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Asleep at the Wheel
Abstract & commentary
By Barbara A. Phillips, MD, MSPH, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips is a consultant for Cephalon and Ventus, and serves on the speaker's bureaus for Cephalon and Boehringer Ingelheim.
Synopsis: Use of the benzodiazepine-like hypnotics (z-hypnotics), zolpidem and zopiclone, is associated with an increased risk of crash, particularly in young people.
Source: Gustavsen I, et al. Road traffic accident risk related to prescriptions of the hypnotics, zolpidem, flunitrazepam and nitrazepam. Sleep Med 2008;9:818-822.
This report originated with the Norwegian Institute of Public Health. It is a 19-month, retrospective analysis of all (!) Norwegians aged 18-69 years. The authors collected data on prescription medications, road traffic accidents, and emigration/death. They evaluated accidents occurring within both a 1-week period and a 2-week period following dispensing of 4 specific sleeping pills: nitrazepam, flunitrazepam, zopiclone, and zolpidem. The first 2 agents, nitrazepam and flunitra-zepam, are benzodiazepine hypnotics not available in the United States.
The database for this study was 3.1 million. The authors calculated standard incidence ratios (SIRs) for the risk of accident for exposed (e.g., filling a hypnotic prescription) and non-exposed people. Individuals who simultaneously filled prescriptions for other psychoactive drugs (e.g., opiates, benzodiazepines, z-hypnotics, or carisoprodol) were excluded from analysis.
Zopiclone was by far the most commonly prescribed hypnotic in this study. The number of crashes and the SIR for each of the studied agents is presented in the Table.
As can be seen from the table, all 4 of the hypnotics were associated with an increased risk of crash, with statistically significantly increased SIRs. For zopiclone and zolpidem, the risk was slightly more than doubled. The highest SIRs were found in the youngest age groups for all hypnotics; in fact, the increased risk of crash for those who were taking hypnotics was not statistically significant for those older than age 55 years. Men tended to have higher SIRs for all agents than did women. Exclusion of those individuals who were taking other psychoactive drugs did not change the results, nor did evaluation of crash risk for 2 weeks after medication was dispensed compared with 1 week after the prescription was filled.
First of all, the term "accident" is out, and the term "crash" is in. Crash is now the term used by governmental agencies and public health organizations. Use of the word crash is believed to be more effective in describing the devastation of vehicular impact, and also to stigmatize vehicular mishaps. Many are not accidents, and could have been prevented by more responsible behavior by the driver(s) involved.
The relationship between sleep, sleep disorders (including insomnia), and crash is a complicated and frightening one. Inadequate sleep (e.g., from simply not dedicating enough time to sleep [self-imposed sleep deprivation]) and obstructive sleep apnea are well-documented causes of increased crash risk.1-4
The association between insomnia and car crash is less clear. In one published survey, people who experienced chronic insomnia had a 2-fold increased risk of automobile accidents compared to people who were fatigued for other reasons.5 Importantly, that survey did not control for hypnotic use and was based on self-report.
The current report brings some clarity to the issue of insomnia and car crash risk, and suggests that the hypnotics used to treat insomnia may contribute to any increased risk of crash that is associated with sleeping difficulty. Benzodiazepines, which are known to be sedating and anxiolytic, are accepted as contributing to an increased risk of crash. It was hoped that the non-benzodiazepine hypnotics (the "z-hypnotics") would be able to induce safe sleep without this associated risk of crash. Based on the current report, that belief appears to be false. This current study documents an increased crash risk with the z-hypnotics, zolpidem and zaleplon, even after controlling for significant confounders. This increased risk may be independent of the "sleep driving" phenomenon6 that has recently surfaced in relationship to use of the benzodiazepine-receptor hypnotics.
This is not a perfect study. For one thing, it appears not to have controlled for exposure, e.g., the fact that the more a person drives, the more likely he is to crash. While the report seems to suggest that hypnotics do not carry an increased risk for crash in older individuals, that finding may result from the fact that older people drive less.
What to tell patients? First, hypnotics are not the ideal choice for chronic insomnia. Second, patients need to be warned about the increased risk of crash and other mishaps while under the influence of these agents. They should be advised to take them only when they are ready for sleep and have 7 or more hours to devote to sleep.
And we should also advise them about the risk for drug interactions and increased crash risk related to the use of other drugs, including over-the-counter agents. For example, there is an increased vehicular crash risk with narcotic analgesic use and antihistamine use.7 And we don't even know what increased risk the combinations of these agents (and others) brings!
1. George CF. Reduction in motor vehicle collisions following treatment of sleep apnoea with nasal CPAP. Thorax 2001;56:508-512.
2. Horstmann S, et al. Sleepiness-related accidents in sleep apnea patients. Sleep 2000;23:383-389.
3. Teran-Santos J, et al. The association between sleep apnea and the risk of traffic accidents. Cooperative Group Burgos-Santander. N Engl J Med 1999;340: 847-851.
4. Gurubhagavatula I, et al. Occupational screening for obstructive sleep apnea in commercial drivers. Am J Respir Crit Care Med 2004;170:371-376.
5. Gallup Organization. Sleep in America: A National Survey of U.S. Adults. Princeton, NJ: National Sleep Foundation; 1991.
6. Sanofi-Aventis. Ambien Prescribing Information. Bridgewater, NJ; 2008. Available at: http://products.sanofi-aventis.us/ambien/ambien.pdf. Accessed Feb. 11, 2009.
7. Howard ME, et al. Sleepiness, sleep-disordered breathing, and accident risk factors in commercial vehicle drivers. Am J Respir Crit Care Med 2004; 170:1014-1021.