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. (J Clin Endocrinol Metab 38: 356, 1974)

A Case of Syndrome of Inappropriate Secretion of Antidiuretic Hormone Associated with Diabetes Mellitus.

“…To our knowledge, however, there has been only one reported case of SIADH due to diabetes mellitus alone, not to its drug treatment [4]. Carbamazepine and chlorpropamide have been reported to centrally stimulate ADH release and/ or to peripherally enhance the effect of ADH on the renal tubules, thereby resulting in hyponatremia [3,14]. However, the patient described here is not such a case, because he has never received any of these drugs.…”

Carbamazepine-Induced Hyponatremia in a Patient with Partial Central Diabetes insipidus

“…Carbamazepine has been reported to increase the secre tion and production of ADH [12,13], but other authors do not support this notion [5,14]. The reason for this discrep ancy is not yet clear.…”

Chronic Hypernatremia Associated with Holoprosencephaly

“…In our patients, the administration of carbamazepine, which exerted an antidiuretic action by increasing the release of ADH (Kimura et al 1974), was tried without correcting hypernatremia and hyperchloremia. Since these two patients seemed to have also defective thirst center, resulting in sustained mild dehydration it may be difficult to correct hypernatremia and hyperchloremia com pletely.…”