Antiparkinsonian drug-induced sleepiness: a double-blind placebo-controlled study of L-dopa, bromocriptine and pramipexole in healthy subjects

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Dopamine agonists used in Parkinson's disease patients are associated with excessive daytime sleepiness and sleep attacks occurring without prior warning. • Parkinson's disease accounts in itself for a variety of sleep disorders. It is therefore important to study the drug-induced sleepiness in healthy volunteers. • In healthy subjects, pramipexole has proved to decrease alertness and ropinirole to reduce sleep latency. WHAT THIS STUDY ADDS • Results from our study show that pramipexole reduces the mean sleep latency as measured by the Multiple Sleep Latency Test in healthy volunteers, hence providing an objective measure of increased sleepiness. • Furthermore, the reduction in sleep latency was not associated with a subjective impression of increased sleepiness. • Such dissociation may underlie the occurrence of sleep attacks without prior warning. AIMS To assess the sleepiness induced by pramipexole, a D2/D3-dopamine receptor agonist commonly used in Parkinson's disease and restless legs syndrome, without the problem of the confounding factors related to the disease. METHODS Placebo, bromocriptine (2.5 mg), L-dopa (100 mg) and pramipexole (0.5 mg) were administered in a single oral dose on four separate days, with at least a 2-week wash-out period in a randomized cross-over design. Induced somnolence was assessed using Multiple Sleep Latency Test (MSLT) and subjective scaling of vigilance. Twelve male subjects (26.3 ± 5.5 years old) without anxiety, mood, sleep or sedation disorders were enrolled. RESULTS Pramipexole significantly reduced mean sleep latency compared with placebo 3 h 30 min [−6.1 min (−9.8, −2.4), P = 0.002] and 5 h 30 min [−5.6 min (−7.7, −3.5), P = 0.003] after administration. In addition, the total duration of sleep during the tests was higher with pramipexole than with placebo [+6.0 min (2.3, 9.7), P < 0.001]. These differences were not observed with L-dopa and bromocriptine in comparison with placebo. The induced sleepiness was not associated with an increase in subjective somnolence scaling, indicating that this adverse event may occur without prior warning. CONCLUSIONS These results show that a single oral dose of pramipexole induces sleepiness as assessed by MSLT in healthy young subjects, independent of disease-related sleep dysfunction.