Vasopressin receptor antagonists for the treatment of hyponatremia: systematic review and meta-analysis

Am J Kidney Dis. 2010 Aug;56(2):325-37. doi: 10.1053/j.ajkd.2010.01.013. Epub 2010 Jun 9.


Background: In patients with euvolemic and hypervolemic hyponatremia, the effect of vasopressin antagonists is yet undefined.

Study design: Systematic review and meta-analysis of randomized controlled trials (RCTs).

Setting & population: In- and outpatients with euvolemic or hypervolemic hyponatremia.

Selection criteria for studies: We included all RCTs regardless of publication status or language.

Intervention: Vasopressin antagonists with or without fluid restriction versus placebo or no treatment with or without fluid restriction.

Outcomes: Response rate defined as normalization of serum sodium level or significant increase in serum sodium level at 3-7 days (primary) and later, change from baseline serum sodium level at 3-7 days and later, adverse events, rate of rapid sodium level correction, and rate of hypernatremia.

Results: 15 RCTs were identified. Vasopressin antagonist treatment significantly increased response rate both early (RR, 3.15; 95% CI, 2.27-4.37; 11 trials) and late (RR, 2.27; 95% CI, 1.79-2.89; 4 trials). Response rates were high in trials assessing mostly euvolemic patients and those assessing mostly hypervolemic patients, with greater effect estimate in the former. Change from baseline serum sodium level was significantly increased both early (weighted mean difference, 5.27 mEq/L; 95% CI, 4.27-6.26, 13 trials) and late (weighted mean difference, 3.49 mEq/L; 95% CI, 2.56-4.41, 8 trials). Although there was an increased rate of rapid sodium correction (RR, 2.52; 95% CI, 1.26-5.08, 8 trials) with vasopressin antagonists, hypernatremia rates were not significantly higher (RR, 2.21; 95% CI, 0.61-7.96; 5 trials), adverse events were not increased, and there were no reports of osmotic demyelination syndrome.

Limitations: Significant heterogeneity in the primary outcome.

Conclusions: Vasopressin antagonists are effective for the treatment of hypervolemic and euvolemic hyponatremia.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antidiuretic Hormone Receptor Antagonists*
  • Azepines / administration & dosage*
  • Benzamides / administration & dosage*
  • Benzazepines / administration & dosage*
  • Humans
  • Hyponatremia / drug therapy*
  • Morpholines / administration & dosage*
  • Pyrroles
  • Randomized Controlled Trials as Topic
  • Spiro Compounds / administration & dosage*
  • Tolvaptan
  • Treatment Outcome


  • Antidiuretic Hormone Receptor Antagonists
  • Azepines
  • Benzamides
  • Benzazepines
  • Morpholines
  • Pyrroles
  • Spiro Compounds
  • Tolvaptan
  • lixivaptan
  • satavaptan