Randomized, Double-Blind, Placebo-Controlled Study of Clonidine in Restless Legs Syndrome.

Ten patients with idiopathic restless leg syndrome (RLS) were asked to rate their symptoms at baseline during 2 weeks of placebo and 2 weeks of clonidine treatment by using a four-point scale. On two consecutive nights of each treatment period, polysomnography (PSG) and actigraphic studies were performed. Patients subjectively reported improvement in leg sensations (p = 0.02) and motor restlessness (p = 0.001) while receiving clonidine (mean = 0.5 mg/day). On PSG testing, sleep onset occurred faster with clonidine (12 minutes) compared with placebo (30 minutes) and baseline (47 minutes) (p = 0.006). Adverse findings associated with clonidine treatment included decreased percent REM sleep in the clonidine group (4%) compared with placebo (16%) and baseline (16%) (p = 0.001) and increased REM latency in the clonidine group (195 minutes) compared to the placebo (70 minutes) and baseline groups (89 minutes) (p = 0.028). There were no significant changes in total sleep time, stage 1 and 2 sleep, sleep efficiency, awakenings, arousals or periodic limb movements in sleep. There was a nonstatistical trend toward and increase in stage 3 and 4 sleep and a decrease in motor activity as measured by actigraphic recordings. Globally, seven out of 10 patients felt clonidine was more effective than placebo. Four patients chose to continue clonidine after the study. Clonidine may be an effective treatment for RLS patients who don't have large numbers of sleep-disrupting periodic limb movements but have delayed sleep onset due to leg sensations and subsequent motor restlessness.