Original ArticleRoad traffic accident risk related to prescriptions of the hypnotics zopiclone, zolpidem, flunitrazepam and nitrazepam
Introduction
Insomnia is a common condition in the adult population [1], [2], [3], [4]. Benzodiazepines were introduced in the 1960s and provided important pharmacological treatment of insomnia [5], [6]. During the 1990s the benzodiazepine-like hypnotics (zopiclone, zolpidem and zaleplone (z-hypnotics)) took over an increasing share of the market in many countries [7], [8], [9], [10]. The 1-year prevalence of zopiclone usage among individuals 20–69 years in Norway was about 6% in 2006 [11].
Pharmacoepidemiological studies have revealed an increased risk of road traffic accidents related to prescriptions of benzodiazepines [12], [13], [14], [15]. Despite the importance of such studies, there have been limited epidemiological studies on the association between road traffic accidents and prescribed psychotropic drugs. Few previous pharmacoepidemiological studies have investigated benzodiazepine hypnotics separately from benzodiazepine anxiolytics. One cohort study found a highly increased risk of a road traffic accident one week after dispensing prescriptions for a benzodiazepine hypnotic [12]. Another study on both benzodiazepines and z-hypnotics with a case-crossover design found no significant increase in accident risk after hypnotic exposure in general [16]. However, the study did find an increased accident risk related to zopiclone exposure alone.
Since a Norwegian database covering all prescriptions dispensed outside hospitals was established, studies have been carried out on the risk of road traffic accidents related to the prescription of pharmaceuticals [17], [18]. An increased risk was found for individuals using prescribed benzodiazepine hypnotics [17], but z-hypnotics were not included in the study.
The aim of our study was to investigate, using population-based registries: whether picking up a prescribed z-hypnotic increased the road traffic accident risk. The benzodiazepine hypnotics flunitrazepam and nitrazepam were used as comparator drugs.
Section snippets
Method
Data were retrieved from three Norwegian population-based registries; the Norwegian Prescription Database (NorPD), the Road Accident Registry (NRAR), and the Central Population Registry (NCPR). The model has been described in detail elsewhere [17].
Results
Table 2 shows the number of road traffic accidents occurring during exposed person-time, and age and gender of the drivers.
Increased SIRs were observed for all hypnotics (Table 3). Z-hypnotics exposure resulted in a lower SIR than exposure to benzodiazepine hypnotics. The SIR for flunitrazepam was strikingly high. The combined SIR for zopiclone and zolpidem was 2.3; 2.0–2.7 (SIR for all ages and both sexes combined; 95% CI). The highest SIRs were found in the youngest age groups for all
Discussion
In this study, we found an increased risk of being involved in a road traffic accident as a driver for users of prescribed hypnotics. Exposure to z-hypnotics led to a lower SIR than exposure to benzodiazepine hypnotics. The SIR for flunitrazepam was particularly high. Young drivers exposed to any hypnotic had the highest SIRs, and males seemed to have a greater accident risk than females.
High quality data were achieved by using population-based registries which can be linked using unique
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