TY - JOUR
T1 - Double-Blind, Placebo-Controlled, Multicenter Trial of a Vasopressin V2-Receptor Antagonist in Patients with Schizophrenia and Hyponatremia
AU - Josiassen, Richard C.
AU - Goldman, Morris
AU - Jessani, Meera
AU - Shaughnessy, Rita A.
AU - Albazzaz, Ala
AU - Lee, Jennifer
AU - Ouyang, John
AU - Orlandi, Cesare
AU - Czerwiec, Frank
N1 - Funding Information:
This project was supported by Otsuka Pharmaceutical Development and Commercialization. The development of the pivotal SALT protocols was undertaken jointly by the sponsor and investigators. The data analysis of this sub-sample of individuals with schizophrenia was undertaken jointly by the sponsor and the authors. Drs. Josiassen and Goldman assume responsibility for the overall content and integrity of the manuscript, with substantial contributions from the coauthors; all authors vouch for the accuracy and completeness of the reported data. The sponsor holds the data, which were freely available to the authors. The authors would like to thank Jessica Curtis and Dawn Filmyer for technical and editorial support as well as Bruce McNeal for graphic design.
PY - 2008/12/15
Y1 - 2008/12/15
N2 - 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.
AB - 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.
KW - Hyponatremia
KW - schizophrenia
KW - tolvaptan
KW - vasopressin V2-receptor antagonist
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U2 - 10.1016/j.biopsych.2008.06.017
DO - 10.1016/j.biopsych.2008.06.017
M3 - Article
C2 - 18692175
AN - SCOPUS:56349152555
SN - 0006-3223
VL - 64
SP - 1097
EP - 1100
JO - Biological psychiatry
JF - Biological psychiatry
IS - 12
ER -