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      Arch Neurol. 2005 Aug;62(8):1242-8.  

 
Sudden uncontrollable somnolence and medication use in Parkinson disease.

Avorn J, Schneeweiss S, Sudarsky LR, Benner J, Kiyota Y, Levin R, Glynn RJ.

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of 
Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 
02120, USA. [log in to unmask]

BACKGROUND: Episodes of sudden uncontrollable somnolence have been reported in 
patients with Parkinson disease (PD) receiving dopamine agonists, including 
pramipexole and ropinirole, but controversy persists concerning their nature, 
severity, and frequency. OBJECTIVES: To quantify the risk of sudden 
uncontrollable somnolence in patients taking specific PD medications and to 
define its predictors. METHODS: We contacted 929 patients with PD and 
administered a 45- to 60-minute interview addressing medication use, adverse 
events, and the patient's clinical status in the preceding 6 months. Their 
physicians completed record reviews detailing their clinical histories and 
drug regimens. The outcome of interest in this case-control study was an 
episode of somnolence that was uncontrollable, severe, and inappropriate, 
such as while driving or engaged in social activity. For multiple events, the 
first was chosen as the index event. For each case, we sampled control time 
from all respondents who had no event as of the index time for that case. 
Multiple logistic regression was used to adjust for potential confounders. 
RESULTS: Episodes of uncontrollable somnolence were reported by 22% of all 
respondents. After controlling for age, sex, PD duration and severity, 
frailty, and other medication use, we found that patients receiving a 
dopamine agonist (pramipexole, ropinirole, or pergolide) were nearly 3-fold 
as likely to have episodes of sudden uncontrollable somnolence (odds ratio, 
2.8; 95% confidence interval, 1.8-4.2) compared with all other PD medication 
users. Similar risks were seen for the 3 agents, pramipexole, ropinirole, and 
pergolide, each compared with levodopa alone (odds ratio, 2.2, 1.8, and 2.1, 
respectively), with a clear dose-response relationship for each. No increase 
in risk was seen with any other drugs studied. CONCLUSIONS: Dopamine agonists 
widely used for the management of PD significantly increase the risk of 
sudden uncontrollable somnolence in a dose-related manner. Greater attention 
to this potentially serious adverse effect will be necessary to improve the 
safety of use of this important category of PD drugs.

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