Antihypertensive and biochemical effects of chlorthalidone

Thirty-seven patients with mild to moderate essential hypertension completed a dose-finding study in which daily doses of 25, 50, 100, and 200 mg of chlorthalidone were administered in random order for 8 wk. Active treatment periods were double-blind and were interspersed with single-blind placebo intervals which lasted until control blood pressure values were regained. The four doses of chlorthalidone produced similar hypotensive effects, but changes in serum potassium, chloride, and uric acid were clearly related to the dose of chlorthalidone. The reduction in blood pressure was maximal in 25 of the patients on a dose of 25 or 50 mg of chlorthalidone, while maximal reduction was observed in the remaining 12 patients on doses of 100 or 200 mg. The response of an individual to chlorthalidone could not be predicted. Chlorthalidone was well tolerated as evidenced by an acceptable level of compliance and by the relative infrequency with which side effects were reported. On the basis of this study approximately two thirds of patients with mild to moderate hypertension can be expected to respond to 50 mg or less chlorthalidone daily. Such doses are associated with minimal biochemical changes. Some patients failing to respond to low doses of chlorthalidone may respond to higher doses, but these frequently induce biochemical disturbances.