osmotic demyelination syndrome 2, 4
• Monitor closely: Check serum sodium frequently during treatment
• Discontinuation: When stopping vaptans, taper dose or reinstate fluid restriction to prevent hyponatremic relapse 4
• Contraindications for vaptans: Hypovolemic hyponatremia, inability to sense thirst, anuria, concurrent use of strong CYP3A inhibitors 2

Treatment of Underlying Cause

Treating the underlying cause of SIADH is essential for long-term management:

• Cancer treatment for malignancy-associated SIADH 1
• Discontinuation of implicated medications 1
• Management of pulmonary or CNS disorders

Special Considerations

• In cancer patients with SIADH, hyponatremia often improves after successful treatment of the underlying malignancy 1
• For patients with short prognosis, strict fluid restriction may not be appropriate if not aligned with goals of care 1
• Vaptans should not be used for urgent correction of severe symptomatic hyponatremia 2

The treatment approach should be guided by symptom severity, serum sodium level, and patient response to initial therapy, with careful monitoring throughout to prevent complications of both hyponatremia and its correction.