title: Efficacy and safety of oral tolvaptan therapy in patients with the syndrome of inappropriate antidiuretic hormone secretion.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Georgetown University Medical Center, Georgetown University, Washington, DC 20007, USA. verbalis@georgetown.edu
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Verbalis
authors.forename: Suzanne
authors.initials: S
authors.lastname: Adler
authors.forename: Robert W
authors.initials: RW
authors.lastname: Schrier
authors.forename: Tomas
authors.initials: T
authors.lastname: Berl
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhao
authors.forename: Frank S
authors.initials: FS
authors.lastname: Czerwiec
mesh_terms: D000284:Administration, Oral; D000368:Aged; D001552:Benzazepines / Q000008:administration & dosage* / Q000009:adverse effects*; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007177:Inappropriate ADH Syndrome / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D008297:Male; D008875:Middle Aged; D013894:Thirst / Q000187:drug effects / Q000502:physiology; D000077602:Tolvaptan; D016896:Treatment Outcome
chemical_list: D001552:Benzazepines; D000077602:Tolvaptan