Sudden uncontrollable somnolence and medication use in Parkinson disease.
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.


OBJECTIVE
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.
Avorn
Jerry
J
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02120, USA. javorn@partners.org
Schneeweiss
Sebastian
S
Sudarsky
Lewis R
LR
Benner
Joshua
J
Kiyota
Yuka
Y
Levin
Raisa
R
Glynn
Robert J
RJ
D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects; D016022:Case-Control Studies; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D018491:Dopamine Agonists / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D012307:Risk Factors
D000978:Antiparkinson Agents; D018491:Dopamine Agonists