title: Zopiclone's residual effects on actual driving performance in a standardized test: a pooled analysis of age and sex effects in 4 placebo-controlled studies.
abstract: BACKGROUND
  In many European countries, Canada, and Japan, the nonbenzodiazepine zopiclone is now among the most frequently prescribed hypnotic drugs. This finding can be explained by the growing view among physicians that zopiclone is more effective and safer than conventional benzodiazepines. However, in 4 studies using similar procedures, it has been shown that zopiclone 7.5 mg causes moderate to severe impairment in driving performance.
  
  
  OBJECTIVE
  The goal of the present article was to review these studies and analyze the pooled data to determine whether the severity of effects is modified by the sex and age of the subjects.
  
  
  METHODS
  The driving data of the placebo and zopiclone 7.5 mg evening treatment periods from a total of 4 studies conducted at Maastricht University were included in this pooled analysis. All studies were conducted according to balanced double-blind, crossover designs. The effects on driving were always measured the next morning, between 10 and 11 hours after administration, by using a standardized highway driving test. A total of 101 healthy volunteers of both sexes in equal proportions (with no reports of insomnia) participated. Subjects comprised young volunteers (age range, 21-45 years) in 3 studies and older volunteers (age range, 55-75 years) in the fourth study.
  
  
  RESULTS
  Results show that zopiclone 7.5 mg has significant and clinically relevant performance-impairing effects on driving in the morning, until 11 hours after bedtime ingestion. The effects did not differ between male and female subjects and did not increase with age, at least until 75 years. The effects of zopiclone 7.5 mg are comparable to the effects of a mean blood alcohol concentration between 0.5 and 0.8 mg/mL, which has been associated with a 2- to 3-fold increase in the risk of becoming involved in a traffic accident.
  
  
  CONCLUSIONS
  We concluded that patients using an evening dose of zopiclone 7.5 mg should avoid activity in skilled work and participation in traffic the morning after intake. General practitioners' beliefs regarding the beneficial safety profile of zopiclone may need adjustment, and patients using zopiclone 7.5 mg should be warned accordingly. There is no need to differentiate warnings about zopiclone's residual impairing effects depending on the sex of the patient.
authors.affiliation: Philips Group Innovation-Research, Division Information and Cognition, Department of Brain, Body and Behavior, Eindhoven, the Netherlands. Electronic address: tim.leufkens@philips.com.
authors.forename: Tim R M
authors.initials: TR
authors.lastname: Leufkens
authors.affiliation: Experimental Psychopharmacology Unit, Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Vermeeren
mesh_terms: D000328:Adult; D000368:Aged; D001334:Automobile Driving; D053961:Azabicyclo Compounds / Q000008:administration & dosage* / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects*; D011597:Psychomotor Performance / Q000187:drug effects*; D055815:Young Adult
chemical_list: D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; C515050:zopiclone; D000431:Ethanol
keywords: hypnotics; on-the-road driving; residual effects; zopiclone