Decreased antidiuretic response in diabetes insipidus during prolonged treatment with carbamazepine presumably due to enzym-induction.

Carbamazepine (CA)-induced antidiuresis and fluorescence in urinary cortisol assay was compared during short-term and prolonged treatment in 3 patients with pituitary diabetes insipidus. The fluorescence induced by excreted CA-metabolite(s) (probably CA-10-11 epoxide and its derivatives) was used for the rough clinical estimation of the rate of metabolic elimination of the drug. A marked decrease was observed both in the antidiuretic response induced by CA and excretion of CA metabolite(s) during prolonged treatment - with a fixed dose of CA. These findings suggest that diminishing antidiuretic effectiveness might be due to auto-induction of CA. Auto-induction of CA may explain the delay in improvement of renal concentrating operation in patients with DI during long-term treatment with fixed doses of CA. Another clinical consequence of this mechanism may be the prevention of the development of water intoxication in neuro-psychiatric patients undergoing chronic treatment with CA.