Double-blind, placebo-controlled, multicenter trial of a vasopressin V2-receptor antagonist in patients with schizophrenia and hyponatremia.

Abstract

OBJECTIVES:

Hyponatremia (serum sodium [Na+] concentration <136 mmol/L) is a prevalent and potentially life-threatening medical comorbidity for schizophrenic patients. No definitive pharmacological treatments have been established. Tolvaptan (OPC-41061), an oral non-peptide V2-receptor antagonist, was recently shown to correct hyponatremia in a diverse population of 448 hyponatremic patients. Efficacy in a sub-set of 19 schizophrenic patients with idiopathic hyponatremia included in that sample is specifically examined.

METHODS:

Nineteen subjects were randomly assigned to receive placebo (n = 12) or tolvaptan (n = 7) once daily for 30 days. Dosage adjustment was based on serum Na+ changes, initially 15 mg, titratable to 30 or 60 mg. The average daily area under the curve (AUC) changes in serum Na+ from baseline to Day 4 and Day 30 were co-primary end points.

RESULTS:

Increases in serum Na+ concentrations were significantly greater with tolvaptan than placebo at Day 4 (p = .0055) and at Day 30 (p < .0001). Two subjects receiving tolvaptan (28.6%) became dehydrated and experienced hypotension, and five subjects receiving placebo (41.7%) experienced symptoms associated with dilutional hyponatremia.

CONCLUSIONS:

These results suggest that tolvaptan effectively normalizes idiopathic hyponatremia in schizophrenic patients. Clinicians are advised to carefully monitor fluid status especially at the beginning of treatment to prevent dehydration.

• Authors: Richard C Josiassen, Morris Goldman, Meera Jessani, Rita A Shaughnessy, Ala Albazzaz, Jennifer Lee, John Ouyang, Cesare Orlandi, Frank Czerwiec
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 64 Issue 12 Pg. 1097-100 (Dec 15 2008) ISSN: 1873-2402 [Electronic] United States
• PMID: 18692175 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antidiuretic Hormone Receptor Antagonists
• Benzazepines
• Tolvaptan

Topics

• Adult
• Analysis of Variance
• Antidiuretic Hormone Receptor Antagonists
• Area Under Curve
• Benzazepines (therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Hyponatremia (drug therapy, epidemiology)
• Male
• Middle Aged
• Schizophrenia (drug therapy, epidemiology)
• Time Factors
• Tolvaptan