Effects of large and small doses of hydrochlorothiazide in hypertensive patients

The ceiling diuretic dose of hydrochlorothiazide (HCT) is 200 mg. per day. To investigate the antihypertensive effect of doses of HCT greater than that producing maximal diuresis, 21 hypertensive outpatients were studied. These patients were selected from a large group and included only those who, on previous occasions, had failed to obtain adequate blood pressure control from diuretic therapy alone. After stabilization on placebo, all patients received HCT 150 mg. per day for 12 weeks. The dose was increased to 450 mg. per day in the 19 patients whose hypertension was inadequately controlled on the lower dose, and they were followed for a further 20 weeks. At regular intervals, measurements were made of biochemical and hematologic indices as well as serum magnesium and HCT concentration. Despite doubling of serum HCT concentration with the higher dose, the patients had no greater blood pressure lowering and no changes in biochemical measurements when the dose of HCT was tripled.