Rilmenidine and vigilance. Review of clinical studies.
In this study, the possible effects of rilmenidine on vigilance are evaluated. Sedation is the most disturbing side effect of alpha 2-agonists, especially during the first weeks of treatment. The level of vigilance was first determined by assessing drowsiness using visual analogue scales and/or by several psychometric tests in four pharmacoclinical studies in healthy subjects or in hypertensive patients: three studies with single administration of rilmenidine (0.5 to 3.0 mg) and one study with repeated administration for three days. These studies were double-blind, Latin-square designed, and controlled versus placebo (in all studies) and versus clonidine (in three studies). Analysis of these results illustrated that after short-term and repeated administration: (1) the effects on vigilance observed with rilmenidine 1 mg did not differ statistically from data observed with placebo; and (2) sedative effects observed with clonidine were significantly greater than with rilmenidine, at equihypotensive doses. Daytime drowsiness was systematically assessed and graded by inciting questioning at each visit in five clinical studies. Ambulatory hypertensive patients were treated with rilmenidine (1 mg per day or 1 mg twice a day). These studies were controlled versus placebo (one study for two weeks, 120 patients; and one study for one month, 126 patients), hydrochlorothiazide (six weeks, 56 patients), clonidine (six weeks, 333 patients), and methyldopa (three months, 157 patients). The results showed that: (1) drowsiness observed with rilmenidine did not differ statistically from that observed with placebo or diuretic; and (2) drowsiness occurred less frequently with rilmenidine than with reference alpha 2-agonists at equihypotensive doses. In conclusion, these results confirm in current clinical use the dissociation already observed in laboratory animals between the antihypertensive effects and the sedative effects and may distinguish rilmenidine among alpha 2-agonists.