Mechanism of Carbamazepine (Tegretol)-Induced Antidiuresis: Evidence for Release of Antidiuretic Hormone and Impaired Excretion of a Water Load

Abstract

Four patients with central diabetes insipidus were studied to clarify the mechanism of antidiuretic action of carbamazepine (Tegretol). Oral administration of Tegretol to these patients resulted in a significant decrease in urine volume and in an elevation of U/P osmolar ratio to greater than 1. Antidiuretic hormone (ADH) concentrations in plasma also increased to normal range after the treatment. These studies indicated that the drug was acting through the release of endogenous ADH and thereby induced antidiuresis. During the course of therapy, an acute water load did not suppress ADH release, free water clearance remaining negative. Accordingly, it was concluded that the release of ADH during Tegretol therapy was controlled by the drug itself, not by physiological osmo- and volume-regulations. Tegretol was also effective in reducing polyuria in a patient with compulsive water drinking, but danger of water intoxication was great in this patient. Thus, Tegretol should not be given to this type of polyuria and caution should be exercised against water intoxication.