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Influence of dosage and duration of therapy on the rate of response to methyclothiazide in essential hypertension.

One hundred twenty patients with essential hypertension were studied to determine whether patients who had not responded to the usual dose of a thiazide (methyclothiazide, 5 mg daily during a six-week drug trial) would respond to a higher dose (10 mg daily). The 14-week study was divided into three periods: (1) a two-week placebo period; (2) a six-week single-blind trial; and (3) a six-week period for double-blind dose comparison. Among the 77.3 percent of patients who responded to the drug, diastolic blood pressure was reduced to 90 mm Hg or lower. Two types of thiazide responders were identified-early and late. The early responders (50 percent of study patients), showed a significant reduction in diastolic blood pressure within four weeks; the late responders (27.3 percent) showed a modest reduction in diastolic blood pressure during the first four weeks of therapy, followed by a plateau lasting about two weeks, then a further significant reduction in blood pressure during the ensuing six weeks. Hypokalemia was more common in early responders. There were no significant differences in late response among patients who continued on the usual dose of methyclothiazide compared to those whose dosage was doubled, suggesting that the late response was not due to increasing the dose of the drug.