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

Abstract

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.

Figure 1

Comparative time course of sleep latency on Multiple Sleep Latency Test (MSLT) for the four treatments. Data are expressed in minutes and shown as mean values ± SD of each MSLT session for each treatment (*P < 0.01). L-dopa (); Placebo (); Bromocriptine (); Pramipexole ()

Figure 2

Subjective assessment of vigilance levels for each treatment using the Thayer's and Hindmarch's scales. Mean visual analogue scaling scores for items ‘woozy’ (A) and ‘drowsy’ (B) of Hindmarch's scale and mean self-alertness ratio (GA/DS) calculated from items of the Thayer's scale (C). Results are shown for each treatment and each assessment time. Error bars (SD) are indicated. L-dopa (); Placebo (); Bromocriptine (); Pramipexole ()