Pramipexole-induced somnolence and episodes of daytime sleep

Pramipexole is a non-ergot dopamine agonist used to treat Parkinson's disea se (PD). Because of concern regarding driving safety, we evaluated the inci dence and nature of somnolence experienced by patients receiving pramipexol e in clinical trials at our center. A retrospective chart review was perfor med and structured interviews were conducted with patients who had reported moderate or severe somnolence. In addition, two patients underwent polysom nography (PSG) and multiple sleep latency tests (MSLT) while on and 2 weeks after discontinuation of pramipexole. Forty patients with PD participating in pramipexole clinical trials were identified. In the double-blind phases of the studies, 22 patients were randomized to pramipexole and 18 were ran domized to placebo. Six patients assigned to pramipexole reported somnolenc e as an adverse event (1 moderate, 5 mild) compared with two patients assig ned to placebo (1 severe, 1 moderate; p = 0.19, one-tailed Fisher's exact t est). Thirty-seven patients participated in open-label extension studies. T wenty-one (57%) reported somnolence as an adverse event. Eleven (30%) patie nts reported moderate somnolence and three (8%) patients reported severe so mnolence. For patients with moderate or severe somnolence, the onset of wor st-reported somnolence occurred at a mean (+/- standard error) pramipexole dose of 4.0 +/- 0.4 mg (range, 0.75-4.5 mg) per day. Patients had been taki ng pramipexole for a total of 10.0 +/- 1.5 months (range, .03-22 mos) and a t their maximal dose for 6.7 +/- 1.5 months (range, .03-20 mos). During str uctured interviews with 12 of the 14 patients reporting moderate or severe somnolence, seven reported falling asleep while driving and two reported mi nor motor vehicle accidents caused by falling asleep. Most patients reporte d relatively continuous drowsiness that led to falling asleep without acute warning during periods of inactivity. Three patients reported discreet wav es of irresistible sleepiness heralded by prodromal symptoms occurring agai nst a background of normal wakefulness. MSLT in two of these patients revea led decreased latency to sleep without early onset of rapid eye movements. Sleep latency normalized after withdrawal of pramipexole. Intensive patient education is necessary to prevent motor vehicle accidents in patients taki ng pramipexole. We recommend that patients who are experiencing generalized drowsiness and falling asleep during periods of inactivity be instructed n ot to drive because these patients do fall asleep without acute warning. So mnolence usually resolves with pramipexole dose reduction or discontinuatio n. Patients should also be alerted to pull over and stop driving immediatel y if they feel a wave of sleepiness coming on. Patient education and compli ance are critical to maximize safety.