Efficacy and safety of oral tolvaptan therapy in patients with the syndrome of inappropriate antidiuretic hormone secretion

Eur J Endocrinol. 2011 May;164(5):725-32. doi: 10.1530/EJE-10-1078. Epub 2011 Feb 11.


Objective: Tolvaptan, an oral antagonist of the vasopressin V(2) receptor, has been found to improve hyponatremia in patients with mixed etiologies. This study analyzed a subgroup of patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) to evaluate the efficacy and safety of tolvaptan in this group.

Design and patients: Hyponatremic patients in the SALT-1 and SALT-2 studies with a diagnosis of SIADH were identified based on clinical diagnosis by individual study investigators. Subjects were randomized to receive oral placebo (n=52) or tolvaptan 15 mg daily, with further titration to 30 and 60 mg daily, if necessary, based on the response of serum [Na(+)] (n=58).

Results: In patients with SIADH, improvement in serum [Na(+)] was significantly greater (P<0.0001) with tolvaptan than placebo over the first 4 days of therapy as well as the entire 30-day study, with minimal side effects of increased thirst, dry mouth, and urination. Only 5.9% of tolvaptan-treated patients had overly rapid correction of hyponatremia as defined by current guidelines. After discontinuation of tolvaptan, serum [Na(+)] declined to values similar to placebo. A significant positive treatment effect favoring tolvaptan on the physical component, and a near-significant trend on the mental component, was found using the SF-12 Health Survey. Tolvaptan was associated with a significantly reduced incidence of fluid restriction.

Conclusions: Results for the SIADH subgroup were analogous to those of the combined SALT population regarding efficacy and safety but demonstrated a greater improvement in the physical component of the SF-12 Health Survey than in the full mixed etiology SALT patient group.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Benzazepines / administration & dosage*
  • Benzazepines / adverse effects*
  • Dizziness / chemically induced
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Inappropriate ADH Syndrome / blood
  • Inappropriate ADH Syndrome / drug therapy*
  • Inappropriate ADH Syndrome / urine
  • Male
  • Middle Aged
  • Thirst / drug effects
  • Thirst / physiology
  • Tolvaptan
  • Treatment Outcome


  • Benzazepines
  • Tolvaptan