title: Sudden uncontrollable somnolence and medication use in Parkinson disease.
abstract: 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.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02120, USA. javorn@partners.org
authors.forename: Jerry
authors.initials: J
authors.lastname: Avorn
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schneeweiss
authors.forename: Lewis R
authors.initials: LR
authors.lastname: Sudarsky
authors.forename: Joshua
authors.initials: J
authors.lastname: Benner
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kiyota
authors.forename: Raisa
authors.initials: R
authors.lastname: Levin
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Glynn
mesh_terms: 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
chemical_list: D000978:Antiparkinson Agents; D018491:Dopamine Agonists