title: Residual effects of low-dose sublingual zolpidem on highway driving performance the morning after middle-of-the-night use.
abstract: OBJECTIVE
  To evaluate next-morning driving performance after middle-of-the-night use of zolpidem 3.5 mg in a buffered sublingual formulation (ZST).
  
  
  METHODS
  Single-center, four-period, randomized, double-blind, placebo-controlled, crossover study.
  
  
  METHODS
  Maastricht University, The Netherlands.
  
  
  METHODS
  Forty healthy volunteers (20 females).
  
  
  METHODS
  Single dose of ZST administered in the middle of the night at 3 and 4 h before driving, zopiclone 7.5 mg at bedtime 9 h before driving, and placebo.
  
  
  METHODS
  Performance in a 100-km standardized highway driving test in normal traffic measuring standard deviation of lateral position (SDLP) - an index of weaving. Drug-placebo changes in SDLP > 2.5 cm were considered to reflect clinically relevant driving impairment.
  
  
  RESULTS
  For ZST, Max McNemar symmetry analyses showed that the proportion of drivers classified as impaired was increased 3 h after dosing (P < 0.012), but not 4 h after dosing. Mean increases in SDLP from placebo, although statistically significant, were small (1.46 cm [P < 0.0001] at 3 h and 0.83 cm [P = 0.0174] at 4 h). The morning after zopiclone, 45% of the drivers were classified as impaired with a mean increase in SDLP of 2.46 cm (P < 0.0001). There were no significant sex differences in effects of ZST and zopiclone.
  
  
  CONCLUSIONS
  Zolpidem 3.5 mg in a buffered sublingual formulation has a minimal risk of impairing driving performance in the morning ≥ 4 hours after middle-of-the night use. When taken 3 hours before driving, the drug may have impairing effects so caution should be exercised if medication is taken other than as indicated.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT01106859; Trial Name: Driving Performance After Middle of the Night Administration of 3.5 mg Zolpidem Tartrate Sublingual Tablet; http://clinicaltrials.gov/ct2/show/NCT01106859.
authors.affiliation: Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Annemiek
authors.initials: A
authors.lastname: Vermeeren
authors.affiliation: Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Eric F P M
authors.initials: EF
authors.lastname: Vuurman
authors.affiliation: Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Tim R M
authors.initials: TR
authors.lastname: Leufkens
authors.affiliation: Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Cees J
authors.initials: CJ
authors.lastname: Van Leeuwen
authors.affiliation: Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Anita C M
authors.initials: AC
authors.lastname: Van Oers
authors.affiliation: Nathan Kline Institute for Psychiatric Research, Orangeburg, NY and New York University, Langone School of Medicine, New York, NY.
authors.forename: Eugene
authors.initials: E
authors.lastname: Laska
authors.affiliation: Transcept Pharmaceuticals, Inc., Point Richmond, CA.
authors.forename: Salvador
authors.initials: S
authors.lastname: Rico
authors.affiliation: Transcept Pharmaceuticals, Inc., Point Richmond, CA.
authors.forename: Frank
authors.initials: F
authors.lastname: Steinberg
authors.affiliation: Henry Ford Hospital Sleep Disorders and Research Center, Detroit, MI.
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
mesh_terms: D000286:Administration, Sublingual; D000328:Adult; D001334:Automobile Driving / Q000523:psychology*; D053961:Azabicyclo Compounds / Q000008:administration & dosage / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009048:Motor Skills / Q000187:drug effects; D009426:Netherlands; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D012727:Sex Characteristics; D013997:Time Factors; D055815:Young Adult; D000077334:Zolpidem
chemical_list: D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; D011725:Pyridines; C515050:zopiclone; D000077334:Zolpidem
keywords: Driving; hypnotics; sex; zolpidem sublingual; zopiclone