Introduction
Driving is a complex task that places demands on many cognitive skills which can be impaired by
psychoactive substances. Benzodiazepines (BZDs) and non-benzodiazepines (NBZDs) Z-drugs are the
most commonly used medication in the treatment of chronic insomnia and bind to GABAA receptors
in the brain promoting anxiolytic and sedative effects but also psychomotor and cognitive impairment.
Epidemiological data has shown that acute benzodiazepine use is associated with psychomotor and
cognitive impairment as well as an increased risk of being involved in traffic accidents and performing
unsafe driving behavior. However, it has also been suggested that partial tolerance to these adverse
effects occurs after long-term use (three years). Furthermore, former reports also indicated that long-
term BZD use might increase the risk of permanent cognitive impairment, and that long-term use
should be avoided in the elderly. In comparison with BZDs, studies on GABAA receptor agonist NBZDs
Z-drugs, including zolpidem, zopiclone, eszopiclone and zaleplon, are limited and their impact on
cognition in chronic users remains unknown. Nevertheless, because these drugs are used as hypnotics,
residual daytime sedation is one of the most important issues to consider in terms of traffic safety, and
studies have shown that reduced processing speed and decreased alertness may be problematic the
morning after administration depending on the timelapse between usage and driving. Based on the
above, the aim of this study was to evaluate whether cognitive impairment influencing fitness-to-drive
occurs in long-term zolpidem users (more than two years of 10 mg stable usage) using neurocognitive
paper-and pencil tests.
Materials and methods
The individuals recruited for this study included 10 middle-aged male individuals (35-55 y/o) suffering
from chronic insomnia, who were long-term users of 10 mg zolpidem (more than two years of stable
usage), with a frequency of administration of at least five times a week, with no history of secondary
insomnia caused by physical diseases, mental disorders, alcohol or illicit drug abuse or intake, unstable
organic diseases, depression, cognitive impairment, neurological disease or brain trauma, without any
concomitant psychotropic medication administration. Subjects underwent medico-legal fitness-to-
drive assessment requested by the authorities due to a traffic offence in the absence of traffic
accidents and underwent neurocognitive assessment encompassing different neurocognitive tests.
These tests were completed at least 12 hours after the last 10 mg dose of zolpidem was administered.
Results
Overall, cognitive performance was not significantly affected for any of the administered tests in any
of the recruited participants when compared to reference values and standard deviation of test scores
in the provided reference populations.
Discussion and conclusion
The results of the present study seem to indicate that impairing effects of long-term zolpidem use on
cognitive performances may mitigate over time following long-term use of two years. Furthermore,
there was no evidence of cognitive impairment after prolonged use and no evidence of residual
daytime sedation 12 hours after the last 10 mg dose administration. Regarding traffic safety, these
results seem to comfort the ICADTS classification of zolpidem as category II, or as category I when
driving occurs at least 10 hours post-dose. However, several limitations in our study deserve to be
mentioned. First, the individuals recruited represent a relatively homogenous sample due to strict
inclusion criteria. Secondly the limited sample size and the absence of comparative data at treatment
initiation do not allow the results to be generalized and inferred with certainty.