Antiparkinsonian drug-induced sleepiness: a double-blind placebo-controlled study of L-dopa, bromocriptine and pramipexole in healthy subjects.
OBJECTIVE
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.
Micallef
Joëlle
J
Clinical Investigation Centre (CIC-UPCET) and Department of Clinical Pharmacology, UMR-CNRS 6193 Institute of Cognitive Neurosciences, CHU Timone, Marseille, France.
Rey
Marc
M
Eusebio
Alexandre
A
Audebert
Christine
C
Rouby
Frank
F
Jouve
Elisabeth
E
Tardieu
Sophie
S
Blin
Oliver
O
D000293:Adolescent; D000328:Adult; D000978:Antiparkinson Agents / Q000009:adverse effects*; D052160:Benzothiazoles / Q000009:adverse effects*; D001971:Bromocriptine / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D017286:Polysomnography; D000077487:Pramipexole; D012893:Sleep Wake Disorders / Q000139:chemically induced*; D016896:Treatment Outcome; D055815:Young Adult
D000978:Antiparkinson Agents; D052160:Benzothiazoles; D001971:Bromocriptine; D007980:Levodopa; D000077487:Pramipexole