Elsevier

The Lancet

Volume 352, Issue 9137, 24 October 1998, Pages 1331-1336
The Lancet

Articles
Association of road-traffic accidents with benzodiazepine use

https://doi.org/10.1016/S0140-6736(98)04087-2Get rights and content

Summary

Background

Psychomotor studies suggest that commonly prescribed psychoactive drugs impair driving skills. We have examined the association between the use of psychoactive drugs and road-traffic accidents.

Methods

We used dispensed prescribing as a measure of exposure in a within-person case-crossover study of drivers aged 18 years and over, resident in Tayside, UK, who experienced a first road-traffic accident between Aug 1, 1992, and June 30, 1995, and had used a psychoactive drug (tricyclic antidepressant, benzodiazepine, selective serotonin-reuptake inhibitor, or other psychoactive drug [mainly major tranquillisers]) between Aug 1, 1992, and the date of the accident. For each driver, the risks of having a road-traffic accident while exposed and not exposed to a drug were compared.

Findings

19 386 drivers were involved in a first road-traffic accident during the study period. 1731 were users of any study drug. On the day of the accident, 189 individuals were taking tricyclic antidepressants (within-patient exposure odds ratio for an accident 0·93 [95% CI 0·72–1·21]), 84 selective serotonin-reuptake inhibitors (0·85 [0·55–1·33]), 235 benzodiazepines (1·62 [1·24–2·12]), and 47 other psychoactive drugs (0·88 [0·62–1·25]). The risk associated with benzodiazepine use decreased with increasing driver's age and was greater when the breath test for alcohol was positive. A dose-response relation was evident with benzodiazepines. The increased risk with benzodiazepines was significant for long-half-life drugs, used as anxiolytics, and for short-half-life hypnotics (all zopiclone).

Interpretation

Users of anxiolytic benzodiazepines and zopiclone were at increased risk of experiencing a road-traffic accident. Users of anxiolytic benzodiazepines and zopiclone should be advised not to drive.

Introduction

Drugs acting on the central nervous system can have adverse effects, drowsiness and increased reaction time, that may affect driving performance.1 In elderly people, benzodiazepines and tricyclic antidepressants have been associated with increased risks of road-traffic accidents causing injury.2, 3, 4, 5 There have been many suggestions of a causal link between psychotropic drugs and road-traffic accidents.6, 7, 8, 9, 10 A report commissioned for the European Community Directorate on Transport suggested that at least 10% of all people killed or injured in road-traffic accidents were taking some psychotropic medication that could have been a contributory factor.11

Owing to methodological difficulties in carrying out such studies, such as control of confounding, there are few epidemiological data on the association between road-traffic accidents and prescribed psychotropic drugs, despite calls for such data.12 One possible solution is to use a historical within-person comparison design, known also as the case-crossover method.13 This design helps to control for confounding between individuals by assessing the change in risk of an acute event during a hazard period, after exposure to a transient risk factor. With this method, each individual's previous exposure to drugs serves as his or her control information.

We undertook a case-crossover study using a population-based record-linkage database in collaboration with Tayside Police, to investigate the association between road-traffic accidents and use of antidepressants, benzodiazepines, and other psychoactive drugs.

Section snippets

Study population

The study population consisted of 410 306 individuals who were resident in Tayside Region, UK, and who had been registered with a Tayside general practitioner between January, 1992, and January, 1995 (including those who died during that period).

Methods

The study used the record-linkage database of the Medicines Monitoring Unit (MEMO), which contains prospectively gathered data on all dispensed community prescriptions in Tayside. The data-collection methods have been described in detail elsewhere.14, 15 In brief, all dispensed prescriptions in Tayside were obtained from the Pharmacy Practice Division of the Common Services Agency. By use of specially written software and data about all individuals registered with general practitioners in

Analyses

The analyses used a case-crossover design.14 For each case, the odds of having a road-traffic accident while exposed to one of the study drugs were compared with the odds of having an accident while unexposed. The odds ratio was calculated as the measure of association between drug use and a road-traffic accident. The odds ratio was estimated based on within-person matching, according to established epidemiological methods for matched studies.17 We applied three definitions of exposure: first,

Exposure and accident data

Table 1 shows the number of prescriptions dispensed and the number of individuals who received these by age, during the period Jan 1, 1993, to June 30, 1995.

Of 19 386 drivers involved in a first road-traffic accident during the study period, we identified 1731 users of any study drug (table 2). There were 793 users of tricyclic antidepressants, 334 users of selective serotonin-reuptake inhibitors, 916 users of benzodiazepines, and 138 users of other psychoactive drugs.

Odds ratios for major drug classes

Table 3 shows the number of road-traffic accidents that occurred on a day of drug use and the exposure odds ratios. The odds ratio for benzodiazepine use was 1–62, compared with 0·93 for tricyclic antidepressants and 0·85 for selective serotonin-reuptake inhibitors. For other psychoactive drugs there were too few events for further analyses (47 events; odds ratio 0·88 [0·62-1·25]).

Risk associated with benzodiazepine use

The risk associated with benzodiazepine use was highest among drivers younger than 30 years; it decreased with increasing age and was not raised in people aged 65 and over (test for trend p=0·01, table 3). There were no significant differences between men and women.

Particularly high risks were found for use of benzodiazepines and road-traffic accidents involving fatal injuries (table 3), although this result was based on only four exposed cases.

The odds ratio for users of benzodiazepines

Confounding by excess alcohol use

To find out whether a positive breath test for alcohol was more common in benzodiazepine users than in users of other drugs, we examined the rate of positive breath tests in drug users according to whether they were exposed or unexposed to the drug at the time of the accident. The proportion of positive breath tests in exposed and unexposed individuals, respectively, was 3·0% and 2·6% for benzodiazepines; 6·0% and 4·5% for selective serotonin-reuptake inhibitors; and 0·5% and 2·4% for tricyclic

Anxiolytic and hypnotic benzodiazepines

Most of the risks associated with benzodiazepines seemed to be confined to anxiolytics (test for difference from hypnotics p=0·01, table 4). The highest risks were seen in drivers younger than 45. Drivers aged 65 and older were not at increased risk.

Of the four fatal accidents among users of benzodiazepines, three were in users of anxiolytic benzodiazepines.

To check that benzodiazepines were being used according to their classification, prescriptions for these drugs dispensed at the time of the

Discussion

The case-crossover design used in this study overcomes many of the difficulties of selecting an appropriate control series for cases of road-traffic accidents.22 Cases are self-matched for periods not related to road-traffic accidents. This method was used by Redelmeier and Tibshirani23 to investigate the relation between use of cellular telephones and motor-vehicle collisions. Possible confounding effects from differences between individuals were eliminated, and the focus of the analysis was

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